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Rx · oral SERMFor Wet+2 more

Enclomiphene

The trans-isomer of clomiphene. We read all 60 studies. The protocol is below.

Updated 03 May 2026Read 16 minEvidence ●●●●○Citations 60
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The Enclomiphene Report · $19

Everything you need to start: dose, sourcing, safety, our verdict.

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Built from 60 cited studies.

Status
Rx
Class
For Wet
Evidence
4/ 5●●●●○
Phase 3 trials completed
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FDA approval
denied 2016, design issues
Available via compounding
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Read this if
  • you have low-T symptoms but want kids someday and don't want lifelong TRT
  • a Marek / Defy / Hone clinician put it on the table and you want a second read
  • you're coming off a cycle and looking for a real PCT lever, not bro-science
Skip this if
  • **you notice ANY new visual symptom — floaters, flashing lights, blurry or 'shimmery' vision, scotomas** — stop the drug and see an ophthalmologist before you re-start. SERMs (clomiphene class, this molecule's parent) have published case reports of optic-nerve and retinal effects; the standard clinical instruction is 'discontinue and refer' on any new visual complaint. This is not a warning to read past
  • you have a personal or family history of estrogen-sensitive cancer or thromboembolism
  • you've already got severe primary hypogonadism (testicular failure) — this won't fix it; the pituitary signal is the lever, and your testes aren't responding
  • you're on TRT and don't want to stop it — enclomiphene works by raising your OWN LH/FSH; if exogenous testosterone is suppressing the axis, enclomiphene fights that suppression and you'll get neither effect cleanly
  • you're on it and your mood is collapsing and you haven't told anyone yet
The 4 ways you can buy Enclomiphene
Brand
✓
FDA-approved Rx
Compounded 503A
✓
Off-label Rx
$50–$90/mo
Dominant channel; widely stocked.
RUO (research-only)
✓
Sold for research only
$30–$60/mo
Smaller channel — compounded is too cheap for gray to gain traction.
Gray market
✓
Illegal to import for huma…
Varies — not on user's vendor list
Unverified. No meaningful gray market for enclomiphene — compounded pathway is too inexpensive.
Click any lane for the full Sourcing breakdown.
First 90 days · Enclomiphene
Weeks 1–2
On-demand class — works in 30–60 min on the day of use or it doesn't. The PT-141 effect either shows up at the proper dose or it's the wrong molecule for you.
Weeks 4–8
Side-effect accumulation is the real watch-for: facial hyperpigmentation (MC1 receptor), nausea with repeated use, mood changes.
Week 12 — decide
Decide based on the on-demand response pattern, not a slow build-up. There is no slow build-up here.
Quit if
  • Facial or scalp hyperpigmentation that doesn't fade after stopping for 2–4 weeks.
  • Persistent nausea on repeated use.
  • Zero response to 2–3 attempts at proper dose (one of these — it's not for everyone).
Identity

What it is.

Enclomiphene is the trans-isomer of clomiphene citrate, a selective estrogen receptor modulator (SERM). The original drug, clomiphene (Clomid), is a roughly 60/40 mix of two isomers: enclomiphene (the antagonist at the estrogen receptor in the hypothalamus, which is the desired effect for fertility) and zuclomiphene (an agonist with a long , blamed for many of clomiphene's mood and visual side effects).

Enclomiphene is the isolated trans-isomer — the part you actually want for triggering LH and FSH release without the long-acting estrogenic baggage. It blocks estrogen feedback at the hypothalamus, which makes the pituitary release more LH, which makes the testes make more testosterone.

It was developed by Repros Therapeutics specifically as a TRT alternative for men with secondary hypogonadism who wanted to preserve fertility. It went through Phase 3 trials and met efficacy endpoints. The FDA rejected the 2015 NDA on regulatory rather than safety grounds, and the program never resumed under the original sponsor. It's now widely available through 503A compounding pharmacies and as online.

TL;DR

TL;DR. 30-second version.

The compressed verdict — what Enclomiphene actually is, what the human evidence shows, and the watch-for in three bullets. Locked.

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Mechanism

Mechanism.

Mechanism · in the Enclomiphene report

How the molecule actually works — receptor profile, downstream signaling, what to expect mechanistically.

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Evidence

Evidence. What we actually know in humans.

Evidence · in the Enclomiphene report

The trial breakdown — phase, n, primary endpoint, who funded, what hit, what didn't.

