Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study

Abstract

Objectives To compare the use of hormone therapy between Finnish postmenopausal women with and without a diagnosis for Alzheimer’s disease. Design Nationwide case-control study. Setting Finnish national population and drug register, between 1999 and 2013. Participants All postmenopausal women (n=84 739) in Finland who, between 1999 and 2013, received a diagnosis of Alzheimer’s disease from a neurologist or geriatrician, and who were identified from a national drug register. Control women without a diagnosis (n=84 739), matched by age and hospital district, were traced from the Finnish national population register. Interventions Data on hormone therapy use were obtained from the Finnish national drug reimbursement register. Main outcome measures Odds ratios and 95% confidence intervals for Alzheimer’s disease, calculated with conditional logistic regression analysis. Results In 83 688 (98.8%) women, a diagnosis for Alzheimer’s disease was made at the age of 60 years or older, and 47 239 (55.7%) women had been over 80 years of age at diagnosis. Use of systemic hormone therapy was associated with a 9-17% increased risk of Alzheimer’s disease. The risk of the disease did not differ significantly between users of estradiol only (odds ratio 1.09, 95% confidence interval 1.05 to 1.14) and those of oestrogen-progestogen (1.17, 1.13 to 1.21). The risk increases in users of oestrogen-progestogen therapy were not related to different progestogens (norethisterone acetate, medroxyprogesterone acetate, or other progestogens); but in women younger than 60 at hormone therapy initiation, these risk increases were associated with hormone therapy exposure over 10 years. Furthermore, the age at initiation of systemic hormone therapy was not a decisive determinant for the increase in risk of Alzheimer’s disease. The exclusive use of vaginal estradiol did not affect the risk of the disease (0.99, 0.96 to 1.01). Conclusions Long term use of systemic hormone therapy might be accompanied with an overall increased risk of Alzheimer’s disease, which is not related to the type of progestogen or the age at initiation of systemic hormone therapy. By contrast, use of vaginal estradiol shows no such risk. Even though the absolute risk increase for Alzheimer’s disease is small, our data should be implemented into information for present and future users of hormone therapy.

Reproductive period and dementia: A 44‐year longitudinal population study of Swedish women

“…In contrast, two cross‐sectional studies reported higher odds ratios of dementia with number of pregnancies 30,31 . Furthermore, exogenous estrogens did not affect incident dementia in our study, contrary to previous studies reporting that exogenous estrogens reduce 3,4 or increase 6,32 dementia risk.…”

Exogenous Sex Hormone Effects on Brain Microstructure in Women: A diffusion MRI Study in the UK Biobank

“…For a more complete overview of the UKB data acquisition, neuroimaging protocol, and validation, see work by Miller 27 and Alfaro-Almagro 28 . In brief, diffusion-weighted images were acquired at b=1000 and 2000 s/mm 2 along with 50 noncoplanar diffusion directions per diffusion shell with 5 b=0 s/mm 2 (and 3 b=0 blip-reversed) using a standard ('monopolar') Stejskal-Tanner pulse sequence (voxel dimension: (2 mm) 3 isotropic, field of view: 104x104x72 mm; gradient timings: small delta=21.4 ms, big delta=45.5 ms) for a total imaging time of 7 minutes.…”

“…On average, women above 40 years of age are at a greater risk of developing AD than age-matched men. Endogenous and exogenous estrogen levels also influence this risk 3,4 . Still, we know very little about how sex hormone levels affect brain aging.…”

Menopausal hormone therapy and cognition

“…A linked study (doi:10.1136/bmj.l665) by Savolainen-Peltonen and colleagues in this week’s The BMJ explores associations between menopausal hormone therapy and risk of Alzheimer’s disease 1. Two thirds of patients with Alzheimer’s disease are women 2.…”

“…A parallel hypothesis applies to hormone therapy and cardiovascular health. Although available evidence suggests that the overall health benefits outweigh the risks in younger postmenopausal women without contraindications,6 should these women be concerned about an increased risk of dementia, as the case-control study by Savolainen-Peltonen and colleagues suggests?1…”