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Pros, Cons, Ambiguities
Answers Sought on Hormone Replacement Therapy

By Jan Ehrman

On the Front Page...
Hormone replacement therapy (HRT) -- Is it for every postmenopausal woman? Can it really help prevent heart disease, hip fractures and dementia? What if you've had breast cancer? Can you safely take estrogen supplements? Do the benefits of HRT outweigh the risks, and if so, for whom?


The jury is still out on many issues regarding HRT, long a controversial, albeit potentially viable health option for women following menopause. Yet it is questions like the aforementioned that the Women's Health Initiative (WHI) will ultimately help answer, according to experts speaking recently at a seminar held in Masur Auditorium.

Dr. Sally A. Shumaker

"What we now need are clear, unambiguous data so women can make rational decisions," said Dr. Sally A. Shumaker, director of the Women's Health Center of Excellence at Wake Forest University and a lecturer at the Feb. 17 program, "Women's Health Initiative: Finding the Answers on Hormone Replacement Therapy."

The WHI, which began in 1993, is a group of clinical trials and observational studies involving more than 164,000 postmenopausal women across the country. Ongoing protocols test treatments that may prevent heart disease, cancers of the breast and large bowel, fractures due to osteoporosis, and memory loss.

Dr. Jacques Rossouw

"Our job is to find the answers to the questions that are out there," said Dr. Jacques Rossouw, WHI lead project officer, who reviewed coronary heart disease and breast cancer in relation to HRT.

A large body of observational data points to a connection between estrogen and a decreased incidence of heart disease, the leading killer of American women. It is thought that coronary heart disease (CHD) occurs 10-15 years later in females than males primarily because women possess considerably more estrogen than men -- this accounts for higher levels of high density lipoproteins, the beneficial, cardioprotective type of cholesterol. Estrogen, either natural or supplemental, also lowers low density lipoprotein (LDL) cholesterol, which is atherogenic, while the male hormone androgen increases LDL.

The Nurses Health Study, another massive NIH-funded project, has suggested that HRT imparts an immediate cardiovascular benefit for postmenopausal women -- current users showed a 40 percent reduction in CHD. "Yet what cannot be explained," pointed out Rossouw, is "why there is no corresponding decrease in the incidence of coronary grafting or angioplasty in postmenopausal women receiving this treatment." The paradox is but one of many unanswered questions.

While the cardiovascular benefits of HRT still need to be established, there may also be a down side. Data from the Nurses Health Study reveal that as HRT dosage increases, the incidence of stroke rises proportionately. Further, deep vein thrombosis (blood clot) risk is 2-4 times greater in current users, and mainly occurs in the first or second year of use.

Some increased risk of breast cancer among HRT users has also been documented from the same study. In particular, "we saw an overall increased risk for breast cancer, most prominently in women age 60-65 who had been taking hormones 5 years or more," said Rossouw, also noting a 35 percent increased risk among users in a recently published analysis of the world literature. He added, however, that the effects on mortality from breast cancer are not known.

Dr. Jane Cauley

The next speaker, Dr. Jane Cauley, discussed hormones and their role in osteoporosis, or severe bone loss, a condition that markedly raises the risk of hip and vertebral fractures in postmenopausal women. Serving as associate professor of epidemiology and director of the Epidemiology of Aging Training Program at the University of Pittsburgh, Cauley is also principal investigator for the Study of Osteoporosis Fractures and the Fracture Intervention Trial at the same institution.

Low bone density, or osteopenia, is exceedingly common, affecting 53 percent of white women (National Health and Nutrition Examination Survey data), although rates are lower for African-American and Hispanic females. As a result of deterioration of skeletal tissue characteristic of the condition, fractures of the hip, spine and wrist, but especially the hip, take a heavy toll on non-treated, aging women. Some 250,000 (primarily postmenopausal) women fracture a hip annually, while one in six white women will sustain this injury during her lifetime. Of those, many never walk again, and 12-20 percent die during the first year following fracture, according to Cauley. Further, the devastating injury costs almost $14 billion annually to treat.

Can HRT prevent this life-threatening event? Evidence suggests it may. Results from the Postmenopausal Estrogen/Progestin Interventions Trial, a carefully controlled, randomized 3-year study of postmenopausal women, showed that subjects taking placebo (an inert or "dummy" pill) lost bone-mineral density, while those receiving HRT experienced an increase in bone adjacent to the hip. "Additionally, in the study of osteoporotic fractures, a lower rate of bone loss even in elderly women on estrogen -- for those age 80 and older -- was apparent," noted Cauley. This finding is particularly meaningful, since hip fracture occurs on average around age 70.

The evidence indicates, however, that to accumulate and preserve bone, women may need to begin HRT following menopause and continue the regimen.

Can HRT thwart cognitive decline in postmenopausal women, and in particular, lessen the risk of Alzheimer's disease and other dementias? According to Shumaker, "most studies show that estrogen does have a positive effect on cognitive function -- although not all trials have been blinded; some of the studies have other problems, and there are always external variables to take into consideration." Still, in 19 "reasonably well-conducted" investigations, she pointed out, most have shown a positive relation between estrogen and cognition. Also, in self-reports, postmenopausal women have reported that estrogen has helped improve memory, she added.

The bottom line, according to the experts, is that HRT has some potential benefits, but also some risks. The decision of whether a postmenopausal woman should or should not take HRT remains very individualized, and in many cases, is still not crystal clear.

"Estrogens have many biological effects," said Dr. Suzanne Hurd of the National Heart, Lung, and Blood Institute, and acting director of WHI. "What's most important to bear in mind for each woman is the balance of benefits and risks."

In time, results from WHI will enable postmenopausal women to more easily decide on which side of the fence they should be sitting.

The next ORWH-sponsored seminar, "Chronic Pain Conditions in Women," will be held Mar. 26, at 1 p.m. in Lipsett Amphitheater, Bldg. 10. For more information, call 402-1770.

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