The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men.
Level 2 - randomized trial
Randomized placebo-controlled trial in humans
PubMed 22459616 · doi:10.1093/gerona/gls078
What was done
In a randomized, placebo-controlled trial, 76 healthy men aged 21 to 50 years received placebo or one of three daily oral doses of the selective androgen receptor modulator (SARM) LGD-4033 (0.1 mg, 0.3 mg, or 1.0 mg) for 21 days. Researchers evaluated safety, tolerability, pharmacokinetics, blood counts, chemistries, liver enzymes (AST, ALT), lipids, prostate-specific antigen (PSA), electrocardiogram (QT intervals), sex hormones, lean and fat body mass, and muscle strength during the 21-day intervention and across a 5-week recovery follow-up period.
What was found
The abstract reports no exact numerical values or effect sizes. LGD-4033 showed a long elimination half-life with dose-proportional accumulation. There were no drug-related serious adverse events, and adverse event frequency was similar between active and placebo groups. Hemoglobin, PSA, AST, ALT, and QT intervals showed no significant changes at any dose. LGD-4033 produced dose-dependent increases in lean body mass, with no significant change in fat mass. It caused dose-dependent suppression of total testosterone, sex hormone-binding globulin (SHBG), HDL cholesterol, and triglycerides. Free testosterone and follicle-stimulating hormone (FSH) were significantly suppressed only at the highest dose (1.0 mg). Hormone and lipid alterations returned to baseline after discontinuation.
Why it matters
This study provides initial clinical trial evidence in humans that oral LGD-4033 can increase lean body mass in the short term without short-term liver or prostate-specific antigen alterations, while identifying key suppressive effects on endogenous testosterone and HDL cholesterol.
Limits
The abstract reports no numerical estimates, standard deviations, or confidence intervals for changes in lean mass, strength, or hormone suppression. The intervention duration was very short (21 days), sample size was modest (76 participants divided across four study arms), and the sample was restricted to healthy young men, limiting generalizability to target populations such as patients with muscle-wasting conditions. Furthermore, functional muscle outcomes mentioned in the objectives (stair-climbing power and muscle strength) have no results reported in the abstract.
Cited by
- supports Exogenous androgens suppress sex hormone-binding globulin (SHBG) levels in a dose-dependent manner.