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. 2019 Mar 6:364:l665.
doi: 10.1136/bmj.l665.

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

Hanna Savolainen-Peltonen  1   2 , Päivi Rahkola-Soisalo  1 , Fabian Hoti  3 , Pia Vattulainen  3 , Mika Gissler  4   5   6 , Olavi Ylikorkala  1 , Tomi S Mikkola  7   2
Affiliations

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

Hanna Savolainen-Peltonen et al. BMJ. .

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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from Helsinki University Hospital and the Jane and Aatos Erkko Foundation for the submitted work; speaker and consulting fees for Mylan (HS-P, TSM) and Astellas (TSM); funding for congress trips from Merck, Sharp, and Dohme (HS-P), Astellas (PR-S), and Olympus (PR-S); FH and PV work for EPID Research, which performs financially supported studies for several pharmaceutical companies; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Risk of Alzheimer’s disease in women initiating systemic hormone therapy (HT) at different ages, as odds ratios and 95% confidence intervals. Line at 1.0 denotes the risk in the group of women who started systemic use younger than 55. Numbers of cases and controls are given for five years periods
Fig 2
Fig 2
Proportion (%) of women with a diagnosis of Alzheimer’s disease in different age groups according to systemic use of hormone therapy, vaginal use of estradiol, or without any history of hormone therapy (HT) use
See this image and copyright information in PMC

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