Peptide & Experimental
Clomiphene
Selective estrogen receptor modulator (SERM), prescription-only · clomiphene citrate, Clomifen, Clomid, Clomifen-ratiopharm
Clomiphene has been approved for decades to induce ovulation in women who do not ovulate. In men with low testosterone, it is used off-label because it stimulates the body’s own production instead of replacing it. The laboratory effect is well supported, the benefit for symptoms hardly at all. And clomiphene is not the same as enclomiphene: it additionally contains zuclomiphene, which accumulates in the body.
What clomiphene is and how it works
Clomiphene is a selective estrogen receptor modulator, SERM for short, and prescription-only. In Germany it is approved for inducing ovulation in women with infertility due to absent ovulation.
It blocks estrogen receptors in the hypothalamus. The brain registers what appears to be too little estrogen and releases more GnRH, LH and FSH. In women, this causes a follicle to mature; in men, the testes produce more of their own testosterone – unlike testosterone therapy, which slows the body’s own production.
Distinction from enclomiphene. According to the prescribing information, clomiphene consists of 62 percent enclomiphene, the anti-estrogenic trans isomer, and 38 percent zuclomiphene, the cis isomer. The two forms remain in the body for different lengths of time, and the ratio shifts over time: in 15 men on long-term clomiphene therapy, zuclomiphene in the blood was a median of 20 times higher than enclomiphene (Helo 2017). The authors conclude that a pure agent without zuclomiphene is needed – that is enclomiphene. Its data therefore do not automatically apply to clomiphene, and vice versa. Enclomiphene is not approved anywhere; clomiphene has been approved in Germany for decades, but only for women.
What is well supported
- Ovulation and live births. Clomiphene is the classic tablet for inducing ovulation. In a double-blind trial with 750 women with PCOS, 19.1 percent had a live birth on clomiphene; letrozole did better at 27.5 percent.
- More testosterone in men. Across the randomized trials, total testosterone on clomiphene or enclomiphene rose by 274 ng/dl compared with placebo, and LH and FSH rose along with it.
- The body’s own axis stays active. Unlike with testosterone gel, LH and FSH rise. In unexplained male infertility, the pregnancy rate on clomiphene or tamoxifen was higher than in the control groups in a meta-analysis of 11 randomized trials.
What the studies show
Legro 2014: clomiphene versus letrozole in PCOS
750 women with polycystic ovary syndrome received up to five treatment cycles of clomiphene or letrozole, double-blind. Live births occurred in 72 of 376 women on clomiphene (19.1 percent) and in 103 of 374 on letrozole (27.5 percent), rate ratio 1.44. Ovulation was achieved in 48.3 versus 61.7 percent of cycles. Twin pregnancies: 7.4 percent on clomiphene, 3.4 percent on letrozole, a non-significant difference. Clomiphene caused hot flashes more often.
Hohl 2025: review, men with hypogonadism
The meta-analysis of randomized trials on clomiphene and enclomiphene in men with functional hypogonadism found total testosterone 274 ng/dl higher than with placebo (95 percent confidence interval 192 to 356), plus higher LH and FSH levels. Compared with testosterone gel, the testosterone level did not differ. The primary outcomes were laboratory values, that is, surrogate markers; heterogeneity was high. Clomiphene and enclomiphene are analyzed together.
Chua 2013: unexplained male infertility
11 randomized trials on clomiphene or tamoxifen in men with reduced sperm quality without an identifiable cause. The pregnancy rate was higher than in the control groups (odds ratio 2.42; 95 percent confidence interval 1.47 to 3.94); sperm concentration and motility rose, as did FSH and testosterone. There was no significant difference in side effects.
Krzastek 2019: long-term use in 400 men
Retrospective analysis of 400 men with low testosterone, treated with clomiphene for a mean of 25.5 months. Of the 120 men treated for more than three years, 88 percent reached normal testosterone levels, 77 percent reported fewer symptoms, 8 percent side effects. Estradiol rose markedly. There was no control group; a similar analysis of 54 men over one year found a trend toward fewer symptoms on the Aging Males’ Symptoms questionnaire, but no significant improvement in sexual function (Anno 2026).
Where the data stop
- Symptoms instead of laboratory values. That the testosterone level rises is established. Whether energy, libido or muscle mass improve has so far been shown mainly by retrospective analyses without a control group.
- Long-term safety in men. Controlled trials run for weeks to months. For several years there are only analyses from clinical practice, and the effect of the accumulating zuclomiphene is unknown.
- Use after anabolic steroids. There is no controlled trial on restarting the hormone axis after anabolic steroid use.
- Origin of the product. The data apply to the tested medicine, not to products from the gray market.
Status, approval and legal
Clomiphene is approved and prescription-only in Germany, for example as Clomifen-ratiopharm 50 mg (approved on 1990-09-27), for inducing ovulation in women with infertility due to absent ovulation. According to the prescribing information, the approved dose in the first treatment cycle is 50 mg daily for 5 days; no more than 6 treatment cycles should be carried out. There is no approval for men; use for low testosterone or male infertility is off-label use.
The WADA Prohibited List 2026 lists clomiphene under S4.2, the anti-estrogenic substances, prohibited in and out of competition and for all athletes. In the annex of the German Anti-Doping Act, it is listed among the anti-estrogenic substances.
