Clomiphene citrate, sold as Clomid and as generics, is an oral fertility drug. It is a selective estrogen receptor modulator (SERM): a non-steroidal compound that blocks estrogen receptors in some tissues and activates them in others. The FDA first approved it in 1967 (Drugs@FDA), and its only labeled use is to induce ovulation in women who want to become pregnant.
In men, clinicians use it off-label to raise testosterone without shutting down sperm production, and anabolic steroid users take it as “post-cycle therapy” (PCT). The single most important fact for that audience: the label states there are no adequate or well-controlled studies showing that clomiphene treats male infertility, and we found no randomized trial of it for recovery after steroid use.
This page summarizes what the FDA label, clinical trials and observational studies report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Non-steroidal selective estrogen receptor modulator (SERM) |
| Brands / approval | Clomid, NDA 016131, approved February 1, 1967 (that NDA is now discontinued); Clomid (Cosette, ANDA 075528), Milophene and generics |
| Route and strength | Oral tablet, 50 mg clomiphene citrate |
| Labeled dose | 50 mg/day for 5 days; 100 mg/day for 5 days if no ovulation; no more than about 6 cycles |
| Composition | Mixture of two isomers: zuclomiphene (cis, 30–50%) and enclomiphene (trans) |
| Half-life | No single value on the label; zuclomiphene stays detectable in blood for over a month after one dose; reviews cite ≈5 days |
| Use in men | Off-label (hypogonadism, male infertility, post-steroid recovery) |
| US status | Prescription-only (Rx) |
| WADA status | Prohibited at all times (class S4.2, anti-estrogenic substances) |
What it is
Clomiphene is a triphenylethylene, the same chemical family as tamoxifen (Nolvadex). The free base has the formula C₂₆H₂₈ClNO and a molecular weight of 406.0 g/mol (PubChem). The tablet contains the citrate salt, molecular weight 598.1 g/mol, so a 50 mg tablet holds about 34 mg of clomiphene base (FDA label).
It is not a single molecule. The label describes it as a mixture of two geometric isomers:
| Isomer | Share of the tablet | What the label and studies report |
|---|---|---|
| Zuclomiphene (cis) | 30–50% | Longer half-life; detectable for over a month after one dose; some data suggest it has more estrogen-like activity |
| Enclomiphene (trans) | Remainder (50–70%) | Cleared much faster; also studied on its own as a drug for men (see enclomiphene) |
How it works
Estrogen normally acts on the hypothalamus and pituitary to hold back the release of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone). Clomiphene competes with estrogen for its receptors in these areas. The brain reads this as low estrogen and raises LH and FSH output (FDA label).
- In women, higher FSH drives a follicle to mature, which leads to ovulation.
- In men, higher LH tells the testes to make more testosterone, and higher FSH supports sperm production. Unlike testosterone therapy, this does not suppress the body’s own hormone axis (Wu & Sung, Pharmaceuticals 2024).
The label states clomiphene has no apparent progestational, androgenic or anti-androgenic effects. In men, any rise in testosterone therefore comes from the testes being stimulated to make more.
Pharmacokinetics
The label reports that clomiphene is well absorbed by mouth and excreted mainly in the feces. In early studies with radio-labeled drug, about 50% of an oral dose was recovered in urine and feces within 5 days, and some label was still in the feces 6 weeks later. The label suggests that zuclomiphene may be recycled through the liver and gut or stored in tissue.
A single-dose study in 24 healthy women (50 mg) found that the zuclomiphene isomer peaked later and was eliminated much more slowly than enclomiphene, with measurable levels up to 1 month later (Mikkelson et al., Fertil Steril 1986). A second study in 9 women with polycystic ovary syndrome (PCOS) reported these values after one 50 mg dose (Ghobadi et al., J Clin Pharmacol 2009):
| Parameter | Zuclomiphene | Enclomiphene |
|---|---|---|
| Peak level (Cmax) | 15 ng/mL | 15 ng/mL |
| Time to peak | 7 h | 3 h |
| Total exposure (AUC) | 1289 ng·h/mL (over 456 h) | 65 ng·h/mL (over 72 h) |
The authors could not calculate a conventional half-life because the terminal phase was so flat and long-tailed. Reviews often quote a half-life of about 5 days (Wu & Sung, Pharmaceuticals 2024), but that number hides the large difference between the two isomers.
Zuclomiphene builds up in men
Because zuclomiphene clears so slowly, it accumulates with daily dosing. In 15 hypogonadal men taking 25 mg/day for at least 6 weeks, median blood levels were 44.0 ng/mL zuclomiphene vs 2.2 ng/mL enclomiphene, a ratio of about 20:1 (Helo et al., BJU Int 2017).
