EMBARGOED by NEJM
Wednesday, September 9, 1998
5:00 PM Eastern Time
Karin Kolsky, NIA
301-496-1752
Judith Wortman, NIAMS
301-496-8190
Post-menopausal women have low levels of naturally occurring estrogen in their blood which may still be of benefit in protecting them from fractures of the hip and vertebrae, according to scientists at the University of California at San Francisco (UCSF) Prevention Sciences Group. These investigators determined that women over the age of 65 with undetectable levels of estrogen in their blood are two and one-half times more likely to suffer a hip or spine fracture than women who have a measurable but low level of estrogen produced by their own bodies.
Following menopause, although most women experience a marked drop in estrogen levels, some women continue to produce modest quantities. Serious fractures, particularly those of the hip, in older women may lead to permanent disability and loss of mobility and even independence.
"These results will lead to new, more refined strategies for preventing bone loss and osteoporosis in older women, while lowering the long-term risks associated with estrogen therapy as it is prescribed today," commented Sherry Sherman, Ph.D., Director, Clinical Endocrinology and Osteoporosis Research at the National Institute on Aging. "They suggest that in older post-menopausal women, supplementation with low-dose estrogen may be of value in preventing hip and vertebral fractures by countering the bone-weakening effects of reduced estrogen levels many years after menopause."
These findings were reported in the September 10, 1998, issue of the New England Journal of Medicine . The research, conducted by Steven R. Cummings, MD; Warren S. Browner, MD, MPH; Douglas Bauer, MD; Katie Stone, Ph.D.; Kristine Ensrud, MD, MPH; Sophie Jamal, MD; and Bruce Ettinger, MD, was supported by the National Institute on Aging (NIA) and the National Institute of Arthritis and Musculoskeletal and Skin Disorders (NIAMS).
Beginning in 1986, these scientists at UCSF's Study of Osteoporotic Fractures Research Group enrolled 9704 women 65 years of age and older in Baltimore, MD, Minneapolis, MN, Pittsburgh, PA, and Portland, OR. Participants were interviewed about smoking habits, dietary calcium intake, and their use of estrogen, calcium, or multivitamin supplements. Chest and lumbar spine x-rays were taken, and blood was drawn and frozen. The women were contacted by mail every four months and followed for 6 years.
The women who suffered hip or vertebral fractures during the study differed from the fracture-free group in several ways. They were older, weighed less, had lower bone density at the beginning of the study, and were more often smokers. Analysis of the blood samples taken earlier revealed that women with undetectable blood levels of estradiol, the most potent form of estrogen made by the body, had a greater risk of hip and vertebral fracture than those with detectable estradiol levels. The risk of hip fracture increased also as blood levels of sex hormone-binding globulin, a protein that joins with estrogen in the blood, rose. Estrogen bound to these proteins in the blood is less available to the body to maintain bone mass. Women with both high sex-hormone binding globulin levels and undetectable levels of estrogen in their blood were found to be at a 7- fold higher risk for hip fracture and an 8-fold higher risk for a spine fracture. There was also a higher risk of hip, but not vertebral, fracture in women with low blood levels of vitamin D.
"These findings on the impact of endogenous hormone levels could be used to assist women and their physicians in the difficult decision of whether or not to use postmenopausal hormone replacement," according to Joan McGowan, Ph.D., Director of the Bone Diseases Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Previous retrospective studies have produced equivocal findings on the relationship between concentrations of estrogen in women's blood and hip or spine fractures possibly because hormone and vitamin D blood levels may change following fractures. In this prospective study investigators obtained baseline blood samples before the fractures occurred and then analyzed them in light of subsequent fractures.
The National Institute on Aging, part of the National Institutes of Health (NIH), leads the Federal effort supporting basic, clinical, epidemiological and social research on aging and the special needs of older people. The National Institute of Arthritis and Musculoskeletal and Skin Diseases, another of the 24 Institutes and Centers at NIH, is the lead institute for basic, clinical, and epidemiological investigations of osteoporosis.
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