The phenomenon of remission during pregnancy: what role do hormones play?

Up to 75 % of people affected by MS are women, and MS often strikes during the childbearing years. Many expectant mothers ask me, “what does my MS mean for me and my baby?” and they are often understandably concerned that their symptoms might somehow impact their fertility or pregnancy. In the past, women with MS were generally advised to avoid becoming pregnant altogether, although this advice was based on mostly inconclusive and, as it turns out, erroneous data. Over the past two decades, there has been a great deal of research examining the relationship between MS and pregnancy, and in this post I will parse out some of the scientifically-supported evidence from the misconceptions surrounding pregnancy, hormones and MS.

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How shifting reproductive habits have shaped the rate of MS in the population

Studies examining rates of MS in the general population (reviewed here) show us that the incidence of MS in women has increased in many countries around the world over the past several decades. The environmental factors that influence the risk for developing MS are myriad and complex, and continue to be the subject of intense research. One demographic trend that has caught the eye of researchers is the change in women’s reproductive habits: since the 1960s, women living in urban centres in developed countries have had progressively fewer children, likely due to a rise in the number of women joining the workforce coupled with an increase in oral contraceptive use.

Several studies have drawn a link between reproduction rates and the incidence of MS among women. One study from Great Britain found that women with 3 or more children bore half the risk of developing MS than women with 0 – 2 children. Similarly, an Australian study showed that there was a cumulative beneficial effect of pregnancy, since women with a greater number of children had a lower risk of a first clinical demyelinating event – an early indicator of MS – than those with fewer children. The reasons for these demographic trends are still a mystery, although recent research has gained some insight into how the course of MS is affected by pregnancy, which I’ll discuss in the following section.

How does pregnancy affect MS symptoms?

Women with MS who become pregnant experience a considerable improvement in symptoms. In fact, there is strong scientific evidence showing that women with the relapsing-remitting form of MS (RRMS) experience far fewer relapses than usual during pregnancy, particularly during the third trimester.

The first large-scale study to examine the interaction between pregnancy and MS, dubbed the Pregnancy in Multiple Sclerosis (PRIMS) study, published its results in 1998 and showed that the relapse rate in women with MS dropped by 70 % during the third trimester. This observation is not unique to MS, and several other autoimmune disorders also improve during pregnancy, including rheumatoid arthritis and thyroiditis, just to name a few. The PRIMS study also showed that MS symptoms bounced back, or “rebounded”, during the first three months post-partum before returning to pre-pregnancy rates. Many follow-up studies have reproduced those initial findings, and researchers have been trying to determine what aspect(s) of pregnancy offer protection against the symptoms of MS.

To answer this question, it is important to understand how pregnancy normally modifies the body’s immune system. It is hardly surprising that pregnancy presents a serious immune challenge to the mother’s body, since the developing fetus carries antigens inherited from the father that would normally be considered “foreign” invaders by the mother’s immune system, in turn leading to rejection of the fetus by the body. In order to prevent fetal rejection, the mother’s immune system temporarily suppresses certain immune responses (namely, the T-helper cells become anti-inflammatory). The shift in the mother’s immune response is an important step during pregnancy, since in addition to preventing fetal rejection, it also allows maternal antibodies to be transferred across the placenta, thus arming the newborn baby with protective immunity against infection before its own immune system has a chance to develop fully.

It just so happens that this response can temporarily put a damper on MS symptoms. The pro-inflammatory T cells and their related cytokines (small messenger molecules that influence the actions of immune system cells) are believed to be major players in the autoreactive immune response in MS. On the other hand, certain cytokines – which are elevated during pregnancy – reduce inflammation and lead to improvement of symptoms in people with MS. In other words, the adaptations that the mother’s immune system makes to accommodate the developing fetus also result in a physiological environment that can lead to improvements in MS.

Pregnancy is a complex, multifaceted event in which many physiological factors change quite dramatically over the course of gestation. Scientists have been attempting to figure out which of these factors is responsible for the profound reduction in relapse rate in expectant mothers with MS. Sex hormones, particularly estriol and prolactin, have been identified as likely protective factors against MS. I looked into the literature to investigate how these pregnancy-related hormones influence MS.

Estriol

Estriol is a specific type of estrogen that is produced by the placenta and, as such, is only found in the body in appreciable quantities during pregnancy. Over the course of pregnancy, estriol levels in the blood gradually increase until they peak during the third trimester, then rapidly decline after birth. Based on the observation that estriol levels appear to coincide with the greatest remission of MS symptoms, a team of researchers led by Dr. Rhonda Voskuhl at University of California conducted a pilot clinical trial in which 10, non-pregnant women with RRMS were administered estriol. The results, published in the Annals of Neurology in 2002, showed that estriol significantly reduced the number of brain lesions that appeared on an MRI scan. Based on these promising findings, Voskuhl’s group expanded their study to 158 non-pregnant women with RRMS in 16 sites across the United States in a phase II clinical trial, where participants were given either a combination of estriol and Copaxone (glatiramer acetate), or Copaxone and a placebo. Although the results have not yet been published, the research team recently announced that the treatment group receiving combined estriol and Copaxone had a 47 % lower relapse rate after 12 months of treatment compared to Copaxone and placebo. The researchers believe that estriol works via a two-pronged approach: not only does it exert an anti-inflammatory effect to reduce the number of attacks, but it also protects the brain so that it suffers less damage during an attack.

