Menopausal Hormone Therapy Not Linked to Premature Death

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While HRT has been in and out of favor, for the right patient, hormone therapy is safe and effective.

Hormone Therapy, menopausal, menopause, hot flash, menopause symptoms

Women using hormone replacement therapy (HRT) to ease menopause symptoms are no more likely to die prematurely than women not using hormones, a new study suggests.

Since 2002, women have been reluctant to use hormones for menopause symptoms after a study from the federally funded Women’s Health Initiative (WHI) linked treatments containing man-made versions of the female hormones estrogen and progestin to an increased risk of breast cancer, heart attacks and strokes. While adverse health outcomes were previously reported, they did not focus specifically on all-cause mortality and cause-specific mortality.

A new study led by investigators at Brigham and Women’s Hospital examined long-term rates of death from all-causes and cause-specific rates, including cardiovascular disease, cancer and other major illnesses over a follow-up of 18 years from the 2 WHI HRT trials.

JoAnna Manson, MD, DrPH, lead author and chief, division of preventive medicine at Brigham and Women's Hospital, said these findings provide support for clinical guidelines which endorse “the use of hormone therapy for recently menopausal women to manage bothersome hot flashes and other menopausal symptoms.”

However, the findings do not provide support for using hormone therapy in prevention of cardiovascular disease or other chronic diseases, Manson noted.

“In clinical decision making, these considerations must be weighed against the impact of untreated menopausal symptoms that women experience, including impaired quality of life, disrupted sleep, reduced work productivity and increased health care expenditures,” Manson said.

Researchers looked at data from 27,347 postmenopausal women aged 50—79 years who enrolled in 2 randomized clinical WHI trials between 1993–1998 and followed up through 2014.

One trial tested estrogen alone versus placebo, while the other tested estrogen taken in combination with progestin.

The primary outcome was to examine total and cause-specific cumulative mortality during the intervention and extended post-intervention follow-up of the 2 hormone therapy trials.

Researchers found no increase or decrease in total mortality or deaths from cardiovascular disease, cancer or other illnesses in the randomized HRT trials.

The new study results supported that hormone therapy may be appropriate for some women when used short-term to relieve hot flashes and other bothersome menopause symptoms.

During the follow-up, 7,489 deaths occurred, more than twice as many deaths as were included in earlier reports with shorter follow-up periods. When examined by 10-year age groups, mortality rates were greater among younger women receiving hormone therapy, versus older women receiving therapy.

Throughout 5—7 years of treatment, death rates were approximately 30% lower in women receiving HRT versus placebo. However, among women with HRT in their 60s and 70s, no effect on death rate was observed.

After 18 years — which included 10—12 years of follow up after ending hormone therapy — the differences by age group diminished and weren’t statistically significant. Overall mortality rates and deaths from cardiovascular disease and cancer neither increased nor decreased among women receiving HRT.

Deaths from Alzheimer’s Disease and other dementia forms were lower with estrogen-alone than with the placebo during 18 years of follow up, the study found, but the use of estrogen and progestin was not associated with dementia mortality.

Though each individual considering hormone therapy must assess her own risks and benefits, HRT is generally a reasonable tactic for treating tough side effects of menopause like hot flashes, night sweats and sleep disruption, while decreasing the risk of hip fractures and other fractures.

However, HRT has been linked to risks including venous blood clots, stroke and certain cancers.

All-cause mortality is a key component in measuring an intervention like HRT with complex benefits and risks. While it increases the risk of some diseases and decreases the risk of others, mortality rates are the bottom line in looking at the net effect on serious health outcomes.

The study, “Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality,” can be found in the Journal of the American Medical Association.

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