In an observational study, a modestly higher risk for dementia was noted among menopausal hormone users.

Some studies have shown excess risk for dementia in older women (age, 65 years and over) who use menopausal hormone therapy. Whether use of hormone therapy by younger women, around the time of natural menopause, is associated with dementia risk is uncertain.

In this case-control study using Denmark’s national registries, researchers identified 5600 incident cases of dementia in the years 2000 to 2018 among women who were middle-aged (age range, 50 to 60 years) in 2000. Cases were compared with 56,000 age-matched controls, with combined estrogen-progestogen treatment as the primary exposure of interest. In analyses adjusted for potentially confounding factors, the following outcomes were noted:

• compared with never-users, users of hormone therapy had significantly higher incidence of all-cause dementia (hazard ratio, 1.24), late-onset dementia and Alzheimer disease
• longer duration of menopausal hormone therapy was associated with higher risk; HRs ranged from about 1.2 (for less than eight years) to 1.7 (for more than 12 years)
• both cyclical and continuous hormone therapy prescriptions were associated with similar excess dementia risk
• almost 97% of hormone therapy users received oral hormone therapy, precluding evaluation of transdermal hormone therapy.

Comment: Causality cannot be proven in this observational study, given potential residual confounding. Nevertheless, some clinicians will find it reasonable to discuss the possibility of a small excess risk for dementia when counselling women who are considering hormone therapy. One reason to do so is that, during initial discussions, we cannot predict whether some patients will choose to continue treatment into older age – where an association between hormone therapy and dementia risk was shown in randomised trials (NEJM JW Gen Med Jul 1 2003 and JAMA 2003; 289: 2651-2662; NEJM JW Gen Med Aug 1 2004 and JAMA 2004; 291: 2947-2958).

Marie Claire O’Dwyer, MB BCh BAO, MPH, Clinical Assistant Professor in Family Medicine, University of Michigan Medical School, Ann Arbor, USA.

Pourhadi N, et al. Menopausal hormone therapy and dementia: nationwide,nested case-control study. BMJ 2023; 381: e072770.

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine, Women’s Health, Neurology.