What is enclomiphene, and what does the research show?

What enclomiphene is

According to FDA's 2022 review of enclomiphene, enclomiphene citrate is a selective estrogen receptor modulator that acts by blocking the estrogenic suppression of the hypothalamic-pituitary-gonadal axis.[1] According to the same review, enclomiphene's half-life is about 10 hours, and its peak concentration occurs 2 to 3 hours after an oral dose.[1]

Enclomiphene is the trans isomer in clomiphene citrate, which is a mixture of two isomers, so a finding about clomiphene is not a finding about enclomiphene.[1]

Testosterone and other hormone levels

In four published reports of randomized trials lasting 6 weeks to 6 months, enclomiphene raised blood testosterone in men with low testosterone and low or normal luteinizing hormone.[2][3][4][5] Because most of the evidence comes from the manufacturer's program, we grade the findings on blood hormone levels as emerging, for blood levels only.

Of the four published reports, two list authors affiliated with the manufacturer, one carries the manufacturer's copyright line, and the registry lists the manufacturer as sponsor of the trials in the fourth.[2][3][4][5][6]

A 2023 systematic review and meta-analysis of 7 studies in 292 obese men with androgen deficiency reported, for the enclomiphene studies, a pooled rise in testosterone of 7.50 nmol/L (95% confidence interval 6.52 to 8.48).[7] That pooled estimate compares testosterone before and after treatment rather than against placebo or another treatment.[7]

We did not find an FDA-approved enclomiphene drug product for any use, including low testosterone or secondary hypogonadism in men (checked September 30, 2026).

Comparison with testosterone gel in the trials

In the two 16-week phase 3 trials reported together in 2016, which ClinicalTrials.gov lists as sponsored by the drug's manufacturer, luteinizing hormone and follicle-stimulating hormone rose with enclomiphene and fell with testosterone gel in overweight men with low testosterone.[2][6]

We did not find an FDA-approved enclomiphene drug product for any use, including raising testosterone levels (checked September 30, 2026).

Sperm counts

In the two 16-week phase 3 trials reported together in 2016, sperm concentration stayed in the normal range with enclomiphene and fell markedly with testosterone gel.[2] Sperm concentration is a laboratory measure. The comparison in which enclomiphene kept sperm concentration in the normal range was against topical testosterone.

In ClinicalTrials.gov results for two phase 3 trials, 14.2% of enclomiphene-treated men in each trial had a 50% or greater fall in sperm concentration, compared with 2.6% of men on placebo in the first trial (151 men) and 4.3% in the second (181 men), and we found no journal article for either trial.[8][9]

FDA's 2022 review of enclomiphene said that changes in semen parameters alone are not sufficient to establish efficacy and that improvement in semen parameters does not ensure fertility.[1]

In searches of PubMed, Europe PMC and ClinicalTrials.gov on October 1, 2026, we found no trial of enclomiphene that reported pregnancy, live birth or time to conception. As of the registry check of October 14, 2026, ClinicalTrials.gov listed a trial of enclomiphene against placebo in male infertility, with total motile sperm count as the primary outcome, as withdrawn with 0 participants.[10]

We did not find an FDA-approved enclomiphene drug product for any use, including use in men who want to preserve fertility (checked September 30, 2026).

Symptoms, sex drive, body composition and bone

In searches of PubMed, Europe PMC and ClinicalTrials.gov on October 1, 2026, we found no trial of enclomiphene that reported symptoms, sexual function or quality of life. FDA's 2022 review of enclomiphene stated: "Enclomiphene citrate trials did not evaluate improvement in hypogonadal symptoms or quality of life."[1]

The same review said: "it is unclear whether increasing testosterone concentrations alone in men with secondary hypogonadism confers clinical benefit".[1]

A registered 48-week placebo-controlled trial of 50 obese men with low testosterone, all of whom followed a diet and exercise program, listed lean body mass measured by DXA as its first primary outcome, and its registry results show no significant difference from placebo.[11]

In the 48-week trial of 50 obese men, average lean body mass rose by 3.14 kg and 2.40 kg in the two enclomiphene groups and by 1.05 kg on placebo, with p values against placebo of 0.7103 and 0.4529.[11] In the 48-week trial of 50 obese men, changes in chest press and leg press strength did not differ from placebo, with p values from 0.51 to 0.93.[11]

