Enclomiphene Citrate Global Regulatory Status

Is enclomiphene approved by the FDA?

No. The FDA's June 8, 2022 presentation to its Pharmacy Compounding Advisory Committee states plainly that no FDA-approved drugs contain enclomiphene as an active ingredient [1].

That is easy to confuse with clomiphene, which is approved. Clomiphene citrate (Clomid and generics) is an oral tablet approved only for ovulatory dysfunction in women who want to become pregnant. Its label has no male indication and says there are no adequate or well-controlled studies demonstrating effectiveness in the treatment of male infertility [5]. Clomiphene is a mixture of two isomers, enclomiphene (trans) and zuclomiphene (cis); the USP monograph gives enclomiphene content of clomiphene as 50 to 70 percent [1]. They are related drugs, not the same drug.

The Androxal application and the 2015 complete response

Sponsor Repros Therapeutics filed a new drug application for enclomiphene (Androxal) for secondary hypogonadism in fertile men. In 2015 Repros announced a complete response letter; as FDA summarised it, the design of the phase 3 studies was not adequate to demonstrate clinical benefit, and FDA raised concerns about study entry criteria, titration and bioanalytical method validation [1]. No FDA approval has followed [1].

FDA's May 2018 guidance on secondary hypogonadism, as FDA described it in 2022, says trials should show meaningful improvement in at least one symptom or sign, and that changes in semen parameters alone are not enough to establish efficacy [1].

Europe: the 2018 refusal of EnCyzix

The EMA's Committee for Medicinal Products for Human Use adopted a negative opinion on 25 January 2018 recommending refusal of a marketing authorisation for EnCyzix (enclomifene), applicant Renable Pharma Limited, for hypogonadotropic hypogonadism in overweight men with a BMI of at least 25 [2].

The committee's reasons were specific. The studies showed higher testosterone but did not examine whether symptoms improved (bone strength, weight gain, impotence and libido were named), and there was a risk of venous thromboembolism. The assessment rested on four main studies in 588 patients [2].

What 'under evaluation' means in the US

As of 14 May 2026, FDA's list places enclomiphene citrate in Category 1, 'Bulk Drug Substances Under Evaluation.' FDA says it does not intend to take action against a compounder using a Category 1 substance if the conditions in its guidance are met. That is an enforcement-discretion policy, not an approval and not a finding that the product is safe or effective [3].

Enclomiphene has no USP monograph [3], and it is not on FDA's Category 2 list of bulk substances that may present significant safety risks [8]. Compounded enclomiphene products are not FDA-approved and have not been reviewed by FDA for safety, effectiveness or quality [8].

The 2022 FDA advisory committee vote

At the June 8, 2022 meeting of FDA's Pharmacy Compounding Advisory Committee, FDA proposed that enclomiphene citrate not be added to the list of bulk substances allowed in compounding. The committee voted 4 yes, 8 no, 0 abstentions on adding it [4]. Members who voted no cited a lack of clinical efficacy evidence; one said more studies were needed; one member who voted yes noted that clomiphene citrate has a USP monograph [4].

What regulators flagged on safety

FDA's 2022 review listed cardiac and thromboembolic events, including pulmonary embolism and deep vein thrombosis in a safety study, raised estradiol, raised PSA and raised hematocrit, plus a lack of long-term safety data [1]. EMA noted a slightly higher rate of cardiac and thromboembolic events than with testosterone, and cataracts in nonclinical studies, and wanted ocular monitoring [1].

A 2026 position statement from the British Society of Sexual Medicine says enclomiphene is not currently approved by the FDA or EMA, that its manufacturer discontinued development in 2021, and that it should be used only by experienced clinicians in specialist or research settings because long-term efficacy and safety data are lacking [6].

Athletes: WADA

The WADA 2026 Prohibited List places clomifene in S4, hormone and metabolic modulators, prohibited at all times, under S4.2 anti-estrogenic substances and SERMs [7]. Enclomiphene is not named separately, but the list is described as including but not limited to the named substances, and enclomiphene is an isomer of clomifene, so athletes should treat it as prohibited and check with their anti-doping organisation [7].