Enclomiphene vs clomiphene
Every row cites its source. Where a cell reflects our own reading of the evidence rather than an external source, the row says so.
One is inside the other. Clomiphene is the approved 1967 drug, a fixed mixture of two isomers; enclomiphene is its estrogen-blocking isomer sold alone, compounded, at a premium. Every row is cited.
| Dimension | Enclomiphene | Comparator | Source |
|---|---|---|---|
| What it is | The trans isomer of clomiphene, an estrogen receptor antagonist, sold as a single-isomer compounded product | A fixed mixture: 30-50% zuclomiphene (estrogen agonist) plus enclomiphene | source |
| Regulatory status | Never approved anywhere: FDA Complete Response Letter 2015, EMA refusal 2018; compounded under an interim FDA policy, under evaluation since 2022 | FDA-approved since 1967 (Clomid, NDA 016131) with marketed generics; male use is off-label at physician discretion | source |
| Half-life and washout | About 7 hours; essentially cleared in about 2 days | The zuclomiphene fraction has a half-life measured in days, stays detectable beyond a month, and accumulates across cycles | source |
| What circulates at steady state | Enclomiphene only | Mostly zuclomiphene: median 20:1 zu:en serum ratio in men on chronic 25 mg daily | source |
| Testosterone response | Median +166 ng/dL in the within-patient switch series; +7.50 nmol/L pooled in obese men | Median +98 ng/dL in the same patients (difference not significant, p = 0.20); +11.56 nmol/L pooled | source |
| Estradiol behavior | Fell modestly on switch (-5.92 pg/mL) | Rises: +17.50 pg/mL in the switch series; 17 to 34 pg/mL in long-term treatment | source |
| Reported side effects | Lower odds in the one comparative series (OR 0.18, 95% CI 0.07-0.44); no long-term dataset | 8% in a 400-man series up to 7 years (mood, visual symptoms, breast tenderness); no serious adverse events in that series or the 1642-patient meta-analysis | source |
| Depth of male evidence | One development program: phase II and III trials over roughly five years, plus retrospective series since | Two decades of published male cohorts including 400 patients to 7 years and a 19-study meta-analysis | source |
| Manufacturing oversight | Compounded: FDA does not review safety, effectiveness or quality before sale | FDA-approved manufacturing with label, lot standards and generic bioequivalence review | source |
| Head-to-head randomized trial | None published | None published | source |