LGD-4033, also known by the developmental code name VK5211 and by the black-market name Ligandrol, is a selective androgen receptor modulator (SARM) which is under development for the treatment of muscle atrophy in people with hip fracture.

[5] LGD-4033 has been reported to dose-dependently improve lean body mass and muscle strength in preliminary clinical trials, but is still being developed and has not been approved for medical use.

[1][2] Known possible side effects of LGD-4033 include headache, dry mouth, adverse lipid changes like decreased high-density lipoprotein (HDL) cholesterol levels, changes in sex hormone concentrations like decreased testosterone levels, elevated liver enzymes, and liver toxicity.

[5] Aside from its development as a potential pharmaceutical drug, LGD-4033 is on the World Anti-Doping Agency list of prohibited substances[15] and is sold for physique- and performance-enhancing purposes by black-market Internet suppliers.

[11] The drug sold via black-market Internet suppliers and used non-medically is often taken at much higher doses than those used in repeated-dose clinical trials (e.g., 5–10 mg/day), with unknown adverse effects and risks.

[10] This receptor is the biological target of endogenous androgens like testosterone and dihydrotestosterone (DHT) and of synthetic anabolic steroids like nandrolone and oxandrolone.

[12][13] The AR is widely expressed in tissues throughout the body, including in the prostate gland, seminal vesicles, genitals, gonads, skin, hair follicles, muscle, bone, heart, adrenal cortex, liver, kidneys, and brain, among others.

[10][26] In a phase 1 clinical trial in 76 healthy young men, 1 mg/day LGD-4033 increased lean body mass by 1.2 kg after 3 weeks of treatment.

[10][26][2] For comparison, enobosarm, another SARM, increased lean body mass by 1.3 kg at a dose of 3 mg/day after 12 weeks in healthy elderly men and postmenopausal women.

[2][26][27] It was concluded that the employed dose of LGD-4033 produced similar increases in lean body mass compared to enobosarm despite a substantially shorter treatment period.

[2] In a phase 2 clinical trial in 108 women and men with hip fracture, LGD-4033 increased lean body mass by 4.8% at 0.5 mg/day, 7.2% at 1 mg/day, and 9.1% at 2 mg/day after 12 weeks of treatment.

[8] For comparison, lean body mass with enobosarm 3 mg/day after the same time period of 12 weeks increased by about 0.30% at 0.1 mg/day, 0.40% at 0.3 mg/day, 1.2% at 1 mg/day, and 3.1% at 3 mg/day, with only the latter change achieving statistical significance.

[12][4] Reduced activity in stimulating sebaceous gland formation, to about 30 to 50% of that produced by DHT at doses with similar anabolic potency in rats, has also been reported for certain other SARMs, like the steroidal agents TFM-4AS-1 and MK-0773.

[12] In addition, enobosarm and MK-0773 have been reported to limitedly stimulate the sebaceous glands in small short-term clinical studies in women.

[12][1] On 22 May 2014, Viking Therapeutics licensed the developmental rights of LGD-4033 from Ligand Pharmaceuticals and intended to advance the compound into mid-to-late-stage clinical trials.

[17] On 23 October 2017, a nutritional supplement company in Missouri called Infantry Labs was warned by the FDA that the distribution of two of its products violated the Federal Food, Drug, and Cosmetic Act.

In that month, German scientists proposed a new test to detect its metabolites present in human urine, and suggested an expansion of the WADA regime.

[48] On 15 March 2024 cyclist Christos Volikakis was informed of an Adverse Analytical Finding on a re-analysis of a sample from the 2016 Rio Olympics.

[52] In August 2019, it came to light that Canadian sprint canoeist Laurence Vincent Lapointe tested positive for LGD-4033; the athlete denies knowingly taking a forbidden substance that resulted in her suspension from competition.

[55] On 3 September 2022, sprinter Nzubechi Grace Nwokocha was provisionally suspended for the use of banned substances enobosarm and LGD-4033[56] by the Athletics Integrity Unit (AIU).

[58] Oral administration of LGD-4033 to cynomolgus monkeys at daily doses varying from 0 to 75 mg/kg over 13 weeks demonstrated significant body weight gain in both males and females.

[11][4][2] The multi-dose phase 1 trial published in 2013 reported that LGD-4033 dose-dependently improved lean body mass and muscle strength in 76 healthy young men over 21 days.

[2] A phase 2 clinical trial, initiated on 3 November 2016, consisted of 108 women and men recovering from hip fracture surgery.

[8] The randomized study participants received either placebo or varying doses of LGD-4033 over a period of 12 weeks, with improved lean body mass as the primary endpoint.