Multiple sclerosis (MS) is 3 times more common among women than men and is more common among women of childbearing age than in any other age group. Caring for women with MS requires a comprehensive approach to management across a range of unique issues including family planning decisions, hormonal changes, and reproductive health.
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Reproductive and vaginal health are important components of overall female well-being, therefore understanding the potential impact of disease-modifying therapies (DMTs) used to treat MS on gynaecological complications is important. High-efficacy DMTs have been found to increase the risk of opportunistic infections and, theoretically, can reduce immune surveillance and increase cancer risk.1,2 DMTs may also affect how well the body clears germs in the vagina, cervix or uterus that can cause the following:
Inflammatory and infectious vaginitis and susceptibility to bacterial vaginosis2,3
Herpes simplex virus (HSV) 2,4,5
Human papilloma virus (HPV) positivity and related cervical dysplasia/cancers2,6
Women with MS often report that their symptoms feel worse at certain points in their menstrual cycle, typically just before their menstrual cycle, but there is limited research about the effect of menstruation on MS.9
Although the effects of MS on fertility have not been fully determined, the general consensus is that fertility is not significantly affected in women with MS.10 For this reason, contraception is important for those who want to avoid or delay pregnancy.
Women with MS have a number of factors to consider during family planning and when choosing contraception including current MS treatment, safety and effectiveness.11 Current guidance on the selection of appropriate contraception for women with MS is lacking and to address this gap, an expert-led consensus programme developed recommendations to support clinicians in discussing family planning and contraception.12 These recommendations include:
In a French study of 192 women aged 18 to 40 years with MS, although 66.7% of women reported using contraception, 8.3% had an unplanned pregnancy since their diagnosis.14 Among the group of women receiving a potentially teratogenic MS therapy, 26% were using no or inappropriate contraception. This highlights that women with MS require more information on reproductive health and better contraceptive advice. Counselling with a multidisciplinary team can help women with MS evaluate their options for safe and effective contraception and other family planning decisions, including optimal timing of discontinuation/resumption of MS therapies.
Women planning to conceive face numerous concerns, including the impact of MS on fertility, the risk of transmitting MS to the offspring, the effects of medication for MS on the foetus, the impact of pregnancy on disease progression, the impact of MS on the mother’s ability to care for her child, and the socioeconomic burden on the family.15
Pregnancy can affect the course of MS, lowering the risk of relapse between the first and third trimester but increasing the risk of relapse postpartum in some patients.13 Pregnancy has been shown no adverse effect on multiple sclerosis in the long-term and that it does not influence the risk of secondary progression in MS.
Through pre-conception, pregnancy and post-partum periods, there is a need for disease control management, to decrease chances of MS relapses while avoiding potential risks to the mother and the foetus.16 Early treatment in preventing long-term disability in MS is important and delaying treatment until women with MS have completed their families can lead to the development of irreversible disability. It is therefore important to discuss family planning and pregnancy proactively with all women with MS of child-bearing age.17 At or soon after diagnosis, all women with MS of childbearing age should have pre-pregnancy counselling and this should be repeated at regular intervals (at least annually) particularly for those who are on or considering starting medication.
Those wishing to start a family in the future should consider carefully which DMT to choose as they vary in the potential impact they can have on a pregnancy and wash-out periods required before trying to conceive. Treatment with DMTs during pregnancy needs to be adjusted individually taking into consideration the patient’s priorities, age, severity of disability, clinical and MRI disease activity, the rate of relapses and the risk of continuing or terminating the treatment.18 It should be noted that the majority of DMTs are not approved for use in pregnancy but some can be used if the potential benefit is thought to outweigh potential risks. If a woman with MS does become pregnant whilst on a DMT, they should not suddenly stop their medications but should contact their MS team/general practitioner/midwife as soon as possible for advice.17
Because MS typically is diagnosed between 20 and 40 years of age, a majority of women with MS will experience menopause after disease onset. An estimated half of all women with MS are in the perimenopausal or postmenopausal stages.19
Symptoms of the menopausal transition in the general population vary widely and are typically undertreated. These symptoms include changes in cognition (e.g., attention, working memory), mood (e.g., depression, anxiety), fatigue, sleep quality, and cardinal vasomotor symptoms (hot flashes), many of which can overlap with those of MS.20 Women with MS often report that menopause exacerbates subjective symptoms such as fatigue, cognitive difficulties and urinary problems;21 this can mean disease activity and symptoms that were well-controlled in the years before menopause worsening, resulting in a need for more focused care.22 The postmenopausal period can also lead to an increased susceptibility to several comorbidities (ie osteoporosis and vascular comorbidities).
Menopause symptoms can also directly influence MS symptoms. For example, sleep disturbances from menopausal hot flashes may exacerbate MS symptoms, reducing daytime energy and physical activity and function, and worsening cognition and mood. Hot flashes can also themselves trigger the Uthoff phenomenon and consequent worsening of MS symptoms.23
Several studies have reported an increase of disability accumulation after menopause, suggesting that it is a turning point to a more progressive phase of the disease. This may be attributable to the hormonal and immunological changes associated with menopause, with several effects on neuroinflammation and neurodegeneration increasing due to the immunosenescence of aging.24 Several observational studies have also indicated a reduction in the sex differences of disability progression, usually more marked in males, in individuals with MS after age 50. The course of the disease after menopause appears to be more similar to the course of the disease in men in which MS can be more aggressive.25,26
Hormone replacement therapy (HRT), consisting of oestrogen therapy or combined oestrogen–progestogen therapy administered either orally, vaginally or transdermally, can often be overlooked in women with MS. Improvement in MS symptoms and quality of life (QOL) was found in postmenopausal MS patients receiving HRT.27 In particular, HRT is effective for menopause-related vasomotor symptoms, an overactive bladder, and symptoms of vulvar and vaginal atrophy. Additional effects on bone mineral density, and a reduction of the risk of osteoporotic fractures have also been described.28
Individualised HRT treatment should be considered on the basis of a woman’s risk profile and consideration should be given to the history of MS treatment and related risks, as well as to the woman’s susceptibility to other comorbidities.29
Little is known about the effects of HRT on the course of MS and long-term outcomes. There is currently no evidence that HRT use can prevent neurodegeneration directly in those with MS.
Women with MS require comprehensive health screenings, including routine cancer screenings for breast, cervical, colon, and skin cancer, alongside standard cardiovascular risk assessments such as regular blood pressure checks and bone health checks. Reduced participation in preventative health assessments can be an issue in women with MS and the risk of non-participation increases with increasing physical disability.30 Physical and environmental barriers include inaccessible medical offices, lack of transportation and difficulty with patient positioning and discomfort. Additionally, MS has the potential to impact cognition and mood which may negatively affect a patient’s ability to access preventative healthcare.31
In a French study of 192 women aged 18 to 40 years with MS, only 20% of those on immunosuppressive therapy were being screened for cervical cancer annually, and only 35.7% of those meeting guidelines for HPV vaccination based on age had been vaccinated.32 This highlights the need to identify and address barriers to participation in vaccination and screening programmes for women with MS. HCPs need to be aware of the is possible poor participation and strategies should be targeted at optimising engagement.
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9 Mirmosayyeb O, et al. The interplay of multiple sclerosis and menstrual cycle: which one affects the other one? Mult Scler Relat Disorders. 2018;21:46-50
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