Enclomiphene is an oral selective estrogen receptor modulator (SERM) that raises a man's own testosterone by blocking estrogen feedback at the brain, so the pituitary releases more LH and FSH. It is the trans isomer of clomiphene (Clomid), the half that drives this effect. It has no FDA approval: the FDA rejected the Androxal application with a Complete Response Letter in December 2015, and the EMA refused the same molecule (EnCyzix) in 2018 [5][9].
🔑 Key Takeaways
- Enclomiphene is the active isomer of clomiphene — works by blocking estrogen receptors in the hypothalamus, triggering the body to produce more LH and FSH, which drives natural testosterone production
- Unlike TRT, it preserves fertility and testicular function: sperm counts held in phase III while testosterone gel cut them [3]
- Trial results: 25 mg daily reached 604 ± 160 ng/dL at 6 weeks, statistically no different from testosterone gel [1]
- Trial doses: 12.5 mg or 25 mg once daily by mouth
- Not approved by the FDA or the EMA as of November 2026. There is no branded Androxal on sale; what is sold is compounded or vendor-made capsules
- Better tolerated than clomiphene in a 66-man comparison, because zuclomiphene is absent [6]
If your testosterone is low but you want to keep your fertility, you have probably already heard the name. The numbers below come from the trials themselves, and our enclomiphene dosage chart covers the dose and lab schedule in more detail.
What Is Enclomiphene?
Enclomiphene citrate is a selective estrogen receptor modulator (SERM). It's the trans-isomer of clomiphene. Clomiphene citrate is a mixture of two isomers: enclomiphene and zuclomiphene, with 30-50% zuclomiphene according to the FDA label [7].
By blocking estrogen receptors in the hypothalamus, enclomiphene tricks the brain into thinking estrogen is low. The hypothalamus responds by increasing GnRH output, which drives LH and FSH production from the pituitary, which tells the testes to make more testosterone.
The pathway: hypothalamus → more GnRH → more LH + FSH → more testosterone.
The result: your body makes more of its own testosterone, without suppressing the hypothalamic-pituitary-gonadal (HPG) axis like TRT does. In the 6-week phase II trial, enclomiphene raised LH and FSH while testosterone gel suppressed them, and the effect on LH and testosterone lasted at least one week after the last dose [1].
Half-life matters here. Enclomiphene clears in about 10 hours; zuclomiphene, the other half of Clomid, has a half-life of about 30 days, which is why its effects can outlast the drug [4].
Is Enclomiphene FDA-Approved? Approval History
No. Here is what happened, in order.
The core problem in both reviews was the same. The trials proved that testosterone numbers went up, but they did not measure whether men felt or functioned better [5][9]. The EMA also flagged venous thromboembolism (blood clots) as a risk [9].
Enclomiphene vs TRT vs Clomiphene
The honest tradeoff: TRT will get you higher absolute testosterone numbers when it is dosed for that. But if you want to preserve fertility, maintain testicular function, and keep your own production alive, enclomiphene is the closer fit, as long as your testes still work. Against clomiphene, the 66-man comparison found a median testosterone rise of 166 vs 98 ng/dL, a difference that was not statistically significant (P=0.20); the clear win was fewer side effects [6].
The comparison most men actually want is against HCG, since the two are the usual alternatives to straight testosterone. We cover it in full in enclomiphene vs HCG, including why only one of them raises FSH.
What Enclomiphene Does — Effects
- Raises testosterone: in the phase IIb (ZA-203) trial, 12.5 mg took mean testosterone from 217 to 472 ng/dL at 3 months and 25 mg from 210 to 406 ng/dL [2][4]
- Raises FSH and LH: unlike TRT, which suppresses both [1][3]
- Maintains testicular function: the testes stay active because the LH signal continues
- Preserves sperm counts: across 16 weeks of phase III in 265 overweight men, sperm density held on enclomiphene and fell sharply on gel [3][4]
- Symptoms are the open question: none of the trials measured libido, energy or mood with a validated instrument, which is the gap both regulators cited [4][5]
Who Is Enclomiphene For?
