Physical activity and muscle function in females: Impact of ovarian hormones, bazedoxifene, and estrogen receptor alpha

Abstract

Overall, my dissertation work had three main objectives: 1) critically evaluate the literature to determine if hormone therapy increases physical activity in postmenopausal women, 2) determine the effects of estradiol and progesterone on physical activity and skeletal muscle function in female mice, and 3) determine the effects of bazedoxifene on the musculoskeletal system. First, I performed a systematic review and meta-analysis (Chapter 3), which determined that there is a lack of evidence to conclude that hormone therapy does not affect physical activity in postmenopausal women. Although there is not a clear link between ovarian hormones and physical activity in women, there is a clear link in rodent models. I then identified that a combined treatment of estradiol+progesterone after ovariectomy increased physical activity in the form of wheel running distance and blunted susceptibility to fatigue in the soleus muscles of female mice (Chapter 4). Additionally, I determined that estrogen receptor  is likely the predominant receptor through which estradiol functions to elicit its effects on skeletal muscle fatigue (Chapter 4). Finally, due to declines in the clinical use of estrogen-based hormone therapy in postmenopausal women, I investigated the effects of bazedoxifene, a selective estrogen receptor modulator, on the musculoskeletal system. This investigation showed that bazedoxifene has tissue selective effects on adipose tissue, skeletal muscle, and bone (Chapter 5). The work contained in my dissertation highlights a number of hormones or hormone analogues that impact physical activity, as well as identifies estrogen receptor  as a mechanism through which these compounds elicit their effects on skeletal muscle.