Interventions for sexual dysfunction following treatments for cancer (Review)

Miles C, Candy B, Jones L, Williams R, Tookman A, King M

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2012, Issue 8 http://www.thecochranelibrary.com

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 1 Improvement in erections (GAQ). . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.2. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 2 Erectile function domain of IIEF: Bilateral nerve sparing radical retropubic prostatectomy 20mg vardenal. . Analysis 1.3. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 3 Successful vaginal penetration (Sexual Encounter Prole). . . . . . . . . . . . . . . . . . . . Analysis 1.4. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 4 Successful vaginal intercourse (Sexual Encounter Prole). . . . . . . . . . . . . . . . . . . . Analysis 1.5. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 5 Improvement in erections (GAQ) following SD after bilateral nerve sparing radical retropubic prostatectomy. . Analysis 1.6. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 6 Improvement in erections (GAQ) following SD after unilateral nerve sparing radical retropubic prostatectomy. Analysis 1.7. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 7 Erectile function domain of IIEF: Bilateral nerve sparing radical retropubic prostatectomy 10mg vardenal. . Analysis 1.8. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 8 Successful vaginal penetration (SEP): Bilateral nerve sparing radical retropubic prostatectomy 20mg vardenal. Analysis 1.9. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 9 Erectile function domain of IIEF: Bilateral nerve sparing radical retropubic prostatectomy 20mg Tadalal. . . Analysis 1.10. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 10 Erectile function domain of IIEF: Unilateral nerve sparing radical retropubic prostatectomy 20mg vardenal. . Analysis 1.11. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 11 Erectile function domain of IIEF: Unilateral nerve sparing radical retropubic prostatectomy 10mg vardenal. . Analysis 1.12. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 12 Erectile function: IIEF at follow-up: Bilateral nerve sparing radical retropubic prostatectomy 20mg Vardenal. Analysis 1.13. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 13 Successful vaginal penetration (SEP): Bilateral nerve sparing radical retropubic prostatectomy 10mg vardenal. Analysis 1.14. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 14 Successful vaginal penetration(SEP): Unilateral nerve sparing radical retropubic prostatectomy 20mg vardenal. Analysis 1.15. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 15 Successful vaginal penetration(SEP): Unilateral nerve sparing radical retropubic prostatectomy 10mg vardenal. Analysis 1.16. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 16 Successful vaginal intercourse (SEP): Bilateral nerve sparing radical retropubic prostatectomy 20mg vardenal. Analysis 1.17. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 17 Successful vaginal intercourse (SEP): Bilateral nerve sparing radical retropubic prostatectomy 10mg vardenal. Analysis 1.18. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 18 Successful vaginal intercourse(SEP): Unilateral nerve sparing radical retropubic prostatectomy 20mg vardenal. Analysis 1.19. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 19 Successful vaginal intercourse(SEP): Unilateral nerve sparing radical retropubic prostatectomy 10mg vardenal.
Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 1.20. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 20 Erectile function domain of IIEF: Mean difference. . . . . . . . . . . . . . . . . . . . . . Analysis 2.1. Comparison 2 Transurethral alprostadil versus placebo, Outcome 1 Vaginal intercourse rate. . . . . Analysis 2.2. Comparison 2 Transurethral alprostadil versus placebo, Outcome 2 Adverse events: urethral pain/burning. Analysis 2.3. Comparison 2 Transurethral alprostadil versus placebo, Outcome 3 Adverse events: penile pain. . . . Analysis 3.1. Comparison 3 Vacuum constriction device versus observational care following prostatectomy, Outcome 1 Erectile function. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.2. Comparison 3 Vacuum constriction device versus observational care following prostatectomy, Outcome 2 Erectile function in nerve-sparing surgery group. . . . . . . . . . . . . . . . . . . . . . . Analysis 3.3. Comparison 3 Vacuum constriction device versus observational care following prostatectomy, Outcome 3 Successful vaginal intercourse. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.4. Comparison 3 Vacuum constriction device versus observational care following prostatectomy, Outcome 4 Sexual function (IIEF). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.1. Comparison 4 Supportive partners versus usual care, Outcome 1 Sexual function (UCLA Prostate Cancer Index). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.2. Comparison 4 Supportive partners versus usual care, Outcome 2 Sexual bother (UCLA Prostate Cancer Index). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 5.1. Comparison 5 Acetyl-L-Carnitane (ALC) plus propionyl-L-Carnitane (PLC) and sildenal versus sildenal only versus placebo, Outcome 1 Satisfactory sexual intercourse (self report): sidenal +ALC + PLC versus placebo. Analysis 5.2. Comparison 5 Acetyl-L-Carnitane (ALC) plus propionyl-L-Carnitane (PLC) and sildenal versus sildenal only versus placebo, Outcome 2 Satisfactory sexual intercourse: sidenal versus placebo. . . . . . . . . Analysis 5.3. Comparison 5 Acetyl-L-Carnitane (ALC) plus propionyl-L-Carnitane (PLC) and sildenal versus sildenal only versus placebo, Outcome 3 Satisfactory sexual intercourse: sidenal + ALC + PLC versus sidenal. . . . Analysis 6.1. Comparison 6 Oestrogen vaginal cream versus placebo, Outcome 1 Sexual vaginal intercourse (self report). Analysis 6.2. Comparison 6 Oestrogen vaginal cream versus placebo, Outcome 2 Dyspareunia (self report). . . . . Analysis 6.3. Comparison 6 Oestrogen vaginal cream versus placebo, Outcome 3 Severe dyspareunia (self report). . Analysis 7.1. Comparison 7 Sexual counselling versus no counselling in men using prostaglandin E1 intracavernous injection, Outcome 1 Couple satisfaction. . . . . . . . . . . . . . . . . . . . . . . . . ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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[Intervention Review]

Interventions for sexual dysfunction following treatments for cancer

Clare Miles1 , Bridget Candy2 , Louise Jones2 , Rachael Williams3 , Adrian Tookman2 , Michael King4 Curie Palliative Care Research Unit, Department of Mental Health Sciences, Royal Free & University College Medical School, London, UK. 2 Marie Curie Palliative Care Research Unit, UCL Mental Health Sciences Unit, University College Medical School, London, UK. 3 Marie Curie Palliative Care Research Unit, Department of Mental Health Sciences, University College Medical School, London, UK. 4 UCL Mental Health Sciences, University College Medical School, London, UK Contact address: Bridget Candy, Marie Curie Palliative Care Research Unit, UCL Mental Health Sciences Unit, University College Medical School, Charles Bell House, 67 - 73 Riding House Street, London, W1W 7EJ, UK. b.candy@ucl.ac.uk. bridget@metaclarity.com. Editorial group: Cochrane Pain, Palliative and Supportive Care Group. Publication status and date: Edited (no change to conclusions), published in Issue 8, 2012. Review content assessed as up-to-date: 17 August 2007. Citation: Miles C, Candy B, Jones L, Williams R, Tookman A, King M. Interventions for sexual dysfunction following treatments for cancer. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD005540. DOI: 10.1002/14651858.CD005540.pub2. Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
1 Marie

ABSTRACT Background The proportion of people living with and surviving cancer is growing. This has led to increased awareness of the importance of quality of life including sexual function in people with cancer. Sexual dysfunction (SD) is a potential long-term complication of cancer treatments. Objectives Evaluate effectiveness of interventions for SD following treatments for cancer and their adverse effects. Search methods The Cochrane Pain, Palliative & Supportive Care Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycInfo, AMED, CINAHL, Dissertation Abstracts and NHS Research Register were searched. Search ran in January 2007. Selection criteria Randomised controlled trials (RCTs) were included that assessed the effectiveness of a treatment for SD. The trial population comprised of adults of either sex who at trial entry had developed SD as a consequence of cancer treatment. Data collection and analysis Two review authors independently extracted the data and assessed trial quality. Meta-analysis was considered for trials with comparable key characteristics. Main results Eleven RCTs with a total of 1743 participants were identied. The quality of the trials was poor. Ten trials explored interventions for SD in men following treatments for non-metastatic prostate cancer. One trial explored effectiveness in women of a lubricating vaginal cream following radiotherapy for cervical cancer. The strongest evidence (from four trials) was on oral phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction (ED) following radiotherapy of the prostate or radical prostatectomy. The results using validated measures in all trials signicantly favoured those in
Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1

the PDE5 inhibitor group(s). The combined results of two trials indicated a signicantly greater improvement in ED in the PDE5 inhibitor groups (odds ratio (OR) 10.09 95% condence interval (CI) 6.20 to 16.43). Negative effects were few and usually mild to moderate headaches or ushing. One trial reported more clinically serious events including six events of tachycardia and six of chest pain. Following prostate cancer treatments there was some evidence that PDE5 inhibitors are more effective in combination with acetyl-Lcarnitine and propionyl-L-carnitine and that sexual counselling improves self-administration of prostaglandin intra-cavernous injection for SD. There was some evidence following treatment for prostate cancer that transurethral alprostadil and vacuum constriction devices reduce SD, although in both trials negative effects were fairly common. There is some evidence that vaginal lubricating creams reduce SD. Authors conclusions PDE5 inhibitors are an effective treatment for SD secondary to treatments for prostate cancer. Other interventions identied need to be tested in further RCTs. The SD interventions in this review are not representative of the range available for men and women. Further evaluations are needed for these interventions for SD following cancer treatments.

PLAIN LANGUAGE SUMMARY Interventions for sexual dysfunction following treatments for cancer This review evaluated the effectiveness of randomised controlled trials (RCTs) of interventions of any kind for sexual dysfunction following cancer treatments. Sexual dysfunction (SD) is a potential complication of cancer treatment in both men and women. Eleven RCTs were identied that evaluated the effectiveness of an intervention to treat SD following treatment for cancer. Although the quality of these trials was poor, there was sufcient evidence that oral phosphodiesterase inhibitors are an effective treatment for SD in men following treatments for prostate cancer. There was insufcient evidence for the effectiveness of other identied interventions for SD following cancer treatment. There was a relative absence of trials of treatments for SD secondary to cancer treatments in women.

BACKGROUND
Sexual dysfunctions (SDs) are characterised by a disturbance in sexual desire and in the psychological and physiological changes that characterise the sexual response (The Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV-TR] (DSM IV-TR 2000)). SD can occur in men and women and is independent of sexual orientation. The causes may be physical, psychological or a combination of both factors. Depression, anxiety, altered body image, side effects of medications, surgery, impaired circulation, diabetes, alcohol and illicit drug use, and low levels of sex hormones are common causes. The DSM-IV-TR recognises nine SD disorders: sexual desire disorder or decreased libido. These are (1) hypoactive sexual desire (low interest in sex) and (2) sexual aversion disorder (objections to having the genitals touched). sexual arousal disorders, previously called frigidity in women and impotence in men. These are (3) female sexual

arousal disorder and (4) male erectile disorder or erectile dysfunction (ED). premature, delayed or absent orgasm following a normal sexual excitement phase. These are (5) female orgasmic disorder, (6) male orgasmic disorder and (7) premature ejaculation. sexual pain disorders. These disorders are (8) vaginismus (involuntary spasms of the muscles of the outer third of the vagina that interferes with intercourse) and (9) dyspareunia (pain during intercourse in either men or women) SD is one of the more prevalent long-term complications following many types of cancer treatment in both men and women (Ananth 2003; Ganz 1998; Syrjala 1998). Much of the research to date using validated measures of SD has focused on the prevalence of SD in cancers that have an impact on the genitals or other areas of the body involved directly in sexual functioning. It is estimated that up to 50% of women suffer with SD as a result of gynaecological cancer treatments (Schover 1997) and that SD occurs in
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

60 to 90% of men following radical prostatectomy and in 67 to 85% following radiotherapy (Smith 2000; Stanford 2000; Talcott 1998; Walsh 1987). The causes of SD following cancer treatments may be multi-factorial but may result from the direct effects of surgery, radiation, chemotherapy, hormone therapy, changes in serum levels of testosterone, lowered physical functionality and an increase in symptoms of depression or anxiety (Tabano 2002; Pignata 2001). Trials evaluating the effectiveness of treatments for SD often exclude patients with other major health problems, such as cancer. As cancer and its treatments disrupt physiological and anatomical integrity, it is not possible to simply extrapolate the results of these trials into the cancer eld. There have been several discussion papers describing a number of trials evaluating treatments for SD as a result of cancer treatments (Carswell 2002; Hinotsu 1996; Kuczyk 2000; Marmor 1999; Matthew 2005; Montorsi 2004b; Pignata 2001; Redaelli 2004; Rogers 2002; Sciarra 2004; Shell 2002; Stead 2003; Tabano 2002; Thors 2001). The types of interventions for SD following cancer treatment they report on include: Psycho-educational interventions such as counselling and psychotherapy. Pharmacological interventions such as phosphodiesterase-5 (PDE5) inhibitors for ED and hormonal therapies. Mechanical device interventions such as vacuum pumps, penile implants, penile prostheses and lubricating gels. Complementary medicine interventions such as gingko biloba and ginseng. With increased detection of cancer, earlier diagnosis and improved treatments the number of people living with and surviving cancer is growing. Consequently there is increased emphasis on quality of life. Sexual function is an important indicator of quality of life in patients undergoing treatment for cancer (Ozyilkan 1995).

Types of studies Only randomised controlled trials (RCTs) were included. Published and unpublished trials were eligible. There was no language restriction. In the case of crossover trials, only the rst period results (if available) were used in order to exclude any carry over effect. Abstracts and reviews were excluded. Trials undertaken in any care setting were included. Types of participants Trial participants were adults (aged 16 years or over) of either sex, receiving any treatment (or who had previously received any treatment) for any type of cancer, and who at the start of the trial experienced any type of SD (however identied) subsequent to the cancer treatment. Types of interventions Trials were included if they evaluated interventions for SD that occurred as a result of a treatment for cancer. Interventions searched for were psychological, pharmacological, mechanical or complementary and whose primary aim was to ameliorate SD that arose as a direct result of any type of cancer treatment. SD treatment was compared with the following control interventions: placebo, usual care or observation. Types of outcome measures Efcacy was evaluated using the following outcomes: 1) the proportion of participants within each trial arm who showed improved sexual function; 2) mean scores on standardised sexual function scales. Tolerability was evaluated using the following outcomes: 1) adverse effects and side effects; 2) number of participants who dropped out.

Exclusion criteria

OBJECTIVES
To evaluate the effectiveness of interventions for SD following treatments for cancer. To assess adverse events associated with interventions.

Data from observational cohort or cross-sectional studies were not included, nor were RCTs evaluating the effectiveness of preventative measures such as nerve-sparing surgical techniques, breast reconstruction, or avoidance of one particular therapy. Studies comprising healthy volunteers or patients who report SD subsequent to non-cancer treatments were not included.

Search methods for identication of studies METHODS

Electronic searches

Criteria for considering studies for this review

The following electronic databases irrespective of language and publication status were searched:
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

1. Cochrane Pain, Palliative & Supportive Care Register (January 2007) 2. The Cochrane Controlled Trials Register: The Cochrane Library (Issue 4, 2006) 3. MEDLINE (1966 to January 2007) 4. EMBASE (1980 to January 2007) 5. PsycInfo (1966 to January 2007) 6. AMED (1985 to December 2006) 7. CINAHL (1966 to January 2007) 8. Dissertation Abstracts (1980 to January 2007) 9. National Health Service Research Register (containing Medical Research Council Directory) (1990 to January 2007). Please see Appendix 1 for search strategy.

Two review authors extracted the data independently (CM and LJ or BC and LJ).

Assessment of study quality Two review authors (CM and LJ or BC and LJ) independently assessed trial quality according to criteria which is described in the Cochrane Handbook (Higgins 2006) and supported by Juni 2001. Four main sources of systematic bias were assessed for each included trial: a) selection bias (randomisation sequence and concealment of allocation, and at recruitment), b) performance bias, c) detection bias, d) attrition bias (completeness of follow up with less than 10% loss to follow up dened as adequate). Criteria a) and d) were assessed as adequate, inadequate or unclear according to Juni 2001. Criteria b) and c) for masking were assessed by the following questions: i) were the participants aware of their assigned intervention (performance bias)? ii) were those providing the intervention aware of the assigned intervention (performance bias)? iii) were those who were assessing outcomes aware of the assigned intervention (detection bias)?

Searching other resources 1. Reference lists and forward citation of included trials and any relevant reviews. 2. A request for data was posted on SEXNET, an international e-mail discussion group. This multidisciplinary list is a forum to discuss sex research. Members are generally sex researchers/ therapists.

Data collection and analysis

The keywords and abstracts of electronic citations were searched. Where they appeared relevant full texts were obtained. In accordance with the inclusion criteria, two review authors assessed the full text independently (CM and LJ or BC and LJ). Where differences of opinion occurred they were resolved by consensus with the other review authors (RW, MK and AT). If resolution was not possible, an attempt was made to contact the lead author of the trial for clarication. Justication was documented for excluding trials at this stage.

Data synthesis The aim of the review was to assess the effectiveness of the interventions with analyses of the type of: intervention, cancer, and participants: country of residence and age.

Data management Data were extracted using a standard form. Where possible, the following information was obtained for each trial: 1. Trial methods: trial design, duration, allocation method, masking, and care setting. 2. Inclusion criteria. 3. Participants: number, age, sex, and type of cancer, past/ present cancer treatments, and dropouts/withdrawals. 4. SD intervention: type, dose, route of delivery, control used. 5. Outcome data: sexual activity, improvement according to relevant validated scales of quality of life, and adverse effects. Where information was lacking, contact was attempted with the lead author of the trial. It was planned that cost-effectiveness data regarding SD treatments would be collected. Measures of treatment effect

Individual studies

The outcome data were either ordinal or categorical. Effect measures for ordinal data were assessed as continuous data. Weighted mean differences (WMDs) were generated for ordinal data where a mean and a standard deviation were provided or could be generated. Where categorical data were reported, odds ratios (ORs) as appropriate were generated. Treatment effects from trials that were of crossover design that did not present pre-crossover results separately were not transformed.
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Meta-analysis

If the data from trials were sufciently similar and of sufcient quality the data were combined to provide a pooled effects estimate. Trials that were of crossover design were excluded if they did not present pre-crossover results separately (Elbourne 2002). On assessment a diversity of interventions and outcomes were found, limiting the number of trials whose effects could be combined. Where meta-analysis was possible, heterogeneity between trials was assessed using the Chi squared statistic and I squared test. It was planned that if heterogeneity was identied, it would be explored by subgroup analysis. The xed-effects model was used where analysis was possible due to no signicant heterogeneity being found. The random-effects model was then used to test sensitivity of the xed-effects results.

