Enclomiphene Citrate Hair and Skin Changes: What the Clinical Evidence Shows

What the Phase 3 Trials Measured

Two parallel randomized, double-blind, double-dummy, placebo-controlled phase 3 studies compared enclomiphene with AndroGel 1.62% in overweight men aged 18 to 60 with secondary hypogonadism, over 16 weeks [3]. Total testosterone rose in all treatment groups, LH and FSH rose with enclomiphene and fell with testosterone gel, and sperm concentration stayed in the normal range on enclomiphene while spermatogenesis fell markedly on testosterone gel [3]. The outcomes reported were hormone levels and sperm counts.

The same gap runs through both regulators' reviews. FDA's 2022 materials and EMA's 2018 refusal both concluded that testosterone rose without evidence that symptoms improved [1][2]. EMA's committee noted that the four main studies in 588 patients measured testosterone but not whether bone strength, weight gain, impotence or libido improved, and it flagged a risk of venous thromboembolism [2].

Hair Loss: the Androgen Link

Androgens are the main regulator of human hair follicles, and the response is specific to the follicle itself and varies by body site [6]. Androgenetic alopecia is androgen-dependent miniaturization of scalp follicles, with scalp DHT implicated as a contributing cause [4]. Enclomiphene raises testosterone and gonadotropins in men with secondary hypogonadism [3], but hair loss was not an endpoint in the phase 3 trials, so whether it changes hair loss in any man has not been tested.

Acne and Oily Skin

The phase 3 reports describe hormone levels and sperm, not acne or skin oiliness [3]. Acne does appear in the clomiphene citrate label, covered next.

What the Clomid Label Reports

Clomid (clomiphene citrate) is FDA-approved only for ovulatory dysfunction in women desiring pregnancy; its label has no male indication and states that there are no adequate or well-controlled studies showing it is effective for male infertility [5]. The label lists hair loss/dry hair among events reported in fewer than 1% of patients in clinical trials [5]. Acne appears in the label's postmarketing dermatologic reactions, which the label says are voluntarily reported, so frequency and causation cannot be reliably established [5]. Those entries cover clomiphene citrate, a mixture of enclomiphene and zuclomiphene, and cannot establish enclomiphene's own hair or skin effects [1][5].

Finasteride and Male Pattern Hair Loss

Separately from enclomiphene, finasteride 1 mg daily slowed hair loss and increased hair count versus placebo in two 1-year trials of 1,553 men aged 18 to 41 with male pattern hair loss [4]. Those trials tested finasteride on its own, in men with that diagnosis.

Approval and Compounding Status

FDA's 2022 advisory-committee materials state that no FDA-approved drug contains enclomiphene as an active ingredient, and the sponsor's new drug application received a complete response letter in 2015 [1]. EMA's committee recommended refusing marketing authorisation for EnCyzix (enclomifene) in January 2018 [2]. Compounded enclomiphene is not FDA-approved, and FDA does not verify the safety, effectiveness or quality of compounded drugs before they are marketed [8].