Combined hormone therapy still a treatment for menopausal symptoms, but not without risks

Although recent research has found that it increases the risk of dementia in older women, combined hormone therapy remains the only proven treatment for the symptoms of menopause, according to John Robbins, a UC Davis professor of general medicine.

“As with all medications, there is a risk-benefit tradeoff with combination hormone therapy,” said Robbins, the principal investigator of the $10.5 million, 15-year Women’s Health Initiative effort at UC Davis.

Last week, findings from a substudy of the national WHI indicated that older women taking combination hormone therapy had twice the rate of dementia, including Alzheimer’s disease, compared with women who did not take the medication. The research, part of the Women’s Health Initiative Memory Study (WHIMS) and reported in the May 28, 2003, Journal of the American Medical Association (JAMA), found the heightened risk of developing dementia in a study of women 65 and older taking PremproTM, a particular form of estrogen plus progestin hormone therapy.

The study also found that the combination therapy did not protect against the development of Mild Cognitive Impairment, or MCI, a form of cognitive decline less severe than dementia.

Robbins noted that the recent findings are no better than those of a year ago from the WHI, which indicated that the use of combined estrogen and progestin in postmenopausal women increased the risk of breast cancer and cardiovascular disease.

“The risk of dementia applies only to women on the combined therapy,” Robbins said. “My guess, based on no specific data, is that the vascular diseases that are increased by estrogens and progesterone and cause increased strokes and heart attacks also caused the increased dementia. I would not be more worried by these findings than the last, but I would advise against taking these drugs to prevent dementia.”

The women enrolled in the UC Davis portion of the WHI were informed of the JAMA findings and had already been told last year to stop taking the study medications.

Despite the findings of last year and last week, Robbins said that if menopausal symptoms were severe enough to cause a woman to consider harming herself or others, or to behave irrationally, then “it is probably worth taking the combination hormones for a limited time. The additional risk is still small, on the order of 20 out of 10,000 women.”

Robbins said that he and his research team hope to receive funding to conduct cerebral MRIs on a group of WHI participants (both on treatment and controls) to determine if increased subclinical strokes may explain the increased dementia.

“We still have not been told by the Data and Safety Monitoring Board to stop the estrogen alone arm of the trial, so we have no hard reason to think that estrogen alone increases the risk of stroke, heart attacks, dementia or breast cancer,” Robbins said.