Original Article

International Journal of Impotence Research (2011) 23, 257–261; doi:10.1038/ijir.2011.35; published online 21 July 2011

Escitalopram treatment for premature ejaculation has a negative effect on semen parameters

H Koyuncu1, E C Serefoglu2, E Yencilek3, H Atalay4, N B Akbas4 and K Sarıca1

  1. 1Department of Urology, Yeditepe University Medical School, Istanbul, Turkey
  2. 2Department of Urology, Kızıltepe State Hospital, Mardin, Turkey
  3. 3Department of Radiology, Haydarpasa Training and Research Hospital, Istanbul, Turkey
  4. 4Department of Psychiatry, Yeditepe University Medical School, Istanbul, Turkey

Correspondence: Dr H Koyuncu, Department of Urology, Yeditepe University Medical School, Devlet yolu Ankara Cad. 102/104, 34752, Kozyatagı, Istanbul, Turkey. E-mail: hakan.koyuncu@yeditepe.edu.tr

Received 28 January 2011; Revised 5 May 2011; Accepted 14 June 2011; Published online 21 July 2011.

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Abstract

The aim of this study was to determine the impact of long-term escitalopram treatment on semen parameters of patients with lifelong premature ejaculation (PE). Between November 2008 and January 2010, patients admitted to urology outpatient clinic with a self-reported complaint of PE were evaluated. Medical and sexual history of patients were recorded and patients with lifelong PE (a total of 25 patients) who met the International Society of Sexual Medicine definition were asked to record their intravaginal ejaculatory latency time (IELT) for 1 month, complete Premature Ejaculation Diagnostic Tool (PEDT) questionnaire and give semen samples. Afterwards, patients received 10mg escitalopram daily for 12 weeks and were invited for control visits at first and third month of treatment. During control visits, PEDT was administered again whereas IELTs were recorded and semen samples were re-examined. PEDT scores, arithmetic means of IELTs and results of semen analyses, which were recorded at baseline, first and third month were compared. At the third month of treatment, a significant increase in mean IELTs and a significant decrease in PEDT scores were detected. However there was a significant decrease in sperm concentration, motility and morphology when compared with the baseline semen measures. Daily escitalopram treatment effects the semen parameters of patients with lifelong PE. Further investigations with larger series are needed to see whether other serotonin reuptake inhibitors have similar side effects and to expose the exact mechanism underlying it. Different treatment modalities should be suggested to patients who desire fertility.

Keywords:

escitalopram; premature ejaculation; selective serotonin reuptake inhibitors; semen analysis

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Introduction

Premature ejaculation (PE) is one of the most common sexual dysfunctions in men with prevalence rates ranging from 21–31%.1, 2 PE is characterized with a short ejaculatory latency time, lack of ejaculatory control, decreased satisfaction with sexual intercourse causing interpersonal distress, negative impact on man's self-esteem, reduced sexual function and reduced quality of life.3, 4

PE can be classified as either a lifelong condition or acquired condition.5, 6 Lifelong PE is characterized by ejaculation that always or nearly always occurs before or within about 1 min of vaginal penetration, and 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.6

Pharmacotherapy is the basis for the treatment of lifelong PE.7 Although no drug for PE has been approved by either US Food and Drug Administration (FDA) or European Medicines Agency (EMEA), chronic selective serotonin reuptake inhibitors (SSRIs) and on-demand topical anesthetics are proved to be effective in treating PE.7 However, SSRI treatment has adverse effects such as sexual dysfunctions, insomnia, fatigue, nausea and constipation, most of which are usually mild and gradually improve after 2–3 weeks.8 As no universal agreement has been reached on how long SSRIs must be employed to treat PE so as to get ideal effect, there are limited data regarding the adverse effects of long-term SSRI treatment in PE patients.9 Although there are only a few studies, which determined the negative effect of SSRIs on semen parameters of depressed men or healthy volunteers,10, 11 to our knowledge, the impact of this treatment on semen parameters of lifelong PE patients has not been evaluated yet.

