Received: 29 June 2020 | Revised: 10 December 2020 | Accepted: 11 December 2020

DOI: 10.1111/andr.12961

REVIEW ARTICLE

Periodontitis, erectile dysfunction, reproductive hormones, and

semen quality: A systematic review

Bastien Lecaplain1,2 | Zahi Badran1,2,3,4 | Assem Soueidan1,2,3 |

Tony Prud'homme1,2,5 | Alexis Gaudin1,2,3

1
Université de Nantes, UFR Odontologie,
Nantes, France
2
CHU Nantes, PHU4 OTONN, Nantes,
France
3
Inserm, UMR 1229, RMeS, Regenerative
Medicine and Skeleton, Université de
Nantes, ONIRIS, Nantes, France
4
Faculty of Dentistry, McGill University,
Montreal, Canada
5
Inserm, MethodS in Patients-centered
outcomes and HEalth Research, SPHERE,
Nantes, France
Correspondence
Alexis Gaudin, Department of
Endodontics, University of Nantes, 1 place
Alexis Ricordeau, Nantes, 44093 Nantes
Cedex 01, France.
Email: alexis.gaudin@univ-nantes.fr
Abstract
Background: There is increasing evidence that periodontitis may affect male sexual
health (MSH) (erectile function, production of sex hormones, and semen quality).
However, a limited number of clinical studies demonstrate the association between
MSH and periodontitis.
Objectives: The aim of this study was to explore the relationship between periodontitis
and MSF.
Materials and methods: A comprehensive systematic review of the published literature
in MEDLINE, PubMed, Scopus, Cochrane, EMBASE, and Web of Science databases
from the earliest available online indexing year until October 2020 was performed, in
accordance with the PRISMA guidelines. Keywords related to periodontitis were com-
bined with words describing MSH.
Result: A total of 19 studies were included and discussed in the systematic review. The
number of study participants ranged from 53 to 197,136 individuals, aged between 18
and 95 years (mean age, 41.2 years). Six studies did not report the age of the partici-
pants. Out of nine studies, eight found a significant association between erectile dys-
function (ED) and periodontitis. Only three studies evaluated the association between
sex hormone levels and periodontitis, and two of these studies showed that patients
with periodontitis are expected to exhibit higher levels of testosterone. Finally, out of
five studies, two demonstrated a significant association between semen quality and
periodontitis.
Discussion: The findings in this review were limited by the quality and the few available
studies. Results from the observational studies might have been affected by recall bias
and confounded by cofactors.
Conclusion: The results of this systematic review revealed a significant association be-
tween periodontitis and ED, although the responsible mechanisms remain unclear. The
potential associations between sex hormone levels, semen quality, and periodontitis
are yet to be demonstrated. In order to improve patient management, dentists and
physicians need to be aware of the association between male sexual health problems
and periodontitis.

Prud'homme and Gaudin contributed equally as senior investigators.

