A recent comprehensive study examining the correlation between estrogen-only therapy and dementia risk among women has unveiled compelling insights into the association. The study, conducted using extensive Danish registers, offers significant evidence regarding the potential impact of estrogen-only use on dementia rates, particularly in women nearing or experiencing menopause.
This study was published in the journal JAMA Network by Nelsan Pourhadi and colleagues. The study encompassed 29,104 women who underwent hysterectomy, tracking their health over 500,000 person-years. Among these women, 541 were diagnosed with dementia during the follow-up period, with Alzheimer's disease accounting for 92 cases. Notably, estrogen-only users constituted a significant portion, representing 53.2% of dementia cases and 45.0% of controls. The median age at diagnosis stood at 70 years, with a median treatment duration of approximately 5.4 years among users.

The study revealed a concerning trend, showcasing a substantial link between estrogen-only use and an increased risk of dementia. Compared to never users, those who opted for estrogen-only therapy exhibited a notable elevation in dementia rates, with a hazard ratio (HR) of 1.55. This association persisted even among women who initiated therapy closer to menopause, with an HR of 1.58 among those treated until a maximum age of 55 years.
Furthermore, the study highlighted a dose-dependent relationship between estrogen dosage and dementia risk. An increasing daily estradiol dose corresponded to higher hazard ratios, indicating a potential dose-response effect.
While the findings shed light on a concerning association, the study acknowledges several limitations, including potential residual confounding and underregistration of specific dementia diagnoses, notably Alzheimer's disease. Additionally, the study's reliance on primarily hospital memory clinics might have missed cases diagnosed and treated exclusively in primary care settings.
Reference:
Pourhadi, N., Mørch, L. S., Holm, E. A., Torp-Pedersen, C., & Meaidi, A. Dementia in women using estrogen-only therapy. JAMA: The Journal of the American Medical Association,2023. https://doi.org/10.1001/jama.2023.23784