The men in the trials:
- Overweight men aged 18-60 with secondary hypogonadism: morning testosterone at or under 300 ng/dL on two tests, with low or normal LH [3]
- Men who want to keep fertility while raising testosterone, since sperm counts held on enclomiphene in the trials [3]
- Men coming off TRT who want their own production back are a common off-label use, but no enclomiphene trial tested it
Not ideal for:
- Men with primary hypogonadism (testicular failure): the testes must be functional for enclomiphene to work. If LH is already high, stimulating it further won't help
- Men needing the highest testosterone levels: TRT will produce higher numbers if that's the goal
- Anyone with a history of blood clots, given the EMA's VTE concern [9]
- Women: not indicated and can cause hormonal disruption
Enclomiphene Dosage
Two doses were studied in phase III: 12.5 mg and 25 mg, taken by mouth once a day [3][4]. There is no approved label, so these are trial doses, not a labelled regimen. The review literature reports that steady-state levels were maximised at 25 mg/day [4].
- Trial doses: 12.5 mg or 25 mg once daily by mouth
- No trial tested doses above 25 mg
- Your prescriber decides the dose and when to recheck labs; our enclomiphene dosage chart lays out the trial arms side by side
Lab monitoring recommended:
- Testosterone (total and free): baseline and again at follow-up. SHBG can change, so free T is worth checking too
- LH and FSH: should increase on enclomiphene; if they don't, response is limited
- Estradiol: monitor for elevation, which was reported in the trials [4]
- CBC: routine safety check
What to Expect — Timeline
- Weeks 1-2: LH and FSH begin rising; testosterone rose within two weeks in the phase II trial [1]
- Week 6: 25 mg averaged 604 ± 160 ng/dL, versus 500 ± 278 ng/dL on gel (p = 0.23) [1]
- Months 3-4: levels plateau; the phase IIb readout was at 3 months and phase III at 16 weeks [2][3]
- Symptom changes were not measured in the trials, so any week-by-week "feel better" timeline is anecdotal
- After stopping, the effect on LH and testosterone lasted at least a week in the phase II trial [1]
Side Effects
The safety data is thin. The review literature notes that adverse effects of enclomiphene "have not been directly studied" as a primary outcome [4].
Cost and Where Enclomiphene Comes From
Because no approved product exists, there is no Androxal to fill at a pharmacy. Men who use enclomiphene get compounded capsules through a prescriber, or buy capsules from online vendors, where quality and isomer purity depend entirely on the seller. If you are comparing where to buy enclomiphene, ask for a certificate of analysis that shows the isomer content, since zuclomiphene contamination would bring back the long half-life you are trying to avoid. Generic clomiphene, by contrast, is FDA-approved (for women) and pharmacy-standardised [4][7].
Frequently Asked Questions
The information in this article is for educational purposes only and does not constitute medical advice. Always consult a healthcare professional before starting any new supplement or compound. Results vary by individual.
Sources
- Wiehle R, et al. Testosterone restoration by enclomiphene citrate in men with secondary hypogonadism: pharmacodynamics and pharmacokinetics. BJU Int. 2013;112(8):1188-200. PMID 23875626. PubMed
- Wiehle RD, et al.; ZA-203 Clinical Study Group. Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone. Fertil Steril. 2014;102(3):720-7. PMID 25044085. PubMed
- 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):677-85. PMID 26496621. PubMed
- Rodriguez KM, et al. Enclomiphene citrate for the treatment of secondary male hypogonadism. Expert Opin Pharmacother. 2016. PMID 27337642. PMC full text
- Repros Therapeutics Inc. Form 10-K for fiscal year 2015 (filed March 14, 2016), enclomiphene NDA and Complete Response Letter. SEC EDGAR
- Saffati G, et al. Safety and efficacy of enclomiphene and clomiphene for hypogonadal men. Transl Androl Urol. 2024;13(9):1984-1990. PMID 39434750. PubMed
- Clomid (clomiphene citrate) tablets, FDA-approved prescribing information. DailyMed
- Novarel (chorionic gonadotropin for injection), FDA-approved prescribing information. DailyMed
- European Medicines Agency. EnCyzix (enclomifene): refusal of the marketing authorisation, CHMP opinion January 25, 2018 (EMA/CHMP/54473/2018). EMA
- U.S. Food and Drug Administration. Drugs@FDA database (search: enclomiphene; no approved product), checked November 2026. Drugs@FDA