© 2020 American Society of Andrology and European Academy of Andrology

Andrology. 2021;9:769–780.  wileyonlinelibrary.com/journal/andr | 769

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KEYWORDS
gingiva, periodontics, sexual health, infertility, male, testicular hormones
1 | BAC KG RO U N D
According to the definition given by the World Health Organization,
sexual health is a state of physical, mental, and social well-being in
relation to sexuality. It is not merely the absence of disease, dysfunc-
tion, or infirmity. Sexuality, in turn, is a central aspect of a person
throughout life. It includes concepts, such as biological sex, sexual
identity and role, sexual orientation, eroticism, pleasure, intimacy,
and reproduction.1
The previous definition applies to both men and women,
and therefore, they must be differentiated by an organicist
approach that is anatomo-physiological, neurological, and
endocrinological. 2-4
Periodontal diseases are a set of inflammatory conditions con-
sisting of gingival diseases and most commonly plaque-induced
gingivitis. In cases where bone loss occurs, it progresses to peri-
odontitis. Periodontitis is the sixth-most prevalent disease in the
world, the most common bone disease in humans,5 the most com-
mon oral disease contributing to the global burden of chronic dis-
eases, and is thus, a significant public health problem worldwide.6
In the United States alone, recent reports estimate that 64.7 million
adults, that is, 47% of the adult population, suffer from periodontal
disease. Periodontitis is the primary cause for tooth loss in adults,7
severely impairing the individuals' oral health-related quality of life,
self-esteem, and leading to significant economic and medical conse-
quences.8 Previous clinical and epidemiological studies have shown
that periodontitis has been associated with other systemic condi-
9 10
tions, such as respiratory and cardiovascular diseases, risk of pre-
mature delivery,11 and diabetes.12
A study in 2009 showed a possible association between erec-
tile dysfunction (ED) and periodontitis.13 Two more recent stud-
ies hypothesized that periodontitis is linked to ED and it may be
proportional to the severity of periodontitis.14,15 Both the studies
postulated that periodontitis could have a determining role in the
pathogenesis of ED, independent of other comorbidities. To the
best of our knowledge, no correlation has been demonstrated be-
tween semen quality and oral health.16,17 However, an association
between semen quality and periodontitis would seem plausible due
to the decrease in semen quality as a result of periodontal infec-
tions in males. Finally, a study by Orwoll et al in 2009 presented
a hypothesis that steroid levels could influence the progression of
periodontitis and tooth loss.18
After a prospective research, we found the most recent studies
on the relationship between male sexual health and periodontitis.
However, the regularly increasing number of publications prompted
us to reconsider the previously accepted conclusions. In addition,
several mechanisms have been advocated to decipher the impact
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LECAPLAIN et al.
of periodontitis on male sexual health. There is increasing evidence
that periodontitis can cause endothelial dysfunction19,20 or systemic
inflammatory reaction. 21-24 Thenceforth, it seemed interesting to
synthesize all the existing data on the subject. Thus, the aim of this
systematic review was to assess the association between periodon-
titis and male sexual health and semen quality (MSH) (erection, con-
centration of sex hormones, and regulation of ejaculate reflected in
the quantity and quality of spermatozoa).
2 | M E TH O D
On the basis of the PRISMA (preferred reporting items for systematic
reviews and meta-analyses) guidelines, 25 a specific question was de-
veloped in accordance with PICO (Participant, Interventions, Control,
Outcomes) principle.26 The question we elaborated was as follows:
“Do men with periodontitis have an increased risk of having altered
sexual health compared to men without periodontitis?”.
2.1 | Literature search protocol and
eligibility criteria
A systematic search of the literature published in MEDLINE, PubMed,
Scopus, Cochrane, EMBASE, and Web of Science databases from the
earliest available online indexing year until October 2020 was per-
formed, in accordance with the PRISMA guidelines. The search used
a combination of terms as both Medical Subject Headings (MeSH) and
keywords related to MSH (ED, fertility or infertility, semen analysis
and sperm dysfunction, sex hormones). The terms periodontal disease,
periodontitis, gingivitis, and the Boolean connector AND were linked
to the terms male infertility, fertility, semen analysis, sperm dysfunc-
tion, spermatozoa, ED, impotence, sexual dysfunction, sexual function,
erectile function, ejaculation, sex hormones, and sex steroid hormones
each joined by the connector OR, to obtain as many relevant articles as
possible.
The titles and abstracts for all articles were screened for eligi-
bility. Studies were considered eligible for data extraction if they
met the following inclusion criteria: clinical studies, prospective and
retrospective studies, abstracts and articles in English language,
and primary outcome as MSH. The data excluded from this study
were letters to the editor, commentaries, historical reviews, posters,
oral presentations, and experimental studies. The retrieved studies
were appraised by two independent reviewers (B.L. and A.G.), after
screening the titles followed by abstracts, that potentially met the in-
clusion criteria. Any disagreements were resolved through discussion
and reaching consensus with a third review team member (T.P.) for a

