Testosterone Therapy Does Not Show Efficacy in Treating Ejaculatory Dysfunction

Introduction: An estimated 10% to 18% of men have ejaculatory dysfunction such as inability to ejaculate, decreased volume of ejaculation, decreased force of ejaculation and delayed time to ejaculation. Limited data from cross-sectional studies suggest that testosterone deficiency may be a contributing factor to ejaculatory dysfunction. This study was designed to investigate whether testosterone replacement therapy (TRT) is effective in improving ejaculatory dysfunction in men with androgen deficiency in a randomized controlled study.

Methods: The multicenter, double-blind, randomized, placebo-controlled, 16-week trial enrolled 76 men with ejaculatory dysfunction who were assigned to receive either a 2% testosterone solution applied on the skin or a placebo. Sixty-six men completed the study. The men were all age ≥26 years and had total testosterone levels of less <300 ng/dL measured on two separate occasions using liquid chromatography tandem mass spectrometry.

The primary outcome measure was a change in the score of the 3-item Male Sexual Health Questionnaire-Ejaculatory Dysfunction-Short Form (MSHQ-EjD-SF).

Results: Men given TRT showed greater improvement on the MSHQ-EjD-SF than men given placebo (mean score change from baseline, +3.1 and +2.5, respectively); however, this difference was not statistically significant (P=0.596). In addition, no significant differences were found in any of the following secondary outcomes: measured ejaculate volume, scores of the bother/satisfaction item of the MSHQ-EjD-SF, the orgasmic function domain of the International Index of Erectile Function Questionnaire, and sexual activity log.

No significant between-group differences were found in the frequency of treatment-emergent adverse events.

Conclusion: Androgen-deficient men did not experience significant improvements in ejaculatory disorders after undergoing testosterone replacement therapy.


Paduch DA, Polzer PK, Ni X, Basaria S. Testosterone replacement in androgen-deficient men with ejaculatory dysfunction: a randomized controlled trial. J Clin Endocrinol Metab. 2015;100(8):2956-2962.

Commentary by Tamara L Wexler MD, PhD

Tamara L. Wexler, MD, PhD, is an endocrinologist specializing in neuroendocrinology and reproductive endocrinology. She is the Director of the NYU Langone Medical Center Pituitary Center in New York, NY, as well as an Attending in Medicine at Massachusetts General Hospital, Boston, MA.

Testosterone deficiency is associated with decreased libido and with erectile dysfunction, and testosterone replacement with improvements.1-3 However, there is less consistent data on the effect of testosterone replacement* on ejaculatory dysfunction. Paduch and colleagues set out to investigate the impact of testosterone replacement in men with ejaculatory dysfunction.

The study was designed as a phase 2 multicenter, placebo-controlled, randomized trial. Men were >26 years old, with BMI <35 kg/m2, and had one or more ejaculation-related issues, as assessed by the Ejaculatory Function Screening Questionnaire: delayed ejaculation, anejaculation, decreased ejaculatory force, and decreased ejaculatory volume. Men with two separate T levels <300 ng/dL were randomized to testosterone (T) or placebo; standard LC-MS assays were used to measure total and free testosterone. The randomization model took into account the degree of hypogonadism and erectile dysfunction. During the active phase of the study, goal testosterone level was 300-1050 ng/dL. Men in the testosterone group had slightly younger mean age (48.4 vs 52.7 in placebo group; P=0.056) and baseline estradiol levels (21.2 v 25.9 pg/mL; P=0.056). The investigators measured compliance by weighing bottles at each visit and assessing whether at least 70% of expected daily doses were taken.

After the intervention, total and free T, dihydrotestosterone, and estradiol were statistically significantly greater, and hemoglobin level higher, in the intervention group (P<0.001 for all measures.) However, there was little difference in measures of ejaculatory function between the control and intervention arms, and none of the outcomes of interest reached statistical significance.

It is interesting to note that both groups improved over the course of the study. This may be related to the measurement tools: outcome measurements were based on responses to validated survey instruments (other than ejaculatory volume), and were thus subjective.

Time of measurement is important in assessing for T deficiency, which is diagnosed based on levels drawn in the morning (when testosterone peaks) for men on a normal diurnal schedule. Paduch and colleagues collected testosterone samples between 7a and 11am (the time recommended in a 2014 publication by Paduch and other colleagues).4 Of note, others recommend that testosterone level be measured closer to 8a,5 or between 8a-10a.6 While some groups recommend measurement of free or bioavailable testosterone,7 others recommend use of total testosterone unless low sex hormone-binding globulin is suspected, such as in cases of obesity;6 this study excluded men with BMI >35.

Overall, the study suggests that testosterone replacement in deficient men may not lead to improvements in ejaculatory function in the way that it has been shown in other studies (though not in the study by Basaria et al) to improve libido and erectile function. It is possible that testosterone replacement alone is insufficient to improve ejaculatory function; perhaps this reflects the expected suppression of central gonadotropins by exogenous testosterone. It is also possible that a longer treatment period may be necessary to see improvements. It has been suggested that there are threshold levels of testosterone for different effects,8,9 and it would be of interest to identify whether there was a difference, in effect, in men with lower testosterone values (<200 vs <300 ng/dL at baseline, for example).

*Testosterone replacement refers to use in men with unequivocal testosterone deficiency (ie, at least two separate early morning testosterone levels below the reference range, in the presence of signs or symptoms of hypogonadism).

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4. Paduch DA, Brannigan RE, Fuchs EF, et al. The laboratory diagnosis of testosterone deficiency. Urology. 2014;83(5):980-988.

5. Brambilla DJ, Matsumoto AM, Araujo AB, et al. The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men. J Clin Endocrinol Metab. 2009;94(3):907-913.

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9. Ramasamy R, Wilken N, Scovell JM, et al. Hypogonadal symptoms are associated with different serum testosterone thresholds in middle-aged and elderly men. Urology. 2014;84(6):1378-1382.

Scovell JM, Ramasamy R, Wilken N, et al. Hypogonadal symptoms in young men are associated with a serum total testosterone threshold of 400 ng/dL. BJU Int. 2015;116(1):142-146.