Escitalopram, which is the enantiomer of citalopram, is one of the most widely used SSRIs and its efficacy in treating PE has been previously demonstrated.12 The purpose of this study was to determine the impact of long-term escitalopram treatment on semen parameters including sperm concentration, motility and morphology.

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Patients and methods

Between November 2008 and January 2010, patients admitted to urology outpatient clinic with a self-reported complaint of PE were evaluated. Detailed medical and sexual history were taken, with special attention to the duration of the ejaculation time; the onset, course and circumstances of the complaint, such as distress and interpersonal difficulty related to the ejaculatory dysfunction; degree of sexual stimulus; impact on sexual activity and quality of life; drug use or abuse; and concomitant sexual dysfunctions like ED. Patients with lifelong PE were included whereas patients with the complaint of ejaculating prematurely who do not meet the recent definition of lifelong PE, which is introduced by International Society of Sexual Medicine6 were excluded. Moreover, patients with ED, reduced sexual desire, inhibited orgasm, chronic psychiatric or physical illness, alcohol or substance abuse, use of medication, which may interact with SSRIs and history of inguino-scrotal surgery were excluded from the study.

Written informed consent was obtained from all patients before the study inclusion. The study was approved by our institution's relevant review board.

After the initial evaluation of lifelong PE patients, a focused physical examination was given and radiological/laboratory tests were performed in order to identify any underlying medical conditions, which may effect semen parameters. Scrotal ultrasonography was performed and patients underwent fasting glucose and lipid profile tests. In addition, complete blood count was performed, and levels of sex hormones and prolactin were measured. The patients with an abnormality detected with physical examination and/or laboratory tests were excluded.

Patients with lifelong PE were requested to complete the Turkish validation of Premature Ejaculation Diagnostic Tool (PEDT)13 and measure intravaginal ejaculatory latency time (IELT), which was defined as the time that was measured from the initiation of vaginal penetration to ejaculation,6 for a duration of 1 month. It was measured by the female sexual partner using a calibrated stopwatch and expressed in seconds. In addition, patients underwent semen analyses before treatment where concentration, motility and morphology of sperms were examined by the same expert, following an abstinence period of 2–5 days. Semen analyses were performed two times at baseline and evaluated according to the World Health Organization criteria.7

After the initial evaluation, patients received 10mg escitalopram daily for 12 weeks. The drug regimen were given in early morning and continued for 3 months. Patients were given a diary to record the frequency of coitus and instructed to measure IELTs. Couples were also instructed not to use condoms or topical anesthetic cream, not to pause during intercourse or not to have interrupted intromission.

Throughout the study, patients were invited to outpatient clinic for control evaluations at first and third month of treatment. The patients completed PEDT again and semen samples were re-examined during these visits. PEDT scores, arithmetic means of IELTs measured by female partners and results of semen analyses (examined two times in each control visit) were recorded.

PEDT total scores, IELTs and semen parameters including sperm concentration, motility and morphology, which were recorded at baseline, first month and third month, were compared by using Friedman and Wilcoxon tests.

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Results

A total of 25 patients with lifelong PE with normal semen parameters were included into the study. All of the patients were married and the mean age of the patients were 32.84±4.4. The genitourinary examinations of these patients revealed normal testicular volume, normal epididymis bilaterally, no varicoceles and normal digital rectal examination findings. Scrotal ultrasonography of patients also revealed no abnormalities. Complete blood count, fasting blood glucose levels, hormonal and lipid profile of patients were all in normal range.

Mean PEDT scores, IELTs and results of semen analysis of patients at baseline, first and third month are presented in Table 1. At the first month visit, a significant decrease in PEDT scores (P<0.01) and a significant increase in mean IELTs (P<0.01) were observed. However, there was no significant difference in sperm concentration, motility and morphology after 1 month of escitalopram treatment (P=0.41, P=0.45 and P=0.44, respectively).


