March 08, 2019
2 min read

Prolonged postmenopausal hormone therapy may increase Alzheimer's risk

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Undergoing postmenopausal hormone therapy for 10 years or more may increase the risk for Alzheimer’s disease, according to findings published in BMJ.

Tomi Mikkola

“There have been opposing findings in previous smaller studies, and some have even implied that hormone therapy would reduce Alzheimer’s disease,” Tomi Mikkola, MD, associate professor in the department of obstetrics and gynecology at Helsinki University Hospital, told Endocrine Today.

Mikkola and colleagues conducted a nationwide case-control study using data from national registers in Finland. They identified 84,739 women who were diagnosed with Alzheimer’s disease between 1999 and 2013 and, using a national population register, identified 84,739 women without Alzheimer’s disease as the control group. Both groups were matched by age and location.

The researchers also determined HT use via a national register that has reported HT use since 1994. HT initiation was confirmed at first purchase, or at age 52 years if systemic therapy was noted when the register began or age 65 years if vaginal estradiol was noted when the register began, the researchers wrote. Duration of HT exposure was categorized as 3 years or less, 3 to 5 years, 5 to 10 years, or more than 10 years.

Women who used estradiol only (OR = 1.09; 95% CI, 1.05-1.14) or estrogen-progestogen (OR = 1.17; 95% CI, 1.13-1.21) were at increased risk for Alzheimer’s disease, but this did not hold true for those who used vaginal estradiol alone (OR = 0.99; 95% CI, 0.96-1.01).

The researchers found that when estrogen-progestogen therapy was started by women younger than 60 years, there was a risk increase of 8% (OR = 1.08; 95% CI, 1-1.17) to 17% (OR = 1.17; 95% CI, 1.08-1.26) for Alzheimer’s disease development depending on progestogen type. In this same population, at least 10 years of HT was associated with the increased risk for Alzheimer’s disease brought about by estradiol only (OR = 1.07; 95% CI, 1-1.15) and estrogen-progestogen (OR = 1.2; 95% CI, 1.13-1.26) therapies.

The risk for Alzheimer’s disease was also elevated for women who started therapy after age 60 years and used estradiol only (OR = 1.15; 95% CI, 1.06-1.25), estrogen-progestogen (OR = 1.23; 95% CI, 1.14-1.32) or tibolone (OR = 1.38; 95% CI, 1-1.89).

“Even though this absolute risk increase for Alzheimer’s disease is small, it emphasizes that fact that hormone therapy should be used in recently menopausal women for symptom relief, and they benefit from the therapy,” Mikkola said. “However, hormone therapy should not be initiated for Alzheimer’s disease prevention, and in elderly women that have used hormone for more than 10 years, should be aware that the treatment could increase their risk for Alzheimer’s disease in later life.” – by Phil Neuffer


For more information:

Tomi Mikkola, MD, can be reached at

Disclosures: Mikkola reports he has received speaker and consulting fees from Astellas and Mylan. Please see the study for all other authors’ relevant financial disclosures.