Enclomiphene Citrate Compassionate Use and Expanded Access: How to Get It Cheaper in 2026

Is there an enclomiphene expanded access or compassionate use programme?

FDA describes expanded access, sometimes called compassionate use, as one way for patients with serious or life-threatening illnesses to try an investigational drug outside a clinical trial, alongside clinical trials and right to try [3].

For enclomiphene, no programme is confirmed. The manufacturer discontinued development in 2021, according to the British Society of Sexual Medicine's 2026 position statement, which advises use only by experienced clinicians in specialist or research settings because long-term efficacy and safety data are lacking [2]. Repros Therapeutics filed a new drug application for enclomiphene (Androxal) for secondary hypogonadism in fertile men. In 2015 the company announced a complete response letter; FDA's summary said the phase 3 study designs were not adequate to demonstrate clinical benefit and raised concerns about study entry criteria, titration and bioanalytical method validation. No approval has followed [1].

Europe reached a similar outcome. EMA's committee adopted a negative opinion on 25 January 2018 recommending refusal of marketing authorisation for EnCyzix (enclomifene) for hypogonadotropic hypogonadism in overweight men with a BMI of 25 or more, based on 4 main studies in 588 patients. Testosterone rose, but the studies did not look at whether symptoms improved, and there was a risk of venous thromboembolism [6].

Why enclomiphene is not a normal prescription

Enclomiphene is an oral selective estrogen receptor modulator. It blocks estrogen receptors in the pituitary, so the pituitary releases more LH and FSH, which tells the testes to make more testosterone and keep making sperm [1]. Studies have examined it in men with secondary hypogonadism, including effects on testosterone and sperm concentration [10]. No approved enclomiphene product exists [1].

Clomiphene citrate is a mixture of enclomiphene and zuclomiphene. It is FDA-approved, but only for ovulatory dysfunction in women desiring pregnancy. Its label carries no male indication and states that there are no adequate or well-controlled studies demonstrating effectiveness in male infertility, and that testicular tumors and gynecomastia have been reported in males taking clomiphene, with cause and effect not known [8]. Per FDA, the USP monograph gives enclomiphene content of clomiphene as 50 to 70 percent; the two are related but are not the same drug [1].

Compounding status of enclomiphene in 2026

FDA's list, updated 14 May 2026, places enclomiphene citrate in Category 1, 'Bulk Drug Substances Under Evaluation' [4]. FDA says it does not intend to take action against a compounder that uses a Category 1 substance if the conditions in its guidance are met, and that this is an enforcement-discretion policy, not an approval and not a finding that the product is safe or effective [4]. Category 1 status is therefore not a general authorisation to compound.

That evaluation has already gone against enclomiphene once. At the Pharmacy Compounding Advisory Committee meeting on 8 June 2022, FDA proposed that enclomiphene citrate not be added to the list of bulk substances allowed in compounding. The committee voted 4 yes and 8 no; members who voted no cited a lack of clinical efficacy evidence [7].

Enclomiphene is not on FDA's list of bulk substances that may present significant safety risks [11]. Compounded drugs are not FDA-approved, and FDA does not review their safety, effectiveness or quality before they reach patients [5].

Can enclomiphene be got more cheaply?

Enclomiphene has no FDA-approved product [1], so there is no approved-product price to compare against, and no published price data for compounded enclomiphene are available to compare pharmacies or discount tactics. What a compounding pharmacy charges is set by that pharmacy, alongside whatever the prescriber charges for visits and laboratory work.

Two points from the evidence bear on the choice. First, generic clomiphene citrate is an approved drug with a label, but for a different indication and population, ovulation induction in women [8]. The label states that male infertility effectiveness has not been shown in adequate studies, and use in men with low testosterone is off-label [8]. Second, the two drugs have been compared directly. In a retrospective review of 66 men at one academic centre who took clomiphene and later enclomiphene, the median testosterone rise was 166 versus 98 ng/dL (P=0.20), estradiol changed by -5.92 versus +17.50 pg/mL (P=0.001), and side effects were less frequent on enclomiphene (odds ratio 0.18, 95% CI 0.07 to 0.44) [12]. That comparison was not randomised.

