From the Guidelines
Enclomiphene works by blocking estrogen receptors in the hypothalamus and pituitary gland, leading to an increase in gonadotropin-releasing hormone (GnRH) production, which in turn stimulates the testes to produce more testosterone and increase sperm production. This mechanism of action is supported by the most recent and highest quality study available, which highlights the importance of selective estrogen receptor modulators (SERMs) in treating male infertility 1.
Mechanism of Action
The blockade of estrogen receptors by enclomiphene prevents estrogen from exerting its negative feedback on the hypothalamic-pituitary axis, resulting in increased production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. In men, this hormonal cascade stimulates the testes to produce more testosterone, which is essential for spermatogenesis. Enclomiphene is the trans-isomer of clomiphene and has stronger anti-estrogenic properties than the cis-isomer (zuclomiphene) 1.
Clinical Implications
Unlike testosterone replacement therapy, which can suppress natural hormone production, enclomiphene maintains or restores the body's natural hormonal axis. This makes it particularly useful for treating secondary hypogonadism in men who wish to preserve fertility, as it increases testosterone production without impairing sperm production. Typical dosing ranges from 12.5 to 25 mg daily, though protocols may vary based on individual patient needs and response to therapy.
Key Points
- Enclomiphene is a selective estrogen receptor modulator (SERM) that blocks estrogen receptors in the hypothalamus and pituitary gland.
- This blockade leads to an increase in GnRH production, which stimulates the testes to produce more testosterone and increase sperm production.
- Enclomiphene is useful for treating secondary hypogonadism in men who wish to preserve fertility, as it increases testosterone production without impairing sperm production.
- Typical dosing ranges from 12.5 to 25 mg daily, with protocols varying based on individual patient needs and response to therapy 1.
From the FDA Drug Label
Clomiphene citrate is capable of interacting with estrogen-receptor-containing tissues, including the hypothalamus, pituitary, ovary, endometrium, vagina, and cervix. It may compete with estrogen for estrogen-receptor-binding sites and may delay replenishment of intracellular estrogen receptors The two clomiphene isomers have been found to have mixed estrogenic and antiestrogenic effects, which may vary from one species to another. Some data suggest that zuclomiphene has greater estrogenic activity than enclomiphene Clomiphene citrate initiates a series of endocrine events culminating in a preovulatory gonadotropin surge and subsequent follicular rupture.
The mechanism of action of enclomiphene, a Selective Estrogen Receptor Modulator, involves competing with estrogen for estrogen-receptor-binding sites, which may delay replenishment of intracellular estrogen receptors. Enclomiphene has antiestrogenic effects and initiates a series of endocrine events that culminate in a preovulatory gonadotropin surge and subsequent follicular rupture, leading to ovulation 2.
- Key points:
- Competes with estrogen for estrogen-receptor-binding sites
- Delays replenishment of intracellular estrogen receptors
- Initiates a series of endocrine events leading to ovulation
- Has antiestrogenic effects
- Part of the clomiphene citrate mixture, which also includes zuclomiphene (cis) 2
From the Research
Mechanism of Action of Enclomiphene
Enclomiphene, a selective estrogen receptor modulator (SERM), works by increasing testosterone levels while stimulating follicle-stimulating hormone (FSH) and luteinizing hormone (LH) production 3, 4, 5. This is achieved through its antagonistic effects on estrogen receptors, promoting gonadotropin-dependent testosterone secretion by the testes 6.
Key Effects of Enclomiphene
- Increases serum testosterone levels by raising LH and FSH levels 3, 4, 5
- Maintains fertility in men with secondary hypogonadism by conserving sperm production 4, 5
- Reverses the hallmarks of secondary hypogonadism, including low serum total testosterone and low or inappropriately normal LH 5
- Exhibits a favorable effect on fasting plasma glucose, potentially benefiting men with obesity and metabolic syndrome 6
Comparison to Other Treatments
Enclomiphene has been compared to exogenous testosterone replacement therapy, with studies suggesting that it is effective and safe for improving serum testosterone levels, with symptom improvement comparable to that with exogenous testosterone replacement 7. Additionally, enclomiphene has been shown to be equivalent in safety to testosterone gels and placebo in short-term clinical trials 6.