Medical Management of

Ejaculatory Disorders
Professor Geoffrey Hackett
Little Aston Hospital and Aston
University Medical School
Date: NOVEMBER 2023
Premature Ejaculation
Definition – ISSM 2012.
• a male sexual dysfunction characterized by
ejaculation which always or nearly always
occurs prior to or within about one minute
of penetration, and the inability to delay
ejaculation on all or nearly all penetrations,
and
• negative personal consequences, such as
distress, bother, frustration and/or the
• avoidance of sexual intimacy. Althof et al 2012
Epidemiology of Lifelong PE
• Lifelong – exists with all sexual activity but often less so
with masturbation.
• Genetic* – Associated with 5HT transmission
• Serotonin transporter gene polymorphism (5-
HTTLPR and Dopamine transporter protein
(DAT) leading to hyposensitivity of 5-HT2c
and/or hypersensitivity of 5HT1c
receptors.
• Often superimposed performance anxiety
and secondary ED (22%)
• Poor Response – Treatment is long-term
* Jern et al IJIR 2009 – 3946 male twins Mean age 29.
Epidemiology of Acquired PE
• Acquired – men with a previously normal sex life in
relation to ejaculation AND erection.
• Hyper excitability of glans, foreskin and frenulum.
Vanden Brouche J urol 2007 Salonia JSM 2009.

• Often ED associated (33%). McMahon JSM 2007.

• Hyperthyroidism Carani JCEM 2005.
• Raised Prolactin and Leptin levels. Corona Int J Androl 2010.
• Chronic Prostatitis and Chronic Pelvic Pain. Shamloul JSM 2
• Psychological factors. Sexual conditioning, stress,
social phobias and alexithymia. Rosen JSM 2008.
• Better outcomes from therapy.
 Delayed Ejaculation
• Delayed ejaculation is the inability to ejaculate at will, so that
ejaculation takes much longer than desired or does not happen at all.
(30-45 minutes described as excessive)
• Treatment depends on the underlying cause (eg. Hypothyroidism), but
it might include taking a medication or making changes to
medications you currently take ( e.g. anti-depressants, anti-
hypertensives), undergoing psychological counselling, or addressing
alcohol or illegal drug use.
Lifelong vs. acquired. .
Generalized vs. situational.
PREVALENCE
Self-Reported Sexual Problems past 12 Months
PREMATURE
EJACULATION
RAPID RESPONSE
TEAM HQ
Treatments
• Sex Therapy, Squeeze, Stop- Start.
Most effective for couples and in acquired PE.
• Topic Anaesthetics. EMLA,TEMPE, Promescent
• Tramadol 25-50mg on demand, not licensed, concerns with
frequent dosing.
• Clomipramine 25-50mg on demand.
• SSRIs as chronic dosing (off-label). DAPOXETINE is a
SELECTIVE SEROTIN MODULATOR. THE ONLY LICENSED
ORAL MEDICATION.
• Future – Oxytocin antagonists? KH-001 (natural alkaloid)
Pooled analysis: dapoxetine improves IELT
even in severe PE

Pooled data (baseline – Week 12) and 3001 data (Week 24)

Placebo Dapoxetine 30 mg Dapoxetine 60 mg

5.0

4.0 *
Mean IELT (min)

3.6
*
3.1 *
3.0 * 2.8
2.4 *
1.9 * 2.1
2.0 1.7
1.3
0.9 0.9 0.9 (1.83) 0.9
1.0
(1.96)0.6 0.6 0.6 0.3 0.3 0.3
0.0
08

13

68

97

49
11

4
2

5
3

9
1,6
1,6

1,6

1,4

1,4

1,4
93

94

93

35

32
34

85

87

85

32
30

30
n=
n=

n=

n=

n=

n=
n=

n=

n=

n=

n=
n=

n=

n=

n=

n=
n=

n=
Overall IELT ≤1 min IELT≤0.5 min Overall IELT ≤1 min IELT≤0.5 min

Baseline Week 12
Week 12 (012, 013, 3003) or Week 24 (3001) or last visit
* P<0.001 vs. placebo.

McMahon et al. J Sex Med 2011;8:524-539.

Pooled analysis: dapoxetine significantly improves
perceived control over ejaculation

Proportion reporting “good” or “very good”

perceived control over ejaculation

Placebo Dapoxetine 30 Dapoxetine 60

mg mg
*
30%
30 * *
26% 26%
*
24%
*
20%
Subjects (%)

20 *
16%

11%

10 7%
6%

0.3%0.6%0.5% 0.1%0.5%0.2% 0% 0.6% 0.3%

0

60
08

61

89
14

n= 7
13

6
2

4
2

2
4

n= 4

6
6

3
93

84

87
94

30
34

34
35

32

1,4

93
93
1,6

1,4

32
1,4
1,6

1,6

n=

n=

n=

n=

n=
n=

n=

n=
n=

n=
n=
n=

n=

n=
n=

n=

Overall IELT ≤1 IELT ≤0.5 Overall IELT ≤1 IELT ≤0.5 min

min min min

Baseline Week 12
* P<0.001 vs. placebo.

