From WHI to KEEPS: Two Studies on the Effects of Estrogen Therapy
Written by Carol Petersen, RPh, CNP – Women’s International Pharmacy
The much heralded (and widely criticized) Women’s Health Initiative (WHI) was the largest study involving women’s health to date. It investigated differences between the two most frequently prescribed hormone therapies at that time: Premarin, composed of conjugated equine estrogens, and Prempro, a combination of Premarin and the progestin medroxyprogesterone—none of which are bioidentical to the hormones produced by the human body. To much alarm by the media, the WHI study was halted after increased incidences of breast cancer and heart disease among participants. As a result, many people came to view all hormone therapies as suspect, leaving perimenopausal women with few other options for symptom relief.
Fortunately, a group of researchers at the Kronos Longevity Research Institute recognized an opportunity to improve on the WHI study and, in partnership with the National Institute on Aging at the National Institute of Health, initiated KEEPS, the Kronos Early Estrogen Prevention Study.
A four-year project, KEEPS involved women between the ages of 42 and 58, who were within three years of menopause. The two arms of the study evaluated 1) markers of cardiovascular risk and 2) effects on memory and mood, among three groups of participants:
- One group received oral conjugated equine estrogens (Premarin) at a dose of 0.45 mg/day, which is lower than the dose in the WHI study
- A second group used a Climara patch dispensing 50 mcg/day of bioidentical estradiol, equivalent to the estradiol produced by the ovaries
- A third group did not receive any estrogen therapy
All three groups also received micronized oral progesterone (Prometrium) cyclically. This is equivalent to the progesterone produced in the human body, unlike the progestin used in the WHI study.
The KEEPS team released initial results at the annual meeting of the North American Menopause Society in October 2012. The highlights concerning cardiovascular markers included:
- Those in the estrogen groups reported improvements in hot flashes, night sweats, mood, and sexual function, with no changes in atherosclerosis progression and no significant changes in blood pressure
- Bone density also improved with estrogen therapy
- Oral conjugated estrogens had some effects on lipid profiles, but transdermal estradiol was neutral in that aspect
- Insulin sensitivity improved with the transdermal estradiol
Results from the ancillary Cognitive and Affective Study arm of KEEPS at the University of Wisconsin were also encouraging. Their data demonstrated that hormone therapy had positive effects on global cognition, verbal and visual memory, executive functioning, mood, and quality of life. Participants also reported significant improvements with regard to depression, anxiety and tension, according to lead researcher Dr. Sanjay Asthana.
Both arms of the KEEPS project resulted in good news for perimenopausal women. In essence, the preliminary data suggests that hormone therapies—especially bioidentical hormones—can provide significant symptom relief without posing additional cardiovascular risk.