Clomifene

Clomifene is a prescription tablet that blocks oestrogen signals in the brain. It is approved to help women who do not ovulate regularly to become pregnant, and is not approved for use in men.

What it is

Clomifene (also spelled clomiphene) is a tablet medicine from the group called selective oestrogen receptor modulators (SERMs). It is used to treat infertility caused by problems with ovulation ^{[1, 2]}. In the US it has been sold as Clomid, and generic versions are licensed in the UK and EU ^{[1, 2, 3]}. It is a prescription-only medicine and is used under the supervision of a fertility specialist.

How it works

Clomifene competes with oestrogen for binding sites in the hypothalamus, pituitary gland and ovary ^[1]. Because the brain senses less oestrogen, the pituitary releases more of the gonadotropin hormones LH and FSH. In women this can start the growth of an egg follicle and lead to ovulation ^[1]. In men, the same rise in LH and FSH increases testosterone made by the testes ^{[5, 6]}. Clomifene is a mix of two forms. One form (zuclomifene) has a longer half-life, and it can still be detected in the blood more than a month after treatment ^[1].

Approved medical uses

• Women with ovulation problems who want to become pregnant, including those with polycystic ovary syndrome. This is the approved use in the US, UK and EU ^{[1, 2, 3]}.
• Not approved for men. The US label states there are no adequate or well-controlled studies showing that clomifene is effective for male infertility ^[1]. Any use in men is off-label.

What the research shows

• Testosterone levels in men. A 2022 systematic review of 19 studies (4 randomised trials and 15 observational studies, about 1,600 men) found that clomifene raised total testosterone, free testosterone, LH, FSH and oestradiol in men with low testosterone. Symptom scores also improved. Most of the evidence came from observational studies ^[5].
• Randomised trials. A 2025 meta-analysis of 10 randomised trials with 819 men compared clomifene or the related drug enclomifene with placebo, testosterone gel or hCG. These drugs raised testosterone compared with placebo, with no meaningful difference compared with testosterone gel, and sperm counts were better preserved than with testosterone gel ^[6]. The authors rated the evidence as moderate and noted that trials lasted only 2 to 30 weeks and were too small to judge safety well ^[6].
• Guideline position. The American Urological Association (AUA) says clinicians may use selective oestrogen receptor modulators, aromatase inhibitors or hCG, alone or together, in men with testosterone deficiency who want to keep their fertility. This is a conditional recommendation based on lower-quality evidence ^[4].
• Other hormone effects. In a small retrospective study of 20 men treated with clomifene for low testosterone, IGF-1 (a marker of growth hormone activity) fell in 15 of them, and in two it dropped well below the normal range for their age ^[7]. The authors suggested checking IGF-1 during treatment ^[7].

Known risks and side effects

• Visual symptoms such as blurring, spots or flashes. These can occasionally be prolonged or permanent, and may make driving unsafe ^{[1, 2]}.
• Ovarian hyperstimulation syndrome in women, which can progress quickly and has rarely been fatal ^[1].
• Multiple pregnancy, which occurred in about 8% of pregnancies in clinical trials ^[1].
• Ovarian tumours: prolonged use may increase the risk of borderline or invasive ovarian tumours, so the recommended length of treatment should not be exceeded ^{[1, 2]}.
• Common effects in women include ovarian enlargement (about 14%), hot flushes (about 10%), abdominal discomfort or bloating, nausea and headache ^[1].
• In men: testicular tumours and gynaecomastia (breast tissue growth) have been reported in males taking clomifene ^[1]. In studies of men with low testosterone, side effects were reported by fewer than 10% of participants, but long-term safety data are limited ^{[5, 6]}.
• Not to be used in pregnancy or in people with liver disease, some hormone-dependent tumours or unexplained uterine bleeding ^{[1, 2]}.
• Sport: clomifene is prohibited at all times under the World Anti-Doping Agency (WADA) Prohibited List ^[8].

Blood tests commonly monitored

• Testosterone, LH, FSH and oestradiol: these were the main hormone measures in studies of men treated with clomifene ^{[5, 6]}.
• Semen analysis: used in studies of men who want to keep their fertility, as sperm production is an outcome of interest ^[6].
• IGF-1: suggested by one small study, given the falls seen in some men ^[7].
• Liver function: clomifene should not be used in people with liver disease, so liver status is relevant before treatment ^{[1, 2]}.

Sources

1. US Food and Drug Administration. Clomid (clomiphene citrate tablets USP) label. FDA, 2012. accessdata.fda.gov
2. Wockhardt UK Ltd. Clomifene tablets: Summary of Product Characteristics. Electronic Medicines Compendium, 2024. medicines.org.uk
3. Centrafarm B.V. Clomifeencitraat CF tablets: Summary of Product Characteristics. Dutch Medicines Evaluation Board database (Geneesmiddeleninformatiebank). geneesmiddeleninformatiebank.nl
4. American Urological Association (Mulhall, et al.). Evaluation and Management of Testosterone Deficiency: AUA Guideline. Journal of Urology and auanet.org, 2018 (validity confirmed 2024). auanet.org
5. Huijben, Lock, de Kemp, de Kort, van Breda. Clomiphene citrate for men with hypogonadism: a systematic review and meta-analysis. Andrology, 2022. PubMed
6. Hohl, et al. Clomiphene or enclomiphene citrate for the treatment of male hypogonadism: a systematic review and meta-analysis of randomized controlled trials. Archives of Endocrinology and Metabolism, 2025. SciELO
7. Mogar N, Zhang D, Heaney AP. Reduced IGF-1 levels following clomiphene treatment for male hypogonadism. Journal of the Endocrine Society, 2025. academic.oup.com
8. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA, 2025. Prohibited List 2026 (PDF copy hosted by CONMEBOL)

Related

Last reviewed 7 October 2026. General information, not medical advice. Found a mistake? Email [email protected].