At the third month of treatment, a significant increase in mean IELTs (P<0.01) and a significant decrease in PEDT total scores (P<0.01) were detected, when compared with the results recorded both at baseline and first month of treatment. Similarly, there was a statistically significant decrease in sperm concentration, motility and morphology when compared with the baseline results. At the twelfth week of escitalopram treatment, mean sperm concentration decreased from 68±27.1 million per ml to 26.4±16.1 million per ml (P<0.01), mean motility decreased from 58.2%±5.2 to 23.4%±7.5 (P<0.01) and mean normal shaped spermatozoa decreased from 19.2%±4.8 to 7.3%±3.3.3 (P<0.01). Oligospermia (<20 million spermatozoa per ml), asthenospermia (<50% progressive motile spermatozoa) and teratospermia (<14% normal forms) were detected in 14 (56%), 13 (52%) and 25 (100%) patients, respectively.

Escitalopram was generally well tolerated and none of the patients discontinued the study because of the side effects. Fatigue, constipation and insomnia were seen in 1 (4%), 2 (8%) and 1 (4%) patients, respectively.

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Discussion

Lack of knowledge about the exact etiology of PE continues the debate about its definition, diagnosis and treatment. Many times, observational and clinical studies identified patients with PE, in part, according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR).5, 6 This definition was the most widely accepted definition of PE, which defines it as ‘persistent or recurrent onset of orgasm and ejaculation with minimal stimulation before, on, or shortly after penetration and before the person wishes it’, which causes marked distress or interpersonal difficulty’.14 Due to the limitations of this definition, International Society of Sexual Medicine convened a meeting and agreed that current data in the literature are only available for evidence-based definition of lifelong PE, which is recommended as the basis of diagnosis of PE for all PE clinical trials.6, 15, 16 The ideal diagnostic method for PE remains to be unclear, however, recent guidelines suggest to combine stopwatch measured IELT with patient-reported outcome questionnaires in clinical trials.7, 17, 12 Several studies used PEDT in combination with IELT to evaluate the efficacy of SSRIs in the treatment of PE.18, 19

Managing PE has been a challenge for physicians as well because no drug for PE has been approved by FDA and EMEA. Over the past decade, clinical evidence has emerged indicating a beneficial effect of SSRIs for the treatment of men with PE. In the literature, there is an agreement that pharmacotherapy constructs the basis of the treatment of lifelong PE and several drugs have been proposed to treat it.7, 20 As recent guidelines propose chronic use of SSRIs because of their proven efficacy,7 these drugs have been widely used in clinical studies and reported to be effective for treating PE.21, 22 A randomized, comparative study, including 100 normally potent men suffering from PE, has shown the efficacy and safety of fluoxetine, paroxetine and escitalopram.23 This study demonstrated significant increase in mean IELTs with a decrease in PEDT scores after 4 weeks of SSRI treatment.23 Another randomized, double-blind, placebo-controlled, fixed dose study, including 276 PE patients receiving escitalopram, 10mg per day, showed a 4.9-fold increase in the mean IELT after 12 weeks, when compared with placebo.24 Similarly, lifelong PE patients received escitalopram 10mg per day for 12 weeks in our study and the effect of escitalopram on promoting IELTs and decreasing PEDT scores (indicating a better sexual function) were shown.

In spite of their efficacy, adverse effects have constructed the major concern for the chronic use of SSRIs in PE patients and they may prompt discontinuation from therapy. Well-known adverse effects of SSRIs include sexual dysfunctions (sexual desire and arousal difficulties, anejaculation, absent and delayed orgasm), dizziness, nausea, constipation, insomnia, fatigue.8, 20, 25, 26, 27, 28 However, there are only a few studies, which evaluate the impact of these drugs on sperms and consequently on male fertility. Few reports demonstrated that binding to sulfhydryl groups of sperm membrane is important for the spermicidal activity and the curiosity about the impact of SSRIs on semen parameters increased.29, 30 As paroxetine is known to bind serotonin transporters by interacting with sulfhydryl groups, it was suspected that SSRIs could cause a negative impact on spermatozoa31 In an experimental study, separately diluted SSRIs (paroxetine, sertraline and citalopram) and different human semen samples had been mixed in vitro and examined under a microscope.32 The authors observed that these three SSRIs caused a decrease in sperm motility and viability, and suggested that spermicidal action of these SSRIs might be attributed to their possible interaction with sperm cell membrane and inner mitocondrial membrane, which causes an inhibition of ATP synthesis.32

