Outcomes of clomiphene citrate treatment in young hypogonadal men

BJU Int. 2012 Aug;110(4):573-8. doi: 10.1111/j.1464-410X.2011.10702.x. Epub 2011 Nov 1.


Study Type - Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Hypogonadism is a prevalent problem, increasing in frequency as men age. It is most commonly treated by testosterone supplementation therapy but in younger patients this can lead to testicular atrophy with subsequent exogenous testosterone dependency and may impair spermatogenesis. Clomiphene citrate (CC) may be used as an alternative treatment in these patients with hypogonadism when maintenance of fertility is desired. This study shows that CC is a safe and efficacious drug to use as an alternative to exogenous testosterone. Not only have we validated previous findings of other papers but have proven our findings over a much longer period (mean duration of treatment 19 months). This prospective study is the largest to date assessing both the objective hormone response to CC therapy as well as the subjective response based on a validated questionnaire.

Objective: • To prospectively assess the andrological outcomes of long-term clomiphene citrate (CC) treatment in hypogonadal men.

Patients and methods: • We prospectively evaluated 86 men with hypogonadism (HG) as confirmed by two consecutive early morning testosterone measurements <300 ng/dL. • The cohort included all men with HG presenting to our clinic between 2002 and 2006 who, after an informed discussion, elected to have CC therapy. CC was commenced at 25 mg every other day and titrated to 50 mg every other day. The target testosterone level was 550 ± 50 ng/dL. • Testosterone (free and total), sex hormone binding globulin, oestradiol, luteinizing hormone and follicle stimulating hormone were measured at baseline and during treatment on all patients. Once the desired testosterone level was achieved, testosterone/gonadotropin levels were measured twice per year. • To assess subjective response to treatment, the androgen deficiency in aging males (ADAM) questionnaire was administered before treatment and during follow-up.

Results: • Patients' mean (standard deviation [sd]; range) age was 29 (3; 22-37) years. Infertility was the most common reason (64%) for seeking treatment. The mean (sd) duration of CC treatment was 19 (14) months. • At the last evaluation, 70% of men were using 25 mg CC every other day, and the remainder were using 50 mg every other day. • All mean testosterone and gonadotropin measurements significantly increased during treatment. • Subjectively, there was an improvement in all questions (except loss of height) on the ADAM questionnaire. More than half the patients had an improvement in at least three symptoms. • There were no major side effects recorded and the presence of a varicocele did not have an impact on the response to CC.

Conclusion: • Long-term follow-up of CC treatment for HG shows that it appears to be an effective and safe alternative to testosterone supplementation in men wishing to preserve their fertility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Clomiphene / therapeutic use*
  • Fertility Agents, Male / therapeutic use*
  • Gonadal Steroid Hormones / metabolism
  • Humans
  • Hypogonadism / blood
  • Hypogonadism / drug therapy*
  • Male
  • Prospective Studies
  • Surveys and Questionnaires
  • Treatment Outcome
  • Young Adult


  • Fertility Agents, Male
  • Gonadal Steroid Hormones
  • Clomiphene