Endogenous Female Reproductive Hormones and the Risk of Amyotrophic Lateral Sclerosis (P01.097)

Abstract

Objective: To determine whether a longer exposure to endogenous female reproductive hormones decreases the risk of ALS and influences survival in a large population-based study of incident patients, taking confounding factors into account. Background Several epidemiological studies have shown a lower incidence of ALS in women compared to men. The relative protection of women suggests a possible protective effect of female reproductive hormones, especially endogenous estrogens. The association between ALS and endogenous estrogen exposure has been studied using reproductive factors such as age at menopause or menarche as a proxy, but the results of these studies were conflicting. Design/Methods: We performed a population-based, case-control study in the Netherlands between January 1st, 2006 and December 1st, 2009. Only women with a natural menopause were included in the analyses. Multivariate logistic regression analysis was performed in incident patients diagnosed with ALS and population-based, age-matched controls, recruited through the general practitioner. Subjects were sent a questionnaire on reproductive history to calculate the reproductive time-span and lifetime endogenous estrogen exposure (calculated by subtracting the duration of pregnancies and of oral contraceptive use, and the number of post-ovulatory weeks from the reproductive time-span). Results: A total of 209 (85%) of 246 patients and 672 (93%) of 719 controls returned the questionnaire: 131 (63%) patients and 430 (64%) controls had experienced a natural menopause. Multivariate analysis showed that increasing the reproductive time-span by a year decreases the risk of ALS with an OR of 0.95 (p=0.005). Each year longer reproductive time-span (HR 0.90 (p=0.01)) and lifetime endogenous estrogen exposure (HR 0.96 (p=0.025)) were associated with a longer survival of ALS patients. Conclusions: The beneficial effect of a longer reproductive time-span on susceptibility and survival of ALS suggests that longer exposure to female reproductive hormones has a neuroprotective effect on motor neurons. Disclosure: Dr. van den Berg has received personal compensation for activities with Baxter. Dr. De Jong has nothing to disclose. Dr. Huisman has nothing to disclose. Dr. Schelhaas has nothing to disclose. Dr. Van Der Kooi has nothing to disclose. Dr. De Visser has received research support from Biogen Idec. Dr. Veldink has nothing to disclose.