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

Abstract

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.

摘要

复合口服避孕药是西方国家常用的处方药之一。虽然几乎没有证据表明雌激素或促孕激素对肌肉代谢的影响, 雄激素以其合成代谢特征而闻名。在这研究中, 我们试图探讨肌源性GDF-8、IGF-1和人卵泡抑素与女性性激素的潜在相关性, 以及与复方口服避孕药（地诺孕素和炔雌醇）的相互作用。我们采集年轻健康女性的血清样本来检测激素的相关性。此外, 我们模拟复方口服避孕药的血液循环激素浓度, 以确定体外对HSkM细胞系的肌源性影响。GDF-8、IGF-1和人卵泡抑制素在全部患者血清中呈浓度相关性（P=.0050）, 而作为原肌源性蛋白的人卵泡抑制素与睾酮和雌二醇呈正相关（P<.05）。较低的GDF-8水平也与较高的BMI相关（P=.009）。服用复方口服避孕药（COC）后, 与未服用COC患者相比, 患者GDF-8降低（P=.006）, 但人卵泡抑制素浓度升高（P=.0001）。在体外, HSkM细胞中加入炔雌醇和地诺孕素后, 呈现出促肌源性、增殖、化疗增敏剂。我们的数据支持复方口服避孕药的促肌源性的作用。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• Estrogen receptor
• estrogens
• hormonal contraception
• hormone replacement therapy

Disclosure statement

We have no actual or potential conflict of interest in relation to this study.