Anti-Müllerian Hormone May Predict Bone Loss During Menopausal Transition

BOSTON — A new high-sensitive assay that can accurately measure low levels of anti-Müllerian hormone may help identify which women will lose bone mass the fastest during menopause, researchers reported at ENDO 2016.

“What we’re interested in is understanding how much bone mass a woman loses during the menopausal transition,” lead study author Arun S. Karlamangla, MD, PhD, professor medicine at the David Geffen School of Medicine at the University of California, Los Angeles, said during a press conference.

“This transition to menopause is a time of rapid bone loss, and the risk for devastating osteoporotic fracture in the femoral neck or spine later in life depends quite a bit on how much bone mass one loses during this transition.”

Currently, clinicians are unable to determine when a woman’s final menstrual period will be before it occurs, noted Dr Karlamangla, but they do know that loss of bone mass begins about 2 years before this point.

Because anti-Müllerian hormone (AMH) levels are known to decline as women approach the menopausal transition, they may signal when a woman is close to her final menstrual period, he explained. Until recently, while researchers could measure these levels when a woman was premenopausal, tests were not sensitive enough to accurately measure AMH when levels were low, such as when women are approaching menopause. However, the advent of a new high-sensitivity monoclonal ELISA allows researchers to measure serum AMH levels of up to 2 pg/mL.  

“Our hope is that we could use this to recognize whether or not a woman is losing bone mass and maybe even the magnitude of bone loss,” said Dr Karlamangla.

To learn more, the researchers evaluated data from 474 participants in the Study of Women’s Health Across the Nation (SWAN). Women were aged 42 to 52 years at recruitment, were premenopausal or early perimenopausal, had an intact uterus with at least 1 ovary, and were not taking exogenous sex steroid hormones.

Participants were followed annually, and at 5 of 7 study sites, women underwent a bone mineral density (BMD) scan 2 to 4 years before their final menstrual period and a second scan 3 to 4 years later.

Additionally, frozen blood from days 2 to 5 of the follicular phase of the menstrual cycle were collected annually and stored. Dr Karlamangla and colleagues used the new assay to measure AMH in these samples.

The interquartile range of AMH was 11 pg/mL to 146 pg/mL, and median rate of BMD decline was 1.3% per year in the spine and 1% per year in the femoral neck.

After adjustment for age, BMI, smoking, race/ethnicity, and study site, results revealed a linear relationship between AMH and BMD. Specifically, every 4-fold decrement in AMH levels was associated with a 0.15% per year faster decline in BMD at the lumbar spine (P<.001) and a 0.13% per year faster decline in the femoral neck (P=.005).

These results were unchanged after adjustment for estrogen and follicle-stimulating hormone (FSH) levels, suggesting that AMH was providing information that could not be obtained from measuring estrogen or FSH.

Results also showed that each 4-fold decrement in AMH was also associated with an 18% increase in the odds of faster-than-median decline in BMD in the spine (P=.02) and a 17% increase in the odds of faster-than-median decline in BMD in the femoral neck (P=.02).

Moreover, when looking at whether or not women were losing bone mass at all, based on a detectable threshold for bone loss, the researchers found that every 4-fold decrement in AMH was associated with a 24% higher risk for losing bone in the lumbar spine and a 26% higher risk for losing bone in the femoral neck. 

“This study’s findings open up the possibility of identifying the women who are going to lose the most bone mass during the menopause transition and targeting them before they have lost a substantial amount of bone mass,” Dr Karlamangla noted in a press release.

Reference

1. Karlamangla AS, Shieh A, Burnett-Bowie SM, et al. OR01-3: Anti-Müllerian Hormone and Prediction of Trans-Menopausal Bone Loss. Presented at: ENDO 2016; April 1-4, 2016; Boston, MA.