What Is Enclomiphene?
Enclomiphene citrate ยท Last reviewed by the OPTML clinical team on April 20, 2026
Enclomiphene citrate is the trans-isomer of clomiphene, a selective estrogen receptor modulator (SERM). Taken orally, enclomiphene blocks estrogen receptors in the hypothalamus, causing increased secretion of gonadotropins (LH and FSH), which signals the testes to produce more endogenous testosterone. Unlike exogenous testosterone (TRT), enclomiphene preserves fertility, sperm production is maintained or enhanced. In Phase III trials, enclomiphene produced a mean total testosterone increase of ~86% while maintaining sperm parameters (Kim ED et al., J Sex Med 2014).
Mechanism of Action
In the hypothalamus, estrogen exerts negative feedback on the HPG (hypothalamic-pituitary-gonadal) axis. Enclomiphene binds to and blocks estrogen receptors in the hypothalamus, interrupting this feedback. As a result:
- GnRH (gonadotropin-releasing hormone) secretion increases.
- The pituitary releases more LH and FSH.
- LH stimulates testicular Leydig cells to increase testosterone production.
- FSH supports spermatogenesis.
Enclomiphene vs. Clomiphene
Clomiphene citrate (Clomid) is a racemic mixture of two isomers: enclomiphene (trans) and zuclomiphene (cis). Zuclomiphene has estrogen-agonist activity and a very long half-life, potentially causing mood and visual side effects. Enclomiphene alone is purer, has a shorter half-life, and produces fewer estrogenic side effects, making it the preferred option for long-term male testosterone optimization.
Typical Response
Clinical trials and real-world experience show:
- Total testosterone rises approximately 50-100% from baseline within 4-12 weeks.
- LH and FSH rise correspondingly.
- Sperm count and motility are preserved or improved.
- Semen analysis parameters in Phase III trials were non-inferior to placebo.
Indications
Enclomiphene is commonly prescribed off-label for:
- Men with secondary hypogonadism (low T with low or inappropriately normal LH/FSH).
- Men who want to raise testosterone while preserving fertility.
- Men hesitant about committing to lifelong exogenous testosterone.
- Men restarting the HPG axis after discontinuing TRT.
Dosing
Typical dosing is 12.5 to 25 mg orally once daily, sometimes dosed every other day depending on response. Dose is adjusted based on follow-up laboratory values (total T, free T, estradiol, LH, FSH) at 6-12 weeks.
Side Effects
Generally mild and less common than with clomiphene:
- Mood changes (mild).
- Headache.
- Visual disturbances (rare).
- Mild GI upset.
- Elevated estradiol (monitored with labs).
Regulatory Status
Enclomiphene has been evaluated in Phase III trials and has received extensive investigational use. It is currently available via 503A compounding pharmacies in the U.S. and is prescribed off-label for male hypogonadism. An FDA-approved branded enclomiphene product remains in regulatory development as of 2026.
Considering enclomiphene?
$110/month on the 3-month supply or $129/month monthly. Physician-led care. Labs available as an add-on.
Start your consultation →References
- Kim ED, McCullough A, Kaminetsky J. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone. BJU Int. 2016;117(4):677-685.
- Wiehle RD, Fontenot GK, Wike J, et al. Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone. Fertil Steril. 2014;102(3):720-727.
- Rodriguez KM, Pastuszak AW, Lipshultz LI. Enclomiphene citrate for the treatment of secondary male hypogonadism. Expert Opin Pharmacother. 2016;17(11):1561-1567.
- Earl JA, Kim ED. Enclomiphene citrate: A treatment that maintains fertility in men with secondary hypogonadism. Expert Rev Endocrinol Metab. 2019;14(3):157-165.