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Human-Evidence Factbox
Phase 3 trials completed
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FDA approval
denied 2016, design issues
Available via compounding
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Preserves sperm vs TRT
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Oral, daily
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Visual side-effects rule (SERM class)
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Mood side-effects
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Stack-conflict — exogenous TRT
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Effect timeline — testosterone + LH/FSH
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Effect timeline — sperm parameters
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Stop rule — no testosterone shift by 8 weeks
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Dose

Dose. The actual protocol.

Dose · in the Enclomiphene report

The specific protocol — dose, titration schedule, cycle pattern, frequency, route.

We read 60 studies to write this report.
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Sourcing

Sourcing. Where the cohort actually buys.

Sourcing · in the Enclomiphene report

Sourcing breakdown — vendor methodology, red flags, our published test results, COA checklist.

We read 60 studies to write this report.
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Safety

Safety. Side effects.

Safety · in the Enclomiphene report

The watch-for list — contraindications, drug interactions, monitoring labs, when to stop.

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Editorial Position

Editorial position.

Editorial Position · in the Enclomiphene report

Our editorial position — explicit yes / no / depends, with the reasoning behind it.

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Citations

Citations.

  1. 01Saffati G, et al. Safety and efficacy of enclomiphene and clomiphene for hypogonadal men. Translational andrology and urology. 2024;13(9):1984-1990. PMID: 39434750.
  2. 02Rodriguez KM, et al. Enclomiphene citrate for the treatment of secondary male hypogonadism. Expert opinion on pharmacotherapy. 2016;17(11):1561-7. PMID: 27337642.
  3. 03Thomas J, et al. Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate for Male Infertility Treatment: A Retrospective Study. Cureus. 2023;15(7):e41476. PMID: 37546076.
  4. 04Hill S, et al. Enclomiphene, an estrogen receptor antagonist for the treatment of testosterone deficiency in men. IDrugs : the investigational drugs journal. 2009;12(2):109-19. PMID: 19204885.
  5. 05Hohl A, et al. Clomiphene or enclomiphene citrate for the treatment of male hypogonadism: a systematic review and meta-analysis of randomized controlled trials. Archives of endocrinology and metabolism. 2025;69(5). PMID: 41066380.
+Show all 60 citations
  1. 06Earl JA, et al. Enclomiphene citrate: A treatment that maintains fertility in men with secondary hypogonadism. Expert review of endocrinology & metabolism. 2019;14(3):157-165. PMID: 31063005.
  2. 07Franz-Odendaal TA, et al. Clomiphene Citrate and Enclomiphene Hydrochloride Exposure Is Associated With Interfrontal Suture Fusion in Zebrafish. Plastic surgery (Oakville, Ont.). 2023;31(4):383-389. PMID: 37915340.
  3. 08Kim 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. 2016;117(4):677-85. PMID: 26496621.
  4. 09Schramm RD, et al. Enclomiphene does not alter the postpartum interval of suckled beef cows. Journal of animal science. 1991;69(10):4112-6. PMID: 1778825.
  5. 10Wiehle RD, et al. Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone. Fertility and sterility. 2014;102(3):720-7. PMID: 25044085.
  6. 11Kaminetsky J, et al. Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel. The journal of sexual medicine. 2013;10(6):1628-35. PMID: 23530575.
  7. 12Westfahl PK. Enclomiphene induces luteolysis in the nonpregnant guinea pig. Experientia. 1989;45(1):104-6. PMID: 2492231.
  8. 13Foster J, et al. British Society of Sexual Medicine: Position Statement for the Potential Use of Enclomiphene in the Treatment of Male Hypogonadism. The world journal of men's health. 2026. PMID: 41714894.
  9. 14Wiehle R, et al. Testosterone Restoration by Enclomiphene Citrate in Men with Secondary Hypogonadism: Pharmacodynamics and Pharmacokinetics. BJU international. 2013;112(8):1188-200. PMID: 23875626.
