What are the factors that increase the risk of developing Parkinson’s disease in women? The too few scientific studies on the subject are, moreover, sometimes contradictory. Fortunately, new work published in the journal Brain provide answers. Produced by a multidisciplinary team of Center for Research in Epidemiology and Population Health (CESP), this study which involves nearly 100,000 women shows that the age of the first menstruation, the number of pregnancies, the type of menopause but also that a molecule administered to improve fertility, Clomiphene, are linked to a increased risk of developing Parkinson’s disease.
For several years, CESP researchers suspected a link between the reproductive life of women, hormonal treatments and the neurodegenerative disease of Parkinson. “Our first observation was that this disease is more common in men than in women (0.3% of men are affected, compared to 0.2% of women), which suggests a link with sex hormones since it this is one of the main differences between the two sexes, but also because estrogen, the female hormone, has a neuroprotective effect”, explains Marianne Canonico, biologist and epidemiologist, research fellow at Inserm and co-author of the study. There were also a few scientific studies that seemed to point to this link, but they mostly focused on a small number of women, or did not involve long-term follow-up, whereas Parkinson’s is a disease that sometimes develops on fifteen or twenty years.
The world’s largest study on Parkinson’s and women
Based on these findings, scientists have sought the best way to fill the gaps in science. They called on the E3N cohort, made up of 98,000 women recruited in 1990, when they were between 40 and 65 years old. Since then, participants fill out forms every two or three years. They provide details on their reproductive life, such as the number of children they have had, the age of their first menstruation, the age and the cause of their menopause or the taking of an oral contraceptive, etc. “For several years, we identified the women in the cohort who could be suffering from Parkinson’s disease, then we validated the cases in order to rule out any diagnostic errors”, explains the researcher. The scientists thus identified 1,200 sick women, then compared their characteristics to the tens of thousands of other participants in the cohort, making it the largest study on women and Parkinson’s in the world.
They first found that breastfeeding, use of oral contraceptives and length of reproductive life did not appear to be associated with the occurrence of Parkinson’s disease. On the other hand, their results show that women whose first menstruation occurred before or after 12-13 years of age have a greater risk of developing the disease by respectively + 21% and + 18% compared to those whose first menstruation is occurred at 12-13 years of age. The duration and regularity of the menstrual cycle, on the other hand, do not seem to have a significant impact. This is the first time that researchers have pointed to an association between the age of menstruation and a risk of developing this disease. Although they have not been able to explain the cause, they put forward a hypothesis: during puberty, a crucial period for neurodevelopment, hormones could interfere with neural circuits involved in the development of illness.
Increased risk after second and third pregnancy
The study authors also found that having no children, or just one, has no impact on the development of Parkinson’s. On the other hand, the risk increases by 22% during a second birth and by 30% from the third. Artificial menopause is associated with a 28% increase in risk, and even 39% if it occurs before the age of 45. And in the event of menopause caused by the removal of both ovaries – with or without removal of the uterus – the increased risk is 31%. “Menopause is the cessation of ovarian functions – therefore the cessation of estrogen production – which occurs naturally between the ages of 50 and 51 on average in Caucasian women, specifies Marianne Canonico. But in some cases, it is provoked in a artificial, due to drug treatment such as chemotherapy, or following the removal of the ovaries or uterus due to cancer”. The early drop in estrogen production, which protects certain neurological functions, could explain these links.
The researchers also tried to find out whether treatments to improve women’s fertility were associated with an increased risk. According to them, Clomiphene, a drug that stimulates ovulation, could increase the risk by 80% compared to women who have never taken the treatment. “This is a first result based on a small number of people, so it must be taken with caution and confirmed by future studies, but it is not that surprising, since this drug is an anti-oestrogen”, emphasizes the researcher. The hypothesis of the link between estrogen and Parkinson’s takes on more weight when we know that hormonal treatments – which involve estrogen – used during early or artificial menopause seem to reduce the risk of developing the disease.
No link with breastfeeding or use of oral contraceptives
The researchers warn that the various risk factors appear to be cumulative. In other words, women who combine early or late puberty, several pregnancies and an artificial and early menopause would be at greater risk of developing the disease. The co-author of the study nevertheless points out that the risk of developing Parkinson’s is relatively low, especially in women (0.2%) and that the increased risk highlighted in the study does not mean, for example, that a woman who has her first period after 12-13 years will have an 18% risk of developing Parkinson’s, but her baseline risk increases by 18%, from 0.2 to 0.236%.
These results, which could appear anxiety-provoking, are nevertheless promising since they make it possible to better identify the groups of women particularly at risk, who could thus be integrated into early prevention strategies, point out the authors.