LECAPLAIN et al.
final decision. A manual literature search was conducted to ensure a
thorough selection process. The full-text copies of the publications
deemed relevant by title and abstract were studied and evaluated.
2.2 | Quality assessment
Study quality assessment was conducted using the CASP (Critical
Appraisal Skills Program) cohort study, case-control, and rand-
omized controlled trial checklist method to assess the methodo-
logical quality of each study included in this systematic review. 27
This tool is based on 10–12 criteria that receive a “yes,” “no,” or
“cannot tell” response and then quantify a study quality score
(Figure S1).
F I G U R E 1 Article selection flow chart for the systematic review according to PRISMA guidelines. Note. PRISMA = Preferred Reporting
Items for Systematic Reviews and Meta-Analyses
|
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771
3 | R E S U LT S
3.1 | Study selection and characteristics
The initial search identified 2709 titles. After removal of duplicates
and going through references of relevant articles, a total of 1548 re-
cords remained for screening (Figure 1). During the screening pro-
cess, 1511 were excluded as the title and abstract were not relevant
for the purpose of this review. Thirty-seven articles were collected
as full-text copies and examined based on the inclusion and exclu-
sion criteria. Eighteen records were excluded as they did not meet
the inclusion criteria. Among them, three were meta-analyses on the
association with erectile capacity, eight were reviews of the literature
mentioning erection and hormone levels with their relationship on
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periodontitis, one was a written transcript of an oral lecture, one was
a hypothesis, two were studies on an animal model, and two were
on the association of sex hormones on periodontitis but included
women in the study, and one assessed the association between peri-
odontal flap surgery and vasculogenic ED. A total of 19 records met
the eligibility criteria and were included in the quantitative analysis.
3.2 | Quality assessment of included studies
The included studies were assessed for quality using the Critical
Appraisal Skills Programme (CASP) system, as described above. For
cohort studies, the scores ranged from 6/12 to 11/12. The lowest
scores were attributed to the first study that was done on gender
basis by Justo et al13 and the study by Matsumoto et al. 28 This system
showed that the main shortcoming of these studies was the difficulty
of transposing the results to the local population (Figure S2). The
same shortcoming was evident in the evaluation of the quality of the
articles on case-control and randomized controlled trials (Figure S2).
3.3 | Periodontitis
In all the selected studies, the diagnosis of periodontitis was made by
clinical examination.
14-18,29-36
Pocket probing depth was considered in 13 studies,
14-18,29-31,33,34,36,37
of clinical attachment was reported in 12 studies,
and bleeding on probing was reported in 6 studies.15-17,30,33,34 Of
the 17 studies selected, only 4 considered the number of missing
teeth16,18,29,33 and 2 considered tooth mobility.16,36
Intraoral radiographs as diagnostic aids were taken into account
in five studies.13,14,32,35,37 Of these, there were two studies that cited
the International Classification of Diseases, Ninth Revision, Clinical
Modification (ICD-9-CM) classification for the diagnosis of periodon-
32,37 38
titis. Finally, one study used the Oral Hygiene Index by Greene
and Vermillion,39 while another one diagnosed periodontitis using a
self-reported questionnaire that prompts patients to perform the oral
28
examination themselves.
3.4 | Erectile dysfunction
A total of 215,598 patients from 10 retrospective stud-
ies13-15,28,32-35,37,40 with a mean age of 40 years were included in
study investigating the relationship between periodontitis and ED.
35
One study did not report the age of the participants. In three stud-
ies,13,14,28 confounding variables were not assessed. The positive or
negative association was derived after the adjustment for confound-
ers in seven studies (Table 1).15,32-35,37,40
Erectile function is defined by its good functioning rather than
its insufficiency. Erectile dysfunction is a frequent disorder affecting
the quality of a man's sexual life and relationships. It is defined as
the inability to obtain or maintain an erection sufficient for sexual
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LECAPLAIN et al.
intercourse.41 To measure ED, two questionnaires were used in most
of the selected studies. These are the Sexual Health Inventory for
Men (SHIM) questionnaire42 used in three studies,13,14,35 which is
a shortened version of the International Index of Erectile Function
(IIEF)42 used in six studies.15,28,32-34,40 In addition to SHIM, one study
used color Doppler ultrasound for evaluating ED of the penis.14
Another study did not use a questionnaire, but employed a double
assessment of ED by a urologist instead, using the diagnostic criteria
of the ICD-9-CM.37
All the studies except one showed a significant association be-
tween periodontitis and ED. Although this study by Sharma et al,14
demonstrated no significant association, a positive correlation was
observed, where the values for ED tended to increase as the val-
ues for periodontitis increased. However, the study reported that
pocket probing depth and clinical attachment level increase with the
severity of ED, and the prevalence of periodontitis is higher in severe
(81.1%) than in moderate (76.4%) or mild (38.8%) vasculogenic ED
(Table 1).
The study by Uppal et al35 was the only study to use a Pearson
correlation to evaluate the association between ED and periodontitis.
It demonstrated that ED and periodontitis were positively correlated
with each other at p = 0.000 (Table 1).
The study by Zadik et al13 was the first to report a significant
difference in the prevalence of periodontitis in mild (p = 0.004)
and moderate to severe (p = 0.007) ED, compared to those with-
level out ED. Tsao et al37 showed that the prevalence was higher in
those under 30 years of age than in those over 59 years of age
(Table 1).
After a logistic regression analysis, Keller et al32 revealed that
men with ED were 3.35 times (95% confidence interval (CI) 3.25–
3.45; p < 0.001) more likely to have been diagnosed with periodontitis
after adjustment for cofactors. Tsao et al37 obtained the same results
after adjustment for comorbidities (Table 1).
Eltas et al33 reported a significant improvement in the IIEF-5
(SHIM) score in the periodontal treatment group. Statistically sig-
nificant correlation was only noted between the IIEF-5 score and
the ability to keep an erection (p = 0.0223) in a study by Matsumoto
et al. 28 No significant difference was detected between the sever-
ity of ED and periodontitis scores (assessing severity of periodon-
titis); however, there was a significant difference between the
presence of ED and the severity of periodontitis. The results of the
team of Oguz et al34 were consistent with these results; logistic
regression analysis showed a significant difference between the
presence of ED and the severity of periodontitis (odds ratio (OR)
- 3.29, 95% CI = 1.36–9.55; p < 0.01). The same study also showed
that the mean values of the plaque index, bleeding on probing,
and the percentage of sites with pocket probing depth and loss of
clinical attachment greater than 4 mm were significantly higher in
men with ED. Martin et al15 provided results that confirmed this
trend, indicating a significant association between the number of
sites with a loss of clinical attachment greater than 3 mm and a
pocket probing depth between 4 and 6 mm, and the diagnosis of
ED (Table 1). Additionally, this study showed that periodontitis is
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LECAPLAIN et al. 773

TA B L E 1 Characteristics of studies assessing the relationship between periodontitis and erectile dysfunction

Study Patients Age range/ ED diagnosis Periodontitis Confounding

First author Year design enrolled/groups average method diagnostic method variables assessed Relationship