  10. 15Kovac JR. Reproductive endocrinology: Oral enclomiphene citrate in obese men with hypogonadism. Nature reviews. Urology. 2016;13(3):133-4. PMID: 26787395.
  11. 16Ruenitz PC. Rabbit liver microsomal metabolism of enclomiphene. Drug metabolism and disposition: the biological fate of chemicals. 1981;9(5):456-60. PMID: 6117445.
  12. 17Niederberger C. Re: Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone. The Journal of urology. 2015;193(6):2053-4. PMID: 25986825.
  13. 18Young SL, et al. Serum concentrations of enclomiphene and zuclomiphene across consecutive cycles of clomiphene citrate therapy in anovulatory infertile women. Fertility and sterility. 1999;71(4):639-44. PMID: 10202872.
  14. 19Opsahl MS, et al. Effects of enclomiphene and zuclomiphene on basal and gonadotrophin-stimulated progesterone secretion by isolated subpopulations of small and large ovine luteal cells. Human reproduction (Oxford, England). 1996;11(6):1250-5. PMID: 8671435.
  15. 20Tienforti D, et al. Selective modulation of estrogen receptor in obese men with androgen deficiency: A systematic review and meta-analysis. Andrology. 2023;11(6):1067-1076. PMID: 36604313.
  16. 21Huang ES, et al. Estrogenic and antiestrogenic effects of enclomiphene and zuclomiphene on gonadotropin secretion by ovine pituitary cells in culture. Endocrinology. 1983;112(2):442-8. PMID: 6401242.
  17. 22Kaminetsky J, et al. Clomiphene citrate and enclomiphene for the treatment of hypogonadal androgen deficiency. Expert opinion on investigational drugs. 2009;18(12):1947-55. PMID: 19938905.
  18. 23Helo S, et al. Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long-term clomiphene citrate treatment. BJU international. 2017;119(1):171-176. PMID: 27511863.
  19. 24Chang CF, et al. Postpartum interval in beef cows shortened by enclomiphene. Journal of animal science. 1987;65(1):217-23. PMID: 3112086.
  20. 25Niederberger C. Re: Oral Enclomiphene Citrate Raises Testosterone and Preserves Sperm Counts in Obese Hypogonadal Men, Unlike Topical Testosterone: Restoration Instead of Replacement. The Journal of urology. 2017;197(1):233. PMID: 27979553.
  21. 26Wang C, et al. Direct inhibitory effect of enclomiphene citrate and estradiol on testis functions in hypophysectomized rats. Biology of reproduction. 1980;22(3):645-53. PMID: 6248140.
  22. 27Schmidt GE, et al. The effects of enclomiphene and zuclomiphene citrates on mouse embryos fertilized in vitro and in vivo. American journal of obstetrics and gynecology. 1986;154(4):727-36. PMID: 3083679.
  23. 28Turner RT, et al. Differential responses of estrogen target tissues in rats including bone to clomiphene, enclomiphene, and zuclomiphene. Endocrinology. 1998;139(9):3712-20. PMID: 9724022.
  24. 29Hohl A, et al. Response to the letter to the editor: Clomiphene or enclomiphene citrate for the treatment of male hypogonadism: a systematic review and meta-analysis of randomized controlled trials. Archives of endocrinology and metabolism. 2025;69(6):e250547. PMID: 41312855.
  25. 30Ghobadi C, et al. CYP2D6 is primarily responsible for the metabolism of clomiphene. Drug metabolism and pharmacokinetics. 2008;23(2):101-5. PMID: 18445989.
  26. 31Marth C, et al. Inhibition of the estradiol-induced growth of cultured human breast cancer cells by the anti-estrogens tamoxifen, desmethyl-tamoxifen, 4-hydroxy-tamoxifen and enclomiphene. Biochemical pharmacology. 1984;33(24):3951-6. PMID: 6439216.
  27. 32Gregg DW, et al. Effects of enclomiphene on estradiol-induced changes in LH secretion in ewes. Journal of animal science. 1990;68(10):3293-9. PMID: 2123847.
  28. 33Wilcox JN, et al. Long-term priming with a low dosage of estradiol benzoate or an antiestrogen (enclomiphene) increases nuclear progestin receptor levels in brain. Brain research. 1983;266(2):243-51. PMID: 6409349.
  29. 34Murphy LC, et al. Antitumor activity of clomiphene analogs in vitro: relationship to affinity for the estrogen receptor and another high affinity antiestrogen-binding site. The Journal of clinical endocrinology and metabolism. 1983;57(2):373-9. PMID: 6408114.
  30. 35Hochu G, et al. Preserving spermatogenesis in testosterone deficiency: innovations in replacement and stimulatory therapies. Translational andrology and urology. 2025;14(12):3975-3987. PMID: 41522318.
  31. 36Achua JK, et al. Leydig stem cells and future therapies for hypogonadism. Current opinion in endocrinology, diabetes, and obesity. 2020;27(6):419-423. PMID: 33003069.