In an anti-doping study, 12 healthy men took 50 mg/day for 30 days. Urine was collected up to day 261, and the window in which zuclomiphene could still be detected ranged from 121 to more than 261 days (Miller et al., JCEM 2019).
Approved medical use
The label approves clomiphene for ovulatory dysfunction in women desiring pregnancy, after other causes of infertility have been excluded or treated. The women most likely to respond include those with PCOS and some forms of amenorrhea (absent periods).
| Step | Labeled regimen |
|---|---|
| First course | 50 mg once daily for 5 days |
| If no ovulation | 100 mg once daily for 5 days, starting as early as 30 days after the previous course |
| Maximum | Increasing the dose or duration beyond 100 mg/day for 5 days is not recommended |
| Total duration | Stop and re-evaluate after 3 courses without ovulation; long-term therapy not recommended beyond about 6 cycles |
Ovulation usually follows 5–10 days after a course. In the clinical trials behind the label, about 30% of 7,578 treated women became pregnant, and 7.98% of reported pregnancies were multiple (6.9% twins).
The label also includes a direct statement about men: “There are no adequate or well-controlled studies that demonstrate the effectiveness of clomiphene citrate in the treatment of male infertility.”
What the research shows
Ovulation induction in PCOS
When this trial was run, clomiphene was the first-line infertility drug in PCOS. The double-blind trial randomized 750 women with PCOS to letrozole or clomiphene for up to five cycles (Legro et al., NEJM 2014):
| Outcome | Clomiphene | Letrozole |
|---|---|---|
| Cumulative live birth | 19.1% | 27.5% (rate ratio 1.44, 95% CI 1.10–1.87) |
| Ovulation per treatment cycle | 48.3% | 61.7% |
| Twin pregnancy | 7.4% | 3.4% (not significant) |
| Pregnancy loss | 29.1% | 31.8% (not significant) |
Hot flushes were more common with clomiphene; fatigue and dizziness were more common with letrozole.
Low testosterone in men (off-label)
Most data in men come from small trials and retrospective clinic reviews. They consistently show that clomiphene raises LH, FSH and testosterone in men whose testes still work. Doses in the randomized trials ranged from 50 mg three times a week to 25–50 mg daily (Hohl et al., Arch Endocrinol Metab 2025).
| Study | Design and n | Main finding |
|---|---|---|
| Huijben et al., Andrology 2022 | Meta-analysis of 19 studies (4 RCTs, 15 observational), 1,642 men | Testosterone, free testosterone, LH, FSH, SHBG (sex hormone-binding globulin) and estradiol all rose; side effects in under 10%; no serious adverse events reported |
| Hohl et al., Arch Endocrinol Metab 2025 | Meta-analysis of 10 RCTs, 819 men (clomiphene or enclomiphene) | vs placebo: testosterone +274 ng/dL (95% CI 192–356), LH +4.7 IU/L, FSH +4.6 IU/L; testosterone not different from testosterone gel |
| Constantinou et al., Eur J Clin Pharmacol 2026 | Meta-analysis of 11 studies, 1,512 men, clomiphene vs testosterone therapy | No overall difference in testosterone vs testosterone gel; one injectable-testosterone study reached higher levels; libido scores were lower with clomiphene |
| Moskovic et al., BJU Int 2012 | Retrospective, 46 men treated for over 12 months | Testosterone 228 ng/dL at baseline; 612 ng/dL at 1 year, 582 ng/dL at 3 years |
| Krzastek et al., J Urol 2019 | Retrospective, 400 men (120 treated for over 3 years) | In the over-3-year group, 88% reached normal testosterone, 77% reported better symptoms, 8% reported side effects |
The meta-analyses note high heterogeneity, short follow-up (2–30 weeks in the RCT analysis) and a large share of observational data. They show clomiphene raises hormone levels; they do not show long-term outcomes such as fractures, heart events or muscle function.
Male infertility
The evidence is mixed. A 1988 placebo-controlled trial randomized 23 men with low sperm counts to clomiphene 25 mg/day or placebo for 12 months. Hormones rose on clomiphene, but semen quality did not change and pregnancy rates were 9.1% vs 44.4% (not significant). The authors concluded clomiphene was not useful for male infertility (Sokol et al., Fertil Steril 1988).
A later meta-analysis pooled 11 RCTs of clomiphene or tamoxifen in men with unexplained infertility (Chua et al., Andrology 2013):
- pregnancy rate: OR 2.42 (95% CI 1.47–3.94) vs control;
- sperm concentration and motility: modest increases;
- adverse events: no significant difference vs control.