Zadik 2009 Cross- Total: 305 25 and older SHIM Radiograph Age, Education level, Positive
sectional 235 no ED +51 Questionnaire (posterior Smoking
mild ED +19 bitewing)
moderate or Periodontitis was
severe ED defined as
alveolar bone
loss at least one
site in the jaw
with distance of
CEJ to alveolar
bone crest of
6 mm or more
Sharma 2011 Cross- Total: 70 35.3 ± 6.64 SHIM Radiographic, PD, Aggressive Negative
sectional 18 with mild questionnaire, CAL periodontitis,
ED +24 with color Doppler Alcohol,
mild-to- ultrasound for medication
moderate penis periodontal
ED +17 with therapy, systemic
moderate diseases, tobacco
ED +11 with
severe ED
Keller 2012 Case-control Total: 197,136 49.3 IIEF−5 Probing sulcus, Age, urbanization Positive
32,856 with ED Radiographic level, monthly
+162,480 income,
without ED geographic
region,
hyperlipidemia,
diabetes,
hypertension,
coronary heart
disease, obesity,
alcohol abuse or
dependence
Eltas 2013 Randomized Total: 120 30–40 IIEF−5 PI, BOP, CAL, PD Age, body mass, Positive
control 60 in treatment education,
trial group +60 Household
in control incomes,
group Smoking, Marital
status
Oguz 2013 Cross- Total: 162 30–40 IIEF PI, BOP, PD, CAL Age, body mass, Positive
sectional 80 with ED +82 education,
without ED household
income
Uppal 2014 Cross- Total: 53 25–40 Clinical Oral examination, Alcohol, smoking, Positive
sectional 23 mild ED +17 examination (PD) and systemic disease,
moderate ED radiographic aggressive
+13 severe bitewings periodontitis
ED
Tsao 2015 Case-control Total: 15,315 20–80 Clinical Periodontal Age, hypertension, Positive
5105 with ED 48.3 ± 12.5 examination examination, ischemic
+10,210 probing heart disease,
without ED sulcus, and cerebrovascular
radiographic disease, diabetes,
hyperlipidemia,
Obesity
Matsumoto 2014 Cross- Total: 88 20–85 IIEF−5 Oral examination Age Positive
sectional 50.9 ± 16.6 questionnaire and self-check
sheet
(Continues)
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774 LECAPLAIN et al.

TA B L E 1 (Continued)

Study Patients Age range/ ED diagnosis Periodontitis Confounding

First author Year design enrolled/groups average method diagnostic method variables assessed Relationship

Martin 2018 Case-control Total: 158 18–70 IIEF <25 BOP, PD, CAL Age, cardiovascular Positive
80 case with Ed disease, diabetes,
78 control triglyceride
without ED
Chou 2020 Cross- Total: 2191 18–28 IIEF−5 Oral examination Age, weight, waist, Positive
sectional (21.2 ± 2.6) smoking

Abbreviations: ED, erectile dysfunction; SHIM, sexual inventory for men; IIEF, international index of erectile function; CEJ, cemento-enamel junction;
PD, pocket probing depth; PI, plaque index; BOP, bleeding on probing; CAL: clinical attachment level.

an independent risk factor for ED, and after adjustment for cofac-
tors, patients with periodontitis are at a higher risk of having ED
(OR = 2.17) (Table 1).
Finally, Chou et al confirmed the previous results, showing that
there was a statistically significant correlation between the pres-
40
ence of ED and chronic periodontal disease (CPD) (p < 0.001).
Multivariate logistic regression analysis indicated that men with
periodontitis were 1.6 times (95% CI = 1.280–2.009, p < 0.001) more
likely to have ED than men without CPD after adjusting confounders
(Table 1).40
The third study in this group, conducted by Steffens et al, indi-
cated that high total testosterone and calculated bioavailable testos-
terone levels correlated with both the prevalence (OR [95% CI], 2.1
[1–4.5] and 3.9 [1–14.8], respectively) and severity (OR [95% CI], 2.1
[1–4.3] and 3.4 [1.2–9.8]) of periodontitis.31
The study by Martin et al showed no significant difference for
testosterone levels between periodontitis group and control group.15
However, this study demonstrated that triglycerides, C-reactive pro-
teins (CRP), and HbA1c levels were significantly higher in patients
affected by periodontal disease.15

3.5 | Concentration of sex steroids 3.6 | Semen quality

A total of 2346 patients with a mean age of 60 years were included
from one prospective study18 and three retrospective studies15,31,36
investigating the relationship between periodontitis and sex hor-
mones. Two studies15,36 did not report the age of the participants.
Orwoll et al18 performed a blood test in the morning to measure
total serum estradiol and testosterone levels and sex hormone-bind-
ing globulin (SHBG) concentrations by radioimmunoassay. One of
the retrospective studies determined serum testosterone levels by
enzyme immunoassay,36 whereas another quantified testosterone,
estradiol, and SHBG concentrations by competitive electrochemilu-
31
minescence immunoassays (Table 2).
18
The first study in this group, by Orwoll et al, showed no signif-
icant difference between absent teeth and testosterone, estradiol,
and SHBG concentration. Periodontitis was cited as the cause of
extraction in 16% of the cases. The same is true for the progression
of periodontitis, and for the measurement of the clinical level of at-
tachment, pocket probing depth, and bleeding on probing as well.
After adjustment for cofactors, there was no significant difference
between men with periodontitis with low testosterone levels and
men with periodontitis with high levels (43% vs. 37%, p = 0.13).
36
Singh et al (second study of the group) reported significantly
higher testosterone levels (4.41 ± 2.57 ng/dL) in subjects without
tooth loss compared with subjects with tooth loss (2.79 ± 1.15 ng/
dL) (p = 0.001), indicating that testosterone is a good predictor of
tooth loss.36 However, no association was found between testoster-
one and bone mineral density.36
Semen quality was evaluated in all studies using a seminogram (semi-
nal fluid analysis) (Table 3).16,17,29,30,38 The semen quality analysis was
based on criteria defined by the World Health Organization (WHO)
laboratory manual for the examination and processing of human
semen (1999)43 or (2010)44 depending on the selected studies. A
total of 728 patients from six retrospective studies16,17,29,30,38,45 with
a mean age of 33.45 years were included for investigating the rela-
tionship between periodontitis and semen quality. Two studies did
not report the age of the participants (Table 3).30,38
Out of six selected studies, three showed a significant positive
association between semen quality and periodontitis.30,38,45 Nwathor
et al assessed the semen quality using criteria defined by the WHO
(1999).43 The lower reference limits of sperm cell concentration in
ejaculate were taken as values of ≥20 × 106 per mL with motility
≥25%. Nwathor et al were the first to demonstrate a significant asso-
ciation between periodontitis and subnormal sperm count (0.02599
[CI = 0.141089–2.03891]) among subjects and controls between the
30 and 38 years age group, as well as a significant association between
periodontitis and periodontal pocket, and abnormal semen quality.38
Chidambar et al30 demonstrated that there was a positive correlation
between poor periodontal status and semen quality (oligospermia
and sperm motility). In this study, the reference level of sperm cell
concentration in ejaculate was taken as values of ≥20 × 106 per mL or
greater, with at least 25% rapid progressive motility. Sperm concen-
tration values less than the reference value referred to oligozoosper-
mia. Azoospermia was pronounced when there were no spermatozoa
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LECAPLAIN et al. 775

