Smaller Estrogen Doses Improve Mood Without Memory Loss

Ten years ago, the landmark Women’s Health Initiative (WHI) revealed that women older than 65 increased their risk for memory loss if they took estrogen to relieve the symptoms of menopause.

But new research by the University of Wisconsin School of Medicine and Public Health (SMPH) suggests that estrogen given in smaller doses to younger women just entering menopause does not worsen memory and improves mood and symptoms of depression.

The School of Medicine and Public Health was a participant in the Kronos Early Estrogen Prevention Study (KEEPS), which was conducted and supported by the Kronos Longevity Research Institute in Phoenix, Arizona. KEEPS-Cog (Cognitive and Affective Study) is an ancillary study measuring cognitive and emotional outcomes, funded by the National Institute on Aging at the National Institutes of Health (NIH).

Dr. Sanjay Asthana, the lead researcher of the cognitive and affective (emotional) part of the study and professor of medicine (geriatrics) at the UW School of Medicine and Public Health, presented the findings today during the North American Menopause Society annual meeting in Orlando, Florida. The preliminary findings, which are not yet peer-reviewed, will be submitted for publication in a medical journal.

The KEEPS-Cog was a four-year study and involved 662 women (average age 52.7 years) of the 727 women in the Kronos Early Estrogen Prevention Study cohort.

The participants were divided into three groups: One received a daily 0.45 mg dose of the oral estrogen Premarin, a second group used the estrogen patch Climara (0.05 mg/day, changed every third day), and a third group was on a placebo. The women took memory and cognition tests and assessments of their emotional health.

“At the four-year point, the women using the oral estrogen or estrogen patch showed no evidence of adverse effects on memory compared to the placebo group,” said Asthana. “There were also reduced symptoms of depression, anxiety and tension among women taking the oral estrogen.”

“These are very important findings when it comes to menopausal hormone therapy,” he added. “We applied our study to a much younger group that had never been studied before, and we are the first to have done that. This will help physicians understand whether or not it is safe for women to begin treatment for managing their menopausal symptoms.”

The women in the Kronos Early Estrogen Prevention Study also took progesterone in conjunction with estrogen. Progesterone is normally given to women in menopause to reduce the risk of uterine cancer. Asthana said the women showed no bad effects on memory or mood after taking a cyclical (12 days per month) 200 mg dose of Prometrium, a form of progesterone similar to one produced in the ovaries. By contrast, women in the WHI study took medroxyprogesterone acetate (MPA), which is a synthetic progesterone.

A School of Medicine and Public Health research team also monitored the blood pressure of all the women in the Kronos Early Estrogen Prevention Study and determined that blood pressure levels remained steady in those who took oral estrogen or used the estrogen patch over the four-year period. By contrast, the subjects in the Women’s Health Initiative study saw an increase in their blood pressure.

The Women’s Health Initiative involved 150,000 women older than 65 who received 0.625 mg of estrogen. About 4,500 WHI subjects participated in cognition screening.

At that dose, the participants not only showed a risk for memory deficits and high blood pressure, but also evidence of heart problems, breast cancer, and thrombosis (blood clots in the legs and lungs). Yet, the KEEPS participants who took estrogen showed no increased risk of these medical conditions during the four-year follow-up period.

Overall, Asthana said the results of the KEEPS-Cog study show promise for the future treatment of menopause. The findings will be reviewed by experts to determine how they fit in with current data and guidelines.

“This may help many women with menopause who are suffering,” he said. “Many of them can have these symptoms for years. This study shows that hormone therapy will likely be safe in the first few years that women enter menopause and improve their quality of life.”

Asthana, who is also chief of geriatrics at the School of Medicine and Public Health and director of the Geriatric Research Education and Clinical Center (GRECC) at the William S. Middleton Veterans Memorial Hospital in Madison, was assisted by neuropsychologist Dr. Carey Gleason, cognitive neuroscientist Dr. Whitney Wharton, and biostatistician Dr. Maritza Dowling.

Asthana said the next step will be to follow the women in the KEEPS-Cog study over time to determine if changes in memory normally seen with getting old are altered for these women in any way, given they received hormone therapy soon after menopause.

Science news source: 

University of Wisconsin, Madison