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Try out PMC Labs and tell us what you think. Learn More. Multiple sclerosis MS is an autoimmune inflammatory demyelinating central nervous system disorder that is Woman want hot sex Turin common in women, with onset often during reproductive years. The female:male sex ratio of MS rose in several regions over the last century, suggesting a possible sex by environmental interaction increasing MS risk in women.

Since many with MS are in their childbearing years, family planning, including contraceptive and disease-modifying therapy DMT counselling, are important aspects of MS care in women. While some DMTs are likely harmful to the developing fetus, others can be used shortly before or until pregnancy is confirmed.

Overall, pregnancy decreases risk of MS relapses, whereas relapse risk may increase postpartum, although pregnancy does not appear to be harmful for long-term prognosis of MS. However, ovarian aging may contribute to disability progression in women with MS. Here, we review sex effects across the lifespan in women with MS, including the effect of sex on MS susceptibility, effects of pregnancy on MS disease activity, and management strategies around pregnancy, including risks associated with DMT use before and during pregnancy, and while breastfeeding.

We also review reproductive aging and sexual dysfunction in women with MS. Several factors implicate chromosomal sex and hormones in susceptibility and disease course in MS. MS is more common in women, with a female to male sex ratio of1 whereas before puberty and after menopause the sex ratio approaches Whereas relapse rate decreases during pregnancy, there tends to be an increased relapse rate postpartum, 5 and relapse rate decreases after menopause.

Hormonal factors may influence disability progression, as progression tends to occur earlier in men, 7 and later during the perimenopausal period in women. In this review, we discuss effects of sex on disease susceptibility, implications of MS on fertility and pregnancy, including peripartum DMT and other management considerations, the impact of pregnancy on the course of MS, the interaction between reproductive aging and MS, and sexual dysfunction in women with MS.

It has long been recognized that MS is more common in women, but recent observations suggest the sex ratio may be increasing due to a rise in cases in women over the last century. While some question whether the rising incidence is confounded by better diagnostics, others urge searching for an environmental cause of the observed increased incidence in women.

Many of these factors have been examined in the Danish MS Registry. It is likely that the increased susceptibility of women towards MS is influenced by genetic, hormonal, and environmental factors. No susceptibility alleles have been identified on the Y chromosome. Interaction between the genome and sex-specific biological and environmental factors may underlie at least part of the possible increase in MS incidence in women.

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One aspect of this may be sex-specific epigenetic changes. Maternal imprinting of the X chromosome or X dosage effects may contribute to autoimmunity in women. The effects of puberty, pregnancy, and menopause — periods during which sex hormone levels change dramatically — have been the subject of several studies. Puberty represents a risk factor for MS; earlier age of menarche has been associated with increased risk of MS and younger onset of MS symptoms in women.

As mentioned ly, nulliparous women may have higher risk of MS than those who had several pregnancies. Biological sex may interact with some of these factors to increase MS risk.

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Smokers of both sexes have increased risk of developing MS odds ratio 1. United Kingdom UK smoking prevalence has been increasing in women throughout the 20th century, which has been hypothesized to contribute to increasing MS risk. EBV is a ubiquitous gamma herpes virus. The move away from outdoor-based lifestyles may be driving a reduction in serum vitamin D levels in the population. It is not known if women are more susceptible to downstream effects of low vitamin D, 33 but a study in an animal model demonstrated protection from experimental autoimmune encephalitis EAE with vitamin D only in female mice.

More data are needed to identify hormonal and environmental risk factors for MS, which act preferentially in women. There are no studies that directly assess pregnancy success rates in MS, 3637 though some epidemiological studies have shown that women with MS may have fewer children than the general population.

Rigorous analyses for newer drugs are limited. More recent studies have assessed markers of ovarian reserve and function in women with MS, including levels of follicle-stimulating hormone FSHluteinizing hormone LHWoman want hot sex Turin anti-Mullerian hormone AMHand antral follicle count. In summary, ART, particularly the use of GnRH agonists, may increase MS disease activity in the short term, though further work is necessary to elucidate how induced hormonal changes may affect MS course. Contraception is an important topic in MS, particularly as women are often of childbearing age at disease onset and some DMTs are potential teratogens.

Prior studies have reported mixed effects of hormonal contraception on risk of developing MS. As such, definitive conclusions on the effect of OC on MS risk remains unclear. There is scarce information about the effect of OC on long-term prognosis of MS, although, reassuringly, hormonal contraception does not seem to negatively affect disease progression or disability.

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Optimal contraceptive methods should be individualized, as women with MS may suffer from symptoms that make use of some methods difficult such as using Woman want hot sex Turin rings. Caution should be exercised in the use of combined hormonal contraceptives in individuals with prolonged immobility, due to increased thromboembolic risk. The maternal—fetal interface refers to the collocation between the uterus and extra-embryonic tissue. The trophoblast further separates into villous and non-villous cytotrophoblast and syncytiotrophoblast.

