Enclomiphene

How It Works

Enclomiphene is the pharmacologically active trans-isomer of clomiphene citrate, a selective estrogen receptor modulator (SERM) that has been used for decades in fertility treatment. While traditional clomiphene (Clomid) contains both enclomiphene and zuclomiphene isomers, standalone enclomiphene provides the therapeutic anti-estrogenic effect without the estrogenic activity and long half-life of zuclomiphene.

Enclomiphene works by selectively blocking estrogen receptors (primarily ER-alpha) in the hypothalamus and anterior pituitary gland. Under normal physiology, estrogen provides negative feedback that suppresses gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). By blocking this feedback, enclomiphene increases GnRH pulsatility, which in turn elevates LH and FSH secretion. LH stimulates Leydig cells in the testes to produce testosterone, while FSH supports Sertoli cell function and spermatogenesis.

This mechanism makes enclomiphene a compelling alternative to exogenous testosterone replacement therapy for men who wish to increase testosterone while preserving fertility and testicular function. Clinical trials have demonstrated testosterone increases of 200-400+ ng/dL from baseline in hypogonadal men.

Benefits

• Increases endogenous testosterone production — demonstrated 200-400+ ng/dL increases in clinical trials
• Preserves fertility — maintains or improves sperm count and motility, unlike exogenous TRT
• Maintains testicular function — no testicular atrophy as seen with exogenous testosterone
• Oral administration — convenient daily pill, no injections required
• Cleaner profile than Clomid — avoids zuclomiphene-related estrogenic side effects
• Preserves HPG axis function — the body continues to regulate its own hormone production

Side Effects

• Generally well-tolerated with fewer side effects than traditional clomiphene
• Headache — occasional, usually mild
• Nausea — reported by some users, typically transient
• Hot flashes — related to estrogen receptor blockade
• Mood changes — less common than with clomiphene (Clomid) due to absence of zuclomiphene
• Visual disturbances — very rare with enclomiphene alone (more associated with zuclomiphene)
• Elevated estradiol — monitor E2, as increased testosterone may aromatize
• No significant liver toxicity reported at standard doses

Dosing Protocol

What You Will Need

• Enclomiphene citrate capsules (12.5mg or 25mg, from compounding pharmacy)
• Baseline blood work (Total T, Free T, LH, FSH, E2, SHBG, CBC)
• Follow-up labs at 6-8 weeks and then every 3-6 months