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.

Both estrone and estradiol production in visceral AT increased with adiposity, but estradiol was produced more effectively in subcutaneous fat. Both AT depots produced estrone from E1S. Increasing visceral adiposity could increase overall estrogen exposure in postmenopausal women.

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Estrogen metabolism is differentially regulated in the adipose tissue of women with or without cancer. In the sc adipose tissue proximal to breast tumor 17β-hydroxysteroid dehydrogenase type 12 expression is lower than in controls, which could indicate that the conversion of estrone to estradiol is decreased. Further studies are needed to establish the clinical significance of our findings in the development and growth of breast cancer in postmenopausal women.

The production of E₂ by the large adipose mass was not reflected by increased circulating E₂ concentrations in severely obese men or women. However, adipose tissue may contribute to concentrations of serum E₂-FAE.

The inflammation-induced miR-221-3p regulates ANGPTL8 expression in adipocytes. This miRNA impact may become especially prominent under pathologic conditions such as morbid obesity, putatively contributing to the impaired AT lipid metabolism in metabolic disease.

Hot flashes contribute differently to various variables affecting health-related quality of life shortly after menopause. Estradiol or an estradiol-medroxyprogesterone acetate combination similarly alleviates hot flashes and improves health-related quality of life in relation to elimination of hot flashes. Hormone therapy use does not confer any detectable quality-of-life benefit over placebo in women without disturbing baseline flashes.

Estradiol-based HT use is associated with a reduced risk of death from both VD and AD, but the risk reduction is larger and appears sooner in VD than AD.