Anti-Mullerian Hormone as Predictor of Future and Ongoing Bone Loss During the Menopause Transition

Abstract

The menopause transition in women is a period of significant bone loss, with rapid declines in bone mineral density (BMD) commencing a year before the final menstrual period (FMP). Changes in menstrual bleeding patterns cannot reliably tell us if this rapid bone loss has begun or is imminent. We hypothesized that low circulating levels of anti‐Mullerian hormone (AMH), which decline as women approach the FMP, would be associated with future and ongoing rapid bone loss. We used data from The Study of Women's Health Across the Nation, a multisite, multi‐ethnic, prospective cohort study of the menopause transition to test this hypothesis. Adjusted for age, body mass index, race/ethnicity, and study site, every 50% decrement in AMH level in premenopause and early perimenopause was associated with 0.14% per year faster decline over the following 3 to 4 years in lumbar spine BMD and 0.11% per year faster decline in femoral neck BMD (p < 0.001 for both). AMH in late perimenopause was not associated with the rate of future BMD decline. AMH was also associated with the magnitude of ongoing bone loss, measured as percent of peak BMD lost by the end of the next 2 to 3 years. Every 50% decrement in AMH level was associated with 0.22% additional loss in spine BMD in premenopause, 0.43% additional loss in early perimenopause, and 0.50% additional loss in late perimenopause (p < 0.001 for all three). If a woman will lose more of her peak BMD than the site‐specific least significant change (LSC) at either the lumbar spine or femoral neck by the next 2 to 3 years, then AMH below 100 pg/mL will detect it with sensitivity of 50% in premenopause, 80% in early perimenopause, and 98% in late perimenopause. These findings suggest that AMH measurement can help flag women at the brink of significant bone loss for early intervention. © 2022 American Society for Bone and Mineral Research (ASBMR).

Serum AMH Levels: An Early Reproductive Marker for Bone Loss?

“…Although several commercial manual and automated AMH assays are currently available, their limit of detection varies and AMH values obtained by the various assays cannot be directly compared. ( 6 ) Even though a highly sensitive AMH ELISA, which measures AMH in the pg/mL range, was used in this study by Karlamangla and colleagues, ( 8 ) the majority of late perimenopausal women had undetectable AMH levels. Although estrogen levels are still relatively stable during MT when rapid bone loss is initiated, FSH levels are increasing.…”

“…( 9 ) In a Japanese cohort of 518 pre‐ and postmenopausal women, an AMH value below 0.08 ng/mL resulted in an odds ratio of 8.28 for early knee osteoarthritis. ( 10 ) However, the study by Karlamangla and colleagues ( 8 ) is unique as it has longitudinal AMH measurements, whereas these other studies used a single measurement. The predictive value of a single AMH measurement can be debated because it has been shown that each woman has a specific AMH decline rate.…”

“…The study of Karlamangla and colleagues (8) holds promise that AMH may serve as a prognostic marker of bone health. However, further studies are warranted to unravel the association between AMH levels and BMD, particularly because specific confounders may influence both BMD and AMH levels such as smoking and vitamin D. (5,14) Smoking is associated with lower BMD but also with advanced reproductive aging.…”

“…Based on a meta-analysis, serum AMH levels indeed predict the time to menopause, although the added value compared with age was limited. (7) In this issue of JBMR, Karlamangla and colleagues (8) have analyzed whether serum AMH levels could predict the rate of future BMD decline. Analyzing more than 3000 participants of the SWAN study, a prospective cohort study of menopause transition, repeated AMH measurements were performed from each woman before becoming postmenopausal.…”

Correlation of serum anti-Mullerian hormone and Inhibin-B levels with osteoporosis of menopausal woman in Chinese Daur ethnic group

“…8,9 Anti-Mullerian hormone (AMH) is a hormone secreted by the granulosa cells of the antral and small antral follicles of the ovary, which is one of the indicators of ovarian function that changes with age. 10 The concentration of AMH is decreased with age in the menopause transition of women and it has a possibility in predicting bone loss, 11 indicating that AMH is a confounder of osteoporosis. Inhibin B (InhB) is secreted by reproductive system cells, which is of great significance for maintaining female reproductive health.…”