Prenatal Sex Hormone Exposure and Risk of Alzheimer Disease: A Pilot Study Using the 2D:4D Digit Length Ratio

Objective: Our aim was to investigate an association between prenatal sex hormone exposure and dementia diagnosis. Background: Some evidence indicates that relatively low testosterone levels are a risk factor for men to develop Alzheimer disease (AD). Most research has examined current rather than premorbid testosterone levels, and little research has addressed testosterone and AD in women. Methods: In 20 men and women diagnosed with AD and 20 controls, we estimated prenatal exposure to testosterone and estrogen using the ratio of the length of the second to the fourth digit (2D:4D). We analyzed the data using a 2 (men versus women) x 2 (controls versus AD participants) analysis of variance. Results: The men with AD had significantly higher 2D: 4D ratios than the male controls, indicating lower levels of prenatal testosterone and higher levels of prenatal estrogen exposure. The women with AD had significantly lower 2D: 4D ratios than the female controls, indicating higher levels of prenatal testosterone and lower levels of prenatal estrogen exposure. Conclusions: These findings suggest that lower levels of prenatal testosterone and higher levels of estrogen exposure are a risk factor for AD in men, and that higher levels of prenatal testosterone and lower levels of prenatal estrogen exposure are a risk factor for women. Risk for AD may be related to prenatal exposure to a sex hormone different from an individual's chromosomal sex.