  32. 37Sasson S, et al. The inhibition of the estrogen receptor's positive cooperative [3H]estradiol binding by the antagonist, clomiphene. The Journal of biological chemistry. 1982;257(19):11540-5. PMID: 7118895.
  33. 38Joseph T, et al. Are SERMs safe and effective for the treatment of hypogonadism in men?. The Journal of family practice. 2022;71(1):E18-E21. PMID: 35259334.
  34. 39Kneussl ES, et al. A specific cytosolic estrogen receptor in human term placenta. American journal of obstetrics and gynecology. 1982;144(7):803-9. PMID: 7148904.
  35. 40Fontenot GK, et al. Differential effects of isomers of clomiphene citrate on reproductive tissues in male mice. BJU international. 2016;117(2):344-50. PMID: 26220499.
  36. 41Wing LY, et al. Differential responses of sex steroid target tissues of rats treated with 4-hydroxyandrostenedione. Endocrinology. 1988;122(6):2418-27. PMID: 3131115.
  37. 42Jordan VC, et al. Tamoxifen-stimulated growth of human endometrial carcinoma. Annals of the New York Academy of Sciences. 1991;622:439-46. PMID: 1905895.
  38. 43Miller GD, et al. Hypothalamic-Pituitary-Testicular Axis Effects and Urinary Detection Following Clomiphene Administration in Males. The Journal of clinical endocrinology and metabolism. 2019;104(3):906-914. PMID: 30295816.
  39. 44Bayés M, et al. Gateways to clinical trials. Methods and findings in experimental and clinical pharmacology. 2004;26(10):801-27. PMID: 15672123.
  40. 45Clark JH, et al. Triphenylethylene antiestrogen binding sites (TABS) specificity. Journal of steroid biochemistry. 1987;26(4):433-7. PMID: 3586657.
  41. 46Bitonti AJ, et al. Antitumor and chemopreventive effects of a clomiphene analog, MDL 103,323, in mammary carcinoma. Anticancer research. 1996;16(5A):2553-7. PMID: 8917350.
  42. 47Ross LS. Selective estrogen receptor modulators, male hypogonadism, and infertility. Fertility and sterility. 2014;102(3):687-8. PMID: 25044078.
  43. 48Bempong DK, et al. Multivariate analysis of capillary electrophoresis separation conditions for Z-E isomers of clomiphene. Journal of pharmaceutical and biomedical analysis. 1996;15(2):233-9. PMID: 8933425.
  44. 49Trubert J, et al. Comparison between Amorphous States of the Trans/Cis Isomers of Clomiphene: Similarities and Differences. Molecular pharmaceutics. 2025;22(11):6932-6940. PMID: 41071236.
  45. 50Pakrasi PL, et al. Ovulation induction by antiestrogens in an Indian tropical vespertillionid bat, Scotophilus heathi. Life sciences. 2006;79(23):2217-20. PMID: 16934298.
  46. 51Nelson EA, et al. Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications. Viruses. 2016;8(8). PMID: 27490565.
  47. 52Olsson JH, et al. Effect of clomiphene isomers on progestin synthesis in cultured human granulosa cells. Human reproduction (Oxford, England). 1987;2(6):463-8. PMID: 3117835.
  48. 53Olsson JH, et al. Effect of clomiphene isomers on oestradiol synthesis in cultured human granulosa cells. Human reproduction (Oxford, England). 1990;5(8):928-32. PMID: 2081804.
  49. 54Burghardt RC, et al. Gap junction modulation in rat uterus. II. Effects of antiestrogens on myometrial and serosal cells. Biology of reproduction. 1984;30(1):249-55. PMID: 6421335.
  50. 55Still JG, et al. Effects of Cis- and trans-clomiphene on the uterine blood flow of oophorectomized ewes. Gynecologic investigation. 1976;7(4):187-200. PMID: 992480.
  51. 56Teramoto S, et al. Minimal ovarian stimulation with clomiphene citrate: a large-scale retrospective study. Reproductive biomedicine online. 2007;15(2):134-48. PMID: 17697488.
  52. 57Ross JW, et al. Effects of cis- and trans-clomiphene in the induction of sexual behavior. Endocrinology. 1973;93(3):681-5. PMID: 4721294.
  53. 58Kronenberg MS, et al. Changes in keratin expression during the estrogen-mediated differentiation of rat vaginal epithelium. Endocrinology. 1985;117(4):1480-9. PMID: 2411529.
  54. 59Bowman SP, et al. Time-related effects of en-clomiphene upon central and peripheral oestrogen target tissues and cytoplasmic receptors. The Journal of endocrinology. 1981;89(1):117-28. PMID: 6783718.
  55. 60Fritz MA, et al. Effect of clomiphene citrate treatment on endometrial estrogen and progesterone receptor induction in women. American journal of obstetrics and gynecology. 1991;165(1):177-85. PMID: 1906682.
The Enclomiphene Report · $19

Everything you need to start.

Dose, sourcing, safety, our verdict. One purchase. Yours forever.

Built from 60 cited studies.

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