McMahon et al. J Sex Med 2011;8:524-539.

Pooled analysis: dapoxetine significantly improves
satisfaction with sexual intercourse

Proportion reporting “good” or “very good”

satisfaction with sexual intercourse

Placebo Dapoxetine 30 Dapoxetine 60

mg mg

50 ** **
** 43% 40%
38%
Subjects (%)

40 ** **
33% 33%
*
(%)

30 27%
24%
20% 18%
20 16%15%16% 17%15%15% 16% 15%
10%
10
0

59
08

61

89
14

13

6
2

4
7

0
4

n= 3
6

n= 2

84

87
94

30
93

34

85

31
35

32
93

34

1,4
1,6

1,4

1,4
1,6

1,6

-10

n=

n=
n=
n=

n=

n=
n=

n=
n=

n=

n=
n=

n=

n=
n=

n=

Overall IELT ≤1 IELT ≤0.5 Overall IELT ≤1 IELT≤0.5 min

min min min

Baseline Week 12
* P=0.005 vs. placebo.
**P<0.001 vs. placebo.

McMahon et al. J Sex Med 2011;8:524-539.

Dapoxetine tolerability

Most common adverse events (AEs) reported in the clinical studies were
nausea, diarrhoea, headache, dizziness and somnolence
• Incidence of AEs higher with 60 mg dapoxetine than with 30 mg group
• AEs led to the discontinuation of 1.0%, 3.5% 8.8% of subjects with placebo, dapoxetine
30 mg PRN, dapoxetine 60 mg PRN respectively
• Most AEs associated with dapoxetine are mild-to-moderate in intensity: integrated analysis
of two clinical trials (N=2,614)
‒ Serious AEs were infrequent: 0.3% and 0.6% respectively for 30 mg and 60 mg dapoxetine vs.
0.9% for placebo
CCGS
‒ Sexual side effects (i.e. ED, abnormal ejaculation, decreased libido, abnormal sexual function) reported in RECOMMEND
fewer than 1·5% (n=13) of patients on placebo and 3·8% (n=33) of patients taking dapoxetine CHEAP
UNLICENSED
• Tolerability of both doses of dapoxetine is maintained with long-term use SSRIs
• No evidence of deleterious effects on mood and anxiety symptoms or withdrawal syndrome.

McMahon et al. J Sex Med 2011;8:524-539.

Buvat et al. Eur Urology 2009;55:957-968.
Pryor et al. Lancet 2006;368:929-937.
CO-EXISTING ED IS
DIFFICULT TO EXCLUDE
IN PE CASES
 DAILY TADALAFIL
FOR 3 MONTHS IS
ASSOCIATED WITH
MULTIPLE SEXUAL
AND LUTS
BENEFITS

PE COMMONLY ASSOCIATED WITH ED and LUTS

LICENSED SINCE 2007 BUT NOT RECOMMENDED
AS COST EFECTIVE BY CCGs. UNLICENSED OTC
FORMULATIONS WIDELY USED.
 Effect of SSRIs on Ejaculation
140
Placebo
Mean ELT (seconds) 120 Fluvoxamine 100mg
Fluoxetine 20mg
100 Paroxetine 20mg
Sertraline 50mg
80

60 SEXUAL
SIDE-EFFECTS
40 COMMON.
20

0
0 1 2 3 4 5 6
Weeks

1. Waldinger MD, Hengeveld MW, Zwinderman, AH: J.Clin.Psychopharmacol.1998;18:274 ‑81 .

 19

?
DEFINITION 1 MINUTE since 2010
ALL 5 CRITERIA?
HOW MANY RELATIONSHIPS WILL
LAST 6 MONTHS!?
20
 21

TAKE HOME MESSAGE

Off label is first line if it is cheap! Recommended
In preference to labelled medication!!
Paroxetine banned under 18 due
to 3 fold suicide risk. Is it safe at 19?

DAPOXETINE PATENT RUNS OUT IN 2024

EXPECT IT TO BECOME 1st LINE !!
22
 23

HACKETT’s
2 COUGH TEST
 24

Common Scenarios in everyday practice

that require unlicensed medication
 The young man with severe premature ejaculation
• Dapoxetine only licensed oral therapy (Patent expires 2024)
• Not included on most CCG formularies on basis of cost.
• Daily SSRIs being advised off label as “cheap option” with
unacceptable side effects and long-term risks
• Daily tadalafil reasonable first choice as ED often co-exists.
• Young men being denied effective treatment or managed long
term in secondary care at great expense.
• Wrongly perceived by physicians as minor, self-limiting issue.
Sure I only lasted 2 minutes, honey, but in
dog years that nearly 15 minutes …!