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The effect increases with multiple children
WEST PALM BEACH, FLA. – Women who have no history of a full-term pregnancy show an earlier onset of progressive multiple sclerosis (MS) compared to those who do have pregnancies, and the apparent onset-delaying effect appears to increase with the number of pregnancies, according to new research adding to speculation of the effects of pregnancy in MS.
“Our results suggest that a higher number of full-term pregnancies than average is associated with later onset of progressive MS, while having no full-term pregnancies is associated with significantly younger age at progressive MS onset,” first author Burcu Zeydan, MD, an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic in Rochester, Minn., said in an interview.
The study was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The findings, which also link early menopause with faster disease progression, offer important insights into the broader effects of pregnancy on MS, said ACTRIMS president Jeffrey A. Cohen, MD, director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
“We know pregnancy affects the short term disease activity – relapses tend to quiet down during pregnancy – but what has been somewhat conflicting is whether it affects the long-term prognosis or is just a temporary effect,” he said in an interview.
“So that is the main interest in this study, and it does indicate that pregnancy affects the long-term prognosis and provides some insight into the mechanism by which it might do that.”
While being female is in fact considered the most important risk factor for MS susceptibility, pregnancy has been suggested to have a protective role in disease progression, but more research is needed on the nature of the effect – and its mechanisms.
For the study, Dr. Zeydan and colleagues evaluated data on 202 patients with MS who were part of a Mayo Clinic survey, including 134 women and 68 men.
They found that women who had no full-term pregnancies (n = 32), had an earlier onset of progressive MS (mean age 41.4 ± 12.6 years) compared to women giving birth to 1 or more children (n = 95; 47.1 ± 9.7 years; P = .012).
In addition, the mean age of progressive MS onset also increased with a dose-effect trend according to number of full pregnancies (no children, 41.4 ± 12.6 years; 1-3 children: 46.4 ± 9.2 years; 4 or more children: 52.6 ± 12.9 years; P = .002).
A look at a subgroup of patients with secondary progressive MS also showed an earlier mean age of onset among women who had no full pregnancies (n = 19; 41.5 ± 9.2 years) compared to women with 1 or more full pregnancies (n = 57; 47.3 ± 10.6 years; P = .049).
The later disease onset associated with pregnancy was also seen in relapsing-remitting MS: Mean age of onset was earlier women with no pregnancies (27.5 ± 7.0 years) compared to those with one or more children (33.0 ± 9.4 years; P = .021).
The trends of later onset with more pregnancies was also observed with the mean age of onset of secondary progressive MS (no full pregnancies: onset at 41.5 ± 9.2 years; 1-3 pregnancies: 46.2 ± 9.9 years; 4 or more pregnancies, onset 52.6 ± 12.9 years; P = .010).
And likewise, the later mean age of onset of relapsing-remitting MS was seen with additional pregnancies (no full pregnancies: 27.5 ± 7.0 years; 1-3 pregnancies: 32.4 ± 9.3 years; 4 or more pregnancies: 35.8 ± 9.8 years; P = .012).
“The dose effect was clearly a surprise (having no full-term pregnancies vs. 1-3 vs. 4 or more),” Dr. Zeydan said.
“In addition to the significant difference between having no versus one or more full-term pregnancies, the clear dose-effect consolidates our results related to the association between the number of pregnancies and age at progressive MS onset.”
Early menopause also linked to shorter progression to secondary progressive MS
The study also showed that women with premature or early menopause had a shorter duration of progressing from relapsing-remitting MS to secondary progressive MS (n = 26; 12.9 ± 9.0 years) compared to women with normal age at menopause (n = 39; 17.8 ± 10.3 years).
The pattern was similar for women experiencing the onset of secondary progressive MS after menopause, with a shorter progression among those with early menopause (P = .012).
The patterns in early menopause are consistent with previous observations regarding menopause and MS progression, Dr. Cohen said.
“When women go through menopause, estradiol and pregnancy-related factors further decline and we know this coincides temporally with the development of progressive MS in women,” he noted.
Compared to men, women with premature or early menopause furthermore had a longer duration from relapsing-remitting MS to secondary progressive MS (P = .008), and women with secondary progressive MS also had also had an earlier age of relapsing-remitting MS onset than men (P = .018).
Possible mechanisms and applications of the findings
The mechanisms of pregnancy that could include a complex interaction between estrogen and factors such as astrocyte and microglia function, Dr. Zeydan explained.
