Clomiphene Citrate

Men: low testosterone

Use of clomiphene in men is off-label (PMID: 34933414).

• A 2012 prospective series by Katz treated 86 men aged 22 to 37 with testosterone below 300 ng/dL for a mean of 19 months. Testosterone and gonadotropins rose, symptom scores on the ADAM questionnaire improved, and no major side effects were recorded; infertility was the most common reason for seeking treatment (64 percent) (PMID: 22044663).
• In a 2012 uncontrolled series by Moskovic of 46 men with a mean age of 44, treated for more than 12 months, mean testosterone rose from 228 ng/dL to 612, 562 and 582 ng/dL at 1, 2 and 3 years, and bone density scores improved (PMID: 22458540).
• A 2017 double-blind, placebo-controlled crossover trial by Pelusi included 24 obese men with low testosterone taking metformin, with 3 months per period. Testosterone rose from 3.03 to 5.99 ng/mL on clomiphene and did not change on placebo, and fasting glucose, insulin and insulin resistance fell during clomiphene treatment (PMID: 28886024).
• A 2015 randomized double-blind trial by Helo compared clomiphene with anastrozole for 12 weeks in 26 hypogonadal infertile men. Testosterone rose more with clomiphene, estradiol rose with clomiphene and fell with anastrozole, and neither drug changed semen parameters or patient-reported outcomes (PMID: 26176805).
• A 2019 retrospective review by Krzastek covered 400 men at two US centers. Of the 120 men treated for more than 3 years, 88 percent reached normal testosterone and 77 percent reported improved symptoms (PMID: 31216250).
• A 2022 meta-analysis of 19 studies, 4 of them randomized, in 1,642 men found that total and free testosterone, LH, FSH, sex hormone-binding globulin and estradiol all rose during clomiphene treatment (PMID: 34933414). A 2025 meta-analysis of randomized trials found that clomiphene or enclomiphene raised total testosterone by about 274 ng/dL more than placebo and did not differ from testosterone gel (PMID: 41066380). A 2026 meta-analysis of 11 studies comparing clomiphene with testosterone replacement found no overall difference in testosterone, higher levels with injectable testosterone in the one study that used it, and lower libido scores with clomiphene (PMID: 42435198).
• In 10 men whose hypogonadism persisted during cabergoline treatment for macroprolactinoma, 8 of these men kept testosterone above 300 ng/dL on clomiphene over a mean of 3.2 years (PMID: 38578401).

Men: infertility

• A 1992 World Health Organization trial in 190 couples tested 6 months of low-dose clomiphene or placebo. Cumulative pregnancy rates at 8 months were 8.1 percent with clomiphene and 11.7 percent with placebo, and changes in semen quality did not differ (PMID: 1516979).
• In a 2013 meta-analysis by Chua of 11 randomized trials of clomiphene or tamoxifen, treatment with either drug was associated with a higher pregnancy rate (odds ratio 2.42) and with higher sperm concentration and motility (PMID: 23970453).
• A 2021 systematic review found paradoxical falls in semen measures in 17 to 24 percent of treated men, not recovering after stopping in up to 17 percent (PMID: 33108678).
• The US label states that there are no adequate or well-controlled studies showing that clomiphene is effective for male infertility (US prescribing information for clomiphene citrate tablets).

Men: after anabolic steroid use

A 2026 review describes clomiphene as the most commonly used off-label medication for anabolic steroid-induced hypogonadism after steroid use stops, often taken without medical supervision, and states that its clinical efficacy, safety and monitoring remain poorly defined (PMID: 42387872). Of 63 seized samples sold for post-cycle use after anabolic steroids and tested by Poland's official medicines control laboratory, 34.9 percent did not contain the declared active ingredient (PMID: 40177353).

Anti-doping research

In an open-label study of 12 healthy men given clomiphene for 30 days, testosterone rose 146 percent and zuclomiphene stayed detectable in urine for 121 to more than 261 days; the authors described clomiphene as a performance-enhancing drug commonly abused by men in sport (PMID: 30295816).

Visual symptoms

Blurring, spots or flashes and prolonged afterimages are labeled effects that become more frequent with higher total dose and longer treatment and are usually reversible, but the label also reports prolonged and possibly irreversible cases, some occurring after treatment stopped (US prescribing information for clomiphene citrate tablets). In a 1995 neuro-ophthalmology report, three women treated for 4 to 15 months had persistent afterimages (palinopsia), a shimmering of the peripheral vision and sensitivity to light that remained 2 to 7 years after they stopped clomiphene (PMID: 7710399). A case report described a 33-year-old man with presumed clomiphene-induced optic nerve damage, consistent with NAION, that began on the 14th day of treatment for fertility (PMID: 34278201).

Men: side effects in clinical series

In a review of 400 men treated for low testosterone at two US centers, 8 percent of the men treated for more than 3 years reported side effects, most often mood changes, blurred vision and breast tenderness, and no significant adverse event was recorded (PMID: 31216250). A 2022 meta-analysis of 19 studies in 1,642 men found side effects in fewer than 10 percent of study populations and no serious adverse events reported (PMID: 34933414). In a multi-institution retrospective study, polycythemia (a high red cell count) occurred in 1.7 percent of 188 men on clomiphene and 11.2 percent of 175 men on testosterone replacement; the testosterone group was older and treated longer, and the difference held after adjustment for age (PMID: 27984109). The label notes that testicular tumors and gynecomastia have been reported in men using clomiphene, and states that the cause and effect relationship between clomiphene and the testicular tumors is not known (US prescribing information for clomiphene citrate tablets).

Men: semen quality

A 2021 systematic review of 11 studies covering 384 men found decreases in sperm count, concentration, motility or total motile count in 17 to 24 percent of men treated with clomiphene (depending on the measure), and in up to 17 percent the decline did not recover after clomiphene was stopped (PMID: 33108678).

Men: blood clots

Case reports describe venous thrombosis in men taking clomiphene, for example intracranial venous thrombosis 3 weeks after starting it for infertility, isolated cortical vein thrombosis and pulmonary embolism; single case reports cannot show how often such events occur (PMID: 27873748, PMID: 33129205, PMID: 2875958).

Persistence and drug testing

In 12 healthy men who took clomiphene for 30 days, the urinary detection window for zuclomiphene ranged from 121 to more than 261 days (PMID: 30295816), and WADA's 2026 Prohibited List names clomifene as an anti-estrogenic substance prohibited at all times (WADA Prohibited List 2026, class S4.2).

Pregnancy

Clomiphene is contraindicated in pregnancy; the label states that available human data do not suggest an increased risk of congenital anomalies when the drug is used as indicated, while animal studies showed embryo-fetal loss and structural malformations (US prescribing information for clomiphene citrate tablets). The label also states that, because zuclomiphene is detectable for more than a month, some active drug may remain in the body during early pregnancy in women who conceive in a treatment cycle (US prescribing information for clomiphene citrate tablets).

Ovarian tumors

The label states that prolonged use of clomiphene may increase the risk of a borderline or invasive ovarian tumor (US prescribing information for clomiphene citrate tablets). A 2019 Cochrane review rated the evidence linking fertility drugs to ovarian cancer as very low certainty; one cohort found a higher risk of invasive ovarian cancer in women who never became pregnant after using clomiphene (hazard ratio 2.49), and another found more borderline ovarian tumors after clomiphene (standardized incidence ratio 7.47) (PMID: 31207666).