Enclomiphene vs S-23

Mechanism

Enclomiphene is the purified trans-isomer of clomiphene citrate that acts as a selective estrogen receptor antagonist at the hypothalamus and pituitary without the estrogenic agonist activity of the zuclomiphene isomer. By blocking estrogen receptor alpha (ERa) in the hypothalamus, it removes estradiol-mediated negative feedback on GnRH neurons, resulting in increased pulsatile GnRH release and consequent elevation of LH and FSH from the anterior pituitary. This stimulates endogenous Leydig cell testosterone production while preserving spermatogenesis — a critical advantage over exogenous testosterone.

Standard Dosing

Research indicates 12.5-25 mg daily orally for testosterone restoration in secondary hypogonadism.

Timing

Once daily, morning preferred. No food timing requirements. Consistent daily dosing for optimal HPG axis stimulation.

Cycle Duration

Long-term use (months to years) is feasible due to absence of zuclomiphene accumulation issues. Reassess every 3-6 months.

Side Effects

• Headache
• Hot flashes
• Nausea (less common than racemic clomiphene)
• Elevated estradiol (from increased testosterone substrate for aromatase)
• Rare visual disturbances (significantly less than racemic clomiphene)

Contraindications

• Primary hypogonadism (elevated gonadotropins, testicular failure)
• Severe hepatic impairment
• Known hypersensitivity to clomiphene isomers
• Pituitary tumors
• Vision changes or thrombotic history warrant caution

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Mechanism

S-23 is one of the most potent nonsteroidal SARMs developed, originally investigated by GTx, Inc. as a potential male hormonal contraceptive. It binds the androgen receptor with very high affinity, producing near-steroidal anabolic effects in muscle and bone while profoundly suppressing FSH and LH, leading to oligospermia and azoospermia in animal models. S-23 increases lean body mass and bone mineral density while reducing fat mass in a dose-dependent manner. The contraceptive effect was fully reversible in rat studies — spermatogenesis and fertility recovered completely after a 100-day washout period.

Standard Dosing

Research indicates 10-25 mg daily orally for 8-12 weeks. No human clinical trials — dosing extrapolated from rat pharmacology and anecdotal reports.

Timing

Split into 2 daily doses due to relatively short half-life (~12 hours). Morning and evening dosing.

Cycle Duration

8 week cycles maximum recommended. PCT is absolutely mandatory due to profound HPG suppression. Allow full recovery before considering subsequent cycles.

Side Effects

• Profound testosterone suppression (near-complete LH/FSH shutdown)
• Temporary infertility / azoospermia
• Aggression and mood changes (reported frequently)
• Hair loss (strong androgenic binding)
• Testicular atrophy
• Night sweats
• Prostate effects (despite selectivity claims, S-23 had some prostate stimulation in rats)
• HDL suppression

Contraindications

• Desire for fertility in the near term (profound spermatogenic suppression)
• Pre-existing liver disease
• Androgen-sensitive cancers
• Cardiovascular disease
• Pregnancy and breastfeeding
• Individuals under 21

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