“Estrogen, through various mechanisms of eliminating toxicity of highly activated neurons – including preventing proinflammatory molecule release, supporting mitochondria function thereby eliminating energy failure, and promoting remyelination – helps neuronal plasticity and delays neurodegeneration, which is closely related to the progressive phase of MS,” she said.
“One could easily make the probable association, while yet to be proven, that our findings may relate to these mechanisms,” Dr. Zeydan said.
The logical question of whether hormone replacement or some type of therapy that could mimic the effects of pregnancy could also benefit in delaying MS onset remained to be seen, Dr. Zeydan said.
“While we believe that is possible, particularly for delaying the onset of progressive phase, definitive evidence is lacking at this time,” Dr. Zeydan said.
“However, our study ultimately may lead to such a trial.”
In the meantime, the findings provide additional insights that may be beneficial in sharing with patients regarding pregnancy,” she said.
“As the contemporary problem in MS care is to delay or prevent progressive MS onset, our findings may suggest that how we counsel women with MS who are planning to get pregnant, or contemplating surgically induced menopause, or how we consider hormone therapies during perimenopause may impact the course of their disease.”
Dr. Zeydan cautioned, however, that “our findings do not confirm causality beyond an association.”
“More studies are needed in this important issue in a disease that affects women three times more than men.”
Dr. Zeydan had no disclosures to report. Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Zeydan B et al. ACTRIMS Forum 2020, Abstract P135.
The effect increases with multiple children
The effect increases with multiple children
WEST PALM BEACH, FLA. – Women who have no history of a full-term pregnancy show an earlier onset of progressive multiple sclerosis (MS) compared to those who do have pregnancies, and the apparent onset-delaying effect appears to increase with the number of pregnancies, according to new research adding to speculation of the effects of pregnancy in MS.
“Our results suggest that a higher number of full-term pregnancies than average is associated with later onset of progressive MS, while having no full-term pregnancies is associated with significantly younger age at progressive MS onset,” first author Burcu Zeydan, MD, an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic in Rochester, Minn., said in an interview.
The study was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The findings, which also link early menopause with faster disease progression, offer important insights into the broader effects of pregnancy on MS, said ACTRIMS president Jeffrey A. Cohen, MD, director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
“We know pregnancy affects the short term disease activity – relapses tend to quiet down during pregnancy – but what has been somewhat conflicting is whether it affects the long-term prognosis or is just a temporary effect,” he said in an interview.
“So that is the main interest in this study, and it does indicate that pregnancy affects the long-term prognosis and provides some insight into the mechanism by which it might do that.”
While being female is in fact considered the most important risk factor for MS susceptibility, pregnancy has been suggested to have a protective role in disease progression, but more research is needed on the nature of the effect – and its mechanisms.
For the study, Dr. Zeydan and colleagues evaluated data on 202 patients with MS who were part of a Mayo Clinic survey, including 134 women and 68 men.
They found that women who had no full-term pregnancies (n = 32), had an earlier onset of progressive MS (mean age 41.4 ± 12.6 years) compared to women giving birth to 1 or more children (n = 95; 47.1 ± 9.7 years; P = .012).
In addition, the mean age of progressive MS onset also increased with a dose-effect trend according to number of full pregnancies (no children, 41.4 ± 12.6 years; 1-3 children: 46.4 ± 9.2 years; 4 or more children: 52.6 ± 12.9 years; P = .002).
A look at a subgroup of patients with secondary progressive MS also showed an earlier mean age of onset among women who had no full pregnancies (n = 19; 41.5 ± 9.2 years) compared to women with 1 or more full pregnancies (n = 57; 47.3 ± 10.6 years; P = .049).
The later disease onset associated with pregnancy was also seen in relapsing-remitting MS: Mean age of onset was earlier women with no pregnancies (27.5 ± 7.0 years) compared to those with one or more children (33.0 ± 9.4 years; P = .021).
The trends of later onset with more pregnancies was also observed with the mean age of onset of secondary progressive MS (no full pregnancies: onset at 41.5 ± 9.2 years; 1-3 pregnancies: 46.2 ± 9.9 years; 4 or more pregnancies, onset 52.6 ± 12.9 years; P = .010).
And likewise, the later mean age of onset of relapsing-remitting MS was seen with additional pregnancies (no full pregnancies: 27.5 ± 7.0 years; 1-3 pregnancies: 32.4 ± 9.3 years; 4 or more pregnancies: 35.8 ± 9.8 years; P = .012).
