Musculoskeletal Health in Premature Ovarian Insufficiency. Part One: Muscle

Abstract

Accelerated bone loss and muscle decline coexist in women with premature ovarian insufficiency (POI), but there are significant gaps in our understanding of musculoskeletal health in POI. This article is the first of a two-part review which describes estrogen signaling in muscle and its role in musculoskeletal health and disease. Current evidence regarding the utility of available diagnostic tests and therapeutic options is also discussed. A literature review from January 2000 to March 2020 was conducted to identify relevant studies. Women with POI experience significant deterioration in musculoskeletal health due to the loss of protective effects of estrogen. In addition to bone loss, muscle decay and dysfunction is now increasingly recognized. Nevertheless, there is a paucity of validated tools to assess muscle parameters. There is a growing need to acknowledge bone–muscle codependence to design new therapies which target both muscle and bone, resulting in improved physical performance and reduced morbidity and mortality. More high-quality research and international collaborations are needed to address the deficiencies in our understanding and management of musculoskeletal health in women with POI.

Abnormal Trabecular Bone Score, Lower Bone Mineral Density and Lean Mass in Young Women With Premature Ovarian Insufficiency Are Prevented by Oestrogen Replacement

“…In addition, a recent clinical trial in postmenopausal women demonstrated increased muscle mass and function parameters with ERT plus resistance training versus resistance training alone ( 42 ). However, data are lacking regarding women with POI ( 16 ). Our study’s finding of lower muscle mass including ALM and ALMI in women with s-POI or i-POI is consistent with results from Luo et al, which reported a lower muscle distributing coefficient of the lower limbs (MD) in 240 women with POI compared with peri- or postmenopausal women, not on ERT ( 43 ).…”

“…Similarly, in the longitudinal analysis of our POI cohort, an increase in lean mass (ALM, ALMI) was observed in those with continued ERT use over the follow-up period. Multiple pathophysiological oestrogenic influenced mechanisms potentially contribute to reduced muscle mass including: reduced muscle turnover, defective contractility, increased free radical-mediated apoptosis and impaired bone-muscle cross signaling due to compromised skeletal health in POI ( 16 ). Overall, these findings highlight the deleterious effects of oestrogen deficiency on muscle health and potential prevention with ERT.…”

“…With recent insights gained from muscle-bone cross signaling ( 16 ), it is now evident that muscle plays an essential role in maintaining and preserving skeletal health. Studies in typical menopausal women suggest an accelerated decline in muscle mass, increase in abdominal adiposity, and reductions in lean body mass (LBM) due to oestrogen deficiency, with preservation in women using ERT ( 16 ). However, data in women with POI are scant and there is a growing need to analyse changes in body composition, as well as in bone variables in women with POI.…”

Dilemmas in the Management of Osteoporosis in Younger Adults

“…The musculoskeletal effects of premature ovarian insufficiency have been reviewed elsewhere. ( 36 , 37 )…”

“…The musculoskeletal effects of premature ovarian insufficiency have been reviewed elsewhere. (36,37) Similarly, hypogonadism in the setting of cancer treatment is a risk factor for fragility fracture. (38,39) Use of gonadotropinreleasing hormone agonists, aromatase inhibitors, chemotherapeutic agents such as cyclophosphamide, gonadectomy, and pelvic or cranial radiotherapy increases risk of bone loss.…”