Riechman, SE and Lee, CW. Oral contraceptive use impairs muscle gains in young women. J Strength Cond Res XX(X): 000–000, 2021—Many active young women use oral contraceptives (OCs), yet their effects on the body composition and exercise performance have not been thoroughly studied. We examined the effects of OCs on muscle responses to a standardized resistance exercise training (RET) program. Two groups of young healthy women (18–29 years old, non-OC: n = 38, OC: n = 34) underwent 10 weeks of whole-body RET (3 days·wk−1, 3 sets, 6–10 repetitions, at 75% of maximum strength, 13 exercises). Body composition was determined using hydrostatic weighing, and blood samples were taken before and after training to measure dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), IGF-1, and cortisol levels. There were significant differences in lean mass gains between the groups (non-OC: 3.5 ± 0.4% vs. OC: 2.1 ± 0.5% and non-OC: 1.6 ± 0.2 kg vs. OC: 1.0 ± 0.2 kg, p < 0.05). Plasma concentrations of DHEA, DHEAS, and IGF-1 were significantly lower, and cortisol levels were higher in the OC group before and after training (p < 0.05). In addition, there were significant differences in lean mass gains depending on the androgenicity of progestin between the non-OC and medium-high groups (non-OC: 1.6 ± 0.2 kg, Low = 1.1 ± 0.2 kg, med-high = 0.3 ± 0.5 kg, p < 0.05). Oral contraceptive use impaired lean mass gains in young women after RET and was associated with lower DHEA, DHEAS, and IGF-1 and higher cortisol. The diminished lean mass gain may be related to the effect of OCs on anabolic and catabolic hormone levels or the androgenicity of progestin that may bind to androgen receptors and inhibit its function.