Because the two drugs were pooled, this does not isolate clomiphene’s own effect.
Recovery after anabolic steroid use (PCT)
This is the use most relevant to steroid users, and it has the weakest evidence.
- A 2014 review set out to be a meta-analysis of treatment for anabolic steroid-induced hypogonadism, but no quality studies met the inclusion criteria (Rahnema et al., Fertil Steril 2014).
- The best available data are retrospective. A two-center cohort followed 79 men who had used steroids for 6 months or less and had normal hormones and semen before use (İbis et al., BJU Int 2026). Men chose no treatment, clomiphene 25 mg/day, or clomiphene plus hCG.
| Group | Normal semen analysis at 12 months |
|---|---|
| No treatment | 58.6% |
| Clomiphene alone | 69.2% |
| Clomiphene + hCG | 87.5% |
Both treated groups normalized hormones faster, but hormones had normalized in all three groups by month 6, including the untreated men. Treatment was not randomized, so the groups may have differed in other ways.
About “Clomid restores your natural testosterone after a cycle.” Clomiphene does raise LH and testosterone in men whose hormone axis can respond. But we found no randomized trial of it after steroid use, and in the one comparative cohort, untreated men also recovered hormonally within 6 months. Whether it changes long-term outcomes, or helps after longer or heavier steroid use, is unknown.
Testosterone in healthy men
In 12 healthy recreational athletes, 50 mg/day for 30 days raised mean testosterone by 146%, LH by 177% and FSH by 170% over baseline (Miller et al., JCEM 2019). This open-label, single-arm study was designed for anti-doping detection; it did not measure muscle or performance.
Side effects and risks
Rates from the label (women)
The label reports these adverse events in over 1% of 8,029 women in clinical studies:
| Adverse event | Rate |
|---|---|
| Ovarian enlargement | 13.6% |
| Hot flushes | 10.4% |
| Abdominal or pelvic discomfort, bloating | 5.5% |
| Nausea and vomiting | 2.2% |
| Breast discomfort | 2.1% |
| Visual symptoms | 1.5% |
| Headache | 1.3% |
| Abnormal uterine bleeding | 1.3% |
Visual disturbances
The label warns of blurred vision, spots or flashes (scintillating scotomata) and prolonged after-images. These rise with total dose and duration. They are usually reversible, but prolonged cases have been reported, and the label says they may be irreversible, especially at higher doses or longer use. Anyone with visual symptoms should stop the drug and have a full eye exam. In men treated for over 3 years in the Krzastek series, 3 of 120 reported blurred vision.
Estradiol and gynecomastia in men
Because clomiphene raises LH, the testes make more testosterone, and more of it is converted to estradiol. In the Helo study, median estradiol doubled from 17.0 to 34.0 pg/mL (Helo et al., BJU Int 2017), and estradiol rose significantly in the Krzastek series. The label notes that gynecomastia and testicular tumors have been reported in males using clomiphene; whether the drug caused the tumors is not known.
Clomiphene is often listed as an anti-gynecomastia drug in steroid-using circles. We found no controlled trials of clomiphene for that purpose, and the label lists gynecomastia as a reported effect in men.
Mood
Mood changes were the most common side effect (5 of 120 men) in men treated for over 3 years (Krzastek et al., J Urol 2019). The label lists anxiety, irritability, mood changes and psychosis among post-marketing reports.
Red blood cells
Testosterone therapy commonly raises hematocrit (the share of blood made up of red cells). In a retrospective comparison of 188 men on clomiphene and 175 on testosterone, polycythemia occurred in 1.7% vs 11.2% (p = 0.0003) (Wheeler et al., J Urol 2017). The men on testosterone were older and treated longer, though the difference held after adjustment for age.
Other label warnings
- Ovarian hyperstimulation syndrome (OHSS) in women, which can become serious within 24 hours to several days.
- Hypertriglyceridemia, sometimes with pancreatitis, more likely with pre-existing lipid problems or higher doses or longer use.
- Ovarian tumors: prolonged use may increase the risk of borderline or invasive ovarian tumors.
- Multiple pregnancy: 7.98% of pregnancies in the label’s trials.
Who should not use it
The label lists these contraindications:
- pregnancy;
- liver disease or a history of liver dysfunction;
- abnormal uterine bleeding of unknown cause;
- ovarian cysts or enlargement not due to PCOS;
- uncontrolled thyroid or adrenal disease;
- an organic intracranial lesion such as a pituitary tumor.
The label reports no documented drug interactions.
Legal status and use in sport
In the US, clomiphene is a prescription-only drug. Its use in men is off-label.