In the 48-week trial of 50 obese men, average body weight fell by 4.36 kg and 6.15 kg in the two enclomiphene groups and by 14.51 kg on placebo, with p values of 0.0139 and 0.0225.[11] All participants in the 48-week trial of 50 obese men also followed a diet and exercise program, so weight changes cannot be credited to the drug alone.[11]

We graded the claim that enclomiphene increases lean body mass or muscle strength in obese men with low testosterone as evidence against, based on this one small phase 2 trial, for which we found no journal article.[11]

On October 1, 2026, ClinicalTrials.gov listed a 12-month phase 3 trial of enclomiphene on bone mineral density, with 300 people enrolled and no results posted, and we found no publication of its results.[12]

We did not find an FDA-approved enclomiphene drug product for any use (checked September 30, 2026).

Trial results at a glance

We did not find an FDA-approved enclomiphene drug product for any use (checked September 30, 2026).

Uses beyond the trial population

In title and abstract searches of PubMed and Europe PMC on October 1, 2026, we found no efficacy trial of enclomiphene in men with normal testosterone, in women, or in people using it after courses of anabolic steroids.

On October 14, 2026, a full read of the 238 ClinicalTrials.gov records from sponsors other than the manufacturer found no enclomiphene trial of those uses; only two records name the drug in their titles or summaries, a withdrawn infertility trial with no participants and a trial in women whose summary mentions the drug's isomers.

We did not find an FDA-approved enclomiphene drug product for any use, including anti-aging or longevity (checked September 30, 2026).

Is enclomiphene FDA-approved?

We did not find an FDA-approved enclomiphene drug product.

Compounded enclomiphene is not FDA-approved. FDA states: 'Compounded drugs are not FDA-approved. This means that FDA does not verify the safety, effectiveness or quality of compounded drugs before they are marketed.' As of FDA's list updated May 14, 2026, enclomiphene citrate is on FDA's list of substances under evaluation for use in compounding under section 503A (Category 1), and this listing is not an FDA approval of any compounded product.

In June 2022, FDA proposed that enclomiphene citrate 'NOT be included on the 503A Bulks List.' As of September 30, 2026, we have not found a final decision.

At its June 8, 2022 meeting, FDA's Pharmacy Compounding Advisory Committee voted 8 to 4, with no abstentions, against placing enclomiphene citrate on the 503A Bulks List. FDA's minutes say several members who voted no 'noted lack of clinical efficacy evidence.' The committee's role is to advise FDA and make recommendations to the FDA Commissioner.

FDA minutes

Regulatory status checked September 30, 2026. Sources: www.fda.gov/…/download; www.fda.gov/…/download; www.fda.gov/…/download; www.fda.gov/…/compounding-and-fda-questions-and-answers

What are the side effects of enclomiphene?

FDA's 2022 review of enclomiphene listed cardiac and thromboembolic events, elevated estradiol, increased PSA and increased hematocrit among its safety concerns for enclomiphene citrate.[1] The same review lists a high hematocrit or hemoglobin level and a high prostate-specific antigen level among the reasons men on the higher enclomiphene dose stopped treatment in the 16-week trials reported in 2016.[1]

In an open-label safety study of 499 men, FDA's 2022 review of enclomiphene lists among the serious adverse events deep vein thrombosis in one man in each dose group and pulmonary embolism in one man in the higher-dose group.[1][13]

The same review lists two deaths in the lower-dose group of the 16-week trials reported in 2016: a road traffic accident that investigators judged unrelated and a cerebrovascular accident judged unlikely to be related.[1]

In a 3-month phase 2 trial of 124 men with secondary hypogonadism, estradiol rose in all groups given active treatment and was still above baseline one month after enclomiphene was stopped.[1][3]

In one 3-month phase 2 trial, a man in the higher-dose group stopped treatment after an inability to climax and a loss of sensation during intercourse.[1]

A 2026 case report describes a 46-year-old man with a prior mitral valve repair who developed new atrial flutter soon after taking twice the intended daily dose of enclomiphene.[14] The authors wrote that causality cannot be established, and that a formal causality assessment placed the association in the possible category only.[14] A case report cannot show how often this happens.

If you are thinking about taking enclomiphene, talk to a licensed clinician first.

If you have severe symptoms, call 911 or seek emergency care. Report side effects to FDA MedWatch.

Related pages

• Hormone health
• Testosterone replacement therapy
• What Does FDA-Approved Mean?
• Compounded Medications Explained
• How We Grade Medical Evidence