Enclomiphene is a selective estrogen receptor modulator (SERM) developed to treat secondary hypogonadism, a condition characterized by low testosterone due to signaling problems from the brain. This medication encourages the body’s natural testosterone production, offering an alternative to traditional hormone replacement. Many men with low testosterone seek clarity on whether this treatment has been formally approved by US regulators. This article addresses the definitive status of enclomiphene regarding its approval and explains how it is currently used in clinical practice.
Enclomiphene’s Regulatory Status
Enclomiphene is not currently a Food and Drug Administration (FDA)-approved drug for the treatment of male hypogonadism. While it was the subject of extensive research, it never received final approval for commercial manufacturing as a standalone medication. Developed under the tentative brand name Androxal, the drug progressed through Phase 3 clinical trials, the final stage before seeking regulatory clearance.
A New Drug Application (NDA) was submitted to the FDA, but the manufacturer received a Complete Response Letter in 2015. This letter indicated the application could not be approved, citing concerns that the design of the Phase 3 studies was inadequate to demonstrate the required clinical benefit. The FDA requested the company conduct additional studies to support its use.
Ultimately, the development of enclomiphene as a proprietary drug was discontinued by the sponsor in 2021. The drug remains in an investigational status, meaning it is not available as a mass-produced, branded pharmaceutical product dispensed by standard retail pharmacies. While clinical data exists supporting its use, enclomiphene lacks the official regulatory endorsement that signifies it has met the FDA’s safety and efficacy standards for a new drug.
The Mechanism of Action
Enclomiphene belongs to the class of selective estrogen receptor modulators (SERMs), which exert targeted effects on estrogen receptors throughout the body. Its primary action is to function as an estrogen receptor antagonist, specifically in the hypothalamus and the pituitary gland. These glands are central components of the hypothalamic-pituitary-gonadal (HPG) axis, which regulates hormone production.
By blocking the estrogen receptors, enclomiphene disrupts the body’s normal negative feedback loop. The hypothalamus perceives a lower level of circulating estrogen, signaling the need to increase activity in the HPG axis. This results in a greater release of Gonadotropin-Releasing Hormone (GnRH).
The increased GnRH then travels to the pituitary gland, stimulating it to secrete more Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH). LH stimulates the Leydig cells within the testes to produce testosterone. This cascade boosts the body’s own natural production of testosterone, addressing secondary hypogonadism.
Accessing Enclomiphene Through Compounding
Patients can still access enclomiphene despite its non-approved status because of its relationship to the FDA-approved medication clomiphene citrate (Clomid). Clomiphene is a mixture of two distinct chemical forms, known as isomers: enclomiphene and zuclomiphene. Clomiphene is composed of approximately 62% enclomiphene and 38% zuclomiphene.
Enclomiphene is the trans-isomer, primarily responsible for stimulating testosterone production by blocking estrogen receptors. Conversely, zuclomiphene is the cis-isomer, which has a longer half-life and more estrogenic activity. Isolating the enclomiphene isomer is often preferred for treating male hypogonadism because zuclomiphene’s estrogenic properties can sometimes counteract the therapeutic goal.
Since enclomiphene is not commercially available as a manufactured product, it is primarily obtained through compounding pharmacies. Compounding is the legal process where a licensed pharmacy prepares a specialized medication for an individual patient based on a valid prescription. This practice is permitted because enclomiphene is a component of the FDA-approved drug clomiphene.
Compounding allows physicians to prescribe the purified enclomiphene isomer, often in customized dosages and formulations, such as oral capsules or suspensions. The compounded product is not FDA-approved, as only mass-manufactured drugs undergo that review process. However, the ability to access the isolated, active component via a compounding pharmacy provides a legal pathway for patients seeking this specific treatment for low testosterone.