RESULTS

to cancer treatment (Cavallini 2005; Incrocci 2001; Incrocci 2006) and one trial reported clinical documentation of self report of prior sexual functioning (Montorsi 2004b). In three, prior sexual functioning was not documented (Brock 2003; Canada 2005; Weber 2004). In one trial (Pitkin 1971) SD was not established prior to trial entry, as the aim was to prevent SD that arises from vaginal tissue damage secondary to cervical irradiation. Ten trials excluded participants whose cancer was not conned to one organ, while one trial did not specify this issue (Montorsi 2004b). In the Titta 2006 trial a subgroup had muscle invasive bladder cancer. The mean age of male participants ranged from 57 to 69 years. In the one trial involving women the mean ages were 49 years in the placebo group, and 50 years in the intervention group. SD outcomes commonly assessed were ED, intercourse performance and sexual satisfaction. Six types of interventions for SD following a cancer treatment were evaluated in the identied trials: Pharmacological interventions

Description of studies
See: Characteristics of included studies; Characteristics of excluded studies. The search undertaken at two time points retrieved 10,340 citations. Eighteen per cent (1600/8986) of citations at the initial search were assessed for inclusion independently by two review authors (CM and LJ); there was less than 1% disagreement. In the update search, all 1354 citations were screened by two review authors (BC and LJ) independently. One hundred and forty-ve articles were eligible at citation assessment. At full article assessment 135 were excluded. Papers from ten research groups providing evidence from eleven RCTs met full inclusion criteria. These totaled 1743 participants (Brock 2003; Canada 2005; Cavallini 2005; Costabile 1998; Incrocci 2001; Incrocci 2006; Montorsi 2004b; Pitkin 1971; Raina 2006; Titta 2006; Weber 2004). Two RCTs were of crossover design (Incrocci 2001; Incrocci 2006), the remainder were of parallel design. Trials were undertaken in North American populations (Brock 2003; Canada 2005; Costabile 1998; Pitkin 1971; Raina 2006), Italian (Cavallini 2005; Titta 2006), and Dutch populations (Incrocci 2001; Incrocci 2006). A multi-centred trial included American, Canadian, German, Italian, Dutch, Spanish, and British populations (Montorsi 2004b). Three other trials were also multi-centred (Brock 2003; Cavallini 2005; Costabile 1998). In seven trials it was established at recruitment that participants had suffered SD subsequent to cancer treatments (Cavallini 2005; Costabile 1998; Incrocci 2001; Incrocci 2006; Montorsi 2004b; Raina 2006; Titta 2006). Two trials evaluated participants sexual functioning before cancer treatment (Raina 2006; Titta 2006). Three reported retrospective self report of sexual functioning prior

In men following treatment for prostate cancer: PDE5 inhibitors as a monotherapy or in combination with propionyl-L-carnitine and acetyl-L-carnitine Transurethral alprostadil Mechanical interventions In men following treatment for prostate cancer: Vacuum constriction device (VCD) In women following treatment for cervical cancer: Lubricating oestrogen vaginal cream Psycho-educational interventions In men following treatment for prostate cancer: Supportive peer partners Sexual counselling Most (six) trials evaluated pharmacological interventions. Metaanalysis of pharmacological interventions was limited by the differential reporting of their outcomes. In particular, different pharmaceutical preparations were used, there was little overlap in how outcomes were measured and the two cross-over trials could not be included in any meta-analysis as they did not report pre-cross over outcome data. Excluded studies The main reasons for exclusion were: discussion papers, not an RCT, no inclusion of cancer patients or that the evaluation had no sexual function outcomes. Reasons for exclusion for all excluded studies are listed in the Characteristics of Excluded Studies table.
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Risk of bias in included studies

The quality of trials was poor. All trials were vulnerable to a number of biases including selection, performance, detection and attrition.

Effects of interventions

Pharmaceutical interventions Selection bias Two trials reported adequately the method of randomisation sequence generation (Brock 2003; Montorsi 2004b). The method concealment of allocation was not described adequately in any of the trials. Although all trials provided at least some demographic data none assessed whether or not their trial sample was representative of the target population. Six trials totaling 1343 participants evaluated the effects of a pharmaceutical preparation for men with ED following treatments for prostate cancer (Brock 2003; Cavallini 2005; Costabile 1998; Incrocci 2001; Incrocci 2006; Montorsi 2004b). Oral PDE5 inhibitors were evaluated in ve trials (Brock 2003; Cavallini 2005; Incrocci 2001; Incrocci 2006; Montorsi 2004b). The sixth trial evaluated transurethral alprostadil (Costabile 1998). All six trials were funded or part funded by the pharmaceutical company who manufactured the drug being evaluated. The trial authors were either located at universities or in healthcare settings. In two trials the authors state the pharmaceutical funding was unrestricted (Incrocci 2001; Incrocci 2006). In two trials the authors declare nancial interest or other relationship with a pharmaceutical company (Brock 2003; Montorsi 2004b).

Performance bias Seven trials were described as double-blind (Brock 2003; Cavallini 2005; Costabile 1998; Incrocci 2001; Incrocci 2006; Montorsi 2004b; Pitkin 1971). In ve trials it was clear that it was the participants and the providers (rather than outcome assessor) of the interventions that were masked (Cavallini 2005; Incrocci 2001; Incrocci 2006; Montorsi 2004b; Pitkin 1971); in two trials masking was unclear (Brock 2003; Costabile 1998). By the nature of the intervention in the other four trials, participants would have been aware that they were receiving a particular trial treatment (Canada 2005; Raina 2006; Titta 2006; Weber 2004). In three trials the assessor of the data was unaware of the assigned intervention (Canada 2005; Cavallini 2005; Pitkin 1971); in eight masking of the assessor was unclear (Brock 2003; Costabile 1998; Incrocci 2001; Incrocci 2006; Montorsi 2004b; Raina 2006; Titta 2006; Weber 2004). Testing of masking was not reported by any of the authors.

PDE5 inhibitors PDE5 inhibitors are believed to improve erectile function by preserving intra-corporeal smooth muscle by way of anti-brotic activity (Schwartz 2004). Sildenal (Viagra) was the rst PDE5 inhibitor. It was introduced in 1998. The alternative PDE5 inhibitors are vardenal (Levitra) and taladal (Cialis). Four trials totaling 863 participants assessed the effectiveness of a PDE5 inhibitor as a monotherapy (Brock 2003; Incrocci 2001; Incrocci 2006; Montorsi 2004b). Treatment duration ranged from four to 16 weeks. Two trials were of parallel design (Brock 2003; Montorsi 2004b); two were crossover trials (Incrocci 2001; Incrocci 2006). Neither of these trials reported ndings precrossover.

Attrition bias In eight trials the risk of attrition bias was low (Brock 2003; Costabile 1998; Incrocci 2001 and 2006; Montorsi 2004b; Pitkin 1971; Raina 2006; Weber 2004). In ve of these trials 10% or fewer participants left the trial after randomisation (Costabile 1998; Incrocci 2001; Incrocci 2006; Pitkin 1971; Weber 2004); in two, more than 10% of the randomised sample was lost, and an intention-to-treat analysis was performed (Montorsi 2004b; Brock 2003). In two of the other trials there was a slightly higher risk with 14% of the sample lost in Titta 2006 trial and 13% in Cavallini 2005. In the Canada 2005 trial the risk was higher with 39% not completing the trial. Description of studies Incrocci 2001 evaluated the effect of two weeks of sildenal versus placebo in 60 men with ED as a result of radiotherapy for prostate cancer. The starting dose of sildenal was 50 mg daily. In most men (90%) this was increased to 100 mg because of unsatisfactory response. At six weeks, participants crossed over to the alternative treatment for another two weeks. Two trials (Montorsi 2004b; Incrocci 2006) evaluated the effect of tadalal. The Montorsi 2004b trial evaluated 303 men with ED as a result of bilateral nerve-sparing radical retropubic prostatectomy for prostate cancer who were randomised to receive either 12 weeks of 20 mg tadalal daily or a placebo. The Incrocci 2006 trial evaluated 60 men with ED after radiotherapy who were randomised in a crossover trial to receive either 20 mg of tadalal or a placebo daily for six weeks. Brock 2003 evaluated the effect of vardenal in 440 men with ED subsequent to nerve sparing radical retropubic prostatectomy for prostate cancer. Participants received either 10 to 20 mg vardenal
6

Sample size calculation Four trials provided and met their sample size calculations (Brock 2003; Incrocci 2001; Incrocci 2006; Montorsi 2004b). For further quality assessment details see Additional Table 1.

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or a placebo daily for 12 weeks. See the Characteristics of Included Studies table for further details. Results

Erectile Function (EF)

All trials evaluated EF using the self-administered International Index of Erectile Function (IIEF) (Brock 2003; Incrocci 2001; Incrocci 2006; Montorsi 2004b). All reported a signicant improvement in EF in favour of the PDE5 inhibitor group. In the trial by Brock 2003 the WMD of the mean at follow-up was signicantly in favour of the PDE5 inhibitor group (WMD 6.50 (CI 4.28 to 8.72)). In the trial by Montorsi 2004b the WMD for mean difference at follow up signicantly favoured the PDE5 inhibitor group (WMD 4.20 (CI 2.68 to 5.72). In the crossover trial by Incrocci 2001 the mean frequency of erections was higher after the PDE5 inhibitor than after the placebo (2.9 (SD 1.6) versus 1.8 (SD 1.1)), as was erection rmness (2.8 (SD 1.8) versus 1.5 (SD 1.1)) (P values were not reported). In Incrocci 2006s crossover trial the mean EF was also in favour of the PDE5 inhibitor (17.7 (SD 9.9) versus 9.5 (SD 5.9) P value < 0.0001). In all trials, improvement in erections was also assessed using a Global Assessment Question (GAQ) (Brock 2003; Incrocci 2001; Incrocci 2006; Montorsi 2004b). The combined results of the two parallel group RCTs resulted in a signicant odds ratio (OR 10.09 (CI 6.20 to 16.43)) in favour of PDE5 inhibitors. See Comparison 01. The OR did not differ signicantly between xed and random effects models. In the Incrocci 2001 trial (of cross-over design without the effects of the rst treatment reported separately) there was also a signicant improvement in favour of the PDE5 inhibitor (45% of men improved after sildenal compared with 8% after placebo, P value < 0.001). A similar result was found in the Incrocci 2006 more recent cross-over trial (67% after tadalal and 20% after placebo, P value < 0.001). Incrocci 2006 also measured EF using questions from the Sexual Encounter Prole diary (SEP). They found a signicant improvement after tadalal compared to placebo in achieving at least some enlargement of the penis (64% versus 30%, P value < 0.0001), and in participants satisfaction with the hardness of their erections (43% versus 7%, P value < 0.0001). Intercourse performance Three trials used the SEP to assess whether the man was able to achieve successful vaginal penetration (Brock 2003; Incrocci 2006; Montorsi 2004b). All trials found better outcomes for those taking the PDE5 inhibitor. In the Brock 2003 trial the WMD of the mean, per participant, of vaginal penetration success rate was 23.02 (CI 17.20 to 28.85), in Incrocci 2006 47% were able to penetrate after tadalal, and 19% after placebo (P value < 0.001),

and in Montorsi 2004b the OR for successful penetration was 3.72 (CI 2.23 to 6.20). All trials using the SEP assessed whether the man was able to achieve successful vaginal intercourse. Again all trials found signicant improvement in success in favour of the PDE5 inhibitor. In Brock 2003 the WMD of the mean, per participant, of vaginal intercourse success rate was 25.62 (CI 20.41 to 30.83). In Incrocci 2001 55% of men reported successful intercourse after sildenal compared to 18% after the placebo (P value < 0.001). In Incrocci 2006 46% were able to have successful intercourse after tadalal, and 12% after placebo (P value < 0.001). In Montorsi 2004b the OR was 2.88 (CI 1.62 to 5.12).

Other outcomes In Incrocci 2006 trial, there was signicantly greater satisfaction with sexual intercourse measured on the IIEF after tadalal than after placebo (mean score 8.2 (SD 3.0) versus 5.6 (SD 2.3) P value < 0.0001). Using the IIEF there was also signicantly greater improvement after tadalal than after placebo in orgasmic function (mean 7.4 (SD 3.1) versus 4.9 (SD 3.5), P value < 0.0001) and in sexual desire (mean 8.7 (SD 1.7) versus 7.9 (SD 1.9), P value < 0.006). Treatment satisfaction was assessed in Montorsi 2004b using the ED inventory of treatment satisfaction (EDITS) score. For men treated with tadalal, satisfaction was signicantly greater than for those receiving the placebo (the authors do not provide the statistics).

Dosage In two trials two doses of the PDE5 inhibitor were evaluated ( Brock 2003; Incrocci 2001). In Brock 2003, in the bilateral nerve sparing subgroup improvement in EF was reported in 71% of participants taking 20 mg of vardenal and in 59.7% taking 10 mg. In the unilateral nerve sparing subgroup improvement was reported in 55% taking 20 mg and in 64% taking 10 mg (No tests of signicance were given). In Incrocci 2001 because of insufcient erectile response most participants (90%) increased the dose of sildenal from 50 to 100 mg.

Degree of ED at trial entry Two trials undertook subgroup analysis according to the degree of ED at trial entry (Brock 2003; Montorsi 2004b). In Brock 2003, at follow up in the subgroup randomised to receive 20 mg of vardenal who had less severe ED at trial entry the mean EF score, using the IIEF, was 25.0. In those with severe ED at trial entry the mean score was 12.9. In Montorsi 2004b at follow up in those randomised to tadalal and who had less severe ED the mean improvement in EF, using the IIEF, was 5.9 (SEM 0.7). In the subgroup with more severe ED, the mean was 4.1 (SEM 0.9) (No tests of signicance given).
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Tolerability

Negative effects

Although all trials report negative effects, only two set out a priori to report adverse events (Brock 2003; Montorsi 2004b). Three trials report a low incidence of side effects (1 to 2% of participants), but more of them occurred with PDE5 inhibitors than with placebo. Such events in the intervention group were mild to moderate and commonly were headaches, ushing, myalgia and dyspepsia (Incrocci 2001; Incrocci 2006; Montorsi 2004b). No adverse events were reported in these trials. In the fourth trial more serious events were reported (Brock 2003). These events occurred in 2% (three of 140) of men receiving placebo and in 5% (seven of 140) in the 10 mg vardenal group and 3.4% (ve of 147) of those taking vardenal at the higher dose of 20 mg. The events reported in the intervention groups were tachycardia (6/233); chest pain (6/233); sensitivity to light (4/233); blurred or abnormal vision or both (3/233); red eyes (2/233) and conjunctivitis (1/233). It is unclear if events occurred in the same individuals.

The pharmaceutical preparations propionyl-L-carnitine and acetyl-L-carnitine have similar anti-brotic activity to PDE5 inhibitors (Biagiotti 2001). Cavallini 2005 compared the effects of (i) sildenal 100 mg on demand in combination with acetyl-Lcarnitine x 2 g/day and propionyl-L-carnitine x 2 g/day with (ii) sildenal 100 mg only on demand and (iii) a placebo. The trial was undertaken in 96 men who had ED after bilateral nerve-sparing radical retropubic prostatectomy for prostate cancer. See the Characteristics of Included Studies table for further details. Using the IIEF, the trial authors state a signicantly greater (the authors do not provide P-values and limitations in the data prevent them being derived) improvement in men in group (i) than those in groups (ii) or (iii). The IIEF scores (the authors do not state what the IIEF scores represent) in the order of sildenal in combination with propionyl-L-carnitine and acetyl-L-carnitine, sildenal only, and placebo are: EF 27.3 (+/- 4.6) versus 21.7 (+/- 6.8) versus 11.7 (+/- 3.7) Sexual intercourse satisfaction 8.9 (+/- 4.7) versus 4.8 (+/2.5) versus 3.1(+/- 0.6) Orgasm 8.8 (+/- 2.6) versus 5.9 (+/- 2.9) versus 3.0 (+/- 0.6) Sexual well being 8.6 (+/- 2.0) versus 5.4 (+/-2.7) versus 2.8 (+/- 0.7). The OR for self-report of satisfaction with sexual intercourse in sildenal plus propionyl-L-carnitine and acetyl-L-carnitine versus placebo was in favour of the active treatment (OR 94.50 (CI 15.97 to 559.14)). In comparison with those on sildenal alone, the group receiving sildenal plus propionyl-L-carnitine and acetyl-Lcarnitine was signicantly more likely to report sexual intercourse satisfaction (OR 6.65 (CI 1.96 to 22.56)). These results should be interpreted with caution due to the wide condence intervals reported. There were signicantly fewer negative effects in the placebo group compared to the two actively treated groups, but no signicant difference between the two active drug groups. The negative effects were mild to moderate and were commonly headaches and ushing. Three participants discontinued because of insufcient therapeutic effect: two of these were in the placebo group and one in the sildenal only group. The other 11 participants who discontinued did so because of protocol violations. See Comparison 01 01 to 01 19 for data representing all PDE5 inhibitors trials.

Treatment discontinuation rates Two trials reported that none of the participants discontinued treatment prematurely (Incrocci 2001; Incrocci 2006). In two other trials, Brock 2003 and Montorsi 2004b, a higher proportion discontinued in the placebo groups: in Brock 2003 33% in placebo and 20 to 22% in the treatment groups; in Montorsi 2004b 25% in the placebo group and 20% in the treatment group. The most common reason for discontinuation in the Brock 2003 trial for all trial arms was insufcient therapeutic effect, followed by withdrawal of consent. For ten of the 62 in the treatment groups in Brock 2003 trial, the reason for withdrawal was because of a clinically signicant event including tachycardia and chest pain. In Montorsi 2004b trial the most common reason for discontinuation in both trial arms was withdrawal of consent. In the treatment group eleven out of the 40 withdrew because of mild to moderate side effects including headaches, dyspepsia and myalgia.