“The dose effect was clearly a surprise (having no full-term pregnancies vs. 1-3 vs. 4 or more),” Dr. Zeydan said.
“In addition to the significant difference between having no versus one or more full-term pregnancies, the clear dose-effect consolidates our results related to the association between the number of pregnancies and age at progressive MS onset.”
Early menopause also linked to shorter progression to secondary progressive MS
The study also showed that women with premature or early menopause had a shorter duration of progressing from relapsing-remitting MS to secondary progressive MS (n = 26; 12.9 ± 9.0 years) compared to women with normal age at menopause (n = 39; 17.8 ± 10.3 years).
The pattern was similar for women experiencing the onset of secondary progressive MS after menopause, with a shorter progression among those with early menopause (P = .012).
The patterns in early menopause are consistent with previous observations regarding menopause and MS progression, Dr. Cohen said.
“When women go through menopause, estradiol and pregnancy-related factors further decline and we know this coincides temporally with the development of progressive MS in women,” he noted.
Compared to men, women with premature or early menopause furthermore had a longer duration from relapsing-remitting MS to secondary progressive MS (P = .008), and women with secondary progressive MS also had also had an earlier age of relapsing-remitting MS onset than men (P = .018).
Possible mechanisms and applications of the findings
The mechanisms of pregnancy that could include a complex interaction between estrogen and factors such as astrocyte and microglia function, Dr. Zeydan explained.
“Estrogen, through various mechanisms of eliminating toxicity of highly activated neurons – including preventing proinflammatory molecule release, supporting mitochondria function thereby eliminating energy failure, and promoting remyelination – helps neuronal plasticity and delays neurodegeneration, which is closely related to the progressive phase of MS,” she said.
“One could easily make the probable association, while yet to be proven, that our findings may relate to these mechanisms,” Dr. Zeydan said.
The logical question of whether hormone replacement or some type of therapy that could mimic the effects of pregnancy could also benefit in delaying MS onset remained to be seen, Dr. Zeydan said.
“While we believe that is possible, particularly for delaying the onset of progressive phase, definitive evidence is lacking at this time,” Dr. Zeydan said.
“However, our study ultimately may lead to such a trial.”
In the meantime, the findings provide additional insights that may be beneficial in sharing with patients regarding pregnancy,” she said.
“As the contemporary problem in MS care is to delay or prevent progressive MS onset, our findings may suggest that how we counsel women with MS who are planning to get pregnant, or contemplating surgically induced menopause, or how we consider hormone therapies during perimenopause may impact the course of their disease.”
Dr. Zeydan cautioned, however, that “our findings do not confirm causality beyond an association.”
“More studies are needed in this important issue in a disease that affects women three times more than men.”
Dr. Zeydan had no disclosures to report. Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Zeydan B et al. ACTRIMS Forum 2020, Abstract P135.
WEST PALM BEACH, FLA. – Women who have no history of a full-term pregnancy show an earlier onset of progressive multiple sclerosis (MS) compared to those who do have pregnancies, and the apparent onset-delaying effect appears to increase with the number of pregnancies, according to new research adding to speculation of the effects of pregnancy in MS.
“Our results suggest that a higher number of full-term pregnancies than average is associated with later onset of progressive MS, while having no full-term pregnancies is associated with significantly younger age at progressive MS onset,” first author Burcu Zeydan, MD, an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic in Rochester, Minn., said in an interview.
The study was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The findings, which also link early menopause with faster disease progression, offer important insights into the broader effects of pregnancy on MS, said ACTRIMS president Jeffrey A. Cohen, MD, director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
“We know pregnancy affects the short term disease activity – relapses tend to quiet down during pregnancy – but what has been somewhat conflicting is whether it affects the long-term prognosis or is just a temporary effect,” he said in an interview.
“So that is the main interest in this study, and it does indicate that pregnancy affects the long-term prognosis and provides some insight into the mechanism by which it might do that.”
While being female is in fact considered the most important risk factor for MS susceptibility, pregnancy has been suggested to have a protective role in disease progression, but more research is needed on the nature of the effect – and its mechanisms.
For the study, Dr. Zeydan and colleagues evaluated data on 202 patients with MS who were part of a Mayo Clinic survey, including 134 women and 68 men.
