Clomiphene Citrate

Also known as: clomiphene, clomifene, Clomid (branded), SERM

Hormone Restoration

In plain English

Clomiphene is a pill that nudges the brain to signal the body to make more of its own testosterone (in men) or to trigger ovulation (in women). In men it is used off-label as an alternative to testosterone that preserves fertility. In women it is FDA-approved to help with ovulation. It is taken by mouth.

The science

Clomiphene citrate is a mixture of two isomers (enclomiphene and zuclomiphene) that act as selective estrogen receptor modulators; by blocking estrogen negative feedback at the hypothalamus/pituitary it increases GnRH-driven LH and FSH, stimulating endogenous testosterone production in men and follicular development in women. It is FDA-approved for ovulation induction in women. In men, off-label use is supported by a systematic review/meta-analysis (Huijben 2022) showing meaningful increases in total/free testosterone, LH, and FSH with few adverse events, while preserving spermatogenesis—an advantage over exogenous testosterone for men desiring fertility. Adverse effects include mood changes and visual disturbances; the zuclomiphene isomer has a long half-life and estrogenic activity that may limit some men. Compounded clomiphene capsules for male hypogonadism are off-label.

References

• Huijben et al., Andrology 2022 (clomiphene in hypogonadal men, meta-analysis)
• Legro et al., N Engl J Med 2014 (clomiphene comparator in ovulation induction)