Comparison of type of PDE5 inhibitor

The trials did not compare the effects of the different PDE5 inhibitors. Overall, PDE5 inhibitors produced an improvement in EF in around half to three quarters of participants. Similar levels of mild to moderate side effects were reported in all trials, with the exception of the trial on vardenal where more serious events were reported, but this nding needs to be treated with caution as not all of the other trials set out a priori to report negative effects.

Transurethral alprostadil One trial, Costabile 1998, evaluated self administered transurethrally alprostadil in men with ED following radical prostatectomy. Three hundred and eighty four men underwent clinic titration to determine if alprostadil provided an erection believed sufcient for vaginal intercourse. Of these, 270 had an erection believed sufcient. An effective dose for
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PDE5 inhibitor with propionyl-L-carnitine and acetyl-Lcarnitine

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35% of the men was 1000 mcg, for 31% 500 mcg, for 17% 250 mcg and for 14% 125 mcg. These 270 men then entered the trial and were randomised to receive either transurethral alprostadil or a placebo for three months (the dosages of alprostadil required for those who entered the intervention arm were not provided). See the Characteristics of Included Studies table for further details.

Sexual Function Index, sexual counselling was associated with improvement from baseline in sexual function and satisfaction. Discontinuation rates Thirty-nine per cent of couples withdrew. The most common reason, when reported, was high marital distress. The authors do not state from which arm of the trial the participants who dropped out were from. Negative effects No adverse events were reported. Sexual counselling in male patients and partners using prostaglandin E1 intra cavernous injection One trial evaluated the utility of sexual counselling in improving the use at home of a prostaglandin E1 intra cavernous injection (ICI) in men with ED after non-nerve sparing radical pelvic surgery or cystectomy (Titta 2006). Fifty-seven men with prostate cancer and seven with bladder cancer extending into the muscle wall were recruited. These men, tested by sildenal response, were all considered to have an erection sufcient for vaginal penetration. In the clinic all participants practiced how to use the ICI. Twentynine participants were randomised into the group treated with ICI and ICI focused sexual counselling and the other 28 were treated with ICI without sexual counselling. The sexual counselling intervention included six sessions with a therapist over 18 months to discuss drug administration and couples communication about sexual problems and psychodynamic-oriented sexual therapy to place therapy within the couples sexual behaviours and relationship (it is unclear how many participants had their female partner in attendance). A home telephone call was also made to establish dosage. See the Characteristics of Included Studies table for further details.
Results

Results

The OR of reporting sexual intercourse at least once within the three-month follow-up period was signicantly in favour of the intervention (OR 18.96 (CI 8.85 to 40.65)). The wide condence interval suggests the trial was underpowered and these results should be interpreted with caution.

Negative effects

Signicantly more men in the active group reported penile pain (OR 75.73 (CI 10.27 to 558.40)) and urethral pain/burning (OR 4.88 (CI 1.91 to 12.42)), although the wide condence intervals again suggest that the trial was underpowered. Three patients (2%) reported dizziness in the active group.

Psycho-educational interventions

Three trials assessed the effectiveness of a psychosocial-educational intervention (Canada 2005; Titta 2006; Weber 2004). Sexual counselling with or without partner The efcacy, with or without the attendance of a female sexual partner, of a four session sexual counselling intervention was assessed in a pilot RCT in 84 men who had ED as a result of radiotherapy or prostatectomy for prostate cancer (Canada 2005). The duration of the intervention was unclear but it was under three months. Eighty-four heterosexual couples were recruited and randomised into two groups (the authors do not report the numbers per group). One group received counselling with their female partners present (25 completed the intervention), the second received counselling without their partner present (26 completed the intervention). The sessions provided education on prostate cancer and sexual function, options to treat SD, as well as sexual communication and stimulation skills. Behavioural homework was also given. See the Characteristics of Included Studies table for further details.

Results

Using the IIEF, the presence of a female partner at the counselling sessions did not signicantly affect male sexual function and satisfaction. In men in both groups sexual counselling, using the IIEF, was associated with improvement from baseline in sexual outcomes. In women who attended the sessions, using the Female

The main outcomes were treatment efcacy, compliance and dropout rate at three and six months. Signicantly more participants receiving sexual counselling successfully used, measured by sildenal response (see Characteristics of Included Studies table for further details on this measure), prostaglandins ICI (27.5% versus 17.8% P value < 0.05). In this group it was also more likely that couples were satised with treatment (OR 3.33 (CI 1.01 to 10.97)). Using the IIEF, with the exception of EF at 18 months which was signicantly better in men in the group that had sexual counselling, (mean 26.5 versus 24.3, P value < 0.05), for all outcomes there was no signicant difference between those who received counselling and those that did not: EF at three months (mean score 23.4 versus 21.7), sexual satisfaction (mean score at three months were 8.3
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

versus 8, and at 18 months 9.7 versus 6.8), sexual desire (mean score at three months 8.4 versus 6.5, at 18 months 9 versus 6.2), orgasmic function (at three months mean 8.7 versus 7.5 and at 18 months 9.2 versus 7.8) and in overall satisfaction of EF at three months 7.7 versus 7.4, and at 18 months 9.0 versus 7.3) (P values were not stated and limitations in the data reporting prevented them from being derived). All participants in the intervention groups completed the trial; 71% in the placebo group completed. No adverse events were reported. Supportive peer partner intervention versus usual treatment In one trial (Weber 2004) the effectiveness of a supportive male peer partner intervention was evaluated in 15 men who had ED following a radical retropubic prostatectomy for prostate cancer compared to a control group (n = 15) who received usual care (the authors provide no details on usual care). The support partners were long-term survivors of prostate cancer who previously had a prostatectomy that had resulted in SD and who, at the start of the trial, had 12 months of stable prostate specic antigen levels (PSA: an increase in the measure is an indicator of prostate cancer growth). Each pair met eight times during an eight-week period. The purpose of the intervention was for men to discuss problems typically encountered after surgery. See the Characteristics of Included Studies table for further details.
Results

participants were advised that sexual intercourse was not harmful and would probably have a positive effect in preventing post-irradiation complications in the vagina. The participants were instructed to apply the cream three times a week to the vagina for the purposes of maintaining vaginal patency for sexual intercourse and sexual examinations. Women were seen every six to eight weeks apart until the cream supply ran out. See the Characteristics of Included Studies table for further details.
Results

Signicantly more women in the intervention group reported no dyspareunia (OR 3.81 (CI 1.19 to 12.16). The proportion of women having sexual intercourse was not signicantly different between the trial arms (OR 0.91 (CI 0.40 to 2.10)). There was no signicant difference in the number of women who reported severe dyspareunia (OR 0.07 (CI 0.00 to 1.33). No adverse events were reported. Vacuum constriction device The effectiveness of a vacuum constriction device (VCD) for inducing erection was evaluated in 109 men with ED following retropubic prostatectomy for prostate cancer (Raina 2006). Those in the intervention group (n = 74) were instructed to use the VCD daily for nine months, while the control group had no treatment and were described as observational. See the Characteristics of Included Studies table for further details.
Results

After eight weeks, using the UCLA Prostate Cancer Index, there was no signicant difference between the trial arms in sexual functioning, (WMD 7.40 (-3.35 to 18.15)). The intervention group had signicantly less sexual bother measured via the UCLA Prostate Cancer Index (WMD -30.00 (-56.60 to -3.40)). Bother related to how large a problem their lack of sexual function was to each participant. These results should be interpreted with caution as the wide condence intervals suggest the trial was underpowered. No adverse events were reported. Mechanical interventions Two trials evaluated mechanical interventions (Pitkin 1971; Raina 2006).
Vaginal lubricating cream

Eighty one per cent (60/74) of the intervention group using the VCD device successfully had sexual intercourse (participants in the control group did not use the VCD device). At nine months, using the IIEF, there was a signicant difference in overall sexual function in favour of those in the intervention group (WMD 4.30 (CI 2.53 to 6.07). There was no signicant difference in EF between the two trial arms (OR 0.78 (CI 0.33 to 1.88)).
Negative effects

Twenty-three percent (14/60) of patients in the intervention group discontinued treatment, mostly because of discomfort (55%) or penile bruising (20%).

A vaginal lubricating cream containing 0.01% dienestrol was compared with a placebo cream in 93 women following radiation therapy for cancer of the cervix (Pitkin 1971). Effectiveness was measured by whether the lubricating cream reduced the proportion of women who experienced dyspareunia (pain at intercourse). The

DISCUSSION

Summary of main ndings

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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Eleven trials were included in this review. The quality of the trials was poor: the method to implement allocation concealment was not described adequately in any of the trials; the method used to generate the random allocation sequence was not specied in nine of the trials; eight trials did not have a pre-trial sample size calculation.

Plausible competing explanations of observed effects A competing explanation of observed effects, particularly for interventions tested in a single trial, is that the trial ndings may not be generalisable. In all trials there are also selection and design criteria that may limit the generalisability of the review ndings. The evidence is limited to populations in North America or Europe. Trial ndings may also be affected by the complexity of the problem and its treatments, namely the multi-factorial aetiology of SD and the characteristics of the interventions, for example that the VCD may be difcult to operate. Most trials included only patients with organ-conned cancer. Not all trials explored other characteristics that relate to SD such as psychological morbidity and personal relationship stress. Many of the trials were designed to address single therapies, whereas in practice such therapies may have different effects when used in combination with other therapies (such as pharmacological or mechanical intervention with psychological or supportive therapy). The results of all trials are weakened by the under reporting of key design methods including randomisation and masking.

Evidence on PDE5 inhibitors Despite the relatively poor quality of the trials there is sufcient evidence that oral PHE5 inhibitors, when used to treat ED subsequent to cancer treatment (radiotherapy or radical retropubic prostatectomy), are effective in the medium term (up to four months), are also acceptable to patients and have minimal adverse effects. There is some evidence suggestive that PDE5 inhibitors are more effective in: 1) higher dosages (20 mg vardenal compared to 10 mg; 100 mg sildenal compared to 50 mg); 2) men with less severe ED at baseline; 3) combination with acetyl-L-carnitine and propionyl-L-carnitine.

Overall completeness and applicability of evidence The evidence base identied for the effectiveness of interventions for SD following cancer treatment is not representative of the range of SD interventions available such as types of complementary medicines and other mechanical therapies, (see Additional Table 2 for further descriptions of such interventions). The evidence base identied is also not representative of the known range of SD problems and causes of SD that are encountered by men and women after cancer treatments. In particular, despite the impact of surgical and medical treatment for gynaecological malignancies on a patients quality of life, there is a lack of RCTs of interventions for SD following cancer treatments in women. Perhaps in part it is because the concept of SD in women remains controversial (Moynihan 2005) and the much greater interest in male SD that has resulted from the success of PDE5 inhibitors.

Effectiveness of PDE5 inhibitors in non-cancer populations Reviews of trials in non-cancer populations also report positive effects of PDE5 inhibitors and that negative effects are commonly mild to moderate (Markou 2004; Keating 2004b; Kendirci 2004; Vardi 2007). In particular, Markou 2004 in a meta-analysis of ten controlled trials found a similar effect in favour of the PDE5 inhibitors (WMD 6.18 (CI 5.59 to 6.77)) in men with EF in general settings.

Evidence for other treatments This review identied evidence suggestive of improvement in sexual outcomes from one RCT each, for SD following treatments for prostate cancer from: transurethral alprostadil; sexual counselling for men using prostaglandin E1 ICI; VCD for men with ED following prostate cancer treatments. There was also evidence suggestive of improvement in sexual outcomes from one RCT in women following treatments for cervical cancer from: lubricating vaginal cream.

AUTHORS CONCLUSIONS Implications for practice

This review identies sufcient evidence for the use of oral PDE5 inhibitors in the treatment of ED following treatment for prostate cancer. However, practitioners and clinical decision makers need to be aware that these trials only evaluated PDE5 inhibitors in men with organ conned cancer, who were in heterosexual stable relationships and that the outcomes were evaluated in the medium term (not beyond four months). For other treatments evaluated in this review, specically use of oestrogen vaginal lubricants, a supportive peer partner interven11

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

tion, transurethral alprostadil and sexual counselling, there is insufcient evidence to establish their effectiveness.

peer partners, vaginal lubricating creams, sexual counselling, transurethral alprostadil and vacuum constriction devices. Other interventions that would benet from research are educational programmes, other psychosocial interventions, complementary medicines and testosterone therapy in both sexes as well as penile prostheses in men.

Implications for research

This review shows the potential efcacy of PDE5 inhibitors in men who have ED subsequent to treatments for prostate cancer. Further trials would be useful to explore the efcacy and safety of PDE5 inhibitors for ED in other populations receiving treatment for cancer, in particular in those with non-localised cancer. Future trials should also consider including sexually active single persons as well as people with same-sex partners. Further evidence is needed on the effectiveness of supportive

ACKNOWLEDGEMENTS
The authors wish to thank Phil Wiffen, Sylvia Bickley and Jessica Thomas from the Pain, Palliative and Supportive Care Review Group for their assistance given on the review.

REFERENCES

References to studies included in this review

Brock 2003 {published data only} Brock G, Nehra A, Lipshultz LI, Karlin GS, Gleave M, Seger M, et al.Safety and efcacy of vardenal for the treatment of men with erectile dysfunction after radical retropubic prostatectomy. The Journal of Urology 2003;170: 127883. Canada 2005 {published data only} Canada AL, Neese LE, Sui D, Schover LR. Pilot intervention to enhance sexual rehabilitation for couples after treatment for localised prostate carcinoma. Cancer 2005;104: 2689700. Cavallini 2005 {published data only} Cavallini G, Modenini F, Vitali G, Kpverech A. Acetyl-LCarnitine plus Propionyl-L-Carnitine improve efcacy of Sidenal in treatment of erectile dysfunction after bilateral nerve-sparing radical retropubic prostatectomy. Urology 2005;66:10805. Costabile 1998 {published data only} Costabile RA, Spevak M, Fishman IJ, Govier FE, Hellstrom WJG, Shabsigh R, et al.Efcacy safety of transurethral alprostadil in patients with erectile dysfunction following radical prostatectomy. Journal of Urology 1998;160(4): 13258. Incrocci 2001 {published data only} Incrocci L, Koper PCM, Hop WCJ, Slob K. Sildenal citrate (Viagra) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, doubleblind, placebo-controlled, cross-over study. International Journal of Radiation and Oncology Biology and Physiology 2001;51(5):11905. Incrocci 2006 {published data only} Incrocci L, Slagter C, Koos Slob A, Hop WCJ. A randomised, double-blind, placebo-controlled, cross-over study to assess the efcacy of Tadalal in the treatment of erectile dysfunction following three-dimensional conformal

external-beam radiotherapy for prostatic carcinoma. International Journal of Radiation Oncology 2006;66: 43944. Montorsi 2004a {published data only} Montorsi F, Nathan HP, McCullough A, Brock GB, Broderick G, Ahuja S, et al.Tadalal in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: a randomized, double-blind, placebo controlled trial. The Journal of Urology 2004;172: 103641. Pitkin 1971 {published data only} Pitkin RM, VanVoorhis LW. Postirradiation Vaginitis. Therapeutic Radiology 1971;99:41721. Raina 2006 {published data only} Raina R, Agarwal A, Ausmundson S, Lakin M, Nandipati KC, Montague DK, et al.Early use of vacuum constriction device following radical prostatectomy facilitate early sexual activity and potentially earlier return to erectile function. International Journal of Impotence Research 2006;18:7781. Titta 2006 {published data only} Titta M, Tavolini IM, Dal Moro F, Cisternino A, Bassi P. Sexual counselling improved erectile rehabilitation after non-nerve-sparing radical retropubic prostatectomy or cystectomy - Results of a Randomised Prospective Study. Journal of Sexual Medicine 2006;3:26773. Weber 2004 {published data only} Weber BA, Roberts BL, Resnick M, Deimling G, Zauszniewski JA, Musil C, et al.The effect of dyadic intervention on self-efcacy, social support, and depression for men with prostate cancer. Psycho-Oncology 2004;13: 4760.

