For recently postmenopausal women, oral combined hormone therapy may help with symptoms of depression and anxiety. But hormone therapy did not produce any changes in cognition.
In a large, randomized controlled trial of oral and transdermal estrogens compared with each other and placebo, Carey Gleason, Ph.D., of the University of Wisconsin, Madison, and colleagues found that exogenous estrogen had no effect on cognitive performance in recently postmenopausal women over a 4-year study period. For women taking low-dose oral conjugated equine estrogens, a small to moderate improvement in some mood symptoms occurred; women receiving estrogen via a transdermal patch did not see this improvement in mood.
The results were published in PLOS Medicine (PLoS. Med. 2015;12:e1001833 [doi:10.1371/journal.pmed.1001833]).
Previous studies had shown mixed findings of the effects of menopausal hormone therapy on cognition, largely depending on whether treatment was initiated early on or later in menopause.
The 693 participants in the Kronos Early Estrogen Prevention Study - Cognitive and Affective Study (KEEPS-Cog) were a mean 52.6 years old, and the average time since the last menstrual period was 1.4 years. Enrollees were randomized to one of three study arms where they received either a 0.45 mg/day oral conjugated equine estrogen tablet, 200 mg/day cyclical progesterone capsule, and a placebo skin patch; or a 50 microgram/day transdermal estradiol patch, 200 mg/day cyclical progesterone capsule, and a placebo tablet; or a placebo tablet, capsule and patch. Treatment lasted for 4 years.
Cognitive status was measured over the 4 years using the Modified Mini-Mental State (3MS) exam and an additional battery of cognitive tests that assessed verbal learning, auditory attention and working memory, visual attention and executive function, and mental and linguistic flexibility. The Profile of Mood States (POMS) was used to evaluate mood. This test, designed to detect specific affective states in nondepressed individuals, assessed levels of tension-anxiety, depression-dejection, anger-hostility, fatigue, vigor, and confusion-bewilderment.
Dr. Gleason and her colleagues found no improvement in cognitive function with either formulation of menopausal hormone therapy.
“Contrary to our hypothesis, treatment with t-E2 [transdermal estrogen] did not improve cognition in recently postmenopausal women,” the researchers wrote.
For women taking oral estrogen, POMS subscores for tension-anxiety and depression-dejection showed significant improvement over time (for both, P < 0.001). The effect was not seen for transdermal estrogen; Dr. Gleason and her colleagues hypothesized that differences in the formulations of the two products, which resulted in different levels of estradiol versus estrone in participants, may have contributed to the result.
Most of the study’s enrollees were white women with low risk for cardiovascular disease, and most participants had at least a bachelor’s degree, so the generalizability of the KEEPS-Cog findings may be limited. Also, the study’s length and design did not permit assessment of dementia or other clinical diagnoses.
The KEEPS-Cog study, said Dr. Gleason and colleagues, can be incorporated into clinical decision making for women deciding whether to use menopausal hormone therapy. Using these results, a younger woman in good cardiovascular health “can weigh the known risks of [menopausal hormone therapy] against potential benefits for her unique symptom profile, and make an informed decision as to whether she would benefit from [menopausal hormone therapy] or whether she would prefer to manage symptoms through other means.”
The study was supported by the National Institutes of Health; the parent KEEPS trial was also supported by the Aurora Foundation. Dr. Cedars, Dr. Asthana, Dr. Santoro, and Dr. Taylor reported grant support and other financial relationships with pharmaceutical companies. The other authors reported no relevant financial disclosures.