Confirming aforementioned in vitro findings Tanrikut and Schlegel presented two cases with the history of infertility (oligoastenospermia) who had been taking SSRIs (citalopram and sertraline) for more than 6 months for depression. They demonstrated marked improvement in semen parameters within a few weeks after the discontinuation of SSRIs and considering this rapid recovery they hypothesized that SSRIs might effect sperm transport, rather than sperm production, resulting in a negative impact on sperm quality and number.33 Similarly, Safarinejad10 observed significant impairment in all semen parameters and increased sperm DNA damage in depressive patients who were already receiving different types of SSRIs for more than 6 months.

Finally, in a prospective study, Tanrikut et al.11 assessed serum hormone levels, semen analyses and sperm DNA integrity in 35 healthy men before receiving paroxetine for 5 weeks. After 5 weeks paroxetine administration testosterone and estrogen levels decreased significantly whereas higher DNA fragmentation was detected. Interestingly, Tanrikut et al.11 did not observe any significant changes in semen parameters and advocated their previous hypothesis, which suggests that impairment in sperm transport may cause alterations in sperm DNA integrity without doing any changes in sperm count. However, the duration of paroxetine administration was only 35 days in this study and is not sufficient for evaluating the impact of any medication on sperm production, which takes 74 days.34

To our knowledge, this is the first clinical prospective study investigating the impact of SSRIs on semen parameters of lifelong PE patients whose semen parameters were normal before the 12-week escitalopram treatment. At the end of this period, which was sufficient to evaluate the potential impact of escitalopram on developing spermatozoa, we have demonstrated a statistically significant decrease in sperm concentration, motility and morphology. As suggested by Tanrikut et al.,11 these negative changes may really be related to the impairment of sperm transportation, however, deterioration of sperm cell membrane, alterations in hormonal homeostasis and/or damages in sperm DNA should not be disregarded.

Herein, the risk of male infertility becomes important because in 50% of involuntarily childless couples, a male factor is found together with abnormal semen parameters including oligospermia (<20 million spermatozoa per ml) and/or asthenospermia (<50% progressive motile spermatozoa) and/or teratospermia (<14% normal forms).35 In addition, drug use is noticed as a prognostic factor for male infertility in ~3% of infertile population.36 Therefore, potential effects of SSRIs on reducing fertility must be considered while using these drugs in the treatment of lifelong PE patients, especially in young ones who desire fertility. In such cases, on-demand use of SSRIs can be a rational alternative for long-term daily SSRI treatment. Recent studies established the efficacy and safety of dapoxetine,37, 38 however, further clinical studies analyzing the impact of on-demand use of this medication on semen parameters should be performed as well.

On the other hand several limitations of our study must be addressed: (1) the number of patients included is rather low, therefore further studies with larger study population must be performed; (2) semen parameters of patients after the discontinuation of the treatment could not be recorded. We admit that, demonstrating the improvement of semen parameters after quitting escitalopram treatment would have strengthen the findings of our study, however, the patients included were reluctant to come for longer follow-up visits and give the fourth semen samples. (3) Having a control group, which is composed of lifelong PE patients treated with placebo and comparing their results with lifelong PE patients treated with escitalopram could have increased the reliability of our findings.

Conclusion

Daily escitalopram treatment effects semen parameters of patients with lifelong PE. Further investigations with larger series are needed to see whether other SSRIs have similar side effects and to expose the exact mechanism underlying it. Moreover, physicians and patients must be aware of this effect before the commencement of these medications and different treatment modalities should be suggested to PE patients who desire fertility.

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Conflict of interest

The authors declare no conflict of interest.

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