Implications for estrogens in Parkinson's disease: an epidemiological approach

Evidence from experimental and epidemiological studies suggests a role of sex hormones in the pathogenic process leading to neurodegenerative diseases, (i.e., Alzheimer's and Parkinson's disease). The effects of sexual steroid hormones are complex and vary with the events of women's fertile life. Estrogens are supposed to influence dopamine synthesis, metabolism, and transport; however, there is no consensus regarding the direction, locus, and mechanism of the effect of estrogens on the dopaminergic system. A neuroprotective effect of estrogens has been demonstrated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-animal models of Parkinson's disease (PD). Epidemiological studies indicate gender differences regarding the onset and the prognosis of PD. Most of the analytical studies explored the relationship between PD and exogenous estrogens. Only three studies investigated the role of endogenous estrogens in the risk of developing PD. These studies reported an increased risk of PD in conditions causing an early reduction in endogenous estrogens (early menopause, reduced fertile life length). Longer cumulative length of pregnancies has also been associated with an increased PD risk. A lack of consensus still exists on the effect of the type of menopause (surgical vs. natural) on PD risk. Finally, the effect of postmenopausal estrogen replacement therapy is still debated. Inconsistencies across studies are in part explained by the complexity of the mechanisms of action of sexual hormones and by the paucity of analytical studies.