While the results are promising, it’s still too soon to say whether people affected by MS would benefit from treatment with estriol. Relatively high doses of estriol are in widespread use in Europe and Asia as hormone replacement therapy for women with menopause, thus making this medication readily available in many countries; however, estriol treatment is not currently approved in Canada or the US. Researchers and medical experts have also noted that estriol therapy can increase the risk of certain cancers. As such, any future strategies for treating MS symptoms with estriol will need to balance the benefits against the risks.

Prolactin

Prolactin is a hormone secreted by the brain that, in addition to its well-known role in mammary gland development and lactation, is an important regulator of immune function and neurogenesis, the process by which new cells of the central nervous system are formed. Like estriol, prolactin levels in the blood are high during pregnancy when MS symptoms are suppressed, although prolactin remains high post-partum during the rebound phase, which has led to some confusion in the research community about its role in MS. A study conducted by Canadian researchers Dr. Samuel Weiss, Dr. V. Wee Yong and Dr. Luanne Metz looked at the effects of prolactin on mice with an MS-like disease and noticed some interesting results; on one hand, high doses of prolactin appear to worsen symptoms of the MS-like condition. On the other hand, low doses of prolactin have no effect on disease symptoms, while treating mice with a combination of prolactin and interferon-β – a standard MS drug – leads to improved MS symptoms compared to interferon-β alone.

Additionally, mice in which receptors for prolactin have been genetically switched off experience aggravated MS-like symptoms. These observations are difficult to reconcile with the association between elevated prolactin during the post-partum period and the rebound in MS symptoms. However, recent findings show that breastfeeding, which stimulates elevated prolactin levels, may in fact be protective, since women who breastfed for 2 months post-partum were found to be less likely to experience a relapse than women who did not. Other studies, however, suggest that breastfeeding has no protective effect on post-partum relapses. Although the data is conflicting at times, the general observation is that, at the correct dose and in the appropriate combination, prolactin may have a protective effect against MS.

One way in which prolactin is thought to protect against MS symptoms is by stimulating the production of new cells that repair damage to the myelin following an MS attack. In a 2007 study published in the Journal of Neuroscience, the research team led by Drs. Weiss and Yong found that pregnant mice exhibited an enhanced ability to repair lesions in the brain. When the researchers supplemented prolactin in non-pregnant mice, they found that they were able to promote myelin repair in a similar fashion. Whether prolactin can be used therapeutically in people affected by MS to stimulate repair of lesions while at the same time avoiding exacerbation of symptoms is still a matter of debate, and research in this area is ongoing.

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I am a woman with MS: should I become pregnant?

The decision to become pregnant and start a family is a complex one and requires careful planning by any prospective mother, whether or not she is affected by MS. Many women with MS have gone on to have successful pregnancies and raise healthy children, and as I’ve discussed in this post, pregnancy can occasionally even offer a temporary reprieve from the symptoms of MS. On the other hand, having MS poses its own set of hurdles, and some of the symptoms of MS, particularly ones that involve severe functional disability and/or fatigue, can be unpredictable and add further strain on top of the usual challenges of starting a family. New questions may arise with regards to taking medications for MS while pregnant or planning to get pregnant. As well, the tendency for symptoms to rebound in the first few months following delivery coincides with the time when the newborn infant needs the most care and attention.

If you are a woman with MS and are thinking of starting a family, discuss the benefits and challenges with your neurologist along with your partner and loved ones. Some questions to consider include: how will MS affect my pregnancy? Is it safe to take MS medications during pregnancy? How should I plan to prepare for the post-partum period? By addressing these and other questions head-on, you’ll be far better equipped to decide about whether to embark on the intimidating but remarkable journey that is starting a family.

Are you a mother who is affected by MS? Were your symptoms influenced by your pregnancy? Share your story with us in the comments below.

11 thoughts on “The phenomenon of remission during pregnancy: what role do hormones play?

  1. Judy St. Cyr

    Diagnosed in 1974 and became pregnant in 1975 at which time my neurologist offered to terminate the pregnancy. He had altered the risk of the child developing MS from 5% to 50% which gave me the idea that he really didn’t know what those risks were. This first pregnancy naturally aborted at 16 weeks. Shortly thereafter I was pregnant again with our first child. And two more children followed, so three children in four years. The last two were not planned, but I had already not been taking The Pill as it upset my system unrelated to MS.
    I was never allowed an epidural because of the MS, so had all three children naturally. Breastfed the last two for eight and nine months respectively.
    My MS went into remission for 15 years and recurred when I turned 40. I have not been on any of the MS drug treatments and have been lucky to have a very mild relapsing remitting form of the disease. I have often felt that the timing of my pregnancies had a beneficial effect on the progression of what I call “my MS”. My MRI’s have shown an increase in lesions but nothing significant, and my major symptom now is fatigue and intermittent dizziness.

