Enclomiphene

What it is

Enclomiphene is the purified trans-isomer of clomiphene, an old fertility drug that is a roughly 62:38 mix of two mirror-image molecules. The trans half (enclomiphene) carries most of the testosterone-raising benefit; the cis half (zuclomiphene) is the slow, estrogen-like part that builds up and lingers for weeks, and it is deliberately left out. As a SERM it blocks estrogen's 'stop' signal at the hypothalamus, so the brain sends more LH and FSH to the testicles and they make more of the body's own testosterone. Because it turns the body's own signal back up instead of replacing testosterone from outside, it keeps the testicles working and preserves sperm production - the opposite of what testosterone gel or injections do, which switch off LH/FSH and can drop sperm counts sharply. In head-to-head data, enclomiphene held sperm concentrations near baseline while testosterone gel drove them down. Important status: there is NO FDA-approved enclomiphene product. Repros Therapeutics studied it as Androxal through Phase 3 but it was never approved, so today it exists only as a compounded (pharmacy-mixed) drug, used off-label.

Dose ranges

Study-backed ranges carry a source you can open. Community ranges are widely reported but not clinically established - treat them as what people do, not as advice.

Storage

Tools for Enclomiphene

Interactions & cautions

Enclomiphene is a SERM (estrogen receptor antagonist at the hypothalamus). By blocking estrogen's negative feedback it raises GnRH, then LH and FSH, then the testes' own testosterone output - so it restores testosterone WITHOUT the exogenous hormone that shuts down sperm production (PMC5009465). Visual-symptom class caution: clomiphene, the parent compound, carries a labeled warning that blurring or visual symptoms such as spots or flashes (scintillating scotomata) may occur; these are usually reversible but prolonged and sometimes irreversible cases have been reported, more so with higher dose or longer duration - the clomiphene label advises stopping and getting a prompt eye exam if visual symptoms appear (DailyMed clomiphene citrate label). Reported adverse effects in the enclomiphene trials included elevated estradiol, headache, and abdominal discomfort; long-term effects are not established (PMC5009465). As an estrogen-receptor modulator it is not intended for women who are pregnant or trying to conceive without medical supervision (clomiphene class). Enclomiphene is a compounded, non-FDA-approved drug - it is not a substitute for physician-supervised evaluation of low testosterone or infertility.

Questions people ask

Sources

1. [1]Enclomiphene citrate for the treatment of secondary male hypogonadism (review) PMID 27337642studyEnclomiphene is the trans-isomer of clomiphene, a SERM/estrogen receptor antagonist that blocks hypothalamic negative feedback to raise LH/FSH and endogenous testosterone; half-life ~10 hours; doses 12.5 and 25 mg daily with 25 mg the strongest response; sperm concentration preserved (~176 million/mL) vs testosterone (<12 million/mL) at 3 months; under FDA review since 2007 and not approved, 2015 review canceled over bioanalytical validation concerns; reported side effects elevated estradiol, headache, abdominal discomfort.
2. [2]Clomiphene or enclomiphene citrate for the treatment of male hypogonadism: a systematic review and meta-analysis of randomized controlled trialsstudySERM therapy raised total testosterone by ~273.76 ng/dL, LH by ~4.66 IU/L, FSH by ~4.59 IU/L vs placebo; vs testosterone gel, sperm concentration was ~70.40 million/mL higher with SERMs while total testosterone was comparable; notes off-label SERM use for male hypogonadism has increased.
3. [3]Phase III Study to Evaluate Morning Testosterone Normalization in Men With Secondary Hypogonadism (ZA-301) - Repros TherapeuticsstudyRepros Therapeutics Phase 3 trial of enclomiphene citrate (Androxal) 12.5 mg and 25 mg oral capsules once daily vs placebo in secondary hypogonadism; primary outcomes were the proportion normalizing morning testosterone (300-1040 ng/dL) and the proportion with a 50%+ drop in sperm concentration at 12 weeks.
4. [4]Phase III Study to Evaluate Morning Testosterone Normalization in Overweight Men With Secondary Hypogonadism (ZA-302) - Repros TherapeuticsstudyCompanion Repros Therapeutics Phase 3 trial confirming the 12.5 mg and 25 mg once-daily oral enclomiphene doses, sponsor, phase, and the testosterone-normalization plus sperm-concentration co-outcome design in overweight men with acquired hypogonadotropic hypogonadism.
5. [5]CLOMIPHENE CITRATE tablet - DailyMed labellabelClass visual-disturbance warning for the clomiphene family: blurring or visual symptoms such as spots or flashes (scintillating scotomata) may occur, usually reversible but sometimes prolonged or irreversible especially with higher dose/duration; advises discontinuing and prompt ophthalmological evaluation.