They found that women who had no full-term pregnancies (n = 32), had an earlier onset of progressive MS (mean age 41.4 ± 12.6 years) compared to women giving birth to 1 or more children (n = 95; 47.1 ± 9.7 years; P = .012).
In addition, the mean age of progressive MS onset also increased with a dose-effect trend according to number of full pregnancies (no children, 41.4 ± 12.6 years; 1-3 children: 46.4 ± 9.2 years; 4 or more children: 52.6 ± 12.9 years; P = .002).
A look at a subgroup of patients with secondary progressive MS also showed an earlier mean age of onset among women who had no full pregnancies (n = 19; 41.5 ± 9.2 years) compared to women with 1 or more full pregnancies (n = 57; 47.3 ± 10.6 years; P = .049).
The later disease onset associated with pregnancy was also seen in relapsing-remitting MS: Mean age of onset was earlier women with no pregnancies (27.5 ± 7.0 years) compared to those with one or more children (33.0 ± 9.4 years; P = .021).
The trends of later onset with more pregnancies was also observed with the mean age of onset of secondary progressive MS (no full pregnancies: onset at 41.5 ± 9.2 years; 1-3 pregnancies: 46.2 ± 9.9 years; 4 or more pregnancies, onset 52.6 ± 12.9 years; P = .010).
And likewise, the later mean age of onset of relapsing-remitting MS was seen with additional pregnancies (no full pregnancies: 27.5 ± 7.0 years; 1-3 pregnancies: 32.4 ± 9.3 years; 4 or more pregnancies: 35.8 ± 9.8 years; P = .012).
“The dose effect was clearly a surprise (having no full-term pregnancies vs. 1-3 vs. 4 or more),” Dr. Zeydan said.
“In addition to the significant difference between having no versus one or more full-term pregnancies, the clear dose-effect consolidates our results related to the association between the number of pregnancies and age at progressive MS onset.”
Early menopause also linked to shorter progression to secondary progressive MS
The study also showed that women with premature or early menopause had a shorter duration of progressing from relapsing-remitting MS to secondary progressive MS (n = 26; 12.9 ± 9.0 years) compared to women with normal age at menopause (n = 39; 17.8 ± 10.3 years).
The pattern was similar for women experiencing the onset of secondary progressive MS after menopause, with a shorter progression among those with early menopause (P = .012).
The patterns in early menopause are consistent with previous observations regarding menopause and MS progression, Dr. Cohen said.
“When women go through menopause, estradiol and pregnancy-related factors further decline and we know this coincides temporally with the development of progressive MS in women,” he noted.
Compared to men, women with premature or early menopause furthermore had a longer duration from relapsing-remitting MS to secondary progressive MS (P = .008), and women with secondary progressive MS also had also had an earlier age of relapsing-remitting MS onset than men (P = .018).
Possible mechanisms and applications of the findings
The mechanisms of pregnancy that could include a complex interaction between estrogen and factors such as astrocyte and microglia function, Dr. Zeydan explained.
“Estrogen, through various mechanisms of eliminating toxicity of highly activated neurons – including preventing proinflammatory molecule release, supporting mitochondria function thereby eliminating energy failure, and promoting remyelination – helps neuronal plasticity and delays neurodegeneration, which is closely related to the progressive phase of MS,” she said.
“One could easily make the probable association, while yet to be proven, that our findings may relate to these mechanisms,” Dr. Zeydan said.
The logical question of whether hormone replacement or some type of therapy that could mimic the effects of pregnancy could also benefit in delaying MS onset remained to be seen, Dr. Zeydan said.
“While we believe that is possible, particularly for delaying the onset of progressive phase, definitive evidence is lacking at this time,” Dr. Zeydan said.
“However, our study ultimately may lead to such a trial.”
In the meantime, the findings provide additional insights that may be beneficial in sharing with patients regarding pregnancy,” she said.
“As the contemporary problem in MS care is to delay or prevent progressive MS onset, our findings may suggest that how we counsel women with MS who are planning to get pregnant, or contemplating surgically induced menopause, or how we consider hormone therapies during perimenopause may impact the course of their disease.”
Dr. Zeydan cautioned, however, that “our findings do not confirm causality beyond an association.”
“More studies are needed in this important issue in a disease that affects women three times more than men.”
Dr. Zeydan had no disclosures to report. Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Zeydan B et al. ACTRIMS Forum 2020, Abstract P135.
REPORTING FROM ACTRIMS FORUM 2020