Postmenopausal bone loss is a major concern for orthopedic surgeons.

“Postmenopausal bone loss is a major concern for orthopedic surgeons. We know that 25% of a woman’s total bone mass before menopause is lost by age 65. There are a high emphasis and research trying to deliver methods to restore that bone loss or stop further loss. Some women have striking amounts of bone loss and pathological fractures. Fractures occurring from a standing height are called a “fragility fractures” whether it is the wrist, kneecap, hip or spine. A fragility fracture is an alarm to begin studies of bone mass and metabolism. The odds are high of another fragility fracture occurring without medical intervention.

 Developing methods to restore bone loss years after menopause is the late side of this problem. The early smart approach in medicine is to prevent the bone loss by methods in peri-menopausal women. Many studies were done relating to the safety of using some form of estrogen early in menopause. There are increased risks starting estrogen five years after menopause. These may be lessened by using Estriol, the weakest form of estrogen and avoiding giving the medication orally. By avoiding the oral administration, you avoid the “first pass” metabolism that affects the hormone.  Using estriol intravaginally has increasing research experience to show it does not cause hyperplasia of the endometrium. The data is increasing that it decreases urinary incontinence by its effect on the urethra and vaginal tissue. There have not been extensive studies of estriol vaginally yet. There is a reason to combine testosterone with the estriol vaginally for muscle strength and the bone strengthening result of getting more physical activity.

 Many practitioners are not aware of the most recent developments in my experience. My bigger concern is that so many people I have seen as patients were not aware they need to research safe hormone replacement early in menopause. I posted 14 articles related to postmenopausal hormone deprivation as a “category of posts” on the homepage.” Bill Chesnut, MD.  

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 Anti-Mullerian Hormone and Prediction of Trans-Menopausal Bone Loss                              The Endocrine Society 1016 meeting _ a presentation.  Friday, April 1, 2016          

Arun S Karlamangla*1, Albert Shieh1, Sherri-Ann M Burnett-Bowie2, Elaine W. Yu2, Gail A Greendale1, Patrick M. Sluss2, Deborah Martin3and Joel S Finkelstein2
1University of California, Los Angeles, CA, 2Massachusetts General Hospital, Boston, MA, 3University of Pittsburgh, Pittsburgh, PA
 

The menopause transition (MT) in women is a period of bone loss, with the most rapid declines occurring in a 3-year period bracketing the final menstrual period (FMP). This period of rapid bone loss has been called the trans-menopause, and the rate of BMD decline over this period varies substantially between women (1).  Circulating levels of Anti-Mullerian Hormone (AMH) made by ovarian granulosa cells also decline as women progress through the MT (2). We hypothesized that serum levels of AMH in women early in the MT will predict the rate of bone loss over the trans-menopause. We tested this hypothesis using data from The Study of Women’s Health Across the Nation, a 7-site, multi-ethnic study of the MT. At baseline, participants had to be 42 to 52 years old, pre- or early peri-menopausal, have an intact uterus with 1 or 2 ovaries, and not be taking exogenous sex steroid hormones. Enrollment began in 1996 and women were asked to return annually.  At each visit, blood was collected between 8:00 and 10:00 AM after a 12-hour fast, during the early follicular phase (cycle days 2–5) whenever possible, and serum was stored at -80F.  In all women who had a natural (non-surgical) MT and a dateable FMP, serum level of AMH was measured from frozen blood samples using a new high-sensitivity monoclonal ELISA with a detection limit of 2 pg/mL (Pico AMH, Ansh Labs, Webster, TX). BMD [bone mass density] in the lumbar spine and femoral neck was measured annually in 5 of the 7 study sites.  In 474 women who had AMH and BMD measurements between 2 and 4 years before the FMP, had a 2nd BMD measurement 3-4 years later, and had not taken any medications that affect bone prior to the 2nd BMD measurement, we examined the ability of AMH level to predict the annualized rate of BMD decline between the two visits (% decline per year). AMH inter-quartile range was [11,146] pg/mL. Median rate of BMD decline was 1.3% per year in the spine and 1.0% per year in the femoral neck. Adjusted for age, BMI, smoking, race/ethnicity, and study site, in multivariable linear regression, each 75% (or four-fold) decrement in AMH level was associated with 0.15% per year faster decline in spine BMD (p<0.001) and 0.13% per year faster decline in femoral neck BMD (p=0.005).  These associations persisted even after additional adjustment for time from FMP and serum levels of estradiol and FSH. In multivariable logistic regression, adjusted for age, BMI, smoking, race/ethnicity, and study site, each four-fold decrement in AMH level was also associated with 18% increase in the odds of faster-than-median decline in spine BMD (p=0.02) and 17% increase in the odds of faster-than-median decline in femoral neck BMD (p=0.02). These findings suggest that serum levels of AMH in women going through the MT can indeed predict the rate of trans-menopausal bone loss, and help identify the women at risk of most loss.  AMH levels appear to provide information about the rate of bone loss beyond that provided by serum levels of estradiol and FSH.

(1) Greendale GA et al., JBMR 2012; 27: 111-8. (2) Sowers MFR et al., JCEM 2008; 93: 3478-83.