| The causes of amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), two progressive neurodegenerative diseases, are not known. Neuronal loss in ALS and PD possibly results from injury by environmental toxicants, oxidative stress, and neuroinflammation. Hence, factors that could protect neurons from damage caused by these mechanisms could potentially reduce the risk of ALS and PD. This doctoral dissertation, comprising three papers, evaluates the associations of two such pharmacological agents—postmenopausal estrogen and anti-inflammatory medications—with the risk of developing ALS and PD. In addition, the relationship between reproductive factors and risk of developing ALS and PD was also evaluated as men have a higher incidence than women for both diseases. The first two papers evaluated the relationships of postmenopausal estrogen use and reproductive factors with the risk of developing PD and ALS among postmenopausal women. The first paper used data from 367 postmenopausal women (178 cases, 189 controls) who participated in a large case-control study of PD conducted in the Northern California Kaiser Permanente medical centers (NCKPMC) in 1994–95. Postmenopausal estrogen use was associated with elevated PD risk among women with hysterectomy; however, disease risk was not increased with hormone therapy use among women with natural menopause. Early age at menopause was inversely associated with PD risk among all women. The second paper used data from 196 postmenopausal women (62 cases and 134 controls) who participated in a large case-control study of ALS conducted in NCKPMC (1996–2000). Reproductive factors were not associated with ALS risk and there was a suggestion of a positive association between postmenopausal estrogen use and ALS risk. The third paper evaluated the association of non-steroidal anti-inflammatory drugs (NSAIDS) with risk of ALS using data from all self-respondents (men and women; 113 cases, 258 controls) who participated in the ALS case-control study. The use of non-aspirin MAIDS was associated with a two-fold increased risk of ALS among men only and an inverse association was observed among women. The results observed in these studies warrant further exploration of the associations of postmenopausal estrogen and NSAID use with risk of ALS and PD. |
