The Influence of Estrogen on Skeletal Muscle

Abstract

As women enter menopause, the concentration of estrogen and other female hormones declines. This hormonal decrease has been associated with a number of negative outcomes, including a greater incidence of injury as well as a delay in recovery from these injuries. Over the past two decades, our understanding of the protective effects of estrogen against various types of injury and disease states has grown immensely. In skeletal muscle, studies with animals have demonstrated that sex and estrogen may potentially influence muscle contractile properties and attenuate indices of post-exercise muscle damage, including the release of creatine kinase into the bloodstream and activity of the intramuscular lysosomal acid hydrolase, beta-glucuronidase. Furthermore, numerous studies have revealed an estrogen-mediated attenuation of infiltration of inflammatory cells such as neutrophils and macrophages into the skeletal muscles of rats following exercise or injury. Estrogen has also been shown to play a significant role in stimulating muscle repair and regenerative processes, including the activation and proliferation of satellite cells. Although the mechanisms by which estrogen exerts its influence upon indices of skeletal muscle damage, inflammation and repair have not been fully elucidated, it is thought that estrogen may potentially exert its protective effects by: (i) acting as an antioxidant, thus limiting oxidative damage; (ii) acting as a membrane stabilizer by intercalating within membrane phospholipids; and (iii) binding to estrogen receptors, thus governing the regulation of a number of downstream genes and molecular targets. In contrast to animal studies, studies with humans have not as clearly delineated an effect of estrogen on muscle contractile function or on indices of post-exercise muscle damage and inflammation. These inconsistencies have been attributed to a number of factors, including age and fitness level of subjects, the type and intensity of exercise protocols, and a focus on sex differences that typically involve factors and hormones in addition to estrogen. In recent years, hormone replacement therapy (HRT) or estrogen combined with exercise have been proposed as potentially therapeutic agents for postmenopausal women, as these agents may potentially limit muscle damage and inflammation and stimulate repair in this population. While the benefits and potential health risks of long-term HRT use have been widely debated, controlled studies using short-term HRT or other estrogen agonists may provide future new and valuable insights into understanding the effects of estrogen on skeletal muscle, and greatly benefit the aging female population. Recent studies with older females have begun to demonstrate their benefits.

The relationship between hepatic steatosis and skeletal muscle mass index in men with type 2 diabetes

“…The absolute volume of skeletal muscle differs between genders and estrogen is known to play essential roles in both muscle [47,48] and NAFLD [49]. However, a previous study also showed that the effects of SMI on fatty liver did not differ between preor post-menopausal women [46].…”

Chronic exposure to anabolic steroids induces the muscle expression of oxytocin and a more than fiftyfold increase in circulating oxytocin in cattle

“…Similarly, hypogonadal men who produce lower levels of endogenous testosterone have reduced muscle mass compared with their eugonadal counterparts (62). Exogenous administration of both testosterone (4) and estrogen (11) influences muscle phenotype in humans. Supraphysiologic doses of androgens have been core components of doping programs in elite power sports for decades.…”

“…Testosterone has been shown to induce muscle hypertrophy and lead to increases in voluntary strength (50). Estrogen has been shown to stimulate muscle repair and regenerative processes (11), although the extent and direction of the muscle response does seem contingent on species and circumstance (23,28,33).…”

“…Notable exceptions to this observation include the myostatin blockade, which is initially independent of satellite cell activation (3). Nevertheless, proliferation of satellite cells is activated by sex steroid treatment and is thought to contribute to steroid induced muscle growth (50,11).…”

Postmenopausal Health and Disease from the Perspective of Evolutionary Medicine

“…Along with these definitions, much of the accompanying health information addresses symptoms, risk for associated diseases, and treatment options. This information fits the overall medical paradigm that menopause is not simply Epidemiological evidence indeed shows that the period surrounding and following menopause is associated with an increased prevalence of disease and disease risk factors, particularly those relating to the metabolic syndrome including weight gain, body composition change, obesity, hyperlipidemia, hypertension, and insulin resistance, all of which increase risk for heart attack, stroke, and type 2 diabetes (Torrens et al 2009;Enns and Tiidus 2010). In the…”