TA B L E 2 Characteristics of studies assessing the relationship between periodontitis and sex hormones

Authors Periodontitis Confounding

(Region Patients enrolled/ Age range/ Steroid level diagnosis diagnostic variables
of study) Year Study design groups average method method assessed Relationship

Orwoll 2009 Cross- Total: 1210 66–99 Morning serum Tooth loss, Age, non-white Negative with:
sectional (74.6) samples: CAL and race, college • Testosterone
radioimmunoassay PD education, • Estradiol
body mass • Sex hormone-
index, binding globulin
diabetes, (SHBG)
self-reported
general health
status, and
smoking
Steffens 2015 Cross- Total: 775 45.5 ± 0.5 Serum: competitive CAL and PD Age, Smoking, Positive with:
sectional chemiluminescent alcohol • Testosterone,
enzyme drinking • Estradiol,
immunoassay frequency, • (SHBG)
waist-to-hip • Androstenediol
ratio, race/ glucuronide
ethnicity,
diabetes
Singh 2011 Cross- Total: 203 45–65 Serum: enzyme CAL, PD, Systemic Positive with:
sectional immunoassay teeth conditions, • Testosterone
mobility smoking,
alcohol,
medications
Martin 2018 Case-control Total: 158 18–70 Serum Bleeding on Age, Negative
80 case with Ed probing, cardiovascular • Testosterone
78 control without probing disease,
ED pocket diabetes,
depth, triglyceride
CAL

Abbreviations: BOP, bleeding on probing; CAL: clinical attachment level, PD, pocket probing depth

