Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism

J Urol. 2019 Nov;202(5):1029-1035. doi: 10.1097/JU.0000000000000396. Epub 2019 Oct 9.


Purpose: Clomiphene citrate may be used as an off label treatment of hypogonadism. There are few long-term data on clomiphene citrate efficacy and safety when administered for more than 3 years. We assessed improvements in testosterone and hypogonadal symptoms while on clomiphene citrate for extended periods.

Materials and methods: We performed a retrospective review to identify patients treated with clomiphene citrate for hypogonadism (baseline testosterone less than 300 ng/dl) at a total of 2 institutions from 2010 to 2018. We assessed the duration of clomiphene citrate therapy, serum testosterone levels, symptom improvement and clomiphene citrate side effects.

Results: A total of 400 patients underwent clomiphene citrate treatment for a mean ± SD of 25.5 ± 20.48 months (range 0 to 84). Of the patients 280 received clomiphene citrate for 3 years or less (mean 12.75 ± 9.52 months) and 120 received it for more than 3 years (mean 51.93 ± 10.52 months). Of men on clomiphene citrate for more than 3 years 88% achieved eugonadism, 77% reported improved symptoms and 8% reported side effects. Estradiol was significantly increased following clomiphene citrate treatment. Results did not significantly differ between patients treated for more than 3, or 3 or fewer years. The most common side effects reported by patients treated more than 3 years included changes in mood in 5, blurred vision in 3 and breast tenderness in 2. There was no significant adverse event in any patient treated with clomiphene citrate.

Conclusions: Clomiphene citrate is not typically offered as primary treatment of hypogonadism in men who do not desire fertility preservation. These data demonstrate that clomiphene citrate is safe and effective with few side effects when used as long-term treatment of hypogonadism.

Keywords: clomiphene; hormone replacement therapy; testes, hypogonadism; testosterone.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Biomarkers / blood
  • Clomiphene / administration & dosage*
  • Dose-Response Relationship, Drug
  • Estradiol / blood
  • Follow-Up Studies
  • Gonadotropins / blood
  • Humans
  • Hypogonadism / blood
  • Hypogonadism / drug therapy*
  • Male
  • Prolactin / blood
  • Retrospective Studies
  • Selective Estrogen Receptor Modulators / administration & dosage
  • Testosterone / blood
  • Time Factors
  • Treatment Outcome


  • Biomarkers
  • Gonadotropins
  • Selective Estrogen Receptor Modulators
  • Clomiphene
  • Testosterone
  • Estradiol
  • Prolactin