Download Controversies in Sexual Medicine Are Premature Ejaculation Symptoms Curable?

© 2008 International Society for Sexual Medicine
Controversies in Sexual Medicine
Are Premature Ejaculation Symptoms Curable?
Yoram Vardi, MD,* Chris G. McMahon, MBBS, FAChSHM,† Marcel D. Waldinger, MD, PhD,‡
Eusebio Rubio-Aurioles, MD, PhD,§ and David Rabinowitz, MD¶
*Department of Neuro-Urology, Rambam Medical Center, Haifa, Israel; †Australian Centre for Sexual Health, St.
Leonards, NSW, Australia; ‡Department of Psychiatry and Neurosexology, HagaHospital Leyenburg, The Hague, the
Netherlands; §Asociacion Mexicana para la Salud Sexual AC, Tlalpan, Mexico; ¶Psychiatric Outpatient Service, Rambam
Medical Center, Haifa, Israel
DOI: 10.1111/j.1743-6109.2008.00900.x
ABSTRACT
Introduction. While premature ejaculation (PE) is the most common sexual dysfunction in men under 40, there is
currently no government-approved therapy for its treatment. Is a cure possible?
Methods. Four experts in the area of PE and its treatment were asked to contribute their opinions.
Main Outcome Measure. To provide food for thought, discussion, and possible further research in a poorly
understood area of sexual medicine.
Results. Differences among the different types of PE, and the ability to cure them are discussed. One expert
examines the possible differences in lifelong and acquired PE as an explanation as to why treatment for the former
does not carry over after termination of treatment whereas the latter can be treated successfully. The second and
third experts break PE into four categories, explaining that those forms that are curable at present are not true PE
or are based on anxiety. The last expert discusses the potential of a combined clinical and research platform to better
understand the relative contributions of biological, behavioral, and couple factors to the disorder for potential
curability.
Conclusion. Improved understanding of the types of PE and their various etiologies and pathophysiologies would
improve the potential for cure. Vardi Y, McMahon CG, Waldinger MD, Rubio-Aurioles E, and Rabinowitz D.
Are premature ejaculation symptoms curable? J Sex Med 2008;5:1546–1551.
Key Words. Premature Ejaculation; Cure; Treatment; Ejaculation
Introduction
P
remature ejaculation (PE) is the most
common sexual dysfunction in men younger
than 40 years with significant adverse effects on
their sexual and overall quality of life. Historically,
this entity has been considered a psychological
disorder, the treatment of which has received an
increasing interest in recent years. The underlying
pathophysiology of PE is not well understood,
although both physiological and psychological
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components could contribute to the symptomatology. Traditional management continues to be
psychotherapy, with techniques such as the “stopstart” and “squeeze” most commonly employed.
However, evidence of their short-term efficacy is
limited while support for their long-term benefit is
lacking. The application of local anesthetics to the
glans first described over 60 years ago continues
to be used especially as an “over-the-counter”
therapy. Over the years, a variety of centrally
acting medications, especially antidepressants,
J Sex Med 2008;5:1546–1551
Controversies in Sexual Medicine
have been described as treatments for PE. At the
present time, the selective serotonin re-uptake
inhibitors, licensed for other indications, emerge
as the most used agents to delay ejaculation. Currently, no medications licensed specifically for the
treatment of PE are available. Nevertheless, none
of the current “off-label” pharmacotherapeutic
approaches are probably ideal therapy for these
patients.
In this month’s “Controversies in Sexual Medicine” section, four experts in the field deal with the
curability of the present treatment modalities
available for the treatment of premature ejaculatory symptoms.
Yoram Vardi, MD
PE is often described as one of the most
common male sexual disorders based solely upon
self-diagnosis by as many as 39% of men in the
general community. However, most epidemiological studies are limited by their reliance upon
self-diagnosis or application of the Diagnostic
Statistical Manual of Mental Disorders-IV-Text
revision (DSM-IV-TR) definition of PE, which is
authority-based rather than evidence-based, and
has no support from controlled clinical and/or
epidemiological studies. Recently, an Ad Hoc
Committee of International Society for Sexual
Medicine was given the brief to develop a contemporary, evidence-based definition of PE and proposed that lifelong PE be defined as . . . “a male
sexual dysfunction characterized by ejaculation
which always or nearly always occurs prior to or
within about one minute of vaginal penetration,
and the inability to delay ejaculation on all or
nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy”
[1]. Based on this definition, the incidence of lifelong PE is likely to be much smaller, but despite
achieving substantial insights into this condition
with community-based stop-watch, normative
intravaginal ejaculation latency time (IELT)
studies has yet to be reliably determined [2].
