Clomiphene is approved for ovulation induction in women. In men it is used off-label to raise testosterone while keeping the testes working, mainly for men who want to keep fertility. The male evidence is case series and small trials, not large randomized studies against placebo.
Why it is used in men
Clomiphene blocks estrogen's feedback to the pituitary. The pituitary then sends more LH and FSH, and the testes make more testosterone and sperm. Because the testes keep working, it is used when fertility matters.
Long-term case series
Katz and colleagues followed young men with hypogonadism, average age 29, of whom 64% sought treatment for infertility. Mean duration of treatment was 19 months. The authors called clomiphene a safe and effective alternative to testosterone for men who want to keep fertility. It is a case series with no control group (BJU Int 2012).
Krzastek and colleagues reported 400 men treated for a mean of 25.5 months (range 0 to 84). No significant adverse event was recorded, and the results did not differ between men treated for more or less than three years (J Urol 2019).
Testosterone and bone
Moskovic and colleagues treated 46 men with a mean baseline testosterone of 228 ng/dL. Testosterone was 612 ng/dL at one year, 562 at two years and 582 at three years. Bone density improved, the ADAM symptom score fell from 7 to 3 at one year, and no adverse event was reported (BJU Int 2012).
Against anastrozole
Helo and colleagues randomized hypogonadal infertile men to clomiphene or anastrozole. Testosterone rose by 571 ng/dL with clomiphene and 408 ng/dL with anastrozole. Estradiol rose on clomiphene and fell on anastrozole. Semen parameters and patient-reported outcomes did not differ significantly (J Sex Med 2015).
What this does not say
- Most male data are case series and small trials. A 2013 review of nine clomiphene studies in male infertility found only one with a significant gain in pregnancy rate, while most showed higher sperm concentrations (Willets et al., Reprod Sci 2013).
- Clomiphene is off-label in men. Visual and mood changes are reported side effects, and men with eye disease should be assessed first.
- Long-term outcomes beyond several years depend on monitoring that is not standardized.
How we use this
For men who want to keep fertility, clomiphene is one option that we weigh against hCG, enclomiphene and testosterone. We measure testosterone, LH, FSH and estradiol during treatment, and we review vision and mood.
We do not present the case series as proof of fertility benefit. The evidence is strongest for raising testosterone, and it is weaker for pregnancy outcomes.
Explore weight loss treatmentsSources
- 1.Katz DJ et al. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU Int 2012. BJU International
- 2.Moskovic DJ et al. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int 2012. BJU International
- 3.Krzastek SC et al. Long-term safety and efficacy of clomiphene citrate for the treatment of hypogonadism. J Urol 2019. The Journal of Urology
- 4.Helo S et al. A randomized prospective double-blind comparison trial of clomiphene citrate and anastrozole in raising testosterone in hypogonadal infertile men. J Sex Med 2015. Journal of Sexual Medicine
- 5.Willets AE et al. Clomiphene for the treatment of male infertility. Reprod Sci 2013. Reproductive Sciences