The short version
Enclomiphene is one of the two mirror-image forms (isomers) that make up clomiphene citrate, the fertility drug sold as Clomid. The Clomid label describes clomiphene as a mixture of zuclomiphene (cis) and enclomiphene (trans), with 30% to 50% cis-isomer (Clomid prescribing information, DailyMed).
It works upstream of the testes: by blocking estrogen feedback on the brain, it raises luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which tell the testes to make testosterone and sperm. That is the opposite of testosterone therapy, which suppresses LH and FSH.
There is no FDA-approved enclomiphene product: a search of FDA’s approved-drug database returns no enclomiphene approval. Clinics supply it as a compounded medication, and compounded drugs are not FDA-approved, which means FDA does not verify their safety, effectiveness or quality before they are marketed (FDA, Compounding and the FDA: Questions and Answers).
This article is general information, not medical advice or a dosing recommendation. Decisions about starting, changing or stopping a prescription belong with a licensed clinician who knows your history.
What the trials found
Phase II (2014). In men with secondary hypogonadism, oral enclomiphene raised morning testosterone, estradiol and LH to levels similar to a 1% testosterone gel, increased FSH and LH, and conserved sperm counts (Wiehle et al., Fertil Steril 2014, PMID: 25044085).
Two parallel phase III trials (ZA-304 and ZA-305). Overweight men aged 18 to 60 with early-morning total testosterone at or below 300 ng/dL on two tests and low or normal LH received one of two enclomiphene doses or testosterone gel (AndroGel 1.62%) for 16 weeks. Testosterone rose in every group; LH and FSH rose with enclomiphene and fell with the gel; sperm concentration stayed in the normal range on enclomiphene but dropped markedly on the gel (Kim et al., BJU Int 2016, PMID: 26496621).
What the trials did not show. The phase III trials measured hormone levels and sperm counts over 16 weeks, not symptoms over years, fractures or heart outcomes.
Enclomiphene vs clomiphene vs TRT
| Enclomiphene | Clomiphene (Clomid) | Testosterone therapy | |
|---|---|---|---|
| What it is | Trans isomer of clomiphene | Mix of cis and trans isomers | The hormone itself |
| FDA status | No approved product; compounded | FDA-approved for ovulatory dysfunction in women; off-label in men | FDA-approved for men with hypogonadism |
| Effect on LH/FSH | Raises them | Raises them | Suppresses them |
| Sperm production | Maintained in trials | Maintained in trials of SERMs | Can stop it |
The AUA guideline says exogenous testosterone should not be prescribed to men who are currently trying to conceive (strong recommendation) and that clinicians may use aromatase inhibitors, hCG, selective estrogen receptor modulators (SERMs) or a combination in men with testosterone deficiency who want to maintain fertility (conditional recommendation) (AUA testosterone deficiency guideline). Enclomiphene and clomiphene are SERMs.
For a fuller comparison see our enclomiphene vs TRT article; for clinic prices see enclomiphene online.
Side effects
The trial abstracts above do not list adverse-event rates, so the best-documented side effects come from clomiphene, its parent drug. The AUA guideline lists visual symptoms, flushing, headache and abdominal discomfort as clomiphene adverse effects (AUA guideline, Table 6).
The Clomid label warns that blurring or other visual symptoms such as spots or flashes may occur, become more frequent with higher total dose or longer use, and are usually reversible, though prolonged visual disturbance has been reported, including after stopping (Clomid prescribing information). Report any vision change to your prescriber promptly.
Enclomiphene also raised estradiol in the phase II trial (Wiehle et al., 2014), which is one reason clinicians recheck labs on treatment.
Labs before and during treatment
The AUA guideline uses a total testosterone below 300 ng/dL as a reasonable cut-off and requires two early-morning measurements on separate occasions before diagnosing low testosterone, together with symptoms or signs (AUA guideline). The phase III enclomiphene trials used the same 300 ng/dL threshold on two tests (Kim et al., 2016).
For men on clomiphene, anastrozole or hCG, the guideline recommends follow-up blood work no sooner than 4 weeks after starting (AUA guideline). If you want to check your numbers first, see ordering your own blood work.