The core symptoms of PE include early ejaculation and the inability to delay ejaculation, resulting in personal and interpersonal distress, bother,
frustration and/or the avoidance of sexual intimacy. Cure of a medical illness refers to a completely effective treatment, which results in
resolution of the underlying disease. Many treatments are not cures, and may merely provide temJ Sex Med 2008;5:1546–1551
porary relief from symptoms rather than removal
of the underlying disease.
The population of men with PE is heterogeneous and includes lifelong and acquired PE.
Lifelong PE is characterized by early ejaculation
from the first sexual encounters onward at nearly
every intercourse within 30–60 seconds in the
majority of cases (~90%) or within 1–2 minutes
(~10%) of penetration, with nearly every or every
sexual partner. Acquired PE differs in that sufferers develop early ejaculation at some point in
their life, having previously had normal ejaculation experiences. Acquired PE may be due
to psychological or relationship problems, erectile dysfunction (ED), prostatitis, or thyroid
dysfunction.
Animal psychopharmacological and human epidemiological studies suggest that IELT is probably
a genetically determined biological variable, which
may differ between populations and cultures,
ranging from extremely rapid through average to
slow ejaculation. In a normal population of rats,
a Gaussian distribution biological continuum of
ejaculation latency time has been demonstrated,
suggesting that endophenotypes exist with regard
to ejaculatory performance [3]. IELT is similarly
distributed in humans and is positively skewed
with a median IELT of 5.4 minutes and a range
extending from 0.55 to 44.1 minutes [2]. Inherited
hyposensitivity of the 5-HT2C and/or hypersensitivity of the 5-HT1A receptors have been suggested as a possible explanation of lifelong PE [4].
Men with lifelong PE, putative 5-HT2C receptor
hyposensitivity and resultant low 5-HT neurotransmission may have their ejaculatory threshold genetically “set” at a lower point and ejaculate
quickly and with minimal stimulation. Treatment
with a selective serotonin reuptake inhibitor
(SSRI) class drug activates the 5-HT2C receptor,
elevates the ejaculatory threshold set-point, and
delays ejaculation. Cessation of treatment results
in the reestablishment of the fixed genetic setpoint within 5–7 days in men with lifelong PE.
However, several human PE drug studies report
that some men experience sustained improvement
in IELT at up to 6 months follow-up following
cessation of drug treatment [5–7]. McMahon
reported that staged withdrawal of sertraline
allowed 20 out of 29 patients (67%) to discontinue
treatment after a mean treatment interval of 7.3
months, yet maintain improved ejaculatory latency
and control [6]. Montorsi reported better but not
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Controversies in Sexual Medicine
statistically significant improvement in ejaculatory
control after the cessation of medication in men
with acquired vs. lifelong PE [5]. Furthermore,
McMahon reported that initial integrated treatment with a daily SSRI and use of rate-limiting
ejaculatory control techniques with subsequent
staged SSRI withdrawal resulted in sustained
improvement in IELT and ejaculatory control in
68.2% of men with acquired PE compared to only
17.1% of men with lifelong PE [8]. He suggested
that this variance in response may reflect the
genetic and therefore fixed ejaculation set-point of
lifelong PE and the down-regulated but modifiable set-point of acquired PE.
The notion that acquired PE can be “cured” by
successful treatment of the underlying etiology is
logical but not well supported in the literature.
Recent data demonstrate that almost half of men
with ED also experience PE [9]. A recent systematic review of published data reported that phosphodiesterase type 5 inhibitors (PDE5is) alone or
in combination with an SSRI may have a role in
the management of acquired PE in men with
comorbid ED by improving erectile function and
reducing severity of PE [10].
Chronic prostatitis and chronic pelvic pain syndrome have been reported as causes of acquired
PE [11,12]. Shamloul reported that prostatic
inflammation was found in 64% and chronic bacterial prostatitis in 52% of patients with PE.
El-Nashaar reported that 1 month of antibiotic
treatment resulted in a marked improvement in
PE symptoms in 83.9% of patients with a 2.6-fold
increase in mean IELT compared to 1.4 in an
untreated control group which was sustained at 4
months follow-up [13].