References to studies excluded from this review

Aaronson 1986 {published data only} Aaronson NK, Calais da Silva F, Yoshida O, van Dam FS, Fossa SD, Miyakawa M, et al.Quality of life assessment in
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

bladder cancer clinical trials: conceptual, methodological and practical issues. Progress in Clinical and Biological Research 1986;221:14970. ACOG 2003 {published data only} ACOG 51st Annual Clinical Meeting, New Orleans, Louisiana. Obsetrics and Gynecology 2003. Abstracts. 2003; Vol. 101, issue 4. Alexander 2004 {published data only} Alexander JL, Kotz K, Dennerstein L, Kutner SJ, Wallen K, Notelovitz M. The effects of postmenopausal hormone therapies on female sexual functioning: a review of doubleblind, randomized controlled trials. Menopause 2004;11(6): 74965. Anastasiadis 2003 {published data only} Anastasiadis AG, Benson MC, Rosenwasser MP, Salomon L, El Rashidy H, Ghafar MA, et al.Cavernous nerve graft reconstruction during radical prostatectomy or radical cystectomy: safe and technically feasible. Prostate Cancer and Prostatic Diseases 2003;6:5660. Badger 2005 {published data only} Badger T, Segrin C, Meek P, Lopez AM, Bonham E, Sieger A. Telephone interpersonal counseling with women with breast cancer: symptom management and quality of life. Oncology Nursing Forum 2005;32(2):2739. Balmer 2000 {published data only} Balmer MS, Weber DC, Popowski GY, Kurtz JM. Radiooncologie. Medecine et Hygiene 2000;58(2284):1414. Baniel 2001 {published data only} Baniel J, Israilov S, Segenreich E, Livne PM. Comparative evaluation of treatments for ED in patients with prostate cancer after radical retropubic prostatectomy. BJU International 2001;88:5862. Barber 2002 {published data only} Barber MD, Visco AG, Wyman JF, Fantyl JA, Bump RC. Sexual function in women with urinary incontinence and pelvic organ prolapse. The American college of Obstetrics and Gynecologists 2002;99(2):2819. Barrett-Connor 1996 {published data only} Barrett CE, Timmons C, Young R, Wiita B. Interim safety analysis of a two-year study comparing oral estrogenandrogen and conjugated estrogens in surgically menopausal women. Journal of Womens Health 1996;5(6):593602. Bawa 2004 {published data only} Bawa AS, Sharma DR, Singh R, Singh P. Efcacy and tolerability of sildenal in Indian males with erectile dysfunction: a double-blind, randomized, placebocontrolled, crossover study. Indian Journal of Pharmacology 2004;36(5):31220. Beemsterboer 1998 {published data only} Beemsterboer PMM, De Koning HJ, Birnie E, van der Maas PJ, Schroder FH. Advanced prostate cancer: Course, care, and cost implications. The Prostate 1999;40:97104. Berman 2003 {published data only} Berman JR, Berman LA, Toler SM, Gill J, Haughie S. Safety and efcacy of sildenal citrate for the treatment of female

sexual arousal disorder: a double-blind, placebo controlled study. The Journal of Urology 2003;170:23338. Boccardo 1999 {published data only} Boccardo F, Rubagotti A, Battaglia M, Di Tonno P, Selvaggi FP, Conti G, et al.Bicalutamide monotherapy versus utamide plus goserelin in prostate cancer patients: Results of an Italian prostate cancer project study. Journal of Clinical Oncology 1999;17(7):202738. Brock 2002 {published data only} Brock GB, McMahon CG, Chen KK, Costigan T, Shen W, Watkins V, et al.Efcacy and safety of tadalal for the treatment of erectile dysfunction: results of integrated analyses. The Journal of Urology 2002;168:13326. Burstein 1999 {published data only} Burstein HJ, Gelber S, Guadagnoli E, Weeks JC. Use of alternative medicine by women with early-stage breast cancer. The New England Journal of Medicine 1999;340 (22):17339. Carson 2002 {published data only} Carson CC, Burnett AL, Levine LA, Nehra A. The efcacy of sildenal citrate (Viagra) in clinical populations: an update. Urology 2002;60(2B):1227. Carson 2004 {published data only} Carson CC, Rajfer J, Eardley I, Carrier S, Denne JS, Walker DJ, et al.The efcacy and safety of tadalal: an update. BJU International 2004;93:127681. Carson 2005 {published data only} Carson C, Shabsigh R, Segal S, Murphy A, Fredlund P. Efcacy, safety, and treatment satisfaction of tadalal versus placebo in patients with erectile dysfunction evaluated at tertiary-care academic centers. Urology 2005;65(2):3539. Chen 2001 {published data only} Chen KK, Hsieh JT, Huang ST, Jiaan DP, Lin JN, Wang CJ. ASSESS-3*: A randomised, double-blind, exible-dose clinical trial of the efcacy and safety of oral sildenal in the treatment of men with erectile dysfunction in Taiwan. International Journal of Impotence Research 2001;13:2219. Chen 2004 {published data only} Chen KK, Jiann BP, Lin JN, Lee SS, Huang ST, Wang CJ, et al.Efcacy and safety of on-demand oral tadalal in the treatment of men with erectile dysfunction in Taiwan: A randomized, double-blind, parallel, placebo-controlled clinical study. Journal of Sexual Medicine 2004;1:2018. Christensen 1983 {published data only} Christensen DN. Postmastectomy couple counseling: An outcome study of a structures treatment protocol. Journal of Sex & Marital Therapy 1983;9(4):26675. Davis 2004 {published data only} Davis C. Psychosocial needs of women with breast cancer: how can social workers make a difference?. Health and Social Work 2004;29(4):3304. Daz 2002 {published data only} No author. Improvement of erectile function after radical prostatectomy [Verbesserug der erektilen Funktion nach
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

radikaler Prostatektomie]. Deutsche Apotheker Zeitung 2002; 142:13345. Decruze 1999 {published data only} Decruze SB, Gutherie D, Magnai R. Prevention of vaginal stenosis in patients following vaginal brachytherapy. Clinical Oncology 1999;11:468. Dennerstein 1979 {published data only} Dennerstein L, Burrows GD, Hyman GJ, Sharpe K. Some clinical effects of oestrogen-progestogen therapy in surgically castrated women. Maturitas 1979;2:1928. Doorenbos 2006 {published data only} Doorenbos A, Given B, Given C, Verbitsky N. Effect of behavioural intervention for symptoms among individuals with cancer. Nursing Research 2006;55:16171. Eardley 2005 {published data only} Eardley I, Mirone V, Montorsi F, Ralph D, Kell P, Warner MR, Zhao Y, Beardsworth A. An open-label, multicentre, randomised, cross-over study comparing sildenal citrate and tadalal for treating erectile dysfunction in men naive to phosphodiesterase 5 inhibitor therapy. BJU International 2005;96:132332. Floter 2002 {published data only} Floter A, Nathorst-Boos, Carlstrom K, von Schoultz. 2002. Addition of testosterone to estrogen replacement therapy in oophorectomized women: effects on sexuality and well-being. 2002;5:35765. Ganz 2000 {published data only} Ganz PA, Greendale GA, Petersen L, Zibecchi L, Kahn B, Belin TR. Managing menopausal symptoms in breast cancer survivors: results of a randomized controlled trial. Journal of the National Cancer Institute 2000;92(13):105464. Gasser 1987 {published data only} Gasser TC, Roach RM, Larsen EH, Madsen PO, Bruskewitz RC. Intracavernous self-injection with phentolamine and papaverine for the treatment of impotence. The Journal of Urology 1987;137:67880. Gerber 2001 {published data only} Gerber GS, Kuznetsov D, Johnson BC, Burstein JD. Randomized, double-blind, placebo-controlled trial of saw palmetto in men with lower urinary tract symptoms. Urology 2001;58(6):9603. Giesler 2005 {published data only} Giesler RB, Given B, Given CW, Rawl S, Monahan P, Burns D, et al.Improving the quality of life of patients with prostate carcinoma. Cancer 2005;104:75262. Gilbert 1990 {published data only} Gilbert HW, Gillatt DA, Desai KM, Gingell JC. Intracorporeal papaverine injection in androgen deprived men. Journal of the Royal Society of Medicine 1990;83:161. Given 2004 {published data only} Given C, Given B, Rahbar M, Jeon S, McCorkle R, Cimprich B, et al.Effect of a cognitive behavioral intervention on reducing symptom severity during chemotherapy. Journal of Clinical Oncology 2004;22(3): 50716.

Gontero 2003 {published data only} Gontero P, Fontana F, Bagnasacco A, Panella M, Kocjancic E, Pretti G, Frea B. Is there an optimal time for intracavernous prostaglandin E1 rehabilitation following nonnerve sparing radical prostatectomy? Results from a hemodynamic prospective study. The Journal of Urology 2003;169:21669. Hasenbring 1999 {published data only} Hasenbring M, Schulz KF, Hennings U, Florian M, Linhart D, Ramm G, Zander AR. The efcacy of relaxation/ imagery, music therapy and psychological support for pain relief and quality of life: rst results from a randomized controlled clinical trial [abstract]. Bone Marrow Transplant 1999;23(1):166. Helgeson 2006 {published data only} Helgeson VS, Lepore SJ, Eton DT. Moderators of the benet of psychoeducational interventions for men with prostate cancer. Health Psychology 2006;25:34854. Huntley 2002 {published data only} Huntley AL. Complementary therapies for the relief of menopausal symptoms. Focus on Alternative and Complementary Therapies 2002;7(2):1215. Incrocci 2003a {published data only} Incrocci L, Hop WCJ, Slob KA. Efcacy of sildenal in an open-label study as a continuation of a double-blind study in the treatment of erectile dysfunction after radiotherapy for prostate cancer. Urology 2003;62(1):11620. Incrocci 2003b {published data only} Incrocci L, Hop WC, Slob AK. Favorable effect of sildenal on erectile dysfunction in patients after radiotherapy for prostate cancer; randomised, double-blind, placebocontrolled crossover study [Gunstig effect van sildenal op erectiele disfunctie bij patienten na radiotherapie voor prostaatkanker; gerandomiseerd, dubbelblind, placebogecontroleerd en gekruist onderzoek]. Nederlands tijdschrift voor geneeskunde 2003;147(35):168790. Isidora 2006 {published data only} Isidori AM, Giannetta E, Gianfrilli D, Greco EA, Bonifacio V, Aversa A, et al.Effects of testosterone on sexual function in men: results of a metaanalysis. Clinical Endocronology 2005;63:38194. Iversen 2001 {published data only} Iversen P, Melezinek I, Schmidt A. Nonsteroidal antiandrogens: A therapeutic option for patients with advanced prostate cancer who wish to retain sexual interest and function. BJU International 2001;87:4756. Izuo 1967 {published data only} Izuo M, Fujimori M. Studies on hormonal treatment for mastopathy, particularly its dose-response relationship. Endocrinol Japon 1967;14(1):2733. Jeffries 2006 {published data only} Jeffries SA, Robonson JW, Craighead PS, Keats MR. An effective group psychoeducational intervention for improving compliance with vaginal dilation: A randomized controlled trial. International Journal of Radiation, Oncology, Biology and Physiology 2006;65:40411.
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Jones 2006 {published data only} Jones RB, Pearson J, Cawsey AJ, Bental D, Barrett A, White J, et al.Effect of different forms of information produced for cancer patients on their use of the information, social support and anxiety: randomised trial. BMJ 2006;332: 9428. Jung Hoon 2006 {published data only} Jong-Hoon K, Park CY, Sung-Jae L. Effects of Sun Ginseng on subjective quality of life in cancer patients: a doubleblind, placebo-controlled pilot trial. Journal of Clinical Pharmacy and Therapeutics 2006;31:3314. Kattan 1995 {published data only} Kattan S. Double-blind randomized crossover study comparing intracorporeal prostaglandin E1 with combination of prostaglandin E1 and lidocaine in the treatment of organic impotence. Urology 1995;45(6): 10326. Kearse WS Jr 1996 {published data only} Kearse-Jr WS, Sago AL, Peretsman SJ, Bolton JO, Holcomb RG, Reddy PK, et al.Report of a multicenter clinical evaluation of the dura-II penile prosthesis. Journal of Urology 1996;155(5):16136. Keating 2004a {published data only} Keating GM, Scott LJ. Spotlight on Vardenal in erectile dysfunction. Drugs and Aging 2004;21(2):13540. Kellogg-Parsons 2004 {published data only} Parsons JK, Marschke P, Maples P, Walsh PC. Effect of methylprednisolone on return of sexual function after nerve-sparing radical retropubic prostatectomy. Journal of Urology 2004;64(5):98790. Kendirci 2004 {published data only} Kendirci M, Bivalacqua TJ, Hellstrom WJG. Vardenal: a novel type 5 phosphodiesterase inhibitor for the treatment of erectile dysfunction. Expert Opinion on Pharmacotherapy 2004;5(4):92332. Kiely 1987 {published data only} Kiely EA, Ignotus P, Williams G. Penile function following intracavernosal injection of vasoactive agents or saline. British Journal of Urology 1987;59:4736. Klotz 2000a {published data only} Klotz L. Neurostimulation during radical prostatectomy: Improving nerve-sparing techniques. Seminars in Urologic Oncology 2000;18(1):4650. Klotz 2000b {published data only} Klotz L. Intraoperative cavernous nerve stimulation during nerve sparing radical prostatectomy: how and when?. Current Opinion in Urology 2000;10:23943. Klotz 2000c {published data only} Klotz L, Heaton J, Jewett M, Chin J, Fleshner N, Goldenberg L, Gleave M. A randomized phase 3 study of intraoperative cavernous nerve stimulation with penile tumescence monitoring to improve nerve sparing during radical prostatectomy. The Journal of Urology 2000;164: 15738.

Kongkanand 2003 {published data only} Kongkanand A, Ratana Olarn K, Ruangdilokrat S, Tantiwong A. The efcacy and safety of oral sildenal in Thai men with erectile dysfunction: a randomized, doubleblind, placebo controlled, exible-dose study. Journal of the Medical Association of Thailand 2003;86(3):195205. Kuan 2002 {published data only} Kuan J, Brock G. Selective phosphodiesterase type 5 inhibition using tadalal for the treatment of erectile dysfunction. Expert opinion on investigational drugs 2002; 11(11):160513. Kunelius 1997 {published data only} Kunelius P, Hakkinen J, Lukkarinen O. Is high-dose yohimbine hydrochloride effective in the treatment of mixed-type impotence? A prospective, randomized, controlled double-blind crossover study. Urology 1997;49 (3):4414. Kylstra 1999 {published data only} Kylstra WA, Leenhouts GHMW, Everaerd W, Panneman MJM, Hahn DEE, Weijmar-Schultz WCM, et al.Sexual outcomes following treatment for early-stage gynecological cancer: A prospective and cross-sectional multi-center study. International Journal of Gynecological Cancer 1999;9: 38795. Lee 1988 {published data only} Lee LM, Stevenson RWD, Szasz G. Prostaglandin E1 versus phentolamine/papaverine for the treatment of erectile impotence: A double-blind comparison. The Journal of Urology 1989;141:54950. Lepore 2003 {published data only} Lepore SJ, Helgeson VS, Eton DT, Schulz R. Improving quality of life in men with prostate cancer: a randomized controlled trial of group education interventions. Health Psychology 2003;22(5):44352. Lindsey 2001 {published data only} Lindsey I, George B, Kettlewell M, Mortensen N. Randomized, double-blind, placebo-controlled trial of sildenal (Viagra) for erectile dysfunction after rectal excision for cancer and inammatory bowel disease. Diseases of the Colon and Rectum 2002;45:72732. Lobo 1984 {published data only} Lobo RA, McCormick W, Singer F, Roy S. Depomedroxyprogesterone acetate compared with conjugated estrogens for the treatment of postmenopausal women. Obstetrics and Gynecology 1984;63(1):15. Madsen 2006 {published data only} Madsen LT, Garney-Code E. Assessing and addressing erectile function concerns in patient postprostatectomy. Oncology Nursing Forum 2006;33:20911. Mantovani 2001 {published data only} Mantovani F, Patelli E, Colombo F, Pozzoni F, Confalonieri S, Pisani E. Erectile dysfunction after non-nerve sparing radical pelvic surgery. Therapeutical experience with sildenal and L-Arginine evaluated by Buckling test [Disfunzione erettiva da chirurgia pelvica demolitiva non nervesparing]. Minerva Medica 2001;93(4):2857.
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Markou 2004 {published data only} Markou S, Perimenis P, Gyftopoulos K, Athanasopoulos A, Barbalias. Vardenal (levitra) for erectile dysfunction: a systematic review and meta-analysis of clinical trial reports. International Journal of Impotence Research 2004;16:4708. Marsden 2001 {published data only} Marsden J, Baum M, AHern R, West A, Falloweld L, Whitehead M, Sacks N. The impact of hormone replacement therapy on breast cancer patients quality of life and sexuality. Journal of the British Menopause 2001;7(2): 8591. Meinhardt 1997 {published data only} Meinhardt W, Schmitz PI, Kropman RF, de la Fuente RB, Nijeholt AA, Zwartendijk J. Trazodone, a double blind trial for treatment of erectile dysfunction. International Journal of Impotence Research 1997;9:1635. Merrick 2002 {published data only} Merrick GS, Butler WM, Galbreath RW, Stipetich RL, Abel LJ, Lief JH. Erectile function after permanent prostate brachytherapy. International Journal of Radiation Oncology*Biology*Physics 2002;52:893902. Merrill 1983 {published data only} Merrill DC. Clinical experience with Scott inatable penile prosthesis in 150 patients. Urology 1983;22(4):3715. Merrill 1986 {published data only} Merrill DC. Clinical experience with Mentor inatable penile prosthesis in 206 patients. Urology 1986;28(3): 1859. Meuleman 2001 {published data only} Meuleman E, Cuzin B, Opsomer RJ, Hartmann U, Bailey MJ, Maytom MC, Smith MD, Osterloh IH. A doseescalation study to assess the efcacy and safety of sildenal citrate in men with erectile dysfunction. BJU International 2001;87:7581. Meyhoff 1984 {published data only} Meyhoff HH, Nordling J, Hald T. Clinical evaluation of transurethral versus transvesical prostatectomy. A randomized study. Scandinavian Journal of Urology and Nephrology 1984;18:2019. Montorsi 1997 {published data only} Montorsi F, Luigi GG, Strambi LF, Da Pozzo LF, Nava L, Barbieri L, et al.Recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy with and without early intracavernous injections of alprostadil: results of a prospective, randomized trial. The Journal of Urology 1997;158(4):140810. Moore 1999 {published data only} Moore RA. Livial: a review of clinical studies. British Journal of Obstetrics and Gynecology 1999;106(19):121. Moore 2005 {published data only} Moore RA, Derry S, McQuay HJ. Indirect comparison of interventions using published randomised trials: systematic review of PDE-5 inhibitors for erectile dysfunction. BMC Urology 2005;5:116.