    Reply
    1. drkarenlee Post author

      Hi Judy,

      Thank you for sharing your story. Our general understanding of how MS and pregnancy interact has definitely come a long way over the past several decades. Having said that, although we know that MS symptoms tend to generally go into remission during late pregnancy, there is still comparatively little information about how pregnancy affects the long-term outlook of MS. One recent study tried to answer this question, and found that over a 10-year period, the course of MS (i.e. relapse rate) in women who were pregnant versus women who were never pregnant appeared to be similar, although there was a slightly increased risk of conversion to secondary progressive MS in pregnant women. More research is underway to study the long-term course of MS following pregnancy.

      Reply
  2. ashley

    I was diagnosis in October 2011 with RRMS. I found during my first pregnancy my MS symptoms to be in full remission. After child birth I found that they came back in full force and I was only able to return to work for a few months after being off for a year. I am currently 30 weeks pregnant and have found no relief from my MS symptoms this time. I have not taken my cops one while pregnant but plan to restart once my child is born.
    Fatigue, numbness, headaches and electric shock in my leg thigh seem to be my biggest complaints.

    Reply
  3. Shelly

    I don’t have any experience yet on pregnancy and how it affects MS. I am trying to become pregnant and am at the stage where I am considering IVF. I was wondering what the risks are, if any, to MS symptoms and progression by going through IVF (and taking all of the drugs and hormones that come with it)? Thanks!

    Reply
    1. drkarenlee Post author

      Hi Shelly,

      Thank you for the excellent question. There is some evidence from case reports and a recent population-based study in France which shows that in vitro fertilization (IVF) treatments can increase the risk of relapse in women with MS, particularly in women for whom IVF has failed to lead to conception. Researchers who led the study hypothesized that certain drugs used for IVF, such as gonadotrophin releasing hormone (GnRH) agonists, may increase risk of relapse after IVF treatment. On the other hand, other IVF drugs may have no effect on the risk of relapse. To my knowledge, no study has systematically looked at the relationship between IVF treatments and MS progression.

      It’s always safest to discuss with your family doctor and/or obstetrician how best to manage your MS symptoms during IVF treatment and pregnancy.

      Dr. K

      Reply
  4. Suzy

    Hello. I am 41 years old and pregnant for the first time after years of trying. I’ve had MS for 16 years now, and it’s been relatively mild. Unfortunately, the disease has become quite debilitating during my pregnancy. I am currently 22 weeks along. I hope and pray that the remission starts soon for me. I love everything else about pregnancy. Is it unusual for the disease to worsen in the second trimester and improve in the third, or am I unrealistically optimistic?

    Reply
    1. drkarenlee Post author

      Hi Suzy,

      Thank you for sharing your story. In general, MS relapses tend to decline most appreciably during the third trimester, whereas the relapse rate is similar during the second trimester compared to the year prior to pregnancy. Of course, this is just the average trend and every woman is different. If your relapses persist or worsen further as your pregnancy progresses, your best bet is to consult your physician.

      Dr. K

      Reply
  5. Sandeep

    Just found this by chance. It seems that in terms of the remission and later relapse, MS looks very similar to how few other autoimmune diseases work, such as rheumatoid arthritis. In case of RA, studies report that as many as 75 percent women may have some degree of remission by the end of the first trimester.

    Reply
  6. Celia

    What an excellent article on pregnancy and MS! Thank you!
    I have RRMS and first symptoms started after I had my second baby. I wanted a third baby and my neurologist recommended the DMD Lemtrada. I delayed starting this but eventually did take it because my MS became very aggressive, and I was using a walker pretty quickly (I was 29). I did round one of Lemtrada and ended up getting pregnant by surprise nine months after round one. I gave birth in October 2016 and now have a 4.5 month old daughter. Lemtrada helped me immediately after starting it… and I was walking unassisted within months. I have been in remission ever since starting it in May 2015. I had round two this January and have been doing great! No post partum relapse.

    Quoting my neuro: Lemtrada is a perfect drug for women with aggressive MS who want to start a family. I can certainly attest to that!

    Reply
  7. Angie

    I was diagnosed in September 2011 when my second child was 20 months old. We had originally planned more than two children but I wanted to see how “my MS” treated me. After 4 years we decided to try for a 3rd. In the 4 years between diagnosis and pregnancy I averaged 1 relapse a year and my most significant symptoms were optic neuritis, vertigo, numbness, fatigue and muscle tightness in my left calf. Pregnancy was amazing to me. All of my symptoms disappeared. Postpartum was fairly good to me this time around (I’m breastfeeding still at 9 months and not taking medication although my neurologist would like me to start). I had an MRI at 6 weeks postpartum and another at 6months. I had one new lesion although haven’t noticed new symptoms. Some of my old symptoms have returned but not all of them and I am grateful for that!

    Reply
  8. Amanda

    I was diagnosed at age 27 in 2011. Now at age 32, I am currently 15 weeks pregnant with our first child. I chose to stay on Copaxone, and so far, so good-all praise God. Great article, very timely and thorough.

    Reply

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