Estrogen-only menopause therapy linked to lower Alzheimer's risk in Stanford study

STANFORD, Calif. - Women who used estrogen-only menopausal hormone therapy showed lower odds of Alzheimer's-related brain changes, according to a Stanford Medicine study published Aug. 12 in the journal Neurology.

Researchers examined records from 21,462 participants and compared autopsy findings for 258 women who reported estrogen-only therapy with about 2,701 women who reported no menopausal hormone therapy. Estrogen-only users had 35 percent lower odds of Alzheimer's pathology, including amyloid plaques and neurofibrillary tangles. They also had 39 percent lower odds of a clinical dementia diagnosis during their lifetimes.

Most estrogen-only users had likely undergone hysterectomies. Estrogen-only regimens are generally prescribed for women without a uterus. About two-thirds of Alzheimer's patients are women, and participants in the analysis averaged about 70 years of age.

Senior author Hadi Hosseini, an associate professor of psychiatry and behavioral sciences at Stanford, said the study is unusual because it measured Alzheimer's hallmarks directly in autopsied brains rather than relying only on clinical diagnoses. Co-author Jennifer Bruno said estrogen has neuroprotective effects in animal models and that finding less pathology in estrogen-only users fit that mechanism.

The study is observational. It shows an association, not proof that hormone therapy prevents Alzheimer's. Hosseini said women who used therapy may have differed from non-users in health status or medical care in ways researchers could not fully measure. The team adjusted for age, education, race, hypertension, and APOE4 genetic status.

Earlier research, including the Women's Health Initiative Memory Study, had raised concerns that some hormone regimens might increase dementia risk, especially when started later in life. Stanford researchers noted recent medical literature suggests benefits may be greater when therapy starts during or soon after menopause. Because women in this study tended to be older when treated, the authors said the protective signal might understate benefits of earlier use.

The researchers could not draw firm conclusions about estrogen-plus-progestin formulations because too few autopsied women had used those regimens. Topical estrogen was not counted. Authors said the findings should not by themselves start or stop menopausal hormone therapy for brain health. They called for prospective clinical trials with biomarkers.

The National Institutes of Health funded the work.