Women with multiple sclerosis (MS) who have never given birth and those who began menopause prematurely tend to develop progressive forms of the disease earlier, a study from the Mayo Clinic suggests.
These findings were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2020, running through Saturday, Feb. 29, in Florida.
Burcu Zeydan, MD, a Mayo Clinic physician, shared the results in the oral presentation “Nulliparity Or Early Menopause Are Associated With Earlier Evolution Of Progressive Multiple Sclerosis In Women.“
“Being a woman is the strongest risk factor for developing MS,” Zeydan said.
Gender also has an influence on the different stages of the disease. In those with relapsing-remitting MS (RRMS), women tend to have disease onset at earlier ages, while disability worsening is faster in men. The opposite is seen in the disease’s progressive phase, with men tending to have onset at earlier ages and women showing faster disability worsening.
Pregnancy is known to potentially slow disability worsening and reduce relapse rates in women, while menopause “potentially speeds up disability worsening,” Zeydan said.
However, the influence of pregnancy and menopause on progressive MS has not been thoroughly studied.
Mayo Clinic researchers set out to explore the potential association of progressive MS with female sex, pregnancy, and menopause.
Their study enrolled 134 women and 68 men with progressive MS, and they analyzed various patient characteristics, such as the number of completed pregnancies, the age at menopause — considered premature, or early, if it started at or before age 45 — as well as age at onset of progressive MS and RRMS.
A group of postmenopausal women without MS, serving as controls, were also assessed.
Results showed that women who had never given birth, referred to as nulliparous (32 patients), developed progressive MS at earlier ages, a mean of 41.4 years old, than did women who had given birth at least once (95 patients), a mean age of 47.1.
Interestingly, nulliparity was more common among MS patients (23%) than among controls (15%).
The higher the number of viable pregnancies (those that conclude with a birth), the older the age at onset of progressive MS, the researchers found. Onset ranged from a mean of 41.4 years old in women with no pregnancies, to 52.6 for women with four or more viable pregnancies.
Similar trends were observed in secondary progressive MS (SPMS) and RRMS patient subgroups. Women who never had a viable pregnancy developed SPMS at an earlier age — a mean of 41.5 — than did women who gave birth once or more (47.3 years old). Among those with RRMS, nulliparous women had disease onset at a mean age of 27.5, and women with one or more viable births at a mean age of 33.
Most patients with RRMS eventually develop SPMS, the researchers noted.
The number of pregnancies also had an effect on the age of SPMS onset — ranging from 41.5 years old for no pregnancies, to 52.6 for four or more. A similar effect was seen for RRMS onset — from 27.5 years old for women with no pregnancies, to 35.8 for those four or more.
Among patients with SPMS, women developed RRMS at an earlier age (mean of 31.4) than did men (mean age, 36).
The transition from RRMS to SPMS was faster in women with early menopause (12.9 years) than in patients who began menopause at what’s considered a normal age (17.8 years). This transition, nevertheless, took longer in women than it did in men, who moved from RRMS to SPMS in a mean of 10.4 years.
Among woman who developed SPMS after going through menopause, progression from RRMS was faster in those with premature menopause (13.9 years) than in those who did not go into early menopause (25.4 years).
Overall, “nulliparity or premature/early menopause seem to be associated with earlier onset of progressive MS,” Zeydan said. But she emphasized that the study does not establish a direct causality between the two.
“There is further need for a larger study to understand whether these factors lead to earlier development of progressive MS, or whether MS-associated factors lead to nulliparity or earlier menopause,” the researchers wrote.
Based on these results, Zeydan suggested that women with MS, especially, should “rethink how pregnancy and surgical menopause counseling is done,” and “consider the option of menopausal hormone therapies.”
“Our observations are intriguing as there is evolving knowledge of the impact of estrogen on neuroprotection associated with astrocyte and microglia networks, and their relevance to progressive MS,” she said.
Estrogen levels rise above what’s typical during pregnancy; they drop below typical levels when women go through menopause. Microglia and astrocytes are types of cells that provide support to nerve cells in the brain and spinal cord; both have been implicated in the damaging immune reactions and the formation of lesions seen in MS.
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