Estrogen, progesterone, and human chorionic gonadotropin hCG modulate cells of the innate and adaptive immune system to adopt fetal-friendly phenotypes. More recent data suggests active pro-inflammatory Th1 immunity before and after this period. The Th17 compartment seems unaffected by pregnancy, 88 whereas CD56 bright natural killer NK cells were increased peripherally in one study. In MS, pregnancy also alters the clonal composition of T cells toward a more uniformly distributed repertoire. Tregs changed functionally in the early postpartum period in MS in one study, 89 and decreased numerically in another study.

Further studies investigating functional changes of immune cell subtypes are required to clarify complex relationships between Woman want hot sex Turin and immunomodulation. Indeed, the immune system during pregnancy is dynamic and responsive, promoting tolerance to fetal proteins and allowing fetal growth. Pregnancy planning is an important consideration for many women with MS. It is generally recommended to establish pre-pregnancy baseline, through a clinical neurology visit and an MRI before pregnancy, and to choose a pregnancy-compatible DMT.

Visits during the first and third trimester can be helpful, and, during the latter, breastfeeding and postpartum plans can be confirmed. Recommendations for postpartum management are outlined later in this review. Ideally, women should aim for a period of disease and treatment stability prior to conception.

When women receive maintenance DMT, care should be taken to proactively discuss future plans following conception — including whether or not to continue DMT during pregnancy and plans around breastfeeding. Such discussions are particularly pertinent in women with more active disease. DMTs with potential teratogenicity or contraindicated in pregnancy should be discontinued and replaced with acceptable alternatives prior to conception, or, in case of unintended pregnancy, changed as soon as able. In addition, the tendency for rebound activity after discontinuation of certain DMTs fingolimod and natalizumab, as discussed later in the review should be considered prior to initiating therapy in women with plans for pregnancy in the near future.

The use of highly effective therapies without rebound risk, such as depleting antibodies, in women with more active disease prior to pregnancy may be preferable, as these may enable a balance between disease control and low potential exposure and risk to the fetus. In women with less active disease, continuing injectable therapies until conception, or even through pregnancy, appears safe, and may offer a favorable risk—benefit ratio.

UTIs are associated with both worsening of MS symptoms and adverse pregnancy outcomes, and are of particular concern in this patient group. Women should be counselled about the risk of postpartum depression. Non-pharmacologic management of fatigue, insomnia, spasticity, and other symptoms during and after pregnancy should be pre-emptively discussed. Use of symptomatic therapies with potential fetal risk should be discussed with the neurologist and maternal fetal medicine specialist.

In the past decade, there has been an enormous increase in disease modifying treatment options in MS. Fortunately, most women with mild disease will remain relapse-free during pregnancy, and treatment can be safely stopped during pregnancy. At least first-trimester pregnancy exposures, and preferably total exposures, are needed to assess the possible risk and safety of medication use during pregnancy.

Therefore, very few data on entire pregnancy exposure exist, with the most data available for glatiramer acetate Table 3.

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Immunological changes during pregnancy may not be sufficient to protect women with active disease from relapses or rebound, especially after withdrawal from fingolimod or natalizumab. Oral DMTs should not be continued in pregnancy, whereas depleting antibody therapies can potentially be used in women with active MS, ideally prior to pregnancy, but with biological effects that may persist after drug elimination.

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More data are necessary to fully address this challenging clinical topic, especially for women with more aggressive MS who wish to have children. Although breastfeeding may reduce risk, individuals at high risk for postpartum relapse may require additional strategies to decrease relapse risk, such as restarting DMT.

Mothers have historically faced a choice about whether to breastfeed — which has ificant benefits to both the mother and infant — or treat their MS. Transfer of drugs to breastmilk depends on several factors, including molecular weight, protein binding, lipid solubility, volume of distribution, and transport mechanisms, as well as the stage of breastmilk, with less transfer into mature milk than colostrum.

While additional study of DMT use during lactation is required, when deciding whether to breastfeed while using DMTs, patients and clinicians should consider the risk of postpartum relapse balanced with potential adverse effects to the infant. In patients with high risk of postpartum disease activity, the benefits of breastfeeding despite DMT may outweigh risks for the injectable and monoclonal antibody therapies, while breastfeeding is not suggested while on oral DMTs.

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A recent review similarly suggested breastfeeding while on monoclonal antibody therapies can be considered in neuromyelitis optica spectrum disorders. Management of women with MS during labor and delivery is relevant to obstetricians, neurologists, anesthesiologists, and patients. Disease-related factors such as fatigue, lower limb weakness, and spasticity need to be considered when developing a birth plan, and should be discussed during prenatal care. However, reports of increased cesarean section deliveries in women with MS may be confounded by cultural and geographical influences on cesarean rates.

A systematic review and meta-analysis of women with MS and their pregnancies concluded that women with MS do not have a ificantly increased risk of obstetrical or neonatal complications such as prematurity or neonatal death. In the early 20th century, pregnancy was believed to promote poorer outcomes for women with MS, and was discouraged. Subsequently, Vukusic showed that following the initial postpartum increase in relapses, 81 ARR returned to pre-pregnancy levels. The findings of the seminal PRIMS, 5 and its extension, 81 have been replicated across numerous cohorts in subsequent decades, 39— and confirmed in a meta-analysis.

Postpartum outcomes are not limited to women with live births. Various studies have proposed predictors of postpartum relapses, 581,—, — summarized in Table 5.

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