More common in men than in women, Parkinson’s disease manifests differently in the latter. A study focused on understanding these mechanisms and suggests that early or late puberty, artificial menopause and the number of pregnancies were factors associated with an increased risk of this neurodegenerative pathology. Results that put researchers on the track of the protective role of female hormones.
The specific risk factors for the development of Parkinson’s disease in women are still poorly studied and poorly known. Exposure to hormones involved in female reproductive life is one of the avenues explored within the Center for Research in Epidemiology and Population Health by a research team from Inserm, the University of Paris-Saclay, the University of Versailles Saint-Quentin-en-Yvelines with the Gustave Roussy Institute, which compared the characteristics relating to the reproductive history of nearly 1,200 women with Parkinson’s disease to those of the other women in the E3N cohort — the E3N cohort, promoted by Inserm, Paris-Saclay University and the Gustave Roussy Institute, is the first major French study on women’s health. Since 1990, nearly 100,000 French women have been monitored as part of this vast prospective health study.
Their results show that the age of the first menstruation, the number of pregnancies, the type of menopause as well as a molecule administered to improve fertility, are associated with a higher risk of occurrence of the disease. These works, published in Brainsupport the role of hormonal exposure — notably estrogen levels — during women’s reproductive life in Parkinson’s disease and open avenues for targeted prevention strategies.
Parkinson’s disease is a progressive neurodegenerative disease favored by complex interactions between genetic factors and environmental factors. It now affects more than 6 million people worldwide and is 1.5 times more common in men than in women. Comparatively, it is also less studied and less well known among the latter.
Parkinson’s: less common in women and less studied
Thus, studies on certain specifically female risk factors such as the impact of exposure to hormones linked to reproductive life, whether natural (puberty, menstrual cycles, pregnancies, menopause, etc.) or medical (hormonal treatments such as taking contraceptives, treatments to increase fertility, or even post-menopause treatments), remain few and contradictory.
Within the Exposome, heredity, cancer and health research team of the Center for Research in Epidemiology and Population Health (Inserm/Paris-Saclay University/University of Versailles Saint-Quentin-en-Yvelines), Marianne Canonico, Inserm researcher , in collaboration with Alexis Elbaz, an Inserm researcher, assessed the influence of reproductive life and the taking of hormone-based medical treatments on the risk of onset of Parkinson’s disease in women.
To do this, she examined numerous characteristics relating to the reproductive history of nearly 1,200 women from the E3N cohort, in whom a diagnosis of Parkinson’s disease was made during the 24 years of their follow-up, and compared to those of other women in the cohort.
Very specific female characteristics linked to Parkinson’s disease
The scientists were able to observe several characteristics associated with an increased risk of developing the disease, the effects of which proved to be cumulative — a cumulative effect was observed for the risk criteria cited later in the text. Thus, women who had accumulated precocious or late puberty, several pregnancies and an artificial and premature menopause were at the highest risk of developing the disease.
Thus, women whose first menstruation occurred before or after 12-13 years showed an increased risk of respectively +21% and +18%. The duration and regularity of the menstrual cycle, on the other hand, showed no significant impact.
« This is the first time that such an association has been shown between the age of the first menstrual period and the disease.explains Marianne Canonico, this could be explained, among other things, by an interference – at this crucial period for neurodevelopment that is puberty – of sex hormones with neural circuits involved in the development of Parkinson’s disease ».
Another characteristic observed: if the fact of having or not having children was not associated with the risk of developing the disease, in women who have had children, this risk increases with the number of births (+ 22% for the second child, + 30% from the third).
If the fact of being menopausal did not appear directly associated with an increased risk of Parkinson’s disease, on the other hand, the type of menopause seems to have an impact. Thus, an artificial menopause would be associated with a 28% increased risk compared to a natural menopause, and more pronounced when it occurs before the age of 45 (+ 39% risk compared to a menopause occurring after 45 years) or when it is the consequence of removal of both ovaries – with or without removal of the uterus (+ 31% compared to a natural menopause). In contrast, artificial menopause induced by removal of the uterus alone was associated with a more moderate increased risk.
The trail of female hormone levels and their protective role
Finally, if treatments to improve fertility were not associated with an overall increased risk of Parkinson’s disease, taken individually, clomiphene – a treatment stimulating ovulation – would increase the risk by 80% compared to women who have never taken fertility treatment.
In the two previous cases, exposure to insufficient levels of female hormones (estrogen) could be the cause: ” Artificial and/or premature menopause, causes ovarian failure and consequently, a sudden and anticipated drop in estrogen levels, normally still high before the age of 45explains Marianne Canonico. As for clomiphene, it has an anti-estrogen role ».
This hypothesis is supported by the observation of a protective effect of hormonal treatments used at menopause, which seem to attenuate the risk linked to early or artificial menopause for Parkinson’s disease. “ These results are consistent with the knowledge of the neuroprotective role of estrogens, already demonstrated in other studies. adds Marianne Canonico.
Although this study includes the largest cohort to date of patients with Parkinson’s disease, the researchers point out that the results related to the identified risk factors must be confirmed by long-term studies with more participants. These results could eventually make it possible to identify groups at risk within which prevention strategies could be proposed early.