Sexual performance anxiety is reported as the
most common cause of acquired PE although the
causal link is speculative and is not supported by
empirical evidence. Treatment success with cognitive behavioral therapy (CBT) is relatively good in
the short term but convincing long-term treatment outcome data are lacking [14,15]. The lack of
longitudinal CBT efficacy may reflect a failure of
researchers to distinguish between CBT treatment
responsive anxiety-based acquired PE and minimally responsive genetic lifelong PE and/or poor
long-term patient compliance.
The symptoms of PE will usually improve
during pharmacological treatment especially when
combined with CBT. Withdrawal of treatment is
invariably associated with return of initial symp1548
toms in men with lifelong PE, the most common
type of PE. However, treatment of the underlying
etiology of acquired PE is likely to be associated
with resolution of PE symptoms in a substantial
proportion of sufferers although the data to
support this are limited. Further research into this
interesting aspect of the management of PE is
required.
Chris G. McMahon, MBBS, FAChSHM
In 1970, Masters and Johnson wrote “The
marital unit must be and is assured unequivocally
that a complaint of premature ejaculation can be
reversed successfully” [16] and “if there is full
cooperation from the female partner and an inherent interest in pattern reversal, there is negligible
chance of therapeutic failure to reverse the male’s
rapid ejaculatory tendencies” [16]. We know that
in those years it was not unusual to pose such
statements without the support of medical scientific evidence. Today, in times of evidence-based
medical research, no responsible physician would
insist on his personal views without circumstantial
evidence from published randomized clinical trials
(RCTs).
To answer the question posed in the abovementioned title, it remains essential to categorize
the characteristics of PE and to elucidate the idea
behind the medical concept of the curability of
a disorder or dysfunction. A dysfunction may
be considered “curable” if the symptoms do not
reemerge after treatment. When symptoms of a
dysfunction have disappeared under treatment but
reemerge, such a treatment only temporarily suppressed the symptoms, without a definite cure of
the dysfunction.
We recently emphasized that PE is not a single
well-distinguished dysfunction, but a cluster of
symptoms that can be categorized into four subtypes, each with specific features, pathophysiologies, etiologies, and treatments [17]. Successful
treatment has been argued to be dependent on
the PE-subtype, its pathophysiology, and etiology
[18]. For example, in premature-like ejaculatory
dysfunction, a cluster of PE symptoms disclosing
“complaints” of PE but with normal or even long
IELTs, couple or individual therapy may result in a
change of the subjective appreciation and perception of the male’s ejaculatory performance even
when the durations of the ejaculation time have
not been affected by the psychotherapy. In other
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words, psychotherapy may have the capability to
“cure” premature-like ejaculatory dysfunction just
by altering a man’s perception. That means that
the patient has been “cured” of his perception of
suffering from PE. Another cluster of PE symptoms is called “acquired PE” that may occur in
the case of hyperthyroidism. Thyreostatic treatment may lead to complete and lasting disappearance of PE symptoms meaning complete cure.
In contrast to the aforementioned PE subtypes,
there are no hard scientific data about the curability of lifelong PE. Lifelong PE, which is a cluster
of PE symptoms characterized by IELTs of less
than 1 minute in the majority of sexual encounters [19] associated with negative psychological
consequences, can neither be cured by drug treatment nor psychotherapy. Although numerous
well-controlled RCTs did show very strong efficacy of daily SSRIs and clomipramine in delaying
ejaculation time, all symptoms will recur to the
same extent and often within a few days of when
treatment is stopped. In other words, drug treatment does not “cure” lifelong PE” but only
diminishes its symptoms of objective very short
IELTs. To be able to really cure lifelong PE, we
need more neurobiological insights into its pathogenesis. These novelties may perhaps come from
future genetic research.
Marcel D. Waldinger, MD, PhD
Are premature ejaculatory symptoms curable?
Yes, many times. No, unfortunately most of the
time. A straightforward answer to this question is
not possible because the question assumes that PE
is always the same sort of dysfunction. In my experience, this is not the case. There are very important differences between the man who develops PE
in the course of the evolution of his ED, the man
who experiences very high level of anxiety with his
partner because of fear of losing her and this
anxiety prompts a dramatic increase in the speed
of ejaculation, the man who, after having a very
restrictive education and never masturbated, really
lacks knowledge of his own sexual response and
sensations and hence cannot control his ejaculation, to mention just a few.
