Aug. 1, 2006

Estrogen probably not the only factor  in menopausal bone loss

Podcast: Bone loss and menopause

ANN ARBOR, Mich.—The loss of bone density after menopause has long been linked to the dramatic decrease in the estrogen hormone, estradiol.

But a series of studies that has carefully tracked hormone levels and bone density in women aged 40 to 55 over the course of a decade has found that estrogen may not be the only hormone that should be considered.

“For years, the model has been that ovaries lose their ability to make a potent estrogen at menopause, and that this estrogen decline starts the bone loss,” said epidemiologist MaryFran Sowers, the John G. Searle Professor of Public Health at the University of Michigan.

However, data from the Study of Women’s Health Across the Nation (SWAN) is showing that bone loss begins before the onset of menopause and before estrogen levels have really started to decline.

Until a more precise therapy for menopausal bone loss is developed, Sowers’ advice to younger women is to do weight-bearing activities to build and maintain bone mass. Eating mineral-rich foods and taking supplements alone won’t be enough, she said: exercise and activity are key.

“Having higher bone density in the first place is still your best defense against the impact of menopause-related bone loss,” Sowers said. 

Sowers' team zeroed in on follicle-stimulating hormone, FSH for short, which is produced in the pituitary gland of the brain and serves as the messenger to the ovaries to produce sex hormones. FSH levels begin to rise and become increasingly higher in the peri-menopause, well before the estrogen dip, probably because the ovaries are becoming less responsive to its signal.

“It’s like how you find yourself speaking increasingly louder to someone who’s becoming hard of hearing,” Sowers said. “The FSH signal keeps getting louder as it tries to communicate with the ovaries.”

At the same time FSH increases, the body also steps up bone resorption, the body’s mechanism for mining bone minerals for use elsewhere in the body. Such mining is natural during pregnancy, breastfeeding and starvation. The bones actually serve as a depot for important minerals like calcium and magnesium that might be hard to obtain in sufficient quantities from diet during high demand times. In a healthy, pre-menopausal woman, those minerals would be restored to the bone in a rebuilding process after the high-demand period has passed.

Among the SWAN women, Sowers’ team found that increased FSH levels were much more predictive of bone loss. This suggests that, in addition to signaling the ovary, FSH could signal other cells, including bone cell. Bone tissue has been shown to have receptors sensitive to this hormone and, in lab conditions, molecular biologists have recently established that bone tissue changes its rebuilding rates in response to FSH levels. All of this now makes both FSH and estrogen change the prime candidates responsible for bone loss around the menopause.

As the pituitary produces more FSH in response to sluggish estrogen levels, the unintended consequence may be bone loss, Sowers said.

“A lot of hormone systems are dual systems like this,” she said. “If FSH can signal bone cells, what other cells might also respond to the higher FSH? These findings suggest there is more crosstalk, with more types of signals than we initially recognized.”

Hormone replacement therapy with estrogen has been effective in stemming bone loss in some women, however. Sowers suspects that this new insight into FSH may help explain why estrogen’s effects on bone loss vary from one individual to the next. The findings also suggest new therapies to explore.

 These findings come from the Study of Women’s Health Across the Nation (SWAN), which has followed the 10-year experience of 3,300 women during their menopausal transition. The study is funded by the National Institutes of Health, through the National Institute on Aging, the National Institute of Nursing Research and the NIH Office of Research on Women’s Health.

Sowers’ latest findings on FSH and bone loss appear in the August issue of the Journal of Clinical Endocrinology and Metabolism.

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MaryFran Sowers

Study of Women’s Health Across the Nation

Contact: Karl Leif Bates
Phone: (734) 647-1842