The effect of sex hormones on skeletal muscle adaptation in females

Abstract

Sex steroids, commonly referred to as sex hormones, are integral to the development and maintenance of the human reproductive system. In addition, male (androgens) and female (estrogens and progestogens) sex hormones promote the development of secondary sex characteristics by targeting a range of other tissues, including skeletal muscle. The role of androgens on skeletal muscle mass, function and metabolism has been well described in males, yet female specific studies are scarce in the literature. This narrative review summarises the available evidence around the mechanistic role of androgens, estrogens and progestogens in female skeletal muscle. An analysis of the literature indicates that sex steroids play important roles in the regulation of female skeletal muscle mass and function. The free fractions of testosterone and progesterone in serum were consistently associated with the regulation of muscle mass, while estrogens may be primarily involved in mediating the muscle contractile function in conjunction with other sex hormones. Muscle strength was however not directly associated with any hormone in isolation when at physiological concentrations. Importantly, recent evidence suggests that intramuscular sex hormone concentrations may be more strongly associated with muscle size and function than circulating forms, providing interesting opportunities for future research. By combining cross-sectional, interventional and mechanical studies, this review aims to provide a broad, multidisciplinary picture of the current knowledge of the effects of sex steroids on skeletal muscle in females, with a focus on the regulation of muscle size and function and an insight into their clinical implications. Highlights. Free testosterone, but not total testosterone, is associated with lean mass but not strength in pre-and post-menopausal females. . Progesterone and estrogens may regulate muscle mass and strength, respectively, in females.. Intra-muscular steroids may be more closely associated to muscle mass and strength, compared to systemic fractions.

Skeletal muscle methylome and transcriptome integration reveals profound sex differences related to muscle function and substrate metabolism

“…Moreover, intramuscular, and not circulating, sex hormone levels may be correlated with muscular function [65,66]. A recent review emphasizes the importance of measuring intramuscular sex hormone levels when assessing muscle-related properties in females [67].…”

“…Differences in skeletal muscle fibre-type proportions and circulating levels of sex hormones may contribute to epigenomic and transcriptomic differences between the sexes. Males and females are exposed to differing levels of sex hormones across the lifespan [25], which are primarily ascribed to the reproductive function, but their importance to non-reproductive functions, such as skeletal muscle [26], is becoming more apparent [27,28]. Sex steroid hormones engage through their specific ligand-receptors [4,11,29] and influence transcription and phenotype in a tissue-and sex-specific manner [9,[30][31][32][33].…”

Molecular Regulators of Muscle Mass and Mitochondrial Remodeling Are Not Influenced by Testosterone Administration in Young Women

“…On the other hand, we cannot completely rule out that other enzymes involved in androgen metabolism were affected by the current treatment, i.e., aromatase. Another factor that may have played a critical role for muscle adaptation here is the intramuscular concentration of T and other androgens, as discussed in a recent review ( 44 ). We did however not measure intramuscular levels of androgens in the present study but this is an important aspect that needs to be addressed by future work.…”

Maternal Metformin Treatment during Gestation and Lactation Improves Skeletal Muscle Development in Offspring of Rat Dams Fed High-Fat Diet

“…So far, many studies have explored gender differences related to obesity, including sex hormones [57], adipokine signaling pathway [58] and appetite regulation [59]. Males are more likely to become obese than females because ovarian hormones may protect females from disturbance [60].…”