Under the WADA 2026 Prohibited List, clomifene is listed in class S4.2, anti-estrogenic substances, which is prohibited at all times, in and out of competition, for all athletes (NADA official translation of the WADA 2026 list). Its long urinary detection window, 4 months or more after a 30-day course, makes it easy to detect.
Key takeaways
- A fertility drug for women. Clomiphene’s only FDA-approved use is ovulation induction, at 50–100 mg/day for 5-day courses, for about 6 cycles at most.
- Raises testosterone indirectly. By blocking estrogen feedback in the brain, it raises LH, FSH and testosterone in men whose testes work, without suppressing sperm production the way testosterone does.
- Two isomers, very different kinetics. Zuclomiphene lingers for weeks, builds up about 20-fold over enclomiphene with daily use, and is detectable in urine for months.
- PCT evidence is thin. We found no randomized trial of clomiphene after steroid use; in the only comparative cohort, untreated men also recovered hormonally by 6 months.
- Watch vision, mood and estradiol. Visual disturbances can be prolonged or permanent, mood changes are the most common complaint in long-term male use, and estradiol rises.
- Banned in sport at all times. WADA lists it under S4.2 anti-estrogenic substances.
Sources
- Cosette Pharmaceuticals. Clomid (clomiphene citrate) tablets, USP, prescribing information, revised 08/2023. DailyMed.
- Food and Drug Administration. Drugs@FDA: Clomid, NDA 016131 (Sanofi Aventis), original approval February 1, 1967. FDA.
- National Center for Biotechnology Information. Clomiphene, PubChem CID 2800. PubChem.
- Mikkelson TJ, Kroboth PD, Cameron WJ, et al. Single-dose pharmacokinetics of clomiphene citrate in normal volunteers. Fertil Steril. 1986;46(3):392–396. PubMed.
- Ghobadi C, Mirhosseini N, Shiran MR, et al. Single-dose pharmacokinetic study of clomiphene citrate isomers in anovular patients with polycystic ovary disease. J Clin Pharmacol. 2009;49(2):147–154. PubMed.
- Helo S, Mahon J, Ellen J, et al. Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long-term clomiphene citrate treatment. BJU Int. 2017;119(1):171–176. PubMed.
- Wu YC, Sung WW. Clomiphene citrate treatment as an alternative therapeutic approach for male hypogonadism: mechanisms and clinical implications. Pharmaceuticals (Basel). 2024;17(9):1233. PubMed.
- Miller GD, Moore C, Nair V, et al. Hypothalamic-pituitary-testicular axis effects and urinary detection following clomiphene administration in males. J Clin Endocrinol Metab. 2019;104(3):906–914. PubMed.
- Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(2):119–129. PubMed.
- Huijben M, Lock MTWT, de Kemp VF, et al. Clomiphene citrate for men with hypogonadism: a systematic review and meta-analysis. Andrology. 2022;10(3):451–469. PubMed.
- Hohl A, Chavez MP, Pasqualotto E, et al. Clomiphene or enclomiphene citrate for the treatment of male hypogonadism: a systematic review and meta-analysis of randomized controlled trials. Arch Endocrinol Metab. 2025;69(5):e250093. PubMed.
- Constantinou BT, Benedicto BC, Galligani L, et al. Clomiphene citrate versus testosterone replacement therapy in male hypogonadism: a systematic review of literature and meta-analysis. Eur J Clin Pharmacol. 2026;82(8):204. PubMed.
- Moskovic DJ, Katz DJ, Akhavan A, et al. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int. 2012;110(10):1524–1528. PubMed.
- Krzastek SC, Sharma D, Abdullah N, et al. Long-term safety and efficacy of clomiphene citrate for the treatment of hypogonadism. J Urol. 2019;202(5):1029–1035. PubMed.
- Sokol RZ, Steiner BS, Bustillo M, et al. A controlled comparison of the efficacy of clomiphene citrate in male infertility. Fertil Steril. 1988;49(5):865–870. PubMed.
- Chua ME, Escusa KG, Luna S, et al. Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis. Andrology. 2013;1(5):749–757. PubMed.
- Rahnema CD, Lipshultz LI, Crosnoe LE, et al. Anabolic steroid-induced hypogonadism: diagnosis and treatment. Fertil Steril. 2014;101(5):1271–1279. PubMed.
- İbis MA, Yap T, Satchi M, et al. Post-cycle therapy after short-term anabolic-androgenic steroid use: comparative outcomes in recreational bodybuilders. BJU Int. 2026;137(1):154–165. PubMed.
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- Nationale Anti Doping Agentur Deutschland. Verbotsliste der WADA 2026, informatorische Übersetzung (official German translation of the WADA 2026 Prohibited List). NADA.