Enclomiphene vs Clomiphene: Isomers, Status, Evidence
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Enclomiphene vs clomiphene: what is the difference?

Isomers · FDA status · Zuclomiphene · Studies in men

Short answer: Clomiphene (Clomid) is a mix of two isomers: enclomiphene and zuclomiphene, with 30% to 50% zuclomiphene.1 Enclomiphene is the single isomer. Clomid is FDA approved only for ovulation problems in women; use in men is off label. Enclomiphene is not approved.2 Zuclomiphene lasts much longer and builds up in men on clomiphene.3

How do enclomiphene and clomiphene compare side by side?

Clomiphene from the Clomid label; enclomiphene from FDA records and published studies.
EnclomipheneClomiphene (Clomid)
What it isThe trans isomer of clomiphene on its ownA mix of trans (enclomiphene) and cis (zuclomiphene) isomers, 30% to 50% cis1
MechanismSelective estrogen receptor modulator; raises the body's own LH and FSH4Same class. The label says zuclomiphene may have more estrogen-like activity than enclomiphene1
Approval statusNot FDA approved; complete response letter December 20152FDA approved for ovulatory dysfunction in women who want to become pregnant1
Use in menStudied in phase 2 and 3 trials in men with secondary hypogonadism5Off label. The label says no adequate studies show it works for male infertility1
Dosing scheduleStudied: 12.5 or 25 mg by mouth daily in phase 3 trials6Label (women): 50 mg daily for 5 days per cycle to start1
Time to peak (Tmax)About 3 hours after a single 50 mg clomiphene dose7Zuclomiphene: about 7 hours after the same dose7
How long it staysShorter-lived of the two isomers1Zuclomiphene detectable for longer than a month after a single dose1
Isomer levels in men on long-term useMedian 2.2 ng/mLZuclomiphene median 44.0 ng/mL, about 20 times enclomiphene3
Notable warningsNo label. Phase 3 reported some men with a 50% or larger drop in sperm concentration6Visual symptoms (blurring, spots, flashes); stop and get an eye exam. Testicular tumors and gynecomastia reported in men1

Reviewed . Half-life figures are shown only where the value Dose Track uses agrees with the cited source.

Why does the isomer mix matter?

Clomiphene contains two mirror-image forms. The Clomid label says zuclomiphene has a longer half-life than enclomiphene and was still detectable more than a month after one dose.1 In a single-dose study, enclomiphene peaked at about 3 hours and zuclomiphene at about 7 hours, and a terminal half-life could not be calculated because the curve was so flat.7

In 15 men taking clomiphene daily for at least 6 weeks (median about 26 months), median zuclomiphene was 44.0 ng/mL vs 2.2 ng/mL for enclomiphene, a 20:1 ratio. The authors argued this supports developing a pure isomer for men.3

What do the studies in men show?

  • Clomiphene, long term: in 46 men treated for over a year, average testosterone went from 228 ng/dL to 612 ng/dL at 1 year. This was a review of treated patients with no placebo group.8
  • Enclomiphene, phase 3: raised testosterone and kept sperm counts in the normal range, unlike testosterone gel.5
  • Head to head: the only direct comparison found is a retrospective chart review of 46 men on enclomiphene and 32 on clomiphene. Both raised testosterone; only enclomiphene significantly raised LH, FSH and total motile sperm count.9 No randomized trial has compared the two.
This page summarizes labels and published studies. It is not personalized medical advice; confirm any dose or change with your prescriber.
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Frequently asked questions

Is enclomiphene the same as Clomid?+
No. Clomid is a mix of two isomers, enclomiphene and zuclomiphene. Enclomiphene is just one of them.1
Is clomiphene approved for men?+
No. The Clomid label covers ovulatory dysfunction in women. Prescribing it to men is off label, and the label says there are no adequate studies showing it works for male infertility.1
Why does zuclomiphene build up?+
It is cleared much more slowly. The label reports it was detectable for more than a month after a single dose, and men on daily clomiphene had about 20 times more zuclomiphene than enclomiphene in their blood.13
Is enclomiphene better than clomiphene?+
There is no randomized head-to-head trial. One retrospective chart review found both raised testosterone, with larger LH, FSH and sperm count changes on enclomiphene.9
Can I track enclomiphene or clomiphene in Dose Track?+
Yes. Both are built in, so you can log daily or every-other-day doses with reminders next to your lab results.

Sources

  1. Clomid (clomiphene citrate) tablets prescribing information. DailyMed, revised January 2025.
  2. Repros Therapeutics. Repros receives complete response letter for enclomiphene. News release filed with the SEC, December 1, 2015.
  3. Helo S, et al. Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long-term clomiphene citrate treatment. BJU Int. 2017.
  4. Wiehle RD, et al. Enclomiphene citrate stimulates serum testosterone in men with low testosterone while maintaining sperm counts (ZA-203). Fertil Steril. 2014.
  5. Kim ED, et al. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: two phase 3 trials. BJU Int. 2016.
  6. Enclomiphene ZA-301 phase 3 trial record and posted results (NCT01532414). ClinicalTrials.gov.
  7. Ghobadi C, et al. Single-dose pharmacokinetic study of clomiphene citrate isomers. 2009.
  8. Moskovic DJ, et al. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int. 2012.
  9. Thomas J, et al. Efficacy of clomiphene citrate versus enclomiphene citrate for male infertility treatment: a retrospective study. Cureus. 2023.

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