Morales 2004 {published data only} Morales L, Neven P, Timmerman D, Christiaens MR, Vergote I, Van Limbergen E, et al.Acute effects of tamoxifen and third-generation aromatase inhibitors on menopausal symptoms of breast cancer patients. Clinical Report 2004; 15(8):75360. Mulcahy 1990 {published data only} Mulcahy JJ, Krane RJ, Lloyd LK, Edson M, Siroky MB. Duraphase penile prosthesis--results of clinical trials in 63 patients. The Journal of Urology 1990;143(3):5189. Mulhall 2006 {published data only} Mulhall JP. Neuromodulatory drugs in a radical pelvic surgery patient. Journal of Sexual Medicine 2006;3:7779. Munarriz 2002 {published data only} Munarriz R, Talakoub L, Flaherty E, Gioia M, Hoag L, Kim NN, et al.Androgen replacement therapy with dehydroepiandrosterone for androgen insufciency and female sexual dysfunction: androgen and questionnaire results. Journal of Sex and Marital Therapy 2002;28(s): 16573. Munstedt 1998 {published data only} Munstedt K, Milch W, Reimer C. Epicutaneous breast forms after mastectomy. Support Care Cancer 1998;6: 2959. Nieman 2003 {published data only} Nieman LK. Management of surgically hypogonadal patients unable to take sex hormone replacement therapy. Endocrinology and metabolism clinics of North America 2003; 32:32536. Nikander 2003 {published data only} Nikander E, Kilkkinen A, Metsa HM, Adlercreutz H, Pietinen P, Tiitinen A, Ylikorkala O. A randomized placebocontrolled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients. The American College of Obstetricians and Gynecologists 2003;101(6): 121320. Northouse 2002 {published data only} Northouse LL, Walker J, Schafenacker A, Mood D, Mellon S, Galvin E, et al.A family-based program of care for women with recurrent breast cancer and their family members. Oncology Nursing Forum 2002;29(10):14119. ONS 2002 {published data only} Oncology Nursing Society 27th Annual Congress. The many faces of Oncology Nursing. Oncology Nursing Forum. 2002; Vol. 29, issue 2. ONS 2004 {published data only} Oncology Nursing Society 29th Annual Congress. Conference Abstracts. Oncology Nursing Forum 2004;31(2): 398460. Ormrod 2002 {published data only} Ormrod D, Easthorpe SE, Figgit DP. Vardenal. Drugs and Aging 2002;19(3):21727. Ott 2002 {published data only} Ott MJ. Complementary and alternative therapies in cancer symptom management. Cancer Practice 2002;10(3):1626.
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Padma-Nathan 1997 {published data only} Padma NH, Hellstrom WJG, Kaiser FE, Labasky RF, Lue TF, Nolten WE, Norwood PC, et al.Treatment of men with erectile dysfunction with transurethral alprostadil. The New England Journal of Medicine 1997;336(1):17. Parazzini 2000 {published data only} Parazzini F, Menchini FF, Bortolotti A, Calabro A, Chatenoud L, Colli E, et al.Frequency and determinants of erectile dysfunction in Italy. European Urology 2000;37: 439. Ponzone 2005 {published data only} Ponzone R, Biglia N, Jacomuzzi ME, Maggiorotto F, Mariani L, Sismondi P. Vaginal oestrogen therapy after breast cancer: Is it safe?. European Journal of Cancer 2005; 41:267381. Rashid 2005 {published data only} Rashid A. The efcacy and safety of PDE5 inhibitors. Erectile Dysfunction 2005;7:4755. Rawlins 1999 {published data only} Rawlins S, Burkman RT, Schwarz BE. The Power of the Pill: Making Evidence-Based Decisions. The American Journal for Nurse Practitioners 2000;4(1):2540. Reddy 2004 {published data only} Reddy GK, Jain VK, Sartor O. Abarelix (Plenaxis): A Gonadotropin-Releasing Hormone Antagonist for Medical Castration in Patients with Advanced Prostate Cancer. Clinical Prostate Cancer 2004;2(4):20911. Robinson 1999 {published data only} Robinson JW, Faris PD, Scott CB. Psychoeducational group increases vaginal dilation for younger women and reduces sexual fears for women of all ages with gynecological carcinoma treated with radiotherapy. International Journal of Radiation Oncolocy Biology and Physics 1999;44(3): 497506. Roy 1990 {published data only} Roy JB, Petrone RL, Said SI. A clinical trial of intracavernous vasoactive intestinal peptide to induce penile erection. The Journal of Urology 1990;143:3024. Schroder 2005 {published data only} Schroder M, Mell LK, Hurteau JA, Collins YC, Rotmensch J, Waggoner SE, et al.Clitoral therapy device for treatment of sexual dysfunction in irradiated cervical cancer patients. International Journal of Radiation Oncology*Biology*Physics 2005;61(4):107886. Schulmeister 2002 {published data only} Schulmeister L. Advances in Oncology Care: highlights of the 38th Annual Meeting of the American Society of Clinical Oncology. Clinical Journal of Oncology Nursing 2002;6(4):22931. Schwartz 2004 {published data only} Schwartz EJ, Wong P, Graydon RJ. Sildenal preserves intracorporeal smooth muscle after radical retropubic prostatectomy. The Journal of Urology 2004;171:7714.

Scura 2004 {published data only} Scura KW, Budin W, Garng E. Telephone social support and education for adaptation to prostate cancer: a pilot study. Oncology Nursing Forum 2004;31(2):335. Seidman 1998 {published data only} Seidman SN, Rabkin JG. Testosterone replacement therapy for hypogonadal men with SSRI- refractory depression. Journal of Affective Disorders 1998;48:15761. Seidman 2000 {published data only} Seidman SN. Hormonal aspects of sexual dysfunction: the therapeutic use of exogenous androgens in men and women. Current Psychiatry Reports 2000;2:21522. Serewel 1990 {published data only} Serewel A, Haggie JA, Cade D. A randomised controlled trial of medroxyprogesterone acetate in mastalgia. Annals of the Royal College of Surgeons of England 1990;72:273. Shabsigh 2004 {published data only} Shabsigh R. Testosterone therapy in erectile dysfunction. The Aging Male 2004;7:3128. Shak 2000 {published data only} Shak A, El Sibai O. The anocavernosal erectile dysfunction syndrome II anal ssure and erectile dysfunction. International Journal of Impotence Research 2000;12:27983. Sherryl 2006 {published data only} Sherryl J, Robinson JW, Craighead PS, Keats M. An effective Group Psycho-educational intervention for improving compliance with vaginal dilation: A randomized controlled trial. International Journal of Radiation Oncology, Biology, Physics artcile in press. Sherwin 1984 {published data only} Sherwin BB, Gelfand MM. Effects of parenteral administration of estrogen and androgen on plasma hormone levels and hot ushes in the surgical menopause. American Journal of Obstetrics and Gynecology 1984;148(5): 5527. Sherwin 1985 {published data only} Sherwin BB, Gelfand MM, Brender W. Androgen enhances sexual motivation in females: A prospective, crossover study of sex steroid administration in the surgical menopause. Psychosomatic Medicine 1985;4:33951. Sherwin 2002 {published data only} Sherwin BB. Randomized clinical trials of combined estrogen-androgen preparations: effects on sexual functioning. Fertility and Sterility 2002;4(4):S49S54. Shifren 2000a {published data only} Shifren JL, Braunstein GD, Simon JA, Casson PR, Buster JE, Redmond GP, et al.The efcacy of sildenal citrate (Viagra) in clinical populations: an update. The New England Journal of Medicine 2000;343(10):6828. Sildenal 1998 {published data only} Anon. Sildenal and erectile dysfunction. Prescrire International 1998;38:1635. Sildenal 2003 {published data only} Anon. Prostatic carcinoma. After therapy sildenal brings the potency back [Prostatakarzinom. Nach der Therapie
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

bringt Sildenal die Potenz zuruck]. MMW Fortschr Med 2003;145(24):.. SMFM 2005 {published data only} Society for Maternal-Fetal Medicine (SMFM). American Journal of Obstetrics and Gynecology. 2005; Vol. 25th Annual Meeting:Abstracts. Soderdahl 1997 {published data only} Soderdahl DW, Thrasher JB, Hansberry KL. Intracavernosal drug-induced erection therapy versus external vacuum devices in the treatment of erectile dysfunction. British Journal of Urology 1997;79:9527. Stearns 2004 {published data only} Stearns V. Management of hot ushes in breast cancer survivors and men with prostate cancer. Current Oncology Reports 2004;6:28590. Suckling 2006 {published data only} Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database of Systematic Reviews 2006, Issue 4. [DOI: 10.1002/14651858.CD001500.pub2] Sweeney 2002 {published data only} Sweeney C, Bruera E. Communication in cancer care: recent developments. Journal of Palliative Care 2002;18(4): 3006. Tadalal 2003 {published data only} No author. Tadalal: Slightly more convenient, but poorly assessed in organic disorders. Prescrire International 2003;68:2135. Theobald 2002 {published data only} Theobald DE, Kirsh KL, Holtsclaw E, Donaghy K, Passik SD. An open-label, crossover trial of mirtazapine (15 and 30 mg) in cancer patients with pain and other distressing symptoms. Journal of Pain and Symptom Management 2002; 23(5):4427. Thompson 2003 {published data only} Thompson EA, Reilly D. The homeopathic approach to the treatment of symptoms of oestrogen withdrawal in breast cancer patients. A prospective observational study. Homeopathy 2003;92:1314. Tyrrell 1994 {published data only} Tyrrell CJ. Tolerability and quality of life aspects with the anti-androgen Casodex (ICI 176,334) as monotherapy for prostate cancer. European Urology 1994;26(1):159. Van der Windt 2002 {published data only} Van der WF, Dohle GR, Van Der TJ, Slob AK. Intracavernosal injection therapy with and without sexological counselling in men with erectile dysfunction. BJU International 2002;89:9014. Vos 2006 {published data only} Vos JV, Visser AP, Garssen B, Duivenvoorden HJ, Hanneke CJM de Haes. Effects of delayed psychosocial interventions versus early psychosocial interventions for women with early stage breast cancer. Patient Education and Counseling 2006; 60:2129.

Warkentin 2006 {published data only} Warkentin KM, Gray RE, Wassersug RJ. Restoration of Satisfying sex for a castrated cancer patient with complete impotence. Journal of Sex and Marital Therapy 2006;32: 398399. Watts 1995 {published data only} Watts NB, Morris N, Timmons CM, Allen Addison W, Wiita B, Downey LJ. Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein proles in surgical menopause. Obstetrics and Gynecology 1995;85(4): 52937. Webber 2003 {published data only} Webber R. Erectile dysfunction. Clinical evidence 2002 (7) Jun 796-803 2003;Mens Health:126270. Weber 1999 {published data only} Weber DC, Bieri S, Kurtz JM, Miralbell R. Prospective pilot study of sildenal for treatment of postradiotherapy erectile dysfunction in patients with prostate cancer. Journal of Clinical Oncology 1999;17(11):34449. Wei 2005 {published data only} Wei W, Shuang L, Wu Guang-Jao, Li Li. Inuence of perioperative supportive psychotherapy on the postoperative mental state and sexual life in patients with uterine cervix cancer. Chinese Journal of Clinical Rehabilitation 2005;9: 4243. Wenzel 1999 {published data only} Wenzel LB, Fairclough DL, Brady MJ, Cella D, Garrett KM, Kluhsman BC, et al.Age-related differences in the quality of life of breast carcinoma patients after treatment. American Cancer Society 1999;86(9):176874. Williams 1998 {published data only} Williams G, Abbou CC, Amar ET, Desvaux P, Flam TA, Nijeholt GA, et al.The effect of transurethral alprostadil on the quality of life of men with erectile dysfunction, and their partners. British Journal of Urology 1998;82:84754. Wolfson 1993 {published data only} Wolfson B, Pickett S, Scott NE, DeKernion JB, Rajfer J, Wolfson B. Intraurethral prostaglandin E-2 cream: A possible alternative treatment for erectile dysfunction. Urology 1993;42(1):735. Wright 2006 {published data only} Wright PJ. Comparison of phosphodiesterase type 5(PDE5) inhibitors. International Journal of Clinical Practice 2006; 60:96775. Zelefsky 1999 {published data only} Zelefsky M, McKee AB, Lee H, Leibel SA. Efcacy of oral sildenal in patients with erectile dysfunction after radiotherapy for carcinoma of the prostate. Urology 1999; 53(4):7758. Zippe 1999 {published data only} Zippe CD, Kedia S, Kedia AW, Pasqualotto F. Sildenal citrate (viagra) after radical retropubic prostatectomy: Pro. Urology 1999;54:5836.
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

References to studies awaiting assessment

Berzel 2002 {published data only}

Additional references
Ananth 2003 Ananth H, Jones L, King M, Tookman A. The impact of cancer on sexual function: a controlled study. Palliative Medicine 2003;17(2):2025. Auchincloss 1989 Auchincloss SS. Sexual dysfunction in cancer patients: issues in evaluation and treatment. In Handbook of Psychooncology: Psychological care of the patient with cancer. New York, NY: Oxford University Press, 1989. Biagiotti 2001 Biagiotti G, Cavallini G, Koverech A, et al.Acetyl-LCarnitine vs tamoxifen in the oral therapy of Peyronies disease: a preliminary report. BJU Int 2001;88:637. Carswell 2002 Carswell CI, Figgitt DP. Bicalutamide: in early-stage prostate cancer. Drugs 2002;62(17):24719. Caruso 2001 Caruso S, Intelisano G, Lupo L, Agnello C. Premenopausal women affected by sexual arousal disorder treated with Sildenal: a double-blind cross-over, placebo-controlled study. BJOG 2001;108:623. Chen 1999 Chen J, Wollman Y, Chernichovsky T, Iaina A, Sofer M, Matzkin H. Effect of oral administration of highdose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study. BJU Int 1999;83:26973. Choi 1995 Choi HK, et al.Clinical efcacy of Korean red ginseng in patients with erectile dysfunction. International Journal of Impotence Research 1995;7:1816. DSM IV-TR 2000 American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th Edition., primary care. Washington DC. American Psychiatric Association, 2000. Elbourne 2002 Elbourne DR, Altman DG, Higgins JPT, Curtain F, Worthington HV, Vail A. Meta-analysis involving crossover trials: methodological issues. International Journal of Epidemiology 2002;31:1409. Ganz 1998 Ganz PA, Rowland JH, Desmond K, Meyerowitz BE, Wyatt GE. Life after breast cancer: Understanding womens health-related quality of life and sexual functioning. Journal of Clinical Oncology 1998;16(2):50114. Higgins 2006 Higgins JPT, Green S. Editors. Cochrane Handbook for Systematic Reviews of Interventions 4.2.6 . In: The Cochrane Library, Issue 4, 2006. Chichester, UK: John Wiley & Sons, Ltd, 2006.

Hinotsu 1996 Hinotsu S, Ohasi Y, Akaza H. An overview of clinical trials in endocrine therapy for cancer. Gan To Kagaku Ryoko 1996;23(6):68994. Hong 2002 Hong B, Ji Yh, Hong JH, et al.A double-blind crossover study evaluating the efcacy of Korean red ginseng in patients with erectile dysfunction: A preliminary report. Journal of Urology 2002;168:20703. Juni 2001 Juni P, Altman DG, Egger M. Assessing the quality of controlled clinical trials. In: Egger M, Smith D, Altman DG eds. Systematic Reviews in Healthcare: meta-analysis in context. BMJ Books, 2001. Keating 2004b Keating GM, Scott LJ. Vardenal: A review of its use in erectile dysfunction. Drugs 2003;63:2673703. Kuczyk 2000 Kuczyk M, Machtens S, Bokemeyer C, Schultheiss D, Jonas U. Sexual function and fertility after treatment of testicular cancer. Current opinion in Oncology 2000;10(5):4737. Lamb 1996 Lamb MA. Sexuality and sexual functioning. In McCorkle R; GRant M; Stromberb FM et al, eds.:Cancer Nursing: A comprehensive textbook. 2nd ed. Philadelphia, Pa: WB Saunders Co, 1996. Marmor 1999 Marmor D. Fertility in women after cancer therapy [Fertilite feminine apres traitement anticancereux]. Contraception, fertilite, sexualite 1999;27(6):41722. Matthew 2005 Matthew AG, Goldman A, Trachtenberg J, Robinson J, Horsburgh S, Currie K, Ritvo P. Sexual dysfunction after radical prostatectomy: prevalence, treatments, restricted use of treatments and distress. Journal of Urology 2005;174: 210510. Meston 2002 Meston CM, Worcel M. The effects of yohimbine plus Larginine glutamate on sexual arousal in postmenopausal women with sexual arousal disorder. Archives of sexual behaviour 2002;31 (4):32332. Montorsi 2004b Montorsi F, Briganti A, Salonia A, Rigatti P. Current and future strategies for preventing and managing erectile dysfunction following radical prostatectomy. European Urology 2004;45:12333. Moynihan 2005 Moynihan R. The marketing of a disease: female sexual dysfunction. BMJ 2005;330:1924. Ozyilkan 1995 Ozyilkan O, Karaagaoglu E, Topeli A, Kars A, Baltali E, Tekuzman G, Firat D. A questionnaire for the assessment of quality of life in cancer patients in Turkey. Materia Medica Polona 1995;27(4):1536.
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Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Pelka 2002 Pelka RB, Jaenicke C, Gruenwald J. Impulse magnetic-eld therapy for erectile dysfunction: a double-blind, placebocontrolled study. Advances in Therapy 2002;19:5360. Pignata 2001 Pignata S, Ballatori E, Favalli G, Scambia G. Quality of life: gynaecological cancers. Annals of Oncology 2001;12(Suppl 3):S37S42. Redaelli 2004 Redaelli A, Stephens JM, Brandt S, Botteman MF, Pashos CL. Short- and long-term effects of acute myeloid leukemia on patient health-related quality of life. Cancer Treatment Reviews 2004;30(1):10317. [MEDLINE: 14766128&# 182;] Rogers 2002 Rogers M, Kristjanson LJ. The impact on sexual functioning of chemotherapy-induced menopause in women with breast cancer. Cancer Nursing 2002;25(1):5765. Schover 1997 Schover. Enhancing sexual desire after cancer. In: Sexuality and Fertility after Cancer 1997;USA:John Wiley & Sons. Sciarra 2004 Sciarra A, Cardi A, Di Silverio F. Antiandrogen monotherapy: recommendations for the treatment of prostate cancer. Internal Brazilian Journal of Urology 2004; 72(2):918. Shell 2002 Shell JA. Evidence-based practice for symptom management in adults with cancer: sexual dysfunction. Omcology Nurse Forum 2002;29:5366. Smith 2000 Smith DS, Carvalhal GF, Schneider K, Krygiel J, Yan Y, Catalona WJ. Quality-of-life outcomes for men with prostate carcinoma detected by screening. Cancer 2000;88 (6):145463.

