Endocrine events that signal less exposure to estradiol, such as shorter reproductive span, younger age at menopause, and hysterectomy, increase dementia risk in women, according to a recent study published in Neurology.

Study investigators evaluated women (29.9% nonwhite) who were members of Kaiser Permanente as of January 1, 1996, with health data from 1964 to 1973. Through a series of questions, age at menarche was grouped into: ≤10, 11 to 12, 13, 14 to 15, and 16 to 17 years. Age at menopause was categorized into 5-year age groups except for younger than 40, which were collapsed into ≤30 and 31 to 40.

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Reproductive years were calculated by subtracting age at menarche from age at menopause and were grouped into ≤20, 21 to 30, 31 to 34, 35 to 36, 37 to 38, and 39 to 44. Hysterectomies were included as surgical menopause. Dementia diagnoses occurring between January 1, 1996, and September 30, 2017, were obtained from inpatient and outpatient electronic medical records.

A total of 37,226 women between 45 and 55 years old participated in the checkups from 1964 to 1973. After excluding those who died or were lost to follow-up, dropped out before dementia evaluation started, or did not provide age at menarche, hysterectomy, or menopause, 6137 women provided required data and 4047 were included for analysis.

Women with menarche at age 16 or 17 had a 23% greater risk for dementia compared with menarche at 13 (hazard ratio [HR] 1.23; 95% CI, 1.01-1.50). Women who experienced natural menopause before 47.4 years had 19% elevated dementia risk (HR 1.19; 95% CI, 1.07-1.31) when compared with those who attained menopause at 47.4 years or older.

Reproductive spans of less than 34.4 years were associated with 20% increased dementia risk (HR 1.20; 95% CI, 1.08-1.32). Hysterectomy conferred an 8% increase (HR 1.08; 95% CI, 1.01-1.16), and menopause before age 48.5 was associated with a 15% elevated risk (HR 1.15; 95% CI, 1.03-1.28).

Also, those with dementia and those without did not significantly differ by education, body mass index, midlife hypertension, or late-life diabetes.

Limitations of this study included that it did not account for other factors that affect estrogen exposure like pregnancies, hormone replacement, or use of hormonal birth control. Researchers did not directly measure circulating estrogens and thus were unable to directly examine the association between different forms of estrogen and dementia risk.

Researchers concluded that longer exposure to estrogen lowered dementia risk. Timing these events accurately can lead to the development of good preventive measures.

Reference

Gilsanz P, Lee C, Corrada MM, Kawas CH, Quesenberry CP Jr, Whitmer RA. Reproductive period and risk of dementia in a diverse cohort of health care members [published online March 28, 2019]. Neurology. doi: 10.1212/WNL.0000000000007326