Are sex hormone deficiency and skeletal muscle decline related? Exploring the regulation of satellite cells and protein synthesis in menopause

The menopause is characterised by a marked reduction in ovarian sex hormones –oestradiol (E2) and progesterone. This hormonal decline has been purported to be associated with reductions in skeletal muscle mass and strength observed during the menopausal transition, potentially contributing to the development or progression of sarcopenia. However, the underlying mechanisms remain incompletely understood. Satellite cells (SCs), the resident stem cells of skeletal muscle, play an essential role in repair and hypertrophy, yet their regulation by ovarian hormones in humans has been minimally investigated. Research completed in rodents demonstrates that E2 deficiency, induced via ovariectomy or oestrogen receptor knockout, reduces SC content and impairs activation, while E2 supplementation can partially restore SC function. In humans, albeit limited, longitudinal data indicate that declines in SC number may be related to decreasing E2 levels across the menopause transition, although SC responses to exercise or hormone therapy is lacking. Similarly, E2 has been implicated in the regulation of muscle protein synthesis (MPS); although interactions between SCs and MPS are currently unclear, it has been suggested that a reduction in SC content/activation could be rate limiting in MPS. Furthermore, the role of progesterone in regulating SCs and MPS is even less understood, and potential interactions with E2 have not been studied within skeletal muscle. This review evaluates current work from animal and human studies that examine the effects of ovarian sex hormones, particularly E2, on SC regulation and MPS in the context of menopause. We highlight areas of consensus, limitations, and gaps in the literature and propose future directions to clarify the extent to which SCs and MPS may affect the menopause-associated muscle decline and the role of sex hormone deficiency in these processes.