Enclomiphene Reference

Plain English

What it is

Enclomiphene is one of the two mirror-image halves of clomiphene, an older fertility medicine. It is investigational, meaning it is not approved by the FDA. In the United States you can only get it as a compounded product, which is custom-mixed by a pharmacy from a prescription.

What people use it for

Men in the low-testosterone community talk about it as a way to nudge the body into making more of its own testosterone while keeping fertility, instead of taking testosterone itself. It works by signaling the brain to release more of the hormones (called LH and FSH) that tell the testicles to make testosterone. Some people in lifting circles also use it off label to restart their own testosterone, which is a choice made with a prescriber.

What the science shows

An early human study found that enclomiphene raised men's own LH, FSH, and testosterone into the normal range, and that it pushed those brain hormones up rather than shutting them down the way taking testosterone does. But the company's later trials did not satisfy the FDA, so it was never approved, and development was eventually stopped. That leaves a smaller evidence base and limited long-term data.

The catch

Because it is not FDA-approved, the version sold in the US is custom-compounded, so the quality and exact contents can vary from one source to another. It is also banned in sports at all times by the World Anti-Doping Agency. This is a prescription drug, not a supplement, and off-label use is a decision to make with a prescriber.

Reference summary

Wiehle 2013 BJU Int demonstrated that enclomiphene citrate raises endogenous LH, FSH, and testosterone in secondary hypogonadism men with a pharmacokinetic and pharmacodynamic profile distinct from racemic clomiphene. The argument for enclomiphene over racemic clomiphene is that the zuclomiphene isomer is the longer-half-life estrogen-receptor-agonist component of racemic clomiphene; the enclomiphene-only isomer should produce cleaner antagonist-driven gonadotropin elevation. Phase 3 outcome data for the regulatory submission were the basis of the 2015 FDA non-approval.

Regulatory and posture

Categories

Hormonal, Reproductive

Aliases

Androxal (investigational; not FDA-approved as a single agent), Trans-isomer of clomiphene citrate, Selective estrogen receptor modulator (small molecule, not a peptide)

Evidence posture

human - Investigational; FDA non-approval in 2015. Available only as off-label compounded product in the US.

Regulatory status

Not FDA-approved as a single-agent product for any indication. The Androxal program (Repros Therapeutics) targeted secondary hypogonadism in men but failed Phase 3 FDA approval in 2015 due to the trial design and FDA-identified concerns with the secondary-hypogonadism endpoint framework. Available in the United States only as off-label compounded enclomiphene; the trans-isomer is not separately marketed as a finished pharmaceutical product. WADA-prohibited at all times under S4 (hormone and metabolic modulators).

Content review status

research reference