I have seen patients whose PE is lifelong and
meets the suggested 1 minute of IELT criteria
who, through training with the traditional Seaman’s start-stop technique [20] and psychotherapy, overcome the symptoms and remain
J Sex Med 2008;5:1546–1551
“cured” many years after. Also, I have seen patients
for whom the benefit of the training and psychotherapy with various techniques is null. In a similar
way, I have treated patients with SSRI medications
who benefit from the effect to the point where
the start-stop technique becomes useful and the
control becomes possible even after suspending
the medication, and patients for whom the benefit
of medication is lost short after suspending the
medication.
The current system of classification of sexual
dysfunction creates the illusion that one category
of sexually dysfunctional individuals that share a
diagnosis should have all the same pathophysiological mechanism and therefore the same treatment approaches should work. There is a clear
need to develop classification systems that take
into account the different etiological mechanisms. Not all men with PE share the same
pathophysiology, and treatments should therefore
be ideally directed toward these mechanisms. It
is likely that some of the pathophysiologies
included be more amendable or eliminable
through interventions than others. In my experience, anxiety-related PE cases, and those (rare)
cases where the learning process of ejaculatory
control is defective, are the ones with more possibilities of cure.
The classification proposed by Waldinger [17]
is a significant advance in the need to differentiate
between the various types of premature ejaculators; proposed categories are: lifelong, acquired,
and two new ones: natural variable and PE-like
syndromes. Some previous work by Metz and
McCarthy [21] suggested an even longer list of
nine types of PE according to the possible etiology: neurologic, secondary to physical (urologic)
illness, secondary to trauma, secondary to drug
side effect, psychological system PE, psychological
distress PE, relationship distress PE, psychosexual
skills-deficit PE, and a combined type. There is a
need for more research that provides evidence for
these proposed classifications, but the clinical
experiences of many of us attest to a simple fact:
there are many types of PE.
It is likely and we all hope that the more we
advance in the understanding of the various etiological mechanisms, the better we will become in
predicting which patient has a realistic expectation
for cure and which one will need chronic form of
treatment.
Eusebio Rubio-Aurioles, MD, PhD
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Controversies in Sexual Medicine
Curability implies full recovery from symptoms
and not requiring further treatment. No definitive
position can be taken on the curability of PE in the
absence of long-term follow-up studies. Relapse
rates in the short- and long-term following treatment are unclear. The therapy of PE has been
reviewed [22] and involves pharmacological,
behavioral, and surgical strategies [23], including
the use of selected serotonergic drugs, PDE5
inhibitors, topical applications, hyaluronic acid
gel augmentation of the glans penis [24], and diverse sexological interventions, including directed
genital stimulation [25]. All approaches impact on
the symptom, varying, however, with subgroups
that include primary vs. secondary PE, single
young males, significant medical comorbidity,
medication refusers, and negative intra-couple
environments. Thus, diverse treatments applied to
diverse populations increase the complexity of any
long-term follow-up research strategy. If the jury
is still out on PE curability, PE is best viewed as a
manageable disorder. The optimal management
approach is set out in the review [22] and involves
pharmacological or behavioral approaches, the
first choice varying with the primary or secondary
subtypes and patient preferences, with the possibility of a combined approach as well.
Medical and behavioral interventions are commonly thought of as alternatives to each other; it is
proposed here that this is inherently problematic.
In the mental health literature in general (e.g.,
[24]), studies commonly demonstrate the superiority of combined medical-behavioral interventions over single-paradigm interventions, a
concept that has been explored in clinical and
research work in PE, although in limited fashion
[25]. The contours of a combined approach could
include early medication intervention after diagnosis for rapid symptom control, early sexological
assessment for multifactorial evaluation and intervention, and early educational counseling to
achieve cognitive mastery (psychoeducation [25])
and an increased repertoire of relevant sexual
skills. The latter can be provided by nursing staff
(preferable male) after relatively simple training,
possibly even in a small group setting. In principle,
these modalities could be offered as an integrated
package to all new cases as default mode, customized according to needs.
This combined model permits a team approach
and a relatively easily implemented clinical paradigm. It offers a short- and long-term research
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strategy comparing medical “treatment as usual”
with and without behavioral and/or psychoeducational add-ons. It raises the important question as
to the stability of treatment gains after medication
weaning, as a function of add-on interventions.
Long-term follow-up studies would help confirm
or refute the validity of the combined approach. A
combined package, as a clinical and research platform, may help to achieve a better understanding
of the relative contributions of biological, behavioral, and couple factors to the disorder, and
also help the fine-tuning of interventions. Ultimately, it may bring us closer to the question of
curability.
David Rabinowitz, MD
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