What the trials actually measured

In ZA-301, a randomised double-blind placebo-controlled trial, 151 overweight men aged 18 to 60 with acquired hypogonadotropic hypogonadism (morning testosterone under 300 ng/dL) and normal sperm concentration took 12.5 mg or 25 mg daily, or placebo, for 12 weeks. Pooled across doses, 78.8% (95% CI 70.3 to 85.3) reached an average 24-hour testosterone in the normal range of 300 to 1040 ng/dL, and sperm concentration fell by 50% or more in 14.2% on enclomiphene versus 2.6% on placebo. The results are posted on ClinicalTrials.gov, and no peer-reviewed publication of the trial was found [9].

ZA-302, with the same design, enrolled 181 men; 81.3% (95% CI 73.9 to 87.0) on enclomiphene reached the normal range, and sperm concentration fell by 50% or more in 14.2% on enclomiphene versus 4.3% on placebo [13].

Against testosterone gel, two parallel phase 3 studies, ZA-304 and ZA-305, compared enclomiphene with AndroGel 1.62% for 16 weeks in overweight men aged 18 to 60 with morning testosterone of 300 ng/dL or lower. Total testosterone rose in all treatment groups; LH and FSH rose with enclomiphene and fell with the gel; sperm concentration stayed in the normal range on enclomiphene while there was a marked reduction in spermatogenesis on the gel [10].

A 2025 meta-analysis of randomised trials that pooled clomiphene and enclomiphene found total testosterone a mean 273.76 ng/dL higher than placebo (95% CI 191.87 to 355.66), with high heterogeneity (I² of 89%), and no significant difference versus testosterone gel [14].

None of these trials settled whether raising testosterone this way relieves symptoms. FDA's May 2018 guidance on secondary hypogonadism, as FDA described it in 2022, says it is unclear whether raising testosterone in this population gives clinical benefit, that trials should show meaningful improvement in at least one symptom or sign, and that semen-parameter changes alone are not enough [1]. EMA reached a similar view in 2018 [6].

Safety points

FDA's 2022 review, drawing on published trials, adverse event reports and EMA's assessment, listed cardiac and thromboembolic events (including pulmonary embolism and deep vein thrombosis in a safety study), raised estradiol, raised PSA, raised hematocrit, and no long-term safety data [1]. EMA noted a slightly higher rate of cardiac and thromboembolic events than with testosterone, plus cataracts in nonclinical studies that were not conclusively linked in people, and it wanted ocular monitoring [1].

In the phase 3 and EMA data, the most frequent side effects were headache, hot flushes, nausea and muscle spasm; reasons for stopping included blurred vision, muscle spasm, headache and aggression. In ZA-302, headache occurred in 7 of 112 men on 12.5 mg versus 1 of 47 on placebo, and nausea in 4 of 112 versus 3 of 47 [13].

Visual symptoms need their own note. The Clomid label for the clomiphene mixture says blurring, spots or flashes (scintillating scotomata) may occasionally occur and become more common with higher total dose or longer therapy. They are usually reversible, but prolonged and possibly irreversible visual disturbance has been reported, and the label calls for a complete ophthalmological evaluation of any visual symptoms. This warning is from the clomiphene label and has not been established for enclomiphene alone [8].

Athletes

WADA's 2026 Prohibited List places anti-estrogenic substances and SERMs, naming clomifene, in section S4, prohibited at all times. The list says 'including, but not limited to', and enclomiphene is an isomer of clomifene, so athletes should treat it as prohibited and check with their anti-doping organisation [15].

Bottom line

Enclomiphene in 2026 is an unapproved drug with a failed application behind it, a discontinued development programme, an FDA compounding status of 'under evaluation', and a 2022 advisory committee vote against adding it to the allowed list [1][2][4][7]. No expanded access programme is confirmed, and no approved product carries a list price. Compounding falls under FDA's enforcement-discretion policy only when its guidance conditions are met, and the 2026 position statement describes use only by experienced clinicians in specialist or research settings [2][4].