Ceiling effect of clomiphene citrate on the testosterone to estradiol ratio in eugonadal infertile men

PLoS One. 2022 Jan 31;17(1):e0262924. doi: 10.1371/journal.pone.0262924. eCollection 2022.

Abstract

Introduction: The testosterone to estradiol ratio (T/E2 ratio) reportedly exerts a stronger effect on semen quality and sexual desire than does testosterone alone. Clomiphene citrate is a selective estrogen receptor modulator that has long been used as an empirical treatment option in the management of idiopathic oligozoospermia. Clomiphene may change the hypothalamus-pituitary-gonad axis and result in the alteration of the T/E2 ratio. No reliable data are available regarding the change in the T/E2 ratio after clomiphene use in eugonadism.

Methods: This study included 24 male patients who were diagnosed with idiopathic infertility with eugonadism. They all received clomiphene citrate (25 mg/day) as empirical treatment. Blood tests for serum testosterone, estradiol, prolactin, luteinizing hormone, and follicle stimulating hormone were performed before and after 4 weeks of clomiphene use. Paired t-tests were used to evaluate the significance of the hormone level change.

Results: Overall, the patients' T/E2 ratio did not increase significantly after clomiphene use. In the subgroup analysis, the T/E2 ratio of patients with a baseline ratio of <200 increased significantly after clomiphene use.

Conclusions: Clomiphene citrate may significantly increase the T/E2 ratio in eugonadal men under the premise of its ceiling effect (T/E2 ratio < 200), providing practitioners with guidance on the use of clomiphene in this demographic.

MeSH terms

  • Adult
  • Clomiphene / administration & dosage*
  • Estradiol / blood*
  • Humans
  • Hypogonadism* / blood
  • Hypogonadism* / drug therapy
  • Infertility, Male* / blood
  • Infertility, Male* / drug therapy
  • Male
  • Middle Aged
  • Retrospective Studies
  • Testosterone / blood*

Substances

  • Clomiphene
  • Testosterone
  • Estradiol

Grants and funding

The authors received no specific funding for this work.