Stanford 2000 Stanford JL, Feng Z, Hamilton AS, Gilliland FD, Stephenson RA, Eley JW, et al.Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the prostate cancer outcomes study. New England Journal of Medicine 2000;283(3):35460. Stead 2003 Stead ML. Sexual dysfunction after treatment for gynaecologic and breast malignancies. Current Opinion in Obstetrics & Gynecology 2003;15(1):5761. Syrjala 1998 Syrjala KL, Roth Roemer SL, Abrams JR, Scanlan JM, Chapko MK, Visser S, Sanders JE. Prevalence and predictors of sexual dysfunction in long-term survivors of marrow transplantation. Blood 1998;16(9):314857. Tabano 2002 Tabano M, Condosta D, Coons M. Symptoms affecting quality of life in women with gynaecologic cancer. Seminars in Oncology Nursing 2002;18(3):22330. Talcott 1998 Talcott JA, Rieker P, Clark JA, Propert KJ, Weeks JC, Beard CJ, et al.Patient-reported symptoms after primary therapy for early prostate cancer: results of a prospective cohort study. Journal of Clinical Oncology 1998;16(1):27583. Thors 2001 Thors CL, Broeckel JA, Jacobsen PB. Sexual functioning in breast cancer survivors. Cancer Control 2001;8(5):4428. Vardi 2007 Vardi M, Nini A. Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes melitus. Cochrane Database of Systematic Reviews 2007, Issue 2. [DOI: 10.1002/14651858.CD002187.pub3] Walsh 1987 Walsh PC, Epstein JI, Lowe EC. Potency following radical prostatectomy with wide unilateral excision of the neurovascular bundle. Journal of Urology 1987;138:8237. Indicates the major publication for the study

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CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID]

Brock 2003 Methods Participants Multi-centre randomised controlled parallel trial 440 men in a stable heterosexual relationship with ED after, for prostate cancer, unilateral or bilateral nerve-sparing radical retropubic prostatectomy Surgery was at least six months ago and less than ve years before screening. Those with a Gleason score equal to or more than eight were excluded Mean ages 60 years in placebo group and 61 years in the intervention group All participants had a four week no treatment run in period before randomisation to one of three groups. Participants took one of the following treatments one hour before sexual intercourse: (i) Vardenal 10 mg (ii) Vardenal 20 mg (iii) Matching placebo One dose maximum per day Treatment duration: 12 weeks *International Index of Erectile Function (IIEF) *Sexual Encounter Prole (SEP) *Global Assessment Question (GAQ) Outcome assessed at 12 weeks

Interventions

Outcomes

Notes Risk of bias Bias Allocation concealment? Canada 2005 Methods Participants Single-centre randomised controlled parallel trial 84 heterosexual couples in a stable relationship. Male participants with ED were survivors of localised prostate cancer treated with radical prostatectomy Surgery was performed three to 60 months ago Mean age of men 66 years Couples were randomised to attend four sessions of counselling together or for the man to atttend alone Treatment duration unclear *IIEF Outcome assessed at three and six months Authors judgement Unclear risk Support for judgement B - Unclear

Interventions

Outcomes

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Canada 2005

(Continued)

Notes Risk of bias Bias Allocation concealment? Cavallini 2005 Methods Participants Multi-centre randomised controlled parallel trial 96 men in a stable heterosexual relationship with ED after bilateral nerve-sparing radical retropubic prostatectomy for prostate cancer Surgery was performed at least six months ago Mean age 60 years in placebo group, 61 years in sildenal and 63 years in sildenal and carnitines group There were three trial arms: (i) Propionyl-L-carnitine 2 g/day plus acetyl-L-carnitine 2 g/day plus sildenal 100 mg when needed (ii) Sildenal 100 mg when needed (iii) placebo Treatment duration four months *IIEF *Self report of satisfactory sexual intercourse Outcome assessed at four months Authors judgement Unclear risk Support for judgement B - Unclear

Interventions

Outcomes

Notes Risk of bias Bias Allocation concealment? Costabile 1998 Methods Participants Multi-centre randomised controlled parallel trial 384 men in a stable heterosexual relationship with ED who had undergone a radical retropubic prostatectomy and prepared to perform sexual activity regularly Unclear time frame from surgery to trial entry Mean age 63 years After a 30 day no treatment run-in phase and a clinic titration phase, which determined the effective dose, patients who had erections sufcient for intercourse were randomly assigned to one of two groups: (i) Transurethral alprostadil 500 to 1000 mcg
22

Authors judgement Unclear risk

Support for judgement B - Unclear

Interventions

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Costabile 1998

(Continued)

(ii) Placebo Treatment duration three months Outcomes Frequency and success of intercourse Outcome assessed at one, two, three months

Notes Risk of bias Bias Allocation concealment? Incrocci 2001 Methods Participants Single-centre randomised controlled cross-over trial 60 men with ED treated with radiotherapy (unclear time frame from radiotherapy to trial entry) for prostate cancer Men were in a stable relationship and prepared to perform sexual activity at least once a week Mean time since treatment to study entry was 39 months Mean age 74 years After a four week no treatment run-in phase sildenal 50 mg or placebo for two weeks; at week two the dose was increased to 100 mg if there was unsatisfactory response. At week six patients crossed over to the alternative treatment Treatment duration 12 weeks *IIEF *GAQ Outcome assessed at two, six, eight, and 12 weeks Authors judgement Unclear risk Support for judgement B - Unclear

Interventions

Outcomes

Notes Risk of bias Bias Allocation concealment? Incrocci 2006 Methods Participants Single-centre randomised controlled cross-over trial 60 men with ED following three dimensional conformal external beam radiology for prostate cancer Surgery at least 12 months before trial entry Mean age 69 years
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Authors judgement Unclear risk

Support for judgement B - Unclear

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Incrocci 2006

(Continued)

Interventions

After a four week no treatment run-in phase tadalal 20mg or placebo for six weeks were taken at patients discretion at least once a week and no more than once daily. At six weeks patients cross-over to the alternative treatment Treatment duration 12 weeks *IIEF *SEP *GAQ Outcome assessed at six and 12 weeks

Outcomes

Notes Risk of bias Bias Allocation concealment? Montorsi 2004a Methods Participants Single-centre randomised controlled parallel trial 303 men with ED following bilateral non nerve sparing radical retropubic prostactectomy for prostate cancer Surgery was performed 12 to 48 months before the study Mean age 60 years All patients had a four week no treatment run-in period before randomisation to either: (i): Tadalal 10 mg (ii): Placebo Treatment duration was 12 weeks *IIEF *SEP *GAQ Outcome assessed at 12 weeks Authors judgement Unclear risk Support for judgement B - Unclear

Interventions

Outcomes

Notes Risk of bias Bias Allocation concealment? Authors judgement Unclear risk Support for judgement B - Unclear

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Pitkin 1971 Methods Participants Single-centre randomised, controlled parallel trial 93 women with cervical cancer treated with radiation therapy Unclear time from surgery to trial entry Mean age 49 years in placebo group and 50 years in active group Topical vaginal estrogen cream Treatment duration: until cream used up. The length of time ranged from ve to eight months Self report of intercourse and dyspareunia Assessment time unclear

Interventions

Outcomes

Notes Risk of bias Bias Allocation concealment? Raina 2006 Methods Participants Single-centre randomised, controlled parallel trial 59 men with ED following nerve sparing or non nerve sparing radical prostatectomy for prostate cancer Unclear time from surgery to trial entry Mean age 58 years Men were randomised to receive vacuum constriction devices (VCD) to induce an erection or no treatment An experienced nurse conducted a training session to teach participants how to use the VCD Treatment duration nine months *IIEF Outcome assessed at least at nine months Authors judgement Unclear risk Support for judgement B - Unclear

Interventions

Outcomes

Notes Risk of bias Bias Allocation concealment? Authors judgement Unclear risk Support for judgement B - Unclear

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Titta 2006 Methods Participants Single-centre randomised, controlled parallel trial 57 men with ED after non-nerve sparing radical pelvic surgery: prostatectomy or protectomy (included were men with clinically localized prostate cancer n = 50 and muscle invasive bladder n = 7 cancer) Mean time from surgery was 29 months range 20 to 41 Mean age 63 years Sexual counselling with prostaglandin E1-intracavernous injection therapy (ICI) versus ICI only Participants were instructed to perform ICI twice a week. Before each assessment, to measure compliance with ICI, participants were invited to attempt sexual intercourse after taking sildenal 100 mg one hour beforehand. The authors suggest that sildenal response is likely in these patients only if there has been some restoration of anatomical function and that correct use of the ICI regimen may allow this to occur The participants in the sexual counselling group, with their female partner if in attendance, completed an unvalidated semi-structured questionnaire on sexual history and difculties and satisfaction with drug administration using the ICI Sexual counselling tailored (based on questionnaire response) to each participant involved six sessions over 18 months with a therapist to discuss drug administration and couple communication about sexual problems and psychodynamic-oriented sexual therapy to place therapy within the couples sexual behaviours and relationship (it is unclear if all male participants had their female partner in attendance). Sessions were held at three, six, nine, 12 and 18 months. The intervention also involved a telephone session aimed to identify the lowest efcacious PGE1 home dose and to facilitate home sildenal tests prior to follow up sessions *IIEF * Self report of couple satisfaction * Compliance, with ICI Outcome assessed up to 18 months after surgery

Interventions

Outcomes

Notes Risk of bias Bias Allocation concealment? Weber 2004 Methods Participants Single-centre randomised, controlled parallel trial 100 men with prostate cancer who had undergone radical prostatectomy, resulting in urinary and sexual dysfunction Time from surgery to trial entry six weeks Mean age 58 years Men randomised to control (n = 15) or peer partner support intervention (n = 15). Controls received usual care Peer partners were men recently treated by radical prostatectomy and long-term survivors (more than three years). Each met eight times. The purpose was for men to discuss problems typically encountered
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Authors judgement Unclear risk

Support for judgement B - Unclear

Interventions

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Weber 2004

(Continued)

after surgery Treatment duration eight weeks Outcomes *UCLA Prostate Cancer Index Outcome assessed at three and 18 months

Notes Risk of bias Bias Allocation concealment? Authors judgement Unclear risk Support for judgement B - Unclear

Characteristics of excluded studies [ordered by study ID]

Study Aaronson 1986 ACOG 2003 Alexander 2004 Anastasiadis 2003 Badger 2005 Balmer 2000 Baniel 2001 Barber 2002 Barrett-Connor 1996 Bawa 2004

Reason for exclusion A review article. Not about SD No studies directly relevant from the abstract of this conference A review article Treatments for cancer and not SD SD not mentioned A review of other relevant studies. Relevant studies noted and retrieved A cohort study Article includes sexual functioning, but cancer patients were not included It is unlikely that these healthy menopausal women are cancer patients There is insufcient information from this Research Letter to determine whether these are cancer patients. Have contacted author and no reply This is not an RCT. It is a retrospective case record analysis on costs of cancer. Not about SD No cancer patients Intervention was not a treatment for SD. Intervention was a preventative measure No cancer patients
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Beemsterboer 1998 Berman 2003 Boccardo 1999 Brock 2002

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(Continued)

Burstein 1999 Carson 2002 Carson 2004 Carson 2005 Chen 2001 Chen 2004 Christensen 1983 Davis 2004

This is not an RCT and alternative medicine was not an intervention for SD A review on sildenal No cancer patients No cancer patients It is unclear from the article whether these are cancer patients. Have contacted the author. No reply No cancer patients No baseline of SD provided Exploratory study of psychosocial needs of women with breast cancer. Not an intervention for SD following treatments for cancer A review Not a randomised controlled trial No cancer patients. No sexual function outcomes Does not assess effectiveness of intervention in patients with sexual dysfunction following a cancer treatment No cancer patients Subjects were peri or postmenopausal (they had to have been amenorrheic for at least six months). The cause of sexual dysfunction was not studied in this sample and some women may have had problems that preceded the cancer diagnosis or could have been attributed to treatment No cancer patients No cancer patients No sexual function outcome This was not a controlled study. This study looks at the efcacy of using Intracorporeal Papaverine Injections (ICP) in patients after therapeutic castration No sexual function outcomes Prostaglandin E1: The study focuses on this intervention as a preventative measure to reduce ED No sexual function outcomes

Daz 2002 Decruze 1999 Dennerstein 1979 Doorenbos 2006 Eardley 2005 Floter 2002 Ganz 2000

Gasser 1987 Gerber 2001 Giesler 2005 Gilbert 1990

Given 2004 Gontero 2003 Hasenbring 1999

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(Continued)

Helgeson 2006 Huntley 2002 Incrocci 2003a Incrocci 2003b Isidora 2006 Iversen 2001 Izuo 1967 Jeffries 2006 Jones 2006 Jung Hoon 2006 Kattan 1995 Kearse WS Jr 1996

No sexual function outcomes Review article of complementary therapies, not cancer specic A cohort study A Dutch version of Incrocci 2003a Discussion paper Review article comparing treatments for cancer, not treatments for SD No sexual function outcomes No sexual function outcomes No sexual function outcomes No sexual function outcomes No cancer patients 20% of patients had SD secondary to pelvic surgery. Not sure if these were cancer patients. Unable to contact the author. Was not possible to extract data in regard to cancer patients only Review on Vardenal. No new studies. Not cancer specic There was no established baseline report of SD Review on Vardenal. No new studies No cancer patients Nerve-sparing techniques. Preventative measures Nerve-sparing techniques. Preventative measures Nerve-sparing techniques. Preventative measures No cancer patients A review paper. One of the cited studies reviewed used cancer patients, but this was not an RCT No cancer patients Not a treatment for SD

Keating 2004a Kellogg-Parsons 2004 Kendirci 2004 Kiely 1987 Klotz 2000a Klotz 2000b Klotz 2000c Kongkanand 2003 Kuan 2002 Kunelius 1997 Kylstra 1999

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(Continued)

Lee 1988 Lepore 2003 Lindsey 2001 Lobo 1984 Madsen 2006 Mantovani 2001 Markou 2004 Marsden 2001

No cancer patients There was no established baseline report of SD No separate analysis for subgroup of cancer patients No cancer patients Discussion paper A mixed group of men who have had cystectomies and those who have not. Data not analysed separately No cancer patients Subjects are postmenopausal. The cause of sexual dysfunction was not studied in this sample and some women may have had problems that preceded the cancer diagnosis or could have been attributed to treatment Trazodone treatment unclear if patients had cancer A cohort study. Not an RCT No outcome data No outcome data Sildenal treatment: Not sure if cancer patients. Reason for organic ED was not given. Was not possible to extract outcome data for cancer specically. Have contacted author. No reply Cancer data not reported separately No baseline of SD provided No cancer patients Discussion paper Tamoxifen: Not a treatment for SD Penile Prosthesis. 5% of patients had a prostatectomy and results were not reported separately for each subgroup Discussion paper No cancer patients Not evalauting treatment for SD

Meinhardt 1997 Merrick 2002 Merrill 1983 Merrill 1986 Meuleman 2001

Meyhoff 1984 Montorsi 1997 Moore 1999 Moore 2005 Morales 2004 Mulcahy 1990

Mulhall 2006 Munarriz 2002 Munstedt 1998

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(Continued)

Nieman 2003 Nikander 2003 Northouse 2002 ONS 2002 ONS 2004 Ormrod 2002 Ott 2002 Padma-Nathan 1997

No cancer patients No sexual outcome measures SD not specically mentioned No studies directly relevant from the abstracts of this conference No studies directly relevant from the abstracts of this conference A review of research that did not highlight any new references Review article on Complementary and Alternative Medicines Costabile et al (see included studies) extracts the data from cancer patients in this study. Data used later in this review. As this article stands data for cancer patients only is not evaluable Not about treatments for SD following treatments for cancer Discussion article on vaginal osetrogen therapy after breast cancer Discussion article Discussion article on the contraceptive pill Not a treatment for SD There was no established baseline report of SD Data for cancer patients not provided separately. Clitoral therapy device. Not an RCT, a pilot study No studies relevant from the abstracts of this conference No SD outcomes There was no established baseline report of SD No cancer patients TRT in hypogonadal men Unlikely that these are cancer patients. A Review

Parazzini 2000 Ponzone 2005 Rashid 2005 Rawlins 1999 Reddy 2004 Robinson 1999 Roy 1990 Schroder 2005 Schulmeister 2002 Schwartz 2004 Scura 2004 Seidman 1998 Seidman 2000 Serewel 1990 Shabsigh 2004

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(Continued)

Shak 2000 Sherryl 2006 Sherwin 1984 Sherwin 1985 Sherwin 2002 Shifren 2000a Sildenal 1998 Sildenal 2003 SMFM 2005 Soderdahl 1997 Stearns 2004 Suckling 2006 Sweeney 2002 Tadalal 2003 Theobald 2002 Thompson 2003 Tyrrell 1994 Van der Windt 2002 Vos 2006 Warkentin 2006 Watts 1995 Webber 2003 Weber 1999

Cancer data was not reported separately There was no established baseline report of SD Not about treatments for SD following treatment for cancer Not cancer patients Review article on naturally and surgically menopausal women Testosterone treatment for women. Not cancer patients Review on Sildenal. One study in a cancer population, but its source was a tablets package insert Review of iagra treatment after prostate cancer. No new studies No studies directly relevant from the abstract of this conference Sexual dysfunction intervention versus sexual dysfunction intervention A review article. Not about SD Discussion paper Not an intervention for SD Review on Tadalal in non-cancer populations Mirtazapine treatment: No SD outcomes SD is under other symptoms with other non-SD symptoms. Therefore data is not evaluable Casodex: This is a treatment for cancer and not an intervention for SD Cancer not mentioned. Patients referred to as mainly somatic. Have contacted author. No reply No sexual function outcomes Not RCT Hormone therapy, but not cancer patients Review article about pharmacological medication for SD Not an RCT

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(Continued)

Wei 2005

This is a poor quality report of an RCT of psychotherapy for one week before and one week after an (unspecied) operation for cervical cancer. The baseline level of sexual functioning amongst participants is not reported, either before or after the operation. It is unclear who the male participants were and who answered the questionnaire. The sexual outcome sexual satisfaction is self-reported using what appears to be a single question The gures given are not explained (so it is not clear whether they are means or medians, for example). The randomisation procedure is not well explained. An assessment for SD and not a treatment for Data could not be extracted for cancer patients only Not cancer patients Discussion paper Prospective cohort study Not an RCT

