Peptides›Sexual / hormonal›Enclomiphene

Enclomiphene

/ Selective estrogen receptor modulator (SERM); trans-isomer of clomiphene citrate

TIER 2 · TranslationalN = 0 · TESTING PENDINGMW 405.97 g·mol⁻¹

ALIAS · Trans-clomiphene · Enclomiphene citrate · Repros enclomiphene · Androxal

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequence— sequence not captured —

MW · 405.97CLASS · Selective estrogen receptor modulator (SERM); trans-isomer of clomiphene citrateCATEGORY · Sexual / hormonal

Tier 2. The trans-isomer of clomiphene; advanced through Phase 3 trials by Repros Therapeutics for secondary hypogonadism (low testosterone with preserved fertility) and received an FDA Complete Response Letter rather than approval (2015). Multiple Phase 2 and Phase 3 datasets exist; not currently FDA-approved as a separate product, although clomiphene citrate (a mixture of enclomiphene and zuclomiphene) is approved for ovulation induction.

§ B · Mechanism of action

Enclomiphene is a SERM that competitively blocks estrogen-receptor feedback in the hypothalamus and pituitary, increasing GnRH pulsatility, LH and FSH secretion, and downstream testicular testosterone and spermatogenesis. The pharmacology contrasts with exogenous testosterone replacement, which suppresses the HPG axis and impairs fertility. Zuclomiphene (the cis-isomer of clomiphene) has agonist estrogen-receptor activity that contributes to side-effect profile of clomiphene mixture; isolating the trans-isomer was intended to improve tolerability.

§ C · Human clinical evidence

Tier 2. Phase 3 trials in men with secondary hypogonadism showed significant testosterone elevation and preserved sperm parameters versus testosterone gel. FDA Complete Response Letter (2015) cited concerns about long-term cardiovascular safety and the size of the safety database in the proposed indication.

§ D · Primary literature

PubMed26496621Kim ED et al. — Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement · BJU International · human-phase-2Enclomiphene citrate raised serum testosterone while preserving LH, FSH, and sperm concentration in obese hypogonadal men, in contrast to topical testosterone which suppressed gonadotropins.Limitations: Industry-sponsored; secondary endpoint comparison; modest sample size and duration.2016

PubMed25044085Wiehle RD et al. — Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone · Fertility and Sterility · human-phase-2Phase II RCT showed enclomiphene normalised serum testosterone with maintained sperm counts in secondary hypogonadism, whereas topical testosterone reduced sperm production.Limitations: Industry-sponsored (Repros); 3-month duration; surrogate fertility endpoints.2014

§ F · Safety signal

In Phase 2-3 trials, headaches, hot flashes, nausea, and visual disturbances were the most common adverse events. Long-term cardiovascular data in the male hypogonadism population were the main FDA concern.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved
Compounding:: Compounding eligibility ambiguous

§ I · Notable gaps and controversies

The 'enclomiphene' peptide-vendor product overlaps a pharmacy compounding niche — some 503A-pathway compounding pharmacies prepare enclomiphene as an unapproved drug for hypogonadism. The pharmacological case is reasonable; the regulatory status is the weak point.