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Enc4.2
Enclomiphene Research
Too few graded studies
8 peer-reviewed studies
What the evidence says
Too few graded studies
Enclomiphene doesn't have enough studies with structured effect-size data yet to pool a verdict. Browse the studies below for individual findings.
Most evidence is from medium-quality meta-analyses and randomised trials published 2013–2025 with a typical study size of 15 participants.
Based on 8 studies · 1 meta-analysis · 3 RCTs · 75 total participants
Confidence
Moderate confidence
By outcome
Testosterone & male hormonesPhase-2/3 RCTs show oral enclomiphene raises total testosterone into the normal range, comparably to topical testosterone · Weeks to a few months · Raises LH-driven endogenous testosterone production in hypogonadal men · Weeks to a few months
Too few graded studies8 studies
Fertility (sperm preservation)In the cited trials in men with secondary hypogonadism, enclomiphene increased testosterone while sperm concentration was maintained. These outcomes do not establish a guarantee of fertility, pregnancy or live birth. · Within 3-6 months
Too few graded studies5 studies
Steady research
1 study in the last 5 years · Latest meta-analysis: 2025
201320192025
1Meta-Analysis2025
In plain English: SERM therapy is associated with significantly improved levels of TT, LH, and FSH in hypogonadal men compared to placebo, and significantly enhanced levels of LH and FSH compared to T gel.
Hohl A, Chavez MP, Pasqualotto E, Ferreira ROM, Sande-Lee SV, Ronsoni MF. · Archives of endocrinology and metabolism (2025)
Weighted mean differences (MDs) and risk ratios (RRs) were calculated for continuous and binary endpoints, respectively, with 95% confidence intervals (CIs).
TT levels were significantly higher with SERM therapy and the combined treatment of SERM and hCG compared to hCG alone (158 vs. 153 vs. 134 ng/dL, respectively; p < 0.002 for both comparisons).
In plain English: Enclomiphene citrate reverses the two hallmarks of secondary hypogonadism, namely, low serum total T and low or inappropriately normal LH while preserving sperm production.
In plain English: Enclomiphene citrate consistently increased serum TT, LH and FSH, restoring normal levels of serum TT. Enclomiphene citrate treatment maintained sperm concentrations in the normal range.
Kim ED, McCullough A, Kaminetsky J. · BJU Int (2016)
Two parallel randomized, double-blind, double-dummy, placebo-controlled, multicentre Phase-3 trials (ZA-304/ZA-305) of 12.5 mg and 25 mg enclomiphene vs testosterone gel (AndroGel 1.62%) in overweight men 18-60 with secondary hypogonadism
Total testosterone rose in all groups; FSH and LH rose with enclomiphene but fell with testosterone gel at 16 weeks
Enclomiphene maintained sperm concentration in the normal range, while spermatogenesis was markedly reduced in the testosterone-gel group
In plain English: After six weeks of continuous use, the mean concentration of total testosterone was 604 ng/dL for men taking the highest dose of enclomiphene citrate (25 mg daily) and 500 ng/dL in those treated with transdermal testosterone.
Wiehle R, Cunningham GR, Pitteloud N, Wike J, Hsu K, Fontenot GK, Rosner M, Dwyer A, Podolski J. · BJU Int (2013)
Randomized, single-blind, two-center Phase-2 study of three enclomiphene doses (6.25, 12.5, 25 mg Androxal) vs transdermal testosterone in 48 men with secondary hypogonadism, with 24-hour LH/TT sampling
Defined the dose-response: 25 mg/day produced mean Day-42 testosterone ~604 ng/dL, comparable to or above transdermal testosterone
Characterized the pharmacokinetics of enclomiphene and the LH/testosterone pharmacodynamic profile over 6 weeks
In plain English: Enclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization of endogenous testosterone production and restoration of sperm counts through the hypothalamic-pituitary-testicular axis.
Kaminetsky J, Werner M, Fontenot G, Wiehle RD. · J Sex Med (2013)
Proof-of-principle randomized, open-label, active-control, two-center Phase-2B study in 12 men with secondary hypogonadism previously on topical testosterone
At 6 months total testosterone was ~525 (enclomiphene) vs ~545 pg/dL (gel) — comparable restoration
Only the enclomiphene group showed increased LH and FSH; enclomiphene raised sperm counts (75-334 million/mL) while the gel failed to do so
In plain English: Enclomiphene has been shown to increase testosterone levels while stimulating FSH and LH production... [it] maintains the androgenic benefit of clomiphene citrate without the undesirable effects attributable to zuclomiphene.
Earl JA, Kim ED. · Expert Rev Endocrinol Metab (2019)
Drug-profile review of the trans-isomer enclomiphene, noting that most of clomiphene's benefit comes from the trans-isomer while zuclomiphene contributes little
Summarizes that enclomiphene raises testosterone while stimulating FSH and LH and maintaining fertility
Explicitly reviews the difficulties associated with FDA approval of enclomiphene as a new molecular entity — the honest regulatory caveat
Review of enclomiphene as the trans-isomer of clomiphene — a non-steroidal estrogen-receptor antagonist — for secondary male hypogonadism
Synthesizes the evidence that it raises testosterone via LH/FSH while maintaining semen parameters, supporting use where testosterone therapy is unsuitable
Frames the fertility-sparing rationale against the fertility-suppressing effect of exogenous testosterone
8ObservationalCited 10×n=15 · very small study2017
In plain English: After at least 6 weeks of clomiphene therapy, the median zuclomiphene:enclomiphene serum concentration ratio was 20:1.
Helo S, Mahon J, Ellen J, Wiehle R, Fontenot G, Hsu K, Feustel P, Welliver C, McCullough A. · BJU Int (2017)
Observational study measuring enclomiphene (ENC) and zuclomiphene (ZUC) isomer levels in 15 men on long-term clomiphene citrate 25 mg daily for secondary hypogonadism
On long-term clomiphene the slow-clearing ZUC dominates the serum, with a median ZUC:ENC ratio of ~20:1 — the rationale for using the pure trans-isomer enclomiphene instead
Total testosterone rose from a median 205 to 488 ng/dL on therapy (P<0.001); age, BMI, and duration did not predict isomer levels