LGD-4033 (Ligandrol) vs S-23

Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.

LGD-4033 (Ligandrol)S-23
CategorySARMsSARMs
Standard DoseResearch indicates 5-10 mg daily orally for 8-12 weeks. Phase 1 data showed significant lean mass gains at 1 mg/day.Research indicates 10-25 mg daily orally for 8-12 weeks. No human clinical trials — dosing extrapolated from rat pharmacology and anecdotal reports.
TimingOnce daily, consistent timing. Half-life approximately 24-36 hours. No food timing requirements.Split into 2 daily doses due to relatively short half-life (~12 hours). Morning and evening dosing.
Cycle Duration8-12 week cycles maximum. PCT strongly recommended after all but the shortest/lowest-dose cycles.8 week cycles maximum recommended. PCT is absolutely mandatory due to profound HPG suppression. Allow full recovery before considering subsequent cycles.
Evidence Levelmoderate_humananimal_plus_anecdotal

Mechanism

LGD-4033 is a potent nonsteroidal selective androgen receptor modulator with high AR binding affinity (Ki of approximately 1 nM). It demonstrates strong anabolic activity in muscle and bone with significantly reduced androgenic activity in prostate tissue, achieving an anabolic-to-androgenic ratio of approximately 10:1. LGD-4033 activates the AR with full agonist efficacy in muscle, upregulating the PI3K/Akt/mTOR pathway for protein synthesis and satellite cell recruitment. It produces dose-dependent suppression of SHBG, total testosterone, LH, and FSH, indicating significant HPG axis suppression even at low doses.

Standard Dosing

Research indicates 5-10 mg daily orally for 8-12 weeks. Phase 1 data showed significant lean mass gains at 1 mg/day.

Timing

Once daily, consistent timing. Half-life approximately 24-36 hours. No food timing requirements.

Cycle Duration

8-12 week cycles maximum. PCT strongly recommended after all but the shortest/lowest-dose cycles.

Side Effects

  • Significant testosterone suppression (dose-dependent; occurs even at 1 mg/day)
  • Suppressed SHBG, LH, and FSH
  • Elevated liver enzymes / hepatotoxicity (case reports of cholestatic liver injury)
  • HDL cholesterol suppression
  • Headache
  • Fatigue (late-cycle, from suppression)
  • Water retention

Contraindications

  • Androgen-sensitive cancers
  • Pre-existing liver disease or elevated liver enzymes
  • Pregnancy and breastfeeding
  • Individuals under 21
  • Athletes subject to WADA/anti-doping testing

Best Stacking Partners

Cardarine GW-501516 (endurance without additional suppression)MK-677 (GH secretagogue for recovery)NAC / TUDCA (liver protection)
B

S-23

SARMs

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

Best Stacking Partners

hCG (to maintain testicular function during the profound suppression)MK-677 (non-suppressive GH elevation)NAC / TUDCA (liver support)Enclomiphene (PCT)

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