Wenzel 1999 Williams 1998 Wolfson 1993 Wright 2006 Zelefsky 1999 Zippe 1999

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DATA AND ANALYSES

Comparison 1. Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo

Outcome or subgroup title 1 Improvement in erections (GAQ) 2 Erectile function domain of IIEF: Bilateral nerve sparing radical retropubic prostatectomy 20mg vardenal 3 Successful vaginal penetration (Sexual Encounter Prole) 4 Successful vaginal intercourse (Sexual Encounter Prole) 5 Improvement in erections (GAQ) following SD after bilateral nerve sparing radical retropubic prostatectomy 6 Improvement in erections (GAQ) following SD after unilateral nerve sparing radical retropubic prostatectomy 7 Erectile function domain of IIEF: Bilateral nerve sparing radical retropubic prostatectomy 10mg vardenal 8 Successful vaginal penetration (SEP): Bilateral nerve sparing radical retropubic prostatectomy 20mg vardenal 9 Erectile function domain of IIEF: Bilateral nerve sparing radical retropubic prostatectomy 20mg Tadalal 10 Erectile function domain of IIEF: Unilateral nerve sparing radical retropubic prostatectomy 20mg vardenal 11 Erectile function domain of IIEF: Unilateral nerve sparing radical retropubic prostatectomy 10mg vardenal 12 Erectile function: IIEF at follow-up: Bilateral nerve sparing radical retropubic prostatectomy 20mg Vardenal

No. of studies 2 1

No. of participants 415

Statistical method Odds Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

Effect size 10.09 [6.20, 16.43] Totals not selected

1 1 1

Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)

Totals not selected Totals not selected Totals not selected

Odds Ratio (M-H, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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13 Successful vaginal penetration (SEP): Bilateral nerve sparing radical retropubic prostatectomy 10mg vardenal 14 Successful vaginal penetration(SEP): Unilateral nerve sparing radical retropubic prostatectomy 20mg vardenal 15 Successful vaginal penetration(SEP): Unilateral nerve sparing radical retropubic prostatectomy 10mg vardenal 16 Successful vaginal intercourse (SEP): Bilateral nerve sparing radical retropubic prostatectomy 20mg vardenal 17 Successful vaginal intercourse (SEP): Bilateral nerve sparing radical retropubic prostatectomy 10mg vardenal 18 Successful vaginal intercourse(SEP): Unilateral nerve sparing radical retropubic prostatectomy 20mg vardenal 19 Successful vaginal intercourse(SEP): Unilateral nerve sparing radical retropubic prostatectomy 10mg vardenal 20 Erectile function domain of IIEF: Mean difference

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Comparison 2. Transurethral alprostadil versus placebo

Outcome or subgroup title 1 Vaginal intercourse rate 2 Adverse events: urethral pain/burning 3 Adverse events: penile pain

No. of studies 1 1 1

No. of participants

Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)

Effect size Totals not selected Totals not selected Totals not selected

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Comparison 3. Vacuum constriction device versus observational care following prostatectomy

Outcome or subgroup title 1 Erectile function 2 Erectile function in nerve-sparing surgery group 3 Successful vaginal intercourse 4 Sexual function (IIEF)

No. of studies 1 1 1 1

No. of participants

Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

Effect size Totals not selected Totals not selected Totals not selected Totals not selected

Comparison 4. Supportive partners versus usual care

Outcome or subgroup title 1 Sexual function (UCLA Prostate Cancer Index) 2 Sexual bother (UCLA Prostate Cancer Index)

No. of studies 1 1

No. of participants

Statistical method Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

Effect size Totals not selected Totals not selected

Comparison 5. Acetyl-L-Carnitane (ALC) plus propionyl-L-Carnitane (PLC) and sildenal versus sildenal only versus placebo

Outcome or subgroup title 1 Satisfactory sexual intercourse (self report): sidenal +ALC + PLC versus placebo 2 Satisfactory sexual intercourse: sidenal versus placebo 3 Satisfactory sexual intercourse: sidenal + ALC + PLC versus sidenal

No. of studies 1

No. of participants

Statistical method Odds Ratio (M-H, Fixed, 95% CI)

Effect size Totals not selected

1 1

Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)

Totals not selected Totals not selected

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Comparison 6. Oestrogen vaginal cream versus placebo

Outcome or subgroup title 1 Sexual vaginal intercourse (self report) 2 Dyspareunia (self report) 3 Severe dyspareunia (self report)

No. of studies 1 1 1

No. of participants

Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)

Effect size Totals not selected Totals not selected Totals not selected

Comparison 7. Sexual counselling versus no counselling in men using prostaglandin E1 intracavernous injection

Outcome or subgroup title 1 Couple satisfaction

No. of studies 1

No. of participants

Statistical method Odds Ratio (M-H, Fixed, 95% CI)

Effect size Totals not selected

Analysis 1.1. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 1 Improvement in erections (GAQ).
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 1 Improvement in erections (GAQ)

Study or subgroup

Treatment n/N

Control n/N 12/96 16/68

Odds Ratio M-H,Fixed,95% CI

Weight

Odds Ratio M-H,Fixed,95% CI

Brock 2003 Montorsi 2004a

77/118 94/133

42.5 % 57.5 %

13.15 [ 6.44, 26.84 ] 7.83 [ 4.00, 15.36 ]

Total (95% CI)

251

164

100.0 %

10.09 [ 6.20, 16.43 ]

Total events: 171 (Treatment), 28 (Control) Heterogeneity: Chi2 = 1.07, df = 1 (P = 0.30); I2 =7% Test for overall effect: Z = 9.30 (P < 0.00001)

0.001 0.01 0.1 Favours control

10 100 1000 Favours treatment

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 1.2. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 2 Erectile function domain of IIEF: Bilateral nerve sparing radical retropubic prostatectomy 20mg vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 2 Erectile function domain of IIEF: Bilateral nerve sparing radical retropubic prostatectomy 20mg vardenal

Study or subgroup

Treatment N Mean(SD) 16.2 (8.35)

Control N 96 Mean(SD) 9.7 (7.84)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 6.50 [ 4.28, 8.72 ]

Brock 2003

109

-10

-5

10

Favours control

Favours treatment

Analysis 1.3. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 3 Successful vaginal penetration (Sexual Encounter Prole).
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 3 Successful vaginal penetration (Sexual Encounter Prole)

Study or subgroup

Treatment n/N

Control n/N 32/99

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 3.72 [ 2.23, 6.20 ]

Montorsi 2004a

126/197

0.1 0.2

0.5

10

Favours control

Favours treatment

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 1.4. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 4 Successful vaginal intercourse (Sexual Encounter Prole).
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 4 Successful vaginal intercourse (Sexual Encounter Prole)

Study or subgroup

Treatment n/N

Control n/N 19/99

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 2.88 [ 1.62, 5.12 ]

Montorsi 2004a

80/197

0.1 0.2

0.5

10

Favours control

Favours treatment

Analysis 1.5. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 5 Improvement in erections (GAQ) following SD after bilateral nerve sparing radical retropubic prostatectomy.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 5 Improvement in erections (GAQ) following SD after bilateral nerve sparing radical retropubic prostatectomy

Study or subgroup

Treatment n/N

Control n/N 7/64

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 20.04 [ 8.09, 49.68 ]

Brock 2003

64/90

0.01

0.1

10

100

Favours control

Favours treatment

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 1.6. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 6 Improvement in erections (GAQ) following SD after unilateral nerve sparing radical retropubic prostatectomy.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 6 Improvement in erections (GAQ) following SD after unilateral nerve sparing radical retropubic prostatectomy

Study or subgroup

Treatment n/N

Control n/N 5/32

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 6.23 [ 1.86, 20.88 ]

Brock 2003

15/28

0.01

0.1

10

100

Favours control

Favours treatment

Analysis 1.7. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 7 Erectile function domain of IIEF: Bilateral nerve sparing radical retropubic prostatectomy 10mg vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 7 Erectile function domain of IIEF: Bilateral nerve sparing radical retropubic prostatectomy 10mg vardenal

Study or subgroup

Treatment N Mean(SD) 15.6 (7.96)

Control N 96 Mean(SD) 9.7 (7.84)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 5.90 [ 3.68, 8.12 ]

Brock 2003

99

-10

-5

10

Favours control

Favours treatment

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 1.8. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 8 Successful vaginal penetration (SEP): Bilateral nerve sparing radical retropubic prostatectomy 20mg vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 8 Successful vaginal penetration (SEP): Bilateral nerve sparing radical retropubic prostatectomy 20mg vardenal

Study or subgroup

Treatment N Mean(SD) 50 (36.37)

Control N 98 Mean(SD) 22.9 (36.63)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 27.10 [ 17.12, 37.08 ]

Brock 2003

108

-100

-50

50

100

Favours control

Favours treatment

Analysis 1.9. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 9 Erectile function domain of IIEF: Bilateral nerve sparing radical retropubic prostatectomy 20mg Tadalal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 9 Erectile function domain of IIEF: Bilateral nerve sparing radical retropubic prostatectomy 20mg Tadalal

Study or subgroup

Treatment N Mean(SD) 5.3 (6.3)

Control N 76 Mean(SD) 1.1 (5.2)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 4.20 [ 2.68, 5.72 ]

Montorsi 2004a

161

-10

-5

10

Favours control

Favours treatment

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 1.10. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 10 Erectile function domain of IIEF: Unilateral nerve sparing radical retropubic prostatectomy 20mg vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 10 Erectile function domain of IIEF: Unilateral nerve sparing radical retropubic prostatectomy 20mg vardenal

Study or subgroup

Treatment N Mean(SD) 14 (9.33)

Control N 39 Mean(SD) 10.2 (9.37)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 3.80 [ -0.50, 8.10 ]

Brock 2003

34

-10

-5

10

Favours control

Favours treatment

Analysis 1.11. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 11 Erectile function domain of IIEF: Unilateral nerve sparing radical retropubic prostatectomy 10mg vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 11 Erectile function domain of IIEF: Unilateral nerve sparing radical retropubic prostatectomy 10mg vardenal

Study or subgroup

Treatment N Mean(SD) 15 (9.6)

Control N 39 Mean(SD) 10.2 (9.6)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 4.80 [ 0.45, 9.15 ]

Brock 2003

36

-10

-5

10

Favours control

Favours treatment

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 1.12. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 12 Erectile function: IIEF at follow-up: Bilateral nerve sparing radical retropubic prostatectomy 20mg Vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 12 Erectile function: IIEF at follow-up: Bilateral nerve sparing radical retropubic prostatectomy 20mg Vardenal

Study or subgroup

Treatment N Mean(SD) 16.2 (8.35)

Control N 96 Mean(SD) 9.7 (7.84)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 6.50 [ 4.28, 8.72 ]

Brock 2003

109

-10

-5

10

Favours control

Favours treatment

Analysis 1.13. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 13 Successful vaginal penetration (SEP): Bilateral nerve sparing radical retropubic prostatectomy 10mg vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 13 Successful vaginal penetration (SEP): Bilateral nerve sparing radical retropubic prostatectomy 10mg vardenal

Study or subgroup

Treatment N Mean(SD) 52.3 (34.47)

Control N 98 Mean(SD) 22.9 (36.63)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 29.40 [ 19.42, 39.38 ]

Brock 2003

97

-100

-50

50

100

Favours control

Favours treatment

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 1.14. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 14 Successful vaginal penetration(SEP): Unilateral nerve sparing radical retropubic prostatectomy 20mg vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 14 Successful vaginal penetration(SEP): Unilateral nerve sparing radical retropubic prostatectomy 20mg vardenal

Study or subgroup

Treatment N Mean(SD) 48.9 (43.73)

Control N 37 Mean(SD) 32.5 (4.58)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 16.40 [ 1.63, 31.17 ]

Brock 2003

34

-100

-50

50

100

Favours control

Favours treatment

Analysis 1.15. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 15 Successful vaginal penetration(SEP): Unilateral nerve sparing radical retropubic prostatectomy 10mg vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 15 Successful vaginal penetration(SEP): Unilateral nerve sparing radical retropubic prostatectomy 10mg vardenal

Study or subgroup

Treatment N Mean(SD) 40.2 (44.4)

Control N 37 Mean(SD) 32.5 (4.58)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 7.70 [ -6.68, 22.08 ]

Brock 2003

37

-100

-50

50

100

Favours control

Favours treatment

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Analysis 1.16. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 16 Successful vaginal intercourse (SEP): Bilateral nerve sparing radical retropubic prostatectomy 20mg vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 16 Successful vaginal intercourse (SEP): Bilateral nerve sparing radical retropubic prostatectomy 20mg vardenal

Study or subgroup

Treatment N Mean(SD) 38.8 (36.37)

Control N 98 Mean(SD) 11.7 (3.63)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 27.10 [ 20.04, 34.16 ]

Brock 2003

103

-100

-50

50

100

Favours control

Favours treatment

Analysis 1.17. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 17 Successful vaginal intercourse (SEP): Bilateral nerve sparing radical retropubic prostatectomy 10mg vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 17 Successful vaginal intercourse (SEP): Bilateral nerve sparing radical retropubic prostatectomy 10mg vardenal

Study or subgroup

Treatment N Mean(SD) 41.1 (34.47)

Control N 98 Mean(SD) 11.7 (36.63)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 29.40 [ 19.42, 39.38 ]

Brock 2003

97

-100

-50

50

100

Favours control

Favours treatment

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 1.18. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 18 Successful vaginal intercourse(SEP): Unilateral nerve sparing radical retropubic prostatectomy 20mg vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 18 Successful vaginal intercourse(SEP): Unilateral nerve sparing radical retropubic prostatectomy 20mg vardenal

Study or subgroup

Treatment N Mean(SD) 31.2 (40.23)

Control N 37 Mean(SD) 19.4 (40.15)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 11.80 [ -6.91, 30.51 ]

Brock 2003

34

-100

-50

50

100

Favours control

Favours treatment

Analysis 1.19. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 19 Successful vaginal intercourse(SEP): Unilateral nerve sparing radical retropubic prostatectomy 10mg vardenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 19 Successful vaginal intercourse(SEP): Unilateral nerve sparing radical retropubic prostatectomy 10mg vardenal

Study or subgroup

Treatment N Mean(SD) 34.8 (41.36)

Control N 37 Mean(SD) 19.4 (40.15)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 15.40 [ -3.17, 33.97 ]

Brock 2003

37

-100

-50

50

100

Favours control

Favours treatment

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Analysis 1.20. Comparison 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo, Outcome 20 Erectile function domain of IIEF: Mean difference.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 1 Phosphodiesterase inhibitors (sildenal, vardenal and tadalal) versus placebo Outcome: 20 Erectile function domain of IIEF: Mean difference

Study or subgroup

Treatment N Mean(SD) 5.3 (6.3)

Control N 76 Mean(SD) 1.1 (5.2)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 4.20 [ 2.68, 5.72 ]

Montorsi 2004a

161

-10

-5

10

Favours treatment

Favours control

Analysis 2.1. Comparison 2 Transurethral alprostadil versus placebo, Outcome 1 Vaginal intercourse rate.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 2 Transurethral alprostadil versus placebo Outcome: 1 Vaginal intercourse rate

Study or subgroup

Treatment n/N

Control n/N 9/137

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 18.96 [ 8.85, 40.65 ]

Costabile 1998

72/126

0.01

0.1

10

100

Favours control

Favours treatment

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 2.2. Comparison 2 Transurethral alprostadil versus placebo, Outcome 2 Adverse events: urethral pain/burning.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 2 Transurethral alprostadil versus placebo Outcome: 2 Adverse events: urethral pain/burning

Study or subgroup

Treatment n/N

Control n/N 6/137

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 4.88 [ 1.91, 12.42 ]

Costabile 1998

23/126

0.01

0.1

10

100

Favours treatment

Favours control

Analysis 2.3. Comparison 2 Transurethral alprostadil versus placebo, Outcome 3 Adverse events: penile pain.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 2 Transurethral alprostadil versus placebo Outcome: 3 Adverse events: penile pain

Study or subgroup

Treatment n/N

Control n/N 1/137

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 75.73 [ 10.27, 558.40 ]

Costabile 1998

49/137

0.001 0.01 0.1 Favours treatment

10 100 1000 Favours control

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Analysis 3.1. Comparison 3 Vacuum constriction device versus observational care following prostatectomy, Outcome 1 Erectile function.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 3 Vacuum constriction device versus observational care following prostatectomy Outcome: 1 Erectile function

Study or subgroup

Treatment n/N

Control n/N 13/35

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 0.78 [ 0.33, 1.88 ]

Raina 2006

19/60

0.1 0.2

0.5

10

Favours control

Favours treatment

Analysis 3.2. Comparison 3 Vacuum constriction device versus observational care following prostatectomy, Outcome 2 Erectile function in nerve-sparing surgery group.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 3 Vacuum constriction device versus observational care following prostatectomy Outcome: 2 Erectile function in nerve-sparing surgery group

Study or subgroup

Treatment n/N

Control n/N 13/35

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 0.97 [ 0.39, 2.43 ]

Raina 2006

16/44

0.1 0.2

0.5

10

Favours control

Favours treatment

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Analysis 3.3. Comparison 3 Vacuum constriction device versus observational care following prostatectomy, Outcome 3 Successful vaginal intercourse.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 3 Vacuum constriction device versus observational care following prostatectomy Outcome: 3 Successful vaginal intercourse

Study or subgroup

Treatment n/N

Control n/N 4/13

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 2.50 [ 0.57, 11.01 ]

Raina 2006

10/19

0.01

0.1

10

100

Favours control

Favours treatment

Analysis 3.4. Comparison 3 Vacuum constriction device versus observational care following prostatectomy, Outcome 4 Sexual function (IIEF).
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 3 Vacuum constriction device versus observational care following prostatectomy Outcome: 4 Sexual function (IIEF)

Study or subgroup

Treatment N Mean(SD) 16 (7.33)

Control N 35 Mean(SD) 11.7 (1.76)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 4.30 [ 2.53, 6.07 ]

Raina 2006

74

-100

-50

50

100

Favours control

Favours treatment

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Analysis 4.1. Comparison 4 Supportive partners versus usual care, Outcome 1 Sexual function (UCLA Prostate Cancer Index).
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 4 Supportive partners versus usual care Outcome: 1 Sexual function (UCLA Prostate Cancer Index)

Study or subgroup

Treatment N Mean(SD) 20.4 (13.5)

Control N 15 Mean(SD) 13 (16.4)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 7.40 [ -3.35, 18.15 ]

Weber 2004

15

-100

-50

50

100

Favours control

Favours treatment

Analysis 4.2. Comparison 4 Supportive partners versus usual care, Outcome 2 Sexual bother (UCLA Prostate Cancer Index).
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 4 Supportive partners versus usual care Outcome: 2 Sexual bother (UCLA Prostate Cancer Index)

