LGD-4033

LGD-4033 (Ligandrol) is a nonsteroidal selective androgen receptor modulator, or SARM, developed by Ligand Pharmaceuticals and later studied by Viking Therapeutics as VK5211 (Mohideen et al., 2023).

Published work on LGD-4033 falls into five areas. Each summary below states the model used. Human data come from one fully published phase 1 trial, reports of further phase 1 and phase 2 studies, case reports and anti-doping excretion studies.

Androgen receptor selectivity

SARMs aim to activate androgen signaling in muscle and bone while sparing the prostate. Without citing a preclinical paper, the phase 1 trial report states that LGD-4033 binds the androgen receptor with a Ki of about 1 nM and showed selectivity for muscle over prostate in animal models (Basaria et al., 2013).

A 2025 appraisal argues that much of the apparent selectivity of SARMs may reflect their lack of steroid metabolism, such as 5α-reduction, and that clinically meaningful selectivity remains unclear (Bond et al., 2025). In PC3(AR)2 reporter cells, LGD-4033 and its metabolite M2c induced androgen receptor reporter activity that bicalutamide significantly inhibited, while the metabolite M8 inhibited it (Angelis et al., 2026). Models: receptor binding, reporter cells and a review.

Rat studies

In ovariectomized Sprague-Dawley rats, a postmenopausal model, five weeks of ligandrol at 0.04 to 4 mg/kg a day did not change muscle fiber size; the top level raised uterus weight and intramuscular fat, which the authors considered unfavorable (Roch et al., 2020).

In the same model, five weeks at 3 mg/kg increased trabecular number in the femur, spine and tibia without changing bone biomechanics, and raised uterus and heart weights (Hoffmann et al., 2023). In healthy male rats, eight weeks of ligandrol lowered serum testosterone and follicle-stimulating hormone and raised triglycerides and total cholesterol (Vasilev et al., 2025). Models: female and male rats (animal data only).

Human trials and development

In a randomized, placebo-controlled phase 1 trial, 76 healthy men aged 21 to 50 received placebo or one of three daily amounts of LGD-4033 for 21 days. The authors reported it was well tolerated, with no drug-related serious adverse events, no significant change in PSA or liver enzymes, and an elimination half-life of 24 to 36 hours. Lean body mass rose in step with the amount given, while fat mass and leg press strength did not differ significantly from placebo.

Total testosterone, sex hormone-binding globulin (SHBG) and HDL cholesterol fell, then returned to baseline after it was stopped (Basaria et al., 2013). As VK5211, it entered a 12-week phase 2 trial in 108 older adults after hip fracture; a 2023 review cites a 2018 meeting abstract reporting increases in lean body mass over placebo (Mohideen et al., 2023). No full report is indexed in PubMed. Models: randomized human trials.

Liver injury case reports

A 32-year-old man developed jaundice after about two weeks of ligandrol use, and a biopsy showed cholestatic hepatitis with mild fibrosis (Barbara et al., 2020). A 37-year-old man had painless jaundice, bilirubin 30 times the upper limit of normal and canalicular cholestasis on biopsy (Wallstab et al., 2023).

A 52-year-old man developed jaundice after three months of use; his bilirubin was normal three months after discharge (Labban et al., 2024). A 2023 review tabulated five published cases involving LGD-4033, two with a second SARM, and describes the SARM pattern as bland cholestasis that usually eases once the product is stopped (Mohideen et al., 2023). Models: human case reports and a review.

Metabolism, doping control and product testing

Doping chemists characterized LGD-4033 bought online by NMR and high-resolution mass spectrometry, and human liver microsomes converted it into five main phase I metabolites (Thevis et al., 2015). In a one-volunteer excretion study, dihydroxylated metabolites were the preferred urinary targets over about 21 days (Fragkaki et al., 2018).

Human excretion studies using single microgram amounts found 15 phase I metabolites; the shifting ratio of LGD-4033 to its epimer helps estimate when intake occurred (Wagener et al., 2022). Of 44 products bought online as SARMs in 2016, only 52 percent contained a SARM and 41 percent matched the labeled amount (Van Wagoner et al., 2017). Models: liver microsomes, human urine and purchased products.