In a recent University of California San Francisco study, researchers found that very low levels of estrogen--much lower than women currently achieve from taking hormone supplements--may prevent bone fractures in postmenopausal women without causing adverse effects associated with estrogen therapies, such as uterine cancer and bleeding.
According to the UCSF study, called "The Study of Osteoporotic Fractures," published in the September 10 issue of the New England Journal of Medicine, women who retain low, but detectable levels of their own estrogen after menopause have a much lower risk of suffering hip and spine fractures than one-third of the US female population who have extremely low, almost undetectable levels of the hormone.
A detectable concentration of estradiol, the most potent form of estrogen, is defined as between 5-20 pg per milliliter; an undetectable level of the hormone is classified as less than 5 pg per milliliter.
"Based on our findings, it seems important for women to maintain at least a little estrogen in their systems after menopause," said Steven Cummings, MD, UCSF professor of medicine and epidemiology and lead author of the study. "Our study suggests that for women whose estrogen level is less than 5 pg per milliliter, a much lower than standard dose of estrogen may be effective in preventing bone fractures."
He added that approximately 10 million American postmenopausal women have undetectable estrogen.
Typically, most doctors recommend that postmenopausal women who choose to take estrogen replacement therapies take a dose that produces 40-60 picograms (pg) per milliliter (ml) estrogen levels. However, Cummings said that while the standard dose of the drug is effective in preventing bone loss and osteoporosis in postmenopausal women, it has also been shown to increase the risk of uterine and possibly breast cancer in women.
Women in the UCSF study who had natural estrogen levels as low as five to ten pg per milliliter--significantly lower than the standard 40-60 pg per milliliter estrogen level--had a 62 percent lower risk of hip fractures and a 57 percent lower risk of vertebral fractures than those women with estrogen levels less than 5 pg per milliliter.
Although low doses of estrogen have not been tested yet in postmenopausal women to determine their effects on breast and uterine cancer, Cummings said that average postmenopausal women have low levels of estrogen and also have a very low risk of uterine bleeding and endometrial cancer. Therefore, he added, it is very likely that a small dose of the hormone will prevent bone loss and fractures without increasing a postmenopausal woman's risk of uterine cancer, bleeding and possibly breast cancer.
During the UCSF study, designed to determine the effects of a woman's natural hormones on the risk of hip and vertebral fractures, researchers recruited 9704 women 65 years and older to be followed for four to six years. Black women (because of their low risk of hip fractures), women who had undergone a hip replacement, and those who were unable to walk without help were excluded from the study.
At baseline, the women were asked if they were taking estrogen, calcium supplements, or multivitamins containing vitamin D. Those who were taking estrogen were excluded. In addition, the women were examined for bone fractures and their bone densities and hormone levels were measured.
Participating women were contacted every four months to determine if they had suffered any hip or vertebral fractures. UCSF researchers compared the base line hormone levels of 133 of the women who suffered subsequent hip fractures and 138 of those who had vertebral fractures with the hormone levels of women in a randomly selected control group.
Cummings reported that those women who had undetectable levels of estrogen (less than 5 pg per milliliter) were two and a half times more likely to suffer a subsequent hip or vertebral fracture.
The researchers also found that levels of sex hormone-binding globulin, a normal protein that carries estrogen and testosterone in the blood stream, that were 1.0 ug per deciliter or higher were associated with a relative risk of 2.0 for hip fractures and 2.3 for vertebral fractures.
Women with both undetectable estrogen levels and sex hormone-binding globulin concentrations of 1.0 ug per deciliter or more were seven times more likely to have a hip fracture and eight more times likely to have a vertebral fracture.
Other researchers on the study are Douglas Bauer, MD, UCSF assistant professor of medicine, epidemiology and biostatistics ; Warren S. Browner, MD, MPH, UCSF associate professor of medicine; Kristine Ensrud, MD, MPH, University of Minnesota assistant professor of medicine; Bruce Ettinger, MD, UCSF clinical professor of medicine; Sophie Jamal, MD; and Kate Stone, PhD.
This study was supported by grants from the National Institute for Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging, divisions of the National Institutes of Health.
NOTE TO THE MEDIA:
To interview Steven Cummings, MD, please contact Abby Sinnott in the UCSF News
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Journal
New England Journal of Medicine