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Heart and Brain Health After Menopause: Clinical Trial Examines Protective Effect of Hormone Replacement Therapy

Keck Medicine of USC researchers are testing a unique therapy that may prevent or slow atherosclerosis and cognitive impairment when taken within six years of menopause.

Short-term symptoms often associated with menopause, such as hot flashes, are commonly attributed to changes in reproductive hormones. However, menopause can also put heart and brain health at long-term risk.

Atherosclerosis, a leading cause of death in the U.S., almost always occurs in women after menopause. Cognitive concerns such as memory loss, dementia and Alzheimer’s disease are dramatically more common in postmenopausal than premenopausal women.

Now, Keck Medicine of USC has launched a clinical trial to study the effect of a novel hormone replacement therapy on postmenopausal cardiovascular disease and cognitive decline.

“Data supports the concept that estrogen, a hormone that the ovaries stop producing after menopause, protects both the heart and brain from damage,” said Howard N. Hodis, MD, director of the USC Atherosclerosis Research Unit, an internal medicine specialist with Keck Medicine and lead researcher of the study.

“Our study seeks to determine whether estrogen-containing hormone therapy can prevent or slow atherosclerosis progression and cognitive impairment in women after menopause.”

A key aspect of the study is that it is designed for women who are postmenopausal for six years or less.

“We have studied previous data and conducted clinical trials showing that the timing of when a woman starts hormone therapy is crucial,” Hodis said. “There appears to be a limited window of time wherein women benefit from hormone replacement therapy. Beyond six years of menopause, prevention appears to be too late.”

Improving standard hormone replacement therapies

The hormone therapy being studied has been approved by the Food and Drug Administration since 2013 and consists of estrogen paired with a non-hormone drug known as bazedoxifene.

Traditional hormone replacement therapy combines estrogen with progesterone, or more commonly with progestin, a synthetic progesterone. Estrogen alone can cause the lining of the uterus to thicken, causing bleeding and other health issues, which the progesterone or progestin prevents.

However, progestin/progesterone combined with estrogen has been associated with cancer risks. Bazedoxifene prevents the uterine lining from thickening while appearing not to present the same risks, Hodis said.

Trial eligibility and protocols

The double-blinded, placebo-controlled clinical trial is open to healthy women six years or less post-menopause, who have a uterus, are 45 to 59 years of age and do not have cardiovascular disease. 

Upon enrollment, trial participants receive an ultrasound of their neck artery, which is used as a non-invasive baseline measure of atherosclerosis. They also undergo several tests to gauge their baseline cognitive function and memory.

Every six months, participants have an ultrasound of their neck artery to monitor any progression of atherosclerosis. They also have yearly electrocardiograms to check for different heart conditions.

At the end of the study, which will last approximately three years, women will retake the cognitive and memory tests so researchers can determine whether there has been any change since enrollment.

“Our ultimate goal is to help women and their physicians make informed decisions to promote good health post-menopause,” Hodis said.

So far, some 260 women are participating in the trial; researchers are looking for 100 more women to enroll. If you have a patient that might be interested, contact the USC Atherosclerosis Research Unit at 323-442-2257.