in the ejaculate. Sperm submotility was considered pathologic when
<25% spermatozoa were classified as having a rapid progressive mo-
tility. Poor periodontal status had significant effect on semen quality
and quantity; loss of clinical attachment was significantly correlated
with low ejaculation volume (range of ejaculation volume was con-
sidered normal when it was between 1.5 and 5.5 mL), weak sperm
motility, and subnormal sperm morphology (range of sperm morphol-
30
ogy was considered as the reference level when it was 5% or more).
45
Recently, in a case-control study, Tao et al also using the criteria of
the WHO (2010)44 concluded that after adjusting for confounding
factors, participants with periodontitis had a greater chance of hav-
ing semen abnormalities (sperm concentration below 15 × 106 per
ml, total number below 39 millions per ejaculate, progressive motility
below 32%, and total motility below 40%) (OR = 3.377, p = 0.005)
45
(Table 3).
Conversely, three other retrospective studies failed to demon-
strate any association between periodontitis and semen quality
(Table 3).16,17,29 Klinger et al16 collected, analyzed, and classified
43
semen according to the criteria of the WHO (1999). The lower ref-
erence limits for sperm cell concentration in ejaculate were 20 × 106
per mL, with at least 25% rapid progressive motility and 30% or
more normal morphology. Oligozoospermia occurred when the
sperm concentration was less than the reference value of 20 × 106
per mL; azoospermia occurred when there were no spermatozoa in
the ejaculate. Sperm submotility was defined as sperm pathology
when <25% spermatozoa were classified as having a rapid progres-
sive motility. Prager et al17 and Pásztor et al29 collected, analyzed,
and classified semen according to the criteria of the WHO (2010).44
Normozoospermia was defined as sperm cell concentration 15 × 106
per mL or greater, total sperm count 39 × 106 per ejaculate or greater,
total motility at least 40%, and progressive motility 32% or greater.
Cryptozoospermia was diagnosed when spermatozoa were not ob-
served in the fresh preparation, but they could be found in a cen-
trifuged pellet. In case of oligozoospermia (sperm concentration
<15 × 106 per mL) or asthenozoospermia (progressive motility <32%),
blood sample was taken from the patient for measurement of hor-
mone levels and ultrasound examination of the testis was performed.
3.7 | Cofactors
Age was one of the most common cofactors across all of the
studies selected, with 15 studies taking this factor into ac-
count.13,16-18,28,29,31-34,37,38,40,45,46 The next two common factors were
 |
776
tobacco and systemic diseases, such as diabetes or cardiovascular diseases,
13,14,16-18,29-31,33,35,36,40,45
each with 13 studies taking them into account.
No less than eight studies included different social factors.15,17,18,29,31–34
Among them, marital status, level of education, or level of urbanization
could be retained. A history of medication or surgery that may alter
periodontitis was also considered in 12 studies,13,16,30,32-37,40,45,46 while
body mass figured in nine studies.17,18,29,31,32,34,37,40,45 On the other
hand, alcohol, a cofactor of periodontitis, appeared to have been little
studied considering its mention only in five studies.14,31,32,35,36
4 | DISCUSSION
Controversies still exist on the impact of periodontitis on male sexual
health. Regarding ED, nine articles showed a significant association
with periodontitis.13,28,32-35,37,40,46 Regarding sex hormone levels,
two studies31,36 showed an association with periodontitis and two
out of five studies for semen quality.30,38 In this systematic literature
review, only 19 selected articles were considered relevant. This high-
lights the low number of studies linking periodontitis to male sexual
health. However, it is pertinent to mention that a variety of factors
may bias these results. The use of the term association, in this con-
text, is to be differentiated from that of correlation. The association
simply means the presence of a relationship where certain values col-
lected for periodontitis tend to coexist with certain values obtained
for sex hormone levels or semen quality.
Many cofactors were mentioned in the various studies, and some
seem more important than others, in view of the number of articles
citing them or taking them into account in the results. Tobacco, al-
cohol, and diabetes are most often mentioned as cofactors and the
47-49
mechanisms are known. Semen quality and hormone production
both present tobacco as a cofactor.50,51 However, it is not taken into
account in all the studies collected.
The notion of severity of periodontitis was not the same for all
studies. In fact, only two studies distinguished between the descrip-
tion of chronic periodontitis and aggressive periodontitis.14,35 In all the
19 studies, periodontitis was assessed by visual or radiological clinical
examination. The concept of classification varied from one study to
another. In addition, the selected studies did not take gingivitis into ac-
count, which that may be considered as a mildest form of a periodon-
tal disease. This may explain the conflicting results for semen quality
and sex hormone studies, as each uses a different diagnostic method.
Further studies could be considered using the new classification of the
2017 consensus by Papapanou et al.6 The same applies to ED, which
was either classified into different groups or remained unclassified,
depending on the study. Only four out of nine studies mentioned the
severity of ED.13,14,33,35 Another point of discrepancy is the size of the
samples, which varied greatly from one study to another, from a max-
imum of 197,136 patients to a minimum of 53 patients.32,35 The study
32
conducted by Keller et al can claim to be free of selection bias as it
is based on a national database; however other studies, such as that of
Uppal et al,35 do not provide any indication of the method of recruit-
ment of the patients included in the study.
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LECAPLAIN et al.
The link between ED and periodontitis is thought to be mainly
explained by endothelial dysfunction. This dysfunction is character-
ized by a decrease in the release of nitric oxide from endothelial cells
under the action of biochemical stimuli such as acetylcholine, which
causes smooth muscle vasoconstriction. Tonetti et al52 suggest that
the mechanism between periodontitis and endothelial dysfunction
may be due to the sharp increase in the levels of CRP and interleu-
kin-6 (Il-6). Endothelial dysfunction is known to be associated with ED
and is accompanied by impaired smooth muscle function in patients
with vasculogenic ED.53,54 This is believed to result in decreased nitric
oxide levels and reduced nitric oxide activity in the vessels. In fact,
endothelial dysfunction, when present in the penis, contributes to ED.
Keller et al32 continue the reasoning by explaining that although the
penile vascular networks responsible for erection are distant from the
inflammatory source, in patients with periodontitis, the endothelium
is in contact with blood in the general circulation and may suffer from
oxidative stress.32 A study by Zuo et al55 in rats tends to confirm the
hypothesis of this mechanism. As suggested in this study, periodonti-
tis could cause ED by decreasing the activity of the endothelial nitric
oxide synthase (eNOS) protein in the corpus cavernosum, thus leading
to a reduction in nitric oxide production and a decrease in the activity
of cyclic guanosine monophosphate (cGMP).55
For the measurement of ED, the two most notable methods are
self-questionnaires that are given to patients. They are the IIEF-542
and the SHIM.56 The second is an abbreviated version of the first
questionnaire that allows a score to be established that classifies the
severity of ED into five categories—no dysfunction, mild dysfunction,
mild-to-moderate dysfunction, moderate dysfunction, and severe
dysfunction. It is based on five questions assessing the situation over
the past six months. However, the team of Chen et al57 questioned
the IIEF-5 questionnaire and put forward the idea that it cannot be
used as a differential diagnostic tool for vasculogenic ED and that the
scores established do not reflect the vascular conditions of the penis.
In addition, reporting bias cannot be denied.57 As evident, ED is a
“taboo” topic in many countries, and the responses to questionnaires
may not have been truthfully completed by patients. Within the limits
of the current available evidence, it is reasonable to suggest that peri-
odontitis may be associated with ED, and may be a sign of ED in men.
However, further longitudinal studies and well-designed randomized
control trials assessing confounders are needed.
Contrary to the diagnosis of periodontitis, which is essentially
based on objective criteria (level of clinical attachment, bleeding
on probing, tooth loss), ED for most studies is carried out by means
of a questionnaire, the assessment of which is dependent on each
patient. In fact, each individual has a different perception of sexual
health, and therefore, assessing their “ability to maintain an erection”
is a subjective criterion. The best solution for diagnosing ED, from a
physiological point of view, would be the one developed by Sharma
et al, the only study showing no significant association between ED
and periodontitis.14 The use of color Doppler ultrasound for the penis
allows objective visualization of both the corpus cavernosum and the
corpus spongiosum of the penis. At present, penile Doppler with color
imaging is considered the standard test for vascular impotence.58
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LECAPLAIN et al. 777

TA B L E 3 Characteristics of studies assessing the relationship between periodontitis and semen quality.

