A new look at hormone therapy and dementia
26 June 2017:
Mikkola and colleagues examined the association between use of hormone therapy (HT) and death from Alzheimer’s disease (AD) or vascular dementia (VaD) in a sample of 489,105 Finnish women who had documented use of systemic HT on a nationwide drug reimbursement register [1]. A nationwide Finnish death register indicated that 1057 of those women died of AD and 581 died of VaD. Findings revealed that, compared to population averages, women who used HT for at least 5 years had a 15–19% reduced risk of death from AD, and use of HT for any period of time was associated with a 37–39% reduced risk of death from VaD. No reduction in AD was observed among women who used HT for less than 5 years, nor did age at initiation (< 60 years versus > 60 years) influence risk of AD or VaD.
Comment
Concern about the risks of dementia with HT stems primarily from the Women’s Health Initiative Memory Study (WHIMS), which showed a doubling of the risk of all-cause dementia with conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) [2]. These findings were observed in a sample of women aged 65 years and older, and questions regarding the generalizability of those findings to younger women and to other formulations of HT have been the topic of much debate. A definitive answer to those questions is unlikely to be determined, as it is not feasible to conduct a long-term, large-scale, randomized, controlled trial of HT for primary prevention of dementia among early postmenopausal women. For that reason, we must rely on observational studies to guide understanding of HT and dementia.
Observational studies of HT and dementia risk focus primarily on AD, the most common form of dementia, and less on VaD, the second most common form of dementia. Meta-analyses of HT and AD risk generally provide support for the view that HT lowers AD risk [3,4]. However, observational studies, particularly those in the United States, are difficult to interpret because of the healthy-user bias, the tendency for women who use HT to be healthier and better educated than those who do not use HT, and the tendency to rely on self-report of HT exposure (not optimal for a memory study!). Additionally, the most common form of HT used in those studies is CEE with or without MPA and little is known about estradiol, which is used widely outside of the United States.