The safety and efficacy of clomiphene citrate in hypoandrogenic and subfertile men

Int J Impot Res. 2015 Nov-Dec;27(6):221-4. doi: 10.1038/ijir.2015.21. Epub 2015 Aug 20.


Our objective was to evaluate the safety and efficacy of clomiphene citrate (CC) in infertile and hypoandrogenic men through a retrospective study between September 2013 and May 2014. We identified 47 men between 18 and 55 years placed on 50 mg CC every other day. We evaluated the effect of CC on testosterone after 2 weeks, rates of adverse effects and predictors of CC response. Mean baseline testosterone, bioavailable testosterone and estradiol were 246.8 ng dl(-1), 125.5 ng dl(-1) and 20.8 pg dl(-1), respectively. At 2 weeks, mean testosterone, bioavailable testosterone and estradiol increased to 527.6 ng dl(-1), 281.8 ng dl(-1) and 32.0 pg dl(-1) (all P<0.001). Two patients at 2 weeks and one patient at 3 months had a paradoxical decrease in testosterone. Mean total motile count (TMC) and concentration increased from 59.7 million (s.e.m.: 16.5) and 50.7 millions ml(-1) (s.e.m.: 11.1) at baseline to 90.9 million (s.e.m.: 25.9) and 72.5 millions ml(-1) (s.e.m.: 17.5), respectively, at 3 months, although this was nonsignificant (P=0.09, 0.09). No patient on CC experienced a paradoxical decrease in TMC or sperm concentration. On age-adjusted regression analysis, age, BMI, longitudinal testis axis, baseline follicle-stimulating hormone, LH and estradiol did not correlate with improvement in bioavailable testosterone at 2 weeks. CC improves testosterone and may improve semen parameters, although a small percentage of men may not demonstrate improvement in testosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Body Mass Index
  • Clomiphene / adverse effects*
  • Clomiphene / therapeutic use*
  • Cross-Sectional Studies
  • Estradiol / blood
  • Follicle Stimulating Hormone / blood
  • Humans
  • Infertility, Male / drug therapy*
  • Luteinizing Hormone / blood
  • Male
  • Regression Analysis
  • Retrospective Studies
  • Sperm Count
  • Sperm Motility
  • Testosterone / blood*
  • Testosterone / deficiency*
  • Young Adult


  • Clomiphene
  • Testosterone
  • Estradiol
  • Luteinizing Hormone
  • Follicle Stimulating Hormone