Authors Semen Periodontitis Confounding

(Region of Patients enrolled/ Age range/ quality diagnostic variables
study) Year Study design groups average analysis method assessed Relationship

Klinger 2011 Cross- Total: 71 32.7 Seminogram Missing teeth, Age, smoking, Negative with
sectional 36 with periodontitis (WHO plaque-score, antibiotic • Motility status
+30 with gingivitis 1999) gingival intake during • Sperm counts
+5 healthy index, BOP past year • Morphology
sites, degree
of mobility,
PD, and CAL
Nwhator 2015 Cross- Total: 76 25–56 Seminogram Oral hygiene Age Positive between
sectional 51 subnormal (WHO index, • Subnormal sperm count
spermatozoa 1999) probing and poor oral hygiene
+25 normal (p = 0.048)
spermatozoa • Subnormal sperm count
and periodontitis for
33–38 age group
• Subnormal sperm count
and periodontal pocket
(p = 0.08219)
Pasztor 2016 Cross- Total: (95) 23–51 (35.1) Seminogram PD, BOP, missing Age, place of Negative
sectional 32 normozoospermic (WHO teeth residence, 50.8% of the men with
+63 with sperm 2010) education subnormal sperm count
abnormality level, and 50% of the men with
occupation, normozoospermia had
smoking, poor periodontal status.
post-smoking,
BMI
Prager 2017 Cross- Total: 106 Normospermia: Seminogram Caries, Age, place of Negative
sectional Normospermia 93 33.6 (WHO Periodontal residence, Poor periodontal status
Pathospermia Pathospermia: 2010) probing and educational was found in about
35.4 charting, BOP level, half of the study group
occupation, (45.7%) (oligozoospermia,
smoking, asthenozoospermia,
tobacco, body cryptozoospermia,
mass index combined
oligoasthenozoospermia)
Chidambar 2019 Cross- Total 85: 64 with 21–45 Seminogram Plaque index, Systemic Positive with
sectional Periodontitis (WHO gingival conditions, • Ejaculation volume
+21 with only 2010) a index, BOP, tobacco, • Motility status
gingivitis PD, CAL, periodontal • Sperm counts
recession therapy • Morphology
undertaken
within the
previous
6 months,
and use of
systemic
antibiotics or
non-steroidal
anti-
inflammatory
drugs in
4 months prior
to enrollment
in the study

(Continues)

Regarding sex hormone levels, Steffens et al31 outline several characteristics. Periodontal tissue responses may be exacerbated
mechanisms that may explain the link with periodontitis. In par- by immuno-endocrine interactions. In addition, specific populations
ticular, they address the fact that hormones are likely to increase of fibroblasts and epithelial cells would be modulated in response
the growth of pathogenic microorganisms or modify vascular to steroid hormones. They also hypothesized that the availability of
 |

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778 LECAPLAIN et al.

TABLE 3 (Continued)

Authors Semen Periodontitis Confounding

(Region of Patients enrolled/ Age range/ quality diagnostic variables
study) Year Study design groups average analysis method assessed Relationship

Tao 2020 Case-control Total 192: 129 29–35 (32) Seminogram BOP, PD, CAL Age, smoking, Positive with
Normospermia 63 (WHO alcohol • abnormality of sperm
Pathospermia 2010) consumption, concentration (p = 0.335)
education level • Sperm count (p = 0.169)
• Abnormalities in sperm
progressive motility (sites
of BOP was significantly
higher than control group
(77% vs 49% (p = 0.004))
• Abnormalities in sperm total
motility (sites of BOP was
significantly higher than
those in control group (79%
vs 48% (p = 0.001), CAL was
significantly higher (1.0 vs
0.8 (p = 0.029) than those in
control group.

Abbreviations: PD, pocket probing depth; BOP, bleeding on probing; CAL: clinical attachment level.
a
The lower reference limit of sperm concentration mentioned in this study was 20 × 106 per mL whereas the lower reference limit of sperm
concentration of criteria defined by the WHO (2010) is 15 × 106 per mL; the reference range of ejaculation volume in this study was 1.5–5.5 mL
whereas the lower reference limit of semen volume of criteria defined by the WHO (2010) is 1.5 mL (1.4–1.7); the lower reference limit of sperm
morphology in this study was 5% or more whereas the lower reference limit of sperm morphology (normal forms) of criteria defined by the WHO
(2010) is 4% (3.0–4.0).