Study or subgroup

Treatment N Mean(SD) 26.7 (32)

Control N 15 Mean(SD) 56.7 (41.7)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI -30.00 [ -56.60, -3.40 ]

Weber 2004

15

-100

-50

50

100

Favours treatment

Favours control

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Analysis 5.1. Comparison 5 Acetyl-L-Carnitane (ALC) plus propionyl-L-Carnitane (PLC) and sildenal versus sildenal only versus placebo, Outcome 1 Satisfactory sexual intercourse (self report): sidenal +ALC + PLC versus placebo.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 5 Acetyl-L-Carnitane (ALC) plus propionyl-L-Carnitane (PLC) and sildenal versus sildenal only versus placebo Outcome: 1 Satisfactory sexual intercourse (self report): sidenal +ALC + PLC versus placebo

Study or subgroup

Treatment n/N

Control n/N 2/29

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 94.50 [ 15.97, 559.14 ]

Cavallini 2005

28/32

0.001 0.01 0.1 Favours control

10 100 1000 Favours treatment

Analysis 5.2. Comparison 5 Acetyl-L-Carnitane (ALC) plus propionyl-L-Carnitane (PLC) and sildenal versus sildenal only versus placebo, Outcome 2 Satisfactory sexual intercourse: sidenal versus placebo.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 5 Acetyl-L-Carnitane (ALC) plus propionyl-L-Carnitane (PLC) and sildenal versus sildenal only versus placebo Outcome: 2 Satisfactory sexual intercourse: sidenal versus placebo

Study or subgroup

Treatment n/N

Control n/N 2/29

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 14.21 [ 2.96, 68.14 ]

Cavallini 2005

20/39

0.01

0.1

10

100

Favours control

Favours treatment

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Analysis 5.3. Comparison 5 Acetyl-L-Carnitane (ALC) plus propionyl-L-Carnitane (PLC) and sildenal versus sildenal only versus placebo, Outcome 3 Satisfactory sexual intercourse: sidenal + ALC + PLC versus sidenal.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 5 Acetyl-L-Carnitane (ALC) plus propionyl-L-Carnitane (PLC) and sildenal versus sildenal only versus placebo Outcome: 3 Satisfactory sexual intercourse: sidenal + ALC + PLC versus sidenal

Study or subgroup

Treatment n/N

Control n/N 20/39

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 6.65 [ 1.96, 22.56 ]

Cavallini 2005

28/32

0.01

0.1

10

100

Favours control

Favours treatment

Analysis 6.1. Comparison 6 Oestrogen vaginal cream versus placebo, Outcome 1 Sexual vaginal intercourse (self report).
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 6 Oestrogen vaginal cream versus placebo Outcome: 1 Sexual vaginal intercourse (self report)

Study or subgroup

Treatment n/N

Control n/N 30/49

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 0.91 [ 0.40, 2.10 ]

Pitkin 1971

26/44

0.1 0.2

0.5

10

Favours treatment

Favours control

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Analysis 6.2. Comparison 6 Oestrogen vaginal cream versus placebo, Outcome 2 Dyspareunia (self report).
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 6 Oestrogen vaginal cream versus placebo Outcome: 2 Dyspareunia (self report)

Study or subgroup

Treatment n/N

Control n/N 14/30

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 3.81 [ 1.19, 12.16 ]

Pitkin 1971

20/26

0.01

0.1

10

100

Favours control

Favours treatment

Analysis 6.3. Comparison 6 Oestrogen vaginal cream versus placebo, Outcome 3 Severe dyspareunia (self report).
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 6 Oestrogen vaginal cream versus placebo Outcome: 3 Severe dyspareunia (self report)

Study or subgroup

Treatment n/N

Control n/N 6/30

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 0.07 [ 0.00, 1.33 ]

Pitkin 1971

0/26

0.001 0.01 0.1 Favours treatment

10 100 1000 Favours control

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Analysis 7.1. Comparison 7 Sexual counselling versus no counselling in men using prostaglandin E1 intracavernous injection, Outcome 1 Couple satisfaction.
Review: Interventions for sexual dysfunction following treatments for cancer

Comparison: 7 Sexual counselling versus no counselling in men using prostaglandin E1 intracavernous injection Outcome: 1 Couple satisfaction

Study or subgroup

Treatment n/N

Control n/N 8/20

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 3.33 [ 1.01, 10.97 ]

Titta 2006

20/29

0.01

0.1

10

100

Favours control

Favours treatment

ADDITIONAL TABLES
Table 1. Methodological quality of included studies

Study Brock 2003

Sample size

Recruitment rate

Randomisation

Masking

Attrition 25% of 440 lost to follow up (33% in placebo group and 21% in active groups)

Sample size calcula- 78% of 567 ran- Random codes were States double blind tion domised . Reasons generated by com- - does not state who for not recruiting in- puter is masked cluded protocol violations (n = 90), consent withdrawn (n = 23) No sample size calcu- No details provided lation No details provided NA

Canada 2005

39% of 84 lost to follow-up

Cavalini 2005

No sample size calcu- 79% of 139 ran- No details provided lation domised. Reasons for not recruiting included non compliance (n = 19), protocol violations (n = 10) No sample size calcu- No details provided lation No details provided

Investigators and pa- 13% of 110 lost to tients follow up (ten from intervention group and four from the placebo group)

Costabile 1998

States double blind 10% of 270 lost to - reports that patients follow up (no dewere masked tails on which arm participants were lost from)
55

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Table 1. Methodological quality of included studies

(Continued)

Incrocci 2001

Sample size calcula- 15% of 406 ran- No details provided tion domised. Reasons for not recruiting included no response to invitation letter (n = 324), protocol violation (n = 22) No sample size calcu- 16% of 358 ran- No details provided lation domised. Reasons for not recruiting included either not interested or did not respond to invitation letter (n = 272), protocol violation (n = 26) Sample size calcula- 79% of No details provided tion 381 recruited. Reasons for not recruiting included nine non compliance No sample size calcu- All entered study lation No sample size calcu- No details provided lation No sample size calcu- No details provided lation No details provided

Patients and investi- All patients comgators pleted study

Incrocci 2006

Patients and investi- All patients comgators pleted study

Montorsi 2004

Patients, site person- 22% of 303 lost to nel and sponsors follow up

Pitkin 1971

NA

All patients completed study

Raina 2006

No details provided

Patient and investi- All patients comgators pleted study NA 14% of 57 lost to follow up (all were in the control group) 6% of 30 lost to follow-up (both were lost from the intervention group)

Titta 2006

No details provided

Weber 2004

No sample size calcu- 30% of 100 re- No details provided lation cruited. Reasons for not recruiting included non compliance (n = 42)

NA

Table 2. Examples of SD therapies whose effect following cancer treatment not known

Sexual therapy Clitoral therapy device

Evidence A before and after study suggests benecial effects of a clitoral therapy device for women with SD (Schroder 2005). The device was a hand-held battery powered vacuum that creates a gentle suction to engorge the clitoris and increase sensation
56

Interventions for sexual dysfunction following treatments for cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Table 2. Examples of SD therapies whose effect following cancer treatment not known

(Continued)

Complementary medicines

In men: RCTs for ED have found positive effects of Korean red ginseng (Choi 1995; Hong 2002), L-Arginine (Chen 1999) and magnet therapy (Pelka 2002) In women: A cross-over RCT of yohimbine plus L-arginine versus yohimbine only versus placebo for sexual arousal disorder found the two active treatments increased sexual arousal (Meston 2002)

Psycho-educational interventions

In men: An RCT of a group education for men who had radiotherapy for prostate cancer (but whose level of sexual functioning at trial entry was not established) found positive sexual outcomes (Lepore 2003) In women: RCTs of psycho-educational interventions for women following cancer treatments have found positive outcomes (Robinson 1999; Jeffries 2006). Trials not included in review as sexual functioning not established prior to cancer treatment and trials did have sexual dysfunction outcomes

Intracavernosal injection (ICI) of Trimax for ED

An RCT of ICI therapy of Trimax versus external vacuum constriction (EVD) device in 45 men following cancer treatment found participants in the ICI group were more satised with their erections (Soderdahl 1997). Trial not included in review as did not evaluate effectiveness The aim of Kegel exercises is to restore muscle tone and strength to the puboccygeus muscles that form part of the pelvic oor. When women feel discomfort around the vaginal entrance during penetration kegel exercises can relax the pubococcygeus muscles (Auchincloss 1989; Lamb 1996). (No evaluations of these exercises were identied in the review) Non randomised trials have suggested that PHE-5 inhibitors for women with Female Sexual Arousal Disorder improve outcomes (Berman 2003; Caruso 2001) Non randomised trials have suggested that inatable surgical penile prosthetics for men with ED improve outcomes (Merrill 1983; Merrill 1986). Opioids, chemotherapy and other cancer treatments can reduce testosterone levels which may result in SD in men and potentially in women. (No evaluations of testosterone were identied in this review)

Kegel exercises

PHE-5 inhibitors for women

Surgical penile Prosthetics

Testosterone replacement therapy

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APPENDICES Appendix 1. Search strategy

Electronic database search terms The search terms used reected the three components to our research question: A) interventions for SD, B) SD variants, C) treatments for cancer.

Search strategy prepared for MEDLINE A) Interventions for SD 1) alprostadil (EXPLODE MeSH, all subheadings) 2) papaverine (EXPLODE MeSH, all subheadings) 3) phentolamine (EXPLODE MeSH, all subheadings) 4) yohimbine (EXPLODE MeSH, all subheadings) 5) apomorphine (EXPLODE MeSH, all subheadings) 6) potassium channels (EXPLODE MeSH, all subheadings) 7) alprostadil or prostaglandin E1 or papaverine-phentolamine or papaverine or phentolamine or vasomax or sildenal or viagra or testosterone gel or androgel or vardenal or levitra or yohimbine or apomorphine or potassium channel openers or tadalal or cialis or apomorphine hydrochloride 8) testosterone (EXPLODE MeSH, all subheadings) 9) penile implantation (EXPLODE MeSH, all subheadings) 10) penile prosthesis (EXPLODE MeSH, all subheadings) 11) prosthesis implantation (EXPLODE MeSH, all subheadings) 12) testosterone replacement or testosterone or venous constriction rings or vacuum device* or vacuum erect* or penile implant* or penile arterialisation or venous litigation or prosthesis implant* or vacuum constriction device or vacuum therapy* or vibrat* or vibrostimulation or electroejaculation or prolong ring* 13) aromatase inhibitors (EXPLODE MeSH, all subheadings) 14) vaginal dilator* or arginine or android or methyl testosterone or testosterone cream or vaginal lubricant or vaginal estradiol ring or vaginal estradiol ring or vaginal estrogen ring or vaginal oestrogen ring or topical estrogen cream or vaginal cream or estrogen replacement of ERT or estrogen replacement or aromatase inhibitors 15) estriol (EXPLODE MeSH, all subheadings) 16) conjugated estrogens (EXPLODE MeSH, all subheadings) 17) ortho-gynest or ovestin or premarin or tampovagan or vagifem 18) gingko bilboa (EXPLODE MeSH, all subheadings) 19) pausinystalia (EXPLODE MeSH, all subheadings) 20) Turnera (EXPLODE MeSH, all subheadings) 21) Panax (EXPLODE MeSH, all subheadings) 22) Hypericum (EXPLODE MeSH, all subheadings) 23) gingko or yohimbine or DHEA or dehydroepiandrosterone or damiana or turner diffusa or viacreme or viagel or sensual or ginseng or st johns wort or kegel exercise* or eros therap* or eros clitoral vacuum device 24) patient education (EXPLODE MeSH, all subheadings) 25) psychological techniques (EXPLODE MeSH, all subheadings) 26) psychotherapy (EXPLODE MeSH, all subheadings) 27) counseling (EXPLODE MeSH, all subheadings) 28) sex-counselling (EXPLODE MeSH, all subheadings) 29) cognitive therapy (EXPLODE MeSH, all subheadings) 30) psychological intervention* or psycholog* or behavior* or behaviour* or cognitive behav* therapy or cognitive therapy or sex therapy or psychotherap* or counsel* or sex therap* or patient educat*
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31) anti-depressive agents (EXPLODE MeSH, all subheadings) 32) anti-depressive agents, tricyclic (EXPLODE MeSH, all subheadings) 33) anti-depressant* or antidepressant* or tricyclic antidepressants or amitriptyline or amoxapine or clomipramine or dosulepin or doxepin or imipramine or lofepramine or nortriptyline or trimipramine 34) maprotiline or mianserin or trazodone 35) monoamine-oxidase inhibitors or MOI or phenelzine or isocarboxazid or tranylcypromine or moclobemide 36) selective serotonin re-uptake inhibitors or SSRI or citalopram or escitalopram or uoxetine or prozac or uvoxamine or paroxetine or sertraline 37) upentixol or mirtazapine or reboxetine or tryptophan or venlafaxine 38) alpha adrenoceptor agonist* or alpha adrenoceptor antagonist or midodrin or vasodilan or isoxsuprine or pentoxifylline or trental or delquamine or pseudoephedrine or desipramine or cyproheptadine or lignocaine 39) #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or 19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37 or #38 B) SD variants 40) sexual dysfunction (EXPLODE MeSH, all subheadings) 41) impotence (EXPLODE MeSH, all subheadings) 42) lubrication (EXPLODE MeSH, all subheadings) 43) coitus (EXPLODE MeSH, all subheadings) or copulation (EXPLODE MeSH, all subheadings) 44) (sex* adj3 (dysfunct* or satisf* or problem* or symptom* or arousal* or activit*)) or orgasm or libido or lubricat* or impotence or dyspareunia or hypoactive sexual desire disorder or sexual aversion or coitus or coition 45) sexual intercourse or erectile dysfunction or erect* or sexual attraction or copulation or intimacy or procreat* or relations or sex or sex act or sexual congress or sexual relation or arousal or penile erection or vaginal dryness or sexual pain or pain* adj3 intercourse or sex* adj3 pain* or vaginismus 46) ejaculation dysfunction or premature ejaculation or early ejaculation or delayed ejaculation or retarded ejaculation or anejaculation or painful ejaculation or retrograde ejaculation or anterograde ejaculation or inhibited ejaculation 47) #40 or #41 or #42 or #43 or #44 or #45 or #46 C) Treatments for cancer 48) neoplasms (EXPLODE MeSH, all subheadings) 49) brachytherapy (EXPLODE MeSH, all subheadings) 50) radiotherapy, conformal (EXPLODE MeSH, all subheadings) 51) radiotherapy, adjuvant (EXPLODE MeSH, all subheadings) 52) chemotherapy, adjuvant (EXPLODE MeSH, all subheadings) 53) mastectomy (EXPLODE MeSH, all subheadings) 54) prostatectomy (EXPLODE MeSH, all subheadings) 55) irradiat* or radiotherap* or chemotherap* or mastectom* or breast conserv* or prostatectom* 56) neoplasm* or cancer* or carcinoma* or neoplasia* or adenocarcinoma* or tumor or malignan* or tumour* 57) chemotherapy* or mastectomy or breast conserv*or oophorectomy or hormone therapy or hormone treatment 58) #48 or #49 or #50 or #51 or #52 or #53 or #54 or #55 or #56 or #57 D) Interventions, SD and treatment for cancer 59) #39 and #47 and #58 E) Filter for RCTs 60) random* in ti,ab 61) factorial* in ti,ab 62) (crossover* or cross over* or cross-over*) in ti,ab 63) placebo* in ti,ab 64) (doubl* near blind*) in ti,ab 65) (singl* near blind*) in ti,ab 66) assign* in ti,ab 67) allocat* in ti,ab 68) volunteer* in ti,ab 69) crossover procedure (EXPLODE MeSH, all subheadings) 70) double blind procedure (EXPLODE MeSH, all subheadings)
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71) randomized controlled trial (EXPLODE MeSH, all subheadings) 72) single blind procedure (EXPLODE MeSH, all subheadings) 73) #60 or #61 or #62 or #63 or #64 or #65 or #66 or #67 or #68 or #69 or #70 or #71 or #72 F) Filter for human studies 74) animal in de 75) animal (EXPLODE MeSH, all subheadings) 76) nonhuman (EXPLODE MeSH, all subheadings) 77) animal-experiment (EXPLODE MeSH, all subheadings) 78) #74 or #75 or #76 or #77 79) #78 not #68 80) #73 not #79 G) Final combination 81) #59 and #80

WHATS NEW
Last assessed as up-to-date: 17 August 2007.

Date 27 June 2012

Event Amended

Description Contact details updated.

HISTORY
Protocol rst published: Issue 4, 2005 Review rst published: Issue 4, 2007

Date 8 February 2011 24 September 2010 9 November 2009 13 May 2009 30 October 2008

Event Amended Amended Amended Amended Amended

Description Contact details updated. Contact details updated. Contact details updated. Contact details updated. Converted to new review format.

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CONTRIBUTIONS OF AUTHORS
CM: carried out the searching, reviewed documents, quality assessed and produced the protocol and rst draft review. BC: updated the search (2005 to 6), reviewed updated trials, and produced the nal draft review. LJ: reviewed some of the documents including all included trials and quality assessed. Input was given to the protocol and nal review. RW: advised on statistical analysis and commented on nal draft review. AT: contributed to original idea and writing of review. MK: assisted with data analysis, and writing of protocol and review.

DECLARATIONS OF INTEREST
None known

SOURCES OF SUPPORT Internal sources

Marie Curie Palliative Care Research Unit, UK. Royal Free & University College Medical School, UK.

External sources
No sources of support supplied

INDEX TERMS Medical Subject Headings (MeSH)

Administration, Intravaginal; Erectile Dysfunction [therapy]; Neoplasms [ therapy]; Phosphodiesterase Inhibitors [therapeutic use]; Prostatic Neoplasms [therapy]; Psychotherapy; Randomized Controlled Trials as Topic; Sexual Dysfunction, Physiological [etiology; therapy]; Sexual Dysfunctions, Psychological [ therapy]; Uterine Cervical Neoplasms [therapy]; Vacuum; Vaginal Creams, Foams, and Jellies [administration & dosage]

MeSH check words

Adult; Female; Humans; Male

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