The long-term use of percutaneous estradiol gel and oral micronized progesterone during long-term hormone therapy may reduce cognitive decline in postmenopausal women with mild cognitive impairment, according to a study published in Menopause.
“Dementia is a major public health problem in the aging society,” Byung-Koo Yoon, MD, PhD, president of the Korean Society of Menopause and of the Korean Society for Bone and Mineral Research, director of menopause research and professor in the department of obstetrics, gynecology and women’s health at Samsung Medical Center at Sungkyunkwan University School of Medicine in Seoul, South Korea, told Endocrine Today. “Conventional menopausal hormone therapy, primarily used for menopausal symptoms, is indicated for neither prevention nor treatment of Alzheimer's disease. In this study, we employed percutaneous 0.1% estradiol gel at higher dose (up to 2 mg per day) and also gave oral micronized progesterone (100 mg per day) irrespective of the presence of intact uterus for 2 years. We could expect positive impacts in postmenopausal elders with mild cognitive impairment this way, avoiding possible risks, including thrombosis.”
Yoon and colleagues enrolled 37 postmenopausal women with the multiple-domain amnestic subtype of mild cognitive impairment (aged 57-82 years) in a prospective, randomized, double-blind, placebo-controlled trial. Researchers gave all participants donepezil (Aricept, Pfizer) up to 10 mg per day. Researchers randomly assigned participants to a placebo group (n = 18; mean age, 71.2 years) or a menopausal HT group (n = 19; mean age, 69.5 years). Participants in the treatment group applied percutaneous 0.1% estradiol gel to their forearm before sleep. The dose of estradiol gel began at 0.5 mg per day, with a monthly escalation of up to 2 mg per day if well-tolerated. Researchers added oral micronized progesterone after 3 months. Members of the other group were given placebos that were identical in appearance to the active treatment drugs. Researchers monitored participants’ use of the gel and the oral micronized progesterone by history taking and pill count at every visit.
General cognitive function was the primary endpoint, with activities of daily living, abnormal behavior, depression symptomatology, quality of life and progression to dementia as secondary endpoints.
Researchers tested general cognitive function every 6 months utilizing the modified Alzheimer’s disease Assessment Scale, cognitive subscale, the Korean version of Mini-Mental State Examination and the Korean version of the Montreal Cognitive Assessment (MoCA_K). To examine secondary endpoints, researchers used the Bayer Activities of Daily Living scale and Geriatric Quality of Life biannually and Caregiver Administered Neuropsychiatric Inventory and Geriatric Depression Scale annually.
Beginning at 18 months, participants in the HT group saw significantly reduced deterioration of their MoCA_K scores, a sensitive tool for assessing global cognition in mild cognitive impairment.
“Additional large-scale, long-term trials are needed to confirm our findings and eventually to determine whether menopausal HT could delay or diminish mild cognitive impairment progression to dementia in postmenopausal women,” Yoon said. – by Melissa J. Webb
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Byung-Koo Yoon, MD, PhD, can be reached at firstname.lastname@example.org.
Disclosures: The authors report no relevant financial disclosures.