Associations between Reproductive Hormone Production and Musculoskeletal Health during the Menopause Transition
Date
2024-01-25
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
0009-0002-8787-1521
Type
Thesis
Degree Level
Masters
Abstract
Context: Changes in hormone production and antral follicle count (AFC) occur in women during the transition to menopause. A greater understanding of the physiologic mechanisms by which hormones regulate musculoskeletal health as women age has the potential to improve the diagnosis and treatment of osteoporosis.
Overall Objective: We tested the hypothesis that age-related changes in bone density, size and strength, as well as muscle strength will be associated with serum reproductive hormone concentrations.
Materials and Methods: A prospective observational study was conducted in 26 ovulatory women of mid reproductive age (RA,18-35 years, n=10) and Advanced Reproductive Age (ARA, 45-55, n=16). Transvaginal ultrasonography and venipuncture were conducted every 1-3 days over one Inter-ovulatory Interval (IOI). A peripheral Quantitative Computed Tomography (pQCT) scan was conducted to quantify bone area, content and density within the radius, and tibia. A Dual-Energy X-ray Absorptiometry (DXA) scan was conducted to quantify bone content, area, and density at the lumbar spine and hip, as well as to quantify total lean muscle mass. Isometric grip strength measures of the nondominant hand were collected using a handheld dynamometer. Associations between mean serum concentrations of AntiMullerian Hormone (AMH), estradiol, Follicle Stimulating Hormone (FSH), inhibin B (InhB), inhibin A (InhA), Luteinizing Hormone (LH) and progesterone (over one IOI, Luteal Phase (LP), and Follicular Phase (FP)) versus DXA, and pQCT outcomes were analyzed using Pearson’s correlation coefficient. Correlations were used to guide the development of univariate and multivariate regression analyses (SPSS V28.0.1.1).
Results: In the RA group, distal radius total density (ToD: r=0.56; p=0.008), and bone strength index (BSI: r= 0.45, p=0.019), were positively associated with LP InhB; distal radius trabecular density (TrD: r= 0.59, p=0.031) was negatively associated with FP FSH. Distal tibia total content, (ToC: r= 0.39, p=0.032) distal tibia total density (ToD: r= 0.68; p=0.002), distal tibia trabecular density (TrD: r= 0.55, p=0.008), BSI (r=0.60, p=0.005) as well as total hip density (r= 0.38, p=0.035) were negatively associated with LP Prog. Right-hand grip force was negatively associated with FP InhA (r=0.59, p=0.005).
In the ARA group, distal radius trabecular density (TrD) was positively associated with LP LH (r= 0.30, p= 0.016), Estradiol (r= 0.27; p=0.022), and Inh B (r= 0.47; p= 0.002) as well as FP Prog (r= 0.393, p= 0.009). Ulnar shaft total area (r=0.32, p=0.013) was positively associated with LP FSH. Radial shaft cortical density (CoD) was positively associated with FP Prog (r= 0.46, p=0.011) and InhB (r= 0.46, p= 0.008). Radial shaft strength strain index (SSI) (r= 0.31; p=0.017) and ulnar shaft strength strain index (r= 0.45; p= 0.004) were positively associated with FP LH. Radial shaft strength strain index (SSI) (r= 0.577; p=0.014), radial shaft total area (r= 0.56; p= 0.002), distal radius trabecular area (r= 0.45; p=0.005) and distal radius total area (r= 0.53; p= 0.002) were positively associated with FP FSH . Lower limb muscle area (r= 0.244; p= 0.013) was positively associated with LP estradiol; forearm muscle density was positively associated with FP InhB (r= 0.254; p= 0.032).
When AFC was considered a confounder (all ages combined), distal tibia trabecular density (TrD) was positively associated with LP AMH (r= 0.17, p<0.047); distal radius trabecular content (r= 0.324; p= 0.034) and distal radius total area (r= 0.30; p= 0.041) were negatively associated with FP AMH. Distal radius trabecular density was positively associated with LP InhB (r= 0.43, p=0.018), LP estradiol (r= 0.21, p=0.025) and FP Prog (r= 0.360, p=0.003). Distal radius total area (r= 0.30, p=0.010) and distal radius trabecular area (r= 0.26, p=0.014) were positively associated with FP FSH. Distal radius trabecular content was positively associated with FP FSH (r= 0.31, p=0.024). Similarly, lower limb muscle area (r= 0.16, p=0.05) was positively associated with LP Estradiol. Left hand grip force (r= 0.21, p=0.032) was positively associated with LP LH.
Conclusions: We have provided preliminary evidence that serum reproductive hormone concentrations, in particular LH, estradiol and inhibin B, are positively associated with bone morphology, bone density, muscle mass, and muscle strength during the transition to menopause. Luteal phase progesterone appears to negatively predict MSK outcomes, while follicular phase progesterone positively predicts outcomes. Associations between FSH, AMH and inhibin A versus musculoskeletal health requires further study. Longitudinal studies are required to better understand the relationships between hormones and musculoskeletal health, in order to identify hormonal markers for predicting bone and/or muscle loss as women age.
Description
Keywords
Reproductive Hormones, Musculoskeletal Health,
Peri-menopause
Citation
Degree
Master of Science (M.Sc.)
Department
Medicine
Program
Health Sciences