testosterone and estradiol may be associated with periodontal in-
flammatory changes. Regarding hormone levels, the three reported
studies have different methods of measuring testosterone. For ste-
roid concentration analysis, immunoassays are reliable methods for
measuring testosterone levels; however, there is a lack of standard-
ization for measuring sex hormone levels. Two of the selected stud-
18 31
ies, one by Orwoll et al and the other by Steffens et al, differ in
the methods used to determine testosterone levels, and this may
explain the conflicting results obtained in the two studies.
Default in semen quality could be explained by two theories put
forward by Prager et al,17 one of which is bacteremia that can be caused
by a local infection of periodontal origin, whereas the other highlights
high plasma cytokine levels linked to periodontal inflammatory reac-
16
tions. Klinger et al put forward two hypotheses. The first hypothesis
is that IL-6 detected in seminal plasma is the cause of infertility, and is
present in infertile men at significantly higher levels than in fertile men.
The second hypothesis concerns the immune response to heat-shock
proteins in cases of infertility. Heat-shock proteins are proteins present
in the vascular endothelium in response to increased body tempera-
ture, oxidizing agents, and lipids. There is evidence of similarities be-
tween the antigenicity of bacterial and human heat-shock proteins.59
Porphyromonas gingivalis possesses a heat-shock protein, and antibod-
ies to this protein cross-react with a human heat-shock protein.60,61 In
addition, the presence of these antibodies is significantly associated
with leukocytospermia and elevated levels of interleukin in seminal
plasma. Therefore, the authors suggest a potential role of the immune
response to these heat-shock proteins, in cases of silent infection of the
male genital tract and in infertility.
For semen analysis, the data collection was homogeneous
between the different studies, where an initial macroscopic
examination was carried out, followed by a microscopic investigation
before focusing on sperm motility, vitality, and quantity. However,
the expected lower reference limits used in the seminogram (crite-
ria defined by the WHO) evolved over the years.43,44 Therefore, the
semen results cannot be compared directly between studies, but
only within studies. Two studies were based on the criteria defined
by the WHO (1999),16,38 three studies were based on the criteria
defined by the WHO (2010),17,29,45 and one did not follow the strict
criteria of the WHO (2010) contrary to what was mentioned in the
study.30 Of the six studies selected, only two proved a significant
association between periodontitis and semen quality.30,38 Nwathor
et al38 consider that further investigation is needed to know the
mechanisms of this association, while Chidambar et al30 assert that
periodontitis has consequences on male semen quality. Two stud-
ies that do not show a significant association qualify their results
by indicating a possible association between periodontitis and de-
creased semen quality.17,29 Prager et al conclude that bleeding on
probing may be a prognosis of poor semen quality. Thus, good peri-
odontal health can improve male semen quality.17 However, Pasztor
et al contrast their conclusion by indicating that there is an associ-
ation between semen quality and certain oral conditions; however,
poor periodontal health is not one of them. 29
These results may lead to a change in the common clinical prac-
tice of dentists, especially, in terms of enquiring about the medical
conditions while taking the case history of a new patient, as well
as evaluation of the general health of the known patient. Although
it is difficult to apply the results obtained from this systematic re-
view of the literature to the general population, health professionals
must be more vigilant with regard to overall health, and particularly
male sexual health. In particular, four studies show the effectiveness

LECAPLAIN et al.
of periodontal treatment or the elimination of infectious foci by
tooth extraction in improving erectile function33,37,46 and one study
demonstrated improvement in the IIEF-5 scores after periodontal
treatment. Further studies are needed in this regard.33
Publication bias should be acknowledged as a potential limita-
tion, as reviews of the literature are sensitive to publication bias.
Based on the few available literature on the impact of periodontitis
on MSH, it is not possible to determine whether such a bias exists.
Moreover, the diversity of the outcomes in the studies, the het-
erogeneity of recruitment and periodontal diagnosis, and the small
number of studies for each outcome prevented valid mathemat-
ical combination, and therefore a meta-analysis of this systematic
review.
5 | CO N C LU S I O N
According to the literature reviewed, there is a significant asso-
ciation between ED and periodontitis. In order to improve patient
management, dentists and physicians need to be aware of the as-
sociation between male sexual health problems and periodontitis.
The mechanisms responsible for this association remain unclear, and
the potential associations between sex hormone levels, sperm qual-
ity, and periodontitis are yet to be demonstrated. Although impact
of periodontitis on male sexual health is complex to demonstrate,
increasing evidence may serve as a motivational element for the pa-
tient by highlighting the need to prevent and treat periodontitis.
AC K N OW L E D G M E N T S
This article is based on the work of a resident in periodontology. The
authors would like to thank the Department of Periodontology for
financial support.
C O N FL I C T S O F I N T E R E S T
The authors have no conflict of interest to disclose.
ORCID
Zahi Badran https://orcid.org/0000-0003-2592-4333
Assem Soueidan https://orcid.org/0000-0001-8759-2165
Tony Prud’homme https://orcid.org/0000-0003-4920-4007
Alexis Gaudin https://orcid.org/0000-0003-4139-8927
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S U P P O R T I N G I N FO R M AT I O N
Additional supporting information may be found online in the
Supporting Information section.
How to cite this article: Lecaplain B, Badran Z, Soueidan A,
Prud’homme T, Gaudin A. Periodontitis, erectile dysfunction,
reproductive hormones, and semen quality: A systematic
review. Andrology. 2021;9:769–780. https://doi.org/10.1111/
andr.12961