Study findings have little effect on HRT decision

Status of bones may predict breast cancer risk

Each SD in BMD, often buttressed by HRT, increases a woman’s risk for BC but lowers her risk for CVD. Oh, and by the way, PEPI and CHART show that changes in LDL and HDL are OK.

This may just be zany scientific lingo, but if it’s at all confusing for you, think about how your patients feel, even after you provide the translation: A new study shows that for every standard deviation (SD) from the mean increase in bone mineral density (BMD), a woman has a 30% to 50% higher risk of developing breast cancer (BC).1 Hormone replacement therapy (HRT) can increase bone density, thereby staving off osteoporosis. It is also well-known that HRT can decrease the risk for cardiovascular disease (CVD), the No. 1 killer in the United States. Some women don’t comply with their HRT regimen because it causes menstrual-like bleeding, but a new study, the Continuous Hormones as Replacement Therapy (CHART) study,2 provides evidence that a new formulation can do everything that other combined formulations can while causing amenorrhea for most users after three months.

Lastly, the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial,3 shows that estrogen may not only slow bone loss, it may promote BMD.

No wonder scientists use so many acronyms.

Believe it or not, this is the short version of three studies that appeared in a recent issue of the Journal of the American Medical Association exploring the issue of hormones and BMD. While a new factor has been added to a woman’s lineup of pros and cons to consider before deciding on her use of HRT — high bone mineral density as a risk factor for breast cancer — the three studies offer no new diagnostic or counseling advice. Women along with their providers still need to assess their own risks and benefits, the authors tell Women’s Health Center Management.

Risk small but important

Bone is highly sensitive to circulating estrogen because it contains many estrogen receptors. Jane A. Cauley, DrPH, associate professor in the department of epidemiology at the Graduate School of Public Health at the University of Pittsburgh, studied BMD as a marker for a woman’s exposure to estrogen.1 Cauley says a woman’s relative risk of getting breast cancer is 1.3 to 1.5 if her BMD is one SD from the mean. The mean indicates where most of the values for a group are centered, and the SD is a way of describing how dispersed all the values are from the center. In this case, one SD includes women with the highest BMD, and the mean is women with the lowest BMD.

Epidemiologists usually don’t break a sweat until relative risk is above 2.0, but Cauley warns not to trivialize her team’s findings.

"It’s clear, it’s well-established that bone mineral density predicts fractures, and yet the magnitude of our association, although it is in the opposite direction, is similar to the magnitude of bone mineral density predicting fractures," Cauley asserts. "It’s not something to be minimized."

She says another important finding from her study, which involved 6,854 non-black women over the age of 65, is that women can use the information to make more informed choices about the use of HRT. But some scientists think Cauley’s findings are nothing new.

"Bone density correlates with a woman’s estrogen environment, and we’ve long known that a small percentage of women that get breast cancer have characteristics that are associated with more estrogen exposure," says Leon Speroff, MD, professor of OB/GYN at Oregon Health Sciences University in Portland. Remember that the majority of women who get breast cancer have no such risk factors, Speroff says.

That’s just what makes counseling women about HRT so difficult, says Cindy Dreher, MPH, MAT, director of the Women’s Place at Baptist Medical Center in Columbia, SC.

"We continue to tell women it’s a personal decision they’ll need to make with the guidance of their physician," she points out, adding that they are told to view a family history of breast cancer as a "big red flag."

Three steps to compliance

In addition to presenting all the known facts about the risks and benefits of HRT, Dreher says providers at her center spend a lot of time trying to improve compliance with the regimen. Women become displeased with certain aspects of the treatment — for example, the bleeding that occurs with combined formulations — and they often simply stop taking it without consulting their physician, she says. The three key points women are given are:

• HRT is not an instant cure for ailments caused by menopause.

• There are other formulations to try, so don’t give up if you don’t like the first one.

• Be patient and persistent, and you eventually will find the right formulation for you.

Until research can provide clear parameters for exactly who should take what formulation and when, women’s health providers are still left with the challenge of helping women understand the wealth of information about the pros and cons of HRT. Speroff says it’s not as difficult as it seems. If women want the benefits of HRT, they have to use it, he says. And the breast cancer risk? That’s easy, too.

"There is no agreement among 40-plus studies [linking breast cancer and HRT]," Speroff argues. "There are no consistencies, no uniformity. If there was a big effect, we would have that consistency and that uniformity. I tell patients this is good news."


1. Cauley JA, Lucas FL, Kuller LH, et al. Bone mineral density and risk of breast cancer in older women: The study of osteoporotic fractures. JAMA, 1996; 276:1,404-1,408.

2. Speroff L, Rowan J, Symons J, et al. The comparative effect on bone density, endometrium, and lipids of continuous hormones as replacement therapy (CHART study): A randomized controlled trial. JAMA, 1996; 276:1,397-1,403.

3. The Writing Group for the PEPI Trial. Effects of hormone therapy on bone mineral density: Results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 1996; 276:1,389-1,396.