Differential influence of peripheral and systemic sex steroids on skeletal muscle quality in pre‐ and postmenopausal women

Abstract

SummaryAging is associated with gradual decline of skeletal muscle strength and mass often leading to diminished muscle quality. This phenomenon is known as sarcopenia and affects about 30% of the over 60-year-old population. Androgens act as anabolic agents regulating muscle mass and improving muscle performance. The role of female sex steroids as well as the ability of skeletal muscle tissue to locally produce sex steroids has been less extensively studied. We show that despite the extensive systemic deficit of sex steroid hormones in postmenopausal compared to premenopausal women, the hormone content of skeletal muscle does not follow the same trend. In contrast to the systemic levels, muscle tissue of post-and premenopausal women had similar concentrations of dehydroepiandrosterone and androstenedione, while the concentrations of estradiol and testosterone were significantly higher in muscle of the postmenopausal women. The presence of steroidogenetic enzymes in muscle tissue indicates that the elevated postmenopausal steroid levels in skeletal muscle are because of local steroidogenesis. The circulating sex steroids were associated with better muscle quality while the muscle concentrations reflected the amount of infiltrated fat within muscle tissue. We conclude that systemically delivered and peripherally produced sex steroids have distinct roles in the regulation of neuromuscular characteristics during aging. Key words: endocrine effects of steroid hormones; intracrinology of skeletal muscle; localization of steroidogenic enzymes; menopause; paracrine effects of steroid hormones; systemic and local steroidogenesis.

Muscle Quality in Aging: a Multi-Dimensional Approach to Muscle Functioning with Applications for Treatment

“…Similarly, GH replacement therapy in older adults is associated with a high incidence of adverse effects, [189] and it does not appear to be any more beneficial to muscle strength than resistance training [189]. Finally, in one hormonal study that did measure muscle quality as both relative strength and CT attenuation, circulating concentrations of estrogen, DHEAS, and IGF-1 were correlated with muscle quality while testosterone and DHT (dihydrotestosterone) were not [190]. Regardless of the relationships, the efficacy of these hormones as exogenous treatment to improve muscle quality remains to be examined.…”

Factors contributing to the variability in muscle ageing

“…In post-menopausal women, for instance, the force generating capacity of the muscle was less than that of pre-menopausal women with similar activity levels. This lower force generating capacity was not only due to muscle atrophy [24], but also a sudden decrease in specific tension (force per muscle cross-sectional area) during menopause [24,25]. The reduction in specific tension was at least to some extent attributable to an increased fat infiltration in the muscle of postmenopausal women [24] and a reduction in single fibre specific tension [26].…”

Estrogens maintain skeletal muscle and satellite cell functions

“…Although the effects of androgens on muscle function have been evaluated extensively, the roles of estrogens in muscle have been largely unknown. Recent studies have revealed that the levels of estrogens are associated with muscle mass (McClung et al 2006, Sitnick et al 2006, Sugiura et al 2006, Pollanen et al 2011. Ovariectomized (OVX) mice fail to fully recover muscle mass after hindlimb suspension-induced muscle atrophy followed by reloading (McClung et al 2006).…”