Regulatory aspects of myogenic factors GDF-8 and Follistatin on the intake of combined oral contraceptives

Combined oral contraceptives are one of the most prescribed drugs in the western world. While there is little evidence regarding effects of estrogen or gestagens on muscle metabolism, androgens are well-known for their anabolic characteristics. In this study, we seeked to investigate potential correlations of the myokines GDF-8, IGF-1 and Follistatin with female sexual hormones and likewise possible interactions with combined oral contraceptives (Dienogest and Ethyl Estradiol) intake. We obtained serum samples of young healthy women to measure hormone correlations. Furthermore, we simulated combined oral contraceptive blood circulating hormone concentrations to identify myogenic effects on HSkM in vitro. GDF-8, IGF-1 and Follistatin showed concentration correlations (p = .005) in overall patients' serum, while Follistatin as a promyogenic protein additionally showed a positive correlation with testosterone and estradiol (p < .05). Lower GDF-8 levels were also linked to a higher BMI (p = .009). Upon combined oral contraceptives (COC) intake, patients showed decreased GDF-8 (p = .006) but increased Follistatin (p = .0001) concentrations compared to patients without COC intake. In vitro, addition of Ethyl Estradiol and Dienogest to HSkM cells revealed a pro-myogenic, proliferative, chemosensitized pattern. Our data support a pro-myogenic effect of combined oral contraceptives.