Safety
The best-known side effect concerns the eyes: flickering, blurred vision, seeing spots and prolonged afterimages, often intensified in bright light. According to the prescribing information, they increase with the total dose and usually disappear within days to weeks after stopping; isolated cases with scotomas and a lens opacity have also been described. Anyone who had visual disturbances during previous clomiphene treatment must not receive it again.
In women, there is also ovarian hyperstimulation, in severe cases with an increased risk of thrombosis, and multiple pregnancies: 186 of 2,369 pregnancies according to the prescribing information, that is, 7.9 percent. In men, estradiol rose markedly in the largest long-term analysis; mood changes, blurred vision and breast tenderness were reported. Clomiphene belongs in a physician’s hands, and low testosterone should be investigated beforehand.
BK-Score Supported, with caveats
| Human evidence | 7 | |
|---|---|---|
| Mechanism | 8 | |
| Safety data | 6 | |
| Hype gap | 5 | |
| Track record of use | 9 |
Evidence 7, because the approved use has been tested in large randomized trials – in a double-blind trial with 750 women with PCOS, 19.1 percent had a live birth on clomiphene (Legro 2014) – and a review of randomized trials in men shows a testosterone increase of 274 ng/dl compared with placebo (Hohl 2025), though only in laboratory values. Mechanism 8, because the blockade of estrogen feedback has been measured in humans, but the role of the accumulating zuclomiphene in men remains open (Helo 2017). Safety 6, because the side effects in women have been documented in the prescribing information over decades, but for long-term use in men there are only retrospective analyses without a control group, the largest with 400 men (Krzastek 2019). Hype 5, because the testosterone increase is real, but presenting it as an equivalent alternative to testosterone therapy goes beyond the data: whether symptoms improve has hardly been tested in controlled trials. Use 9, because clomiphene has been approved in Germany for decades (Clomifen-ratiopharm since 1990) and is widely used in fertility treatment. Direction mixed: proven benefit in the approved indication, proven laboratory effect in men, open clinical benefit and thin long-term safety data for men.
The score rates the state of knowledge, not the substance. “Safety data 9” means well studied – not harmless. “Track record of use 9” means used long and widely – that is not proof of efficacy.
Subjective assessment by Biohacking Kompakt based on published scoring rules – not a scientific rating and not a medical recommendation. Rules and all ratings (German)
Frequently asked questions about Clomiphene
What is clomiphene approved for?
In Germany, for inducing ovulation in women whose infertility is due to absent ovulation. According to the prescribing information, treatment in the first cycle starts with 50 mg daily for 5 days; no more than 6 treatment cycles should be carried out. There is no approval for men.
What is the difference between clomiphene and enclomiphene?
Clomiphene is a mixture of two mirror-image forms, according to the prescribing information 62 percent enclomiphene and 38 percent zuclomiphene. Zuclomiphene stays in the body longer: in men on long-term therapy, its blood level was a median of 20 times higher than that of enclomiphene. Enclomiphene is the pure anti-estrogenic form; it is not approved as a medicine anywhere, whereas clomiphene is, though for women.
Does clomiphene raise testosterone in men?
Yes. A review of randomized trials on clomiphene and enclomiphene found total testosterone 274 ng/dl higher than with placebo, plus higher LH and FSH levels. There was no difference in testosterone level compared with testosterone gel. Whether men feel better as a result has hardly been measured in randomized trials.
What side effects does clomiphene have?
Typical are visual disturbances such as flickering, blurred vision and seeing spots, which according to the prescribing information increase with the total dose and usually disappear after stopping. In women, ovarian hyperstimulation and multiple pregnancies are added. In men, estradiol rose in a long-term analysis; mood changes, blurred vision and breast tenderness were reported.
Is clomiphene banned in sport?
Yes. The WADA Prohibited List 2026 lists clomiphene under S4.2 among the anti-estrogenic substances, prohibited in and out of competition. It is also named explicitly in the annex of the German Anti-Doping Act.
Related
- Related topicEnclomiphene
- Related topicTamoxifen
- Related topicLetrozole
- Related topicAnastrozole
- Related topicExemestane
- Related topicRaloxifene
Sources
- Prescribing information Clomifen-ratiopharm 50 mg tablets (as of August 2016)
- Legro RS et al., N Engl J Med 2014 – letrozole versus clomiphene for infertility due to PCOS, double-blind, 750 women
- Hohl A et al., Arch Endocrinol Metab 2025 – meta-analysis of randomized trials on clomiphene and enclomiphene in male hypogonadism
- Chua ME et al., Andrology 2013 – meta-analysis on clomiphene or tamoxifen in unexplained male infertility, 11 randomized trials
- Krzastek SC et al., J Urol 2019 – long-term use of clomiphene in hypogonadism, retrospective, 400 men
- Helo S et al., BJU Int 2017 – enclomiphene and zuclomiphene levels in men on long-term clomiphene therapy, 15 men
- Anno Y et al., Int J Urol 2026 – clomiphene in late-onset hypogonadism, symptom questionnaire over one year, retrospective, 54 men
- WADA Prohibited List 2026, S4.2 anti-estrogenic substances – official publication in the German Federal Law Gazette II 2025 No. 312
- German Anti-Doping Act, annex – III. Hormone and metabolic modulators, 2. Anti-estrogenic substances
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Information only, not medical advice and not a usage or dosage recommendation. Prescription-only and unapproved substances belong in the hands of a physician. Last updated: 2026-10-05.