Reproductive characteristics, use of exogenous hormones and Parkinson disease in women from the E3N study

Giancarlo Pesce (1, 2) , Fanny Artaud (1, 2) , Emmanuel Roze (3, 4) , Isabelle Degaey (1, 2) , Berta Portugal (1, 2) , Thi Thu Ha Nguyen (1, 2) , Agnès Fournier (1, 2) , Marie Christine Boutron-Ruault (1, 2) , Gianluca Severi (1, 2, 5) , Alexis Elbaz (1, 2) , Marianne Canonico (1, 2)

1 CESP - Centre de recherche en épidémiologie et santé des populations
2 IGR - Institut Gustave Roussy
3 CHU Pitié-Salpêtrière [AP-HP]
4 ICM - Institut du Cerveau = Paris Brain Institute
5 UniFI - Università degli Studi di Firenze = University of Florence = Université de Florence

Despite experimental studies suggesting a disease-modifying role of oestrogens, results from epidemiological studies on the relation of reproductive characteristics and hormonal exposures with Parkinson disease in women are conflicting. We used the data from the E3N cohort study including 98 068 women aged 40–65 years in 1990 followed until 2018. Parkinson disease was ascertained using a validation process based on drug claim databases and medical records. Reproductive characteristics and hormonal exposures were self-reported (11 questionnaires). Associations of exposures with Parkinson disease incidence were investigated using time-varying Cox proportional hazards regression with a 5-year exposure lag and age as the timescale adjusted for confounders. We identified 1165 incident Parkinson disease cases during a mean follow-up of 22.0 years (incidence rate = 54.7 per 100 000 person-years). Parkinson disease incidence was higher in women with early (<12 years, HR = 1.21, 95% CI = 1.04–1.40) or late age at menarche (≥14 years, HR = 1.18, 95% CI = 1.03–1.35) than in women with menarche at 12–13 years. Nulliparity was not associated with Parkinson disease, but Parkinson disease incidence increased with the number of children in parous women (P-trend = 0.009). Women with artificial (surgical, iatrogenic) menopause were at greater risk than women with natural menopause (HR = 1.28, 95% CI = 1.09–1.47), especially when artificial menopause occurred at an early age (≤45.0 years). Postmenopausal hormone therapy tended to mitigate greater risk associated with artificial or early menopause (≤45.0 years). While fertility treatments were not associated with Parkinson disease overall, ever users of clomiphene were at greater Parkinson disease risk than never users (HR = 1.81, 95% CI = 1.14–2.88). Other exposures (breastfeeding, oral contraceptives) were not associated with Parkinson disease. Our findings suggest that early and late age at menarche, higher parity, and artificial menopause, in particular at an early age, are associated with increased Parkinson disease incidence in women. In addition, there was some evidence that use of exogenous hormones may increase (fertility treatments) or decrease (postmenopausal hormone therapy) Parkinson disease incidence. These findings support the hypothesis that hormonal exposures play a role in the susceptibility to neurodegenerative diseases. If confirmed, they could help to identify subgroups at high risk for Parkinson disease.

Mots clés: cohort study; hormonal exposure; Parkinson disease; women

Domaines: Neurosciences [q-bio.NC]

Giancarlo Pesce, Fanny Artaud, Emmanuel Roze, Isabelle Degaey, Berta Portugal, et al.. Reproductive characteristics, use of exogenous hormones and Parkinson disease in women from the E3N study. Brain - A Journal of Neurology , 2023, 146 (6), pp.2535-2546. ⟨10.1093/brain/awac440⟩. ⟨hal-04191634⟩