Timing Key in Balancing HT's Risks, Benefits

SAN DIEGO — The scale that weighs risks and benefits tips more favorably for newly menopausal women who begin hormone therapy at age 50-59 years and who use it for 5 years, compared with women who start the therapy in their 60s, according to a systematic review of several studies and position statements.

Younger women who are newly menopausal and who use hormone therapy have a 30%-40% reduction in total mortality, a phenomenon “that's not seen in older women,” said Dr. Richard J. Santen, professor of medicine at the University of Virginia, Charlottesville, who called the findings “very surprising.”

“Physicians and their patients need to rethink the use of menopausal hormonal therapy” on the basis of these findings, said Dr. Santen, who chaired the 12-member task force that wrote a scientific statement on behalf of the Endocrine Society suggesting that menopausal hormone therapy may benefit women who start it in their 50s rather than in their 60s.

Importantly, the new analysis points to the need to look beyond data from the Women's Health Initiative, in which the average age was 63 years, in order to advise younger women. “The therapy clearly needs to be individualized, primarily based on symptoms. But if a woman has an underlying risk of breast cancer … you're going to be very cautious about this,” Dr. Santen said.

He said that the new analysis is more applicable to the typical menopausal patient whom physicians see in practice: the 53-year-old who had her last period a year ago, and is now trying to make a decision about whether to start menopausal hormonal therapy.

Dr. Santen and his associates used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system to evaluate the benefits and risks associated with menopausal hormone therapy based on published randomized controlled trials, cohort studies, and case-control studies, as well as position statements related to the topic.

Overall, the researchers found that women who start menopausal hormone therapy at age 50-59 years experienced a 30%-40% decrease in mortality, no increased risk of heart disease, and a 90% reduction of menopausal symptom such as hot flashes or overactive bladder.

“Relief of symptoms is really the key issue,” Dr. Santen said.

Compared with women who did not take hormone therapy, newly menopausal women experienced 10 fewer diagnoses of diabetes per 1,000 women, 4 fewer cases of heart disease (among those on estrogen only), 5 fewer bone fractures, and 2 fewer cases of colon cancer per 1,000 women (among those on estrogen plus progestin only).

Risks associated with menopausal hormone therapy included gallbladder disease (10 more per 1,000 women), blood clots in the legs and lungs (5 more women), and stroke (2 more women).

Women who were on estrogen therapy alone had no increased risk of developing breast cancer, but there were 7 more cases of breast cancer per 1,000 women among those who took estrogen and progestin for 5 years, compared with non-HT users.

“Our tentative conclusion is that estrogen plus progesterone actually didn't cause tumors; it caused preexisting tumors to grow to a size where they became detectable,” Dr. Santen said.

The statement is published in the July 2010 issue of the Journal of Clinical Endocrinology and Metabolism.

Disclosures: Dr. Santen reported having no conflicts of interest.

My Take

Statement Shores Up NAMS Advice

This has been a banner season for statements regarding postmenopausal hormone therapy (HT). Recently, the North American Menopause Society (NAMS) and the Endocrine Society (ES) issued complementary statements; five senior authors contributed to both documents.

Philosophically, the two societies agree on the fundamentals. While NAMS limits their discussion to estrogen and estrogen combined with progestogen therapy, the ES touches on the use of alternative forms of HT such as tibolone and raloxifene, as well as bioidentical forms of HT, such as testosterone and dehydroepiandrosterone. The NAMS statement, at 14 pages, presents concise, bottom-line risk/benefit assessment and practical clinical recommendations. The ES scientific statement, at 66 pages, presents a tour de force analysis of the literature, carefully weighed according to level of evidence.

The 12 pages dedicated to breast cancer in the ES document clearly illustrate why the relationship between HT and the breast is so complex, and why generalizations regarding risks are so challenging.

Both groups acknowledge the important influences of age and time since menopause on benefits and risks of HT. Both agree that more research is necessary to accurately assess benefits and risks in recently menopausal women most likely to request HT. And both conclude with the familiar mantra to individualize therapy, and use the lowest effective dose for symptom relief for the shortest duration possible.