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MS is the number one cause of neurological disease in young
adults. There is currently no cure for the disease, and it often
results in disability, comorbid physical and mental health
conditions, unemployment, and more, all of which impair
quality of life. Understanding MS from the public health
perspective is necessary, as public health interventions can
help improve outcomes and quality of life. As discussed in this
chapter:
Current research has identified a number of genetic and
environmental risk factors for MS, but there still needs to
be more research to understand how to prevent MS and
improve outcomes in MS. There may be some benefit in
encouraging nutritional modifications, such as vitamin D
supplementation, and eating a diet low in salt and
saturated and trans fats and rich in fruits and vegetables.
General public health efforts to reduce smoking rates,
decrease obesity, encourage physical activity, and reduce
air pollution may also have a positive benefit on MS
outcomes.
Individuals with MS, both in the United States and
globally, face a number of health-related disparities that
influence their ability to manage their disease. Certain
regions may not have the resources to provide the
medical services required to diagnose and treat MS. Even
when such resources are available, an individual’s
socioeconomic and insurance status influence his or her
ability to access disease-modifying therapies and
treatment for comorbid conditions.
Individuals with MS may become underemployed or
unemployed as a result of their illness. Programs that
provide vocational rehabilitation and training services
and employer education regarding MS may be useful.
Support organizations provide a variety of services that
benefit the individual with MS from advocacy at the
government level to support groups to transportation.
Currently, there are many countries where no such groups
exist, but it would be beneficial to ensure that everyone
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with MS has access to such groups (see the Appendix for
more about patient resources and advocacy).
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C H A P T E R 1 5
Multiple Sclerosis in the
Female Patient
Tracy B. Grossman Kathy C. Matthews
A 27-year-old woman presents to you for her yearly
gynecologic examinations. She says she has been feeling more
tired than usual and sometimes has vision problems. She also
mentions that her husband thinks she is clumsier than usual,
although she thinks he is exaggerating. She tells you that they
have been attempting to conceive over the last year, and
although she is trying to be patient, she is concerned that she
has not yet gotten pregnant.
Putting together all of her symptoms, you refer her to a
neurologist who diagnoses her with multiple sclerosis (MS).
She gets placed on medications to help control her disease, and
soon enough, she starts feeling much better and her symptoms
are mostly resolved. She calls you to ask about getting
pregnant. She is scared that the medications she is taking are
not safe for pregnancy and also afraid that she will have
trouble getting pregnant now that her periods are less regular
than they used to be. On top of that, she is worried because
most of the time she is not in the mood for sex but is doing it
just to try to get pregnant. This is putting a strain on her
relationship.
How do you counsel this patient about how MS can affect her
fertility, menstrual cycle, pregnancy, and sexual functioning?
What medications can she use in pregnancy, and what
medications are not considered safe?
MS and the Early Reproductive Years
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Menses
Many studies have demonstrated important hormonal changes
in women with MS. These changes affect the pattern of the
menstrual cycle and, subsequently, fertility and sexual
functioning. Patients with MS have significantly higher
follicle-stimulating hormone and luteinizing hormone levels
but lower estrogen levels in the early follicle phase of the
menstrual cycle.
1,2
These hormonal changes can cause
menstrual cycle irregularities. Additionally, some studies have
found that about half of women with MS have worsened
symptoms or relapse onset during the premenstrual or
menstrual period. 3 Hormonal changes observed in women
with MS may account for this exacerbation of symptoms.
Specifically, progesterone increases nerve conduction speed by
reducing sodium/potassium ATPase, 4 and elevated estrogen
and progesterone levels after ovulation cause increased Th-2
anti-inflammatory cytokine production. 5 It has been theorized
that the precipitous decline in estrogen and progesterone levels
after ovulation, in the premenstrual period, may account for
worsening of symptoms and symptom onset. 6 Of note,
medications such as cyclophosphamide can cause premature
ovarian failure and bring about early menopause in these
patients.
7
Sexual Dysfunction
Women with MS can have complex issues involving
psychosocial, sexual, and family relationships, which often
happens with chronic illness. They often are taking multiple
medications, with side effects that can affect mood and libido
and incite physical symptoms such as decreased vaginal
lubrication.
1,2,8
One study utilizing a Multiple Sclerosis
Intimacy and Sexuality Questionnaire found that 80.4% of the
35 patients with relapsing-remitting MS experienced primary
sexual dysfunction, with decreased libido being the most
frequent complaint. 8 Another study using the Female Sexual
Function Index questionnaire analyzed both hormone levels in
relation to sexual dysfunction in patients with MS. Of the 54
women with MS, more than half (57.4%) manifested at least
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one sexual dysfunction and 36.4% exhibited abnormal
hormone alterations, the most common being low 17 betaestradiol (40%). The study could not find any statistical
significance between hormone abnormalities and sexual
dysfunction.
2
Sexual dysfunction among patients with MS can be considered
multifactorial, and therefore, it can be very challenging to
treat. Sadly, studies have shown that only a small percentage
of patients with MS seek treatment for sexual dysfunction.
9
Possible interventions include counseling, psychotherapy,
lubricants, and medications. It is important to emphasize that
sexual dysfunction can be an inciting cause of, or occur in
conjunction with, depression and associated mood disorders.
Treatment for mood disorders can also have a side effect of
decreasing libido and lubrication, which only exacerbates the
problem. Providers should carefully screen for symptoms of
sexual dysfunction in patients with MS, because few patients
will come forward asking for treatment for this issue, and it
can have a major impact on mental health and psychosocial
functioning.
10
Fertility Concerns and Infertility
Treatment
Fertility does not appear to be decreased in women with MS.
11
This is evidenced by the fact that pregnant patients with MS,
which is an illness typically diagnosed during a woman’s
reproductive years, are well represented in MS clinical trials.
12
However, international studies have shown that patients with
MS have fewer children and are more likely to seek assisted
reproductive technology (ART) services.
13,14
This may be at
least partially due to higher rates of hyperprolactinemia,
decreased estrogen levels, and thyroid disorders, which
patients with MS are at increased risk for because these
disorders are also typically autoimmune in nature.
1,15,16
Sexual
dysfunction, such as decreased libido, vaginal sensory
abnormalities, and insufficient lubrication, which can occur
early in the course of MS, can also interfere with fertility.
Some treatments for MS, such as interferon beta and
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mitoxantrone, have been associated with menstrual
irregularities, which can impact fertility.
8,15,17
Several studies have shown that ART has been associated with
an increased risk of MS relapse, especially in the first
12 weeks after unsuccessful cycle attempts.
17-19
Some studies
have shown that the risk of relapse is greater when using
gonadotropin-releasing hormone (GnRH) agonists for
hormonal downregulation. This may be because GnRH can
stimulate the proliferation of immune cells and increase
cytokine and endothelial-growth factor production. 20 Rapid
hormonal fluctuations, the stress of undergoing fertility
treatment, and possibly an interruption in MS therapy owing to
the risk of teratogenicity also predispose patients with MS
undergoing ART to relapse. 12 One study by Correale et al
followed 16 women with relapsing-remitting MS
prospectively during 26 ART cycles. There was a ninefold
increase in the risk of new brain lesions on magnetic
resonance imaging (MRI) and a sevenfold increase in the risk
of new brain lesions on MRI in the 3 months after ART. 21 All
of the patients in this study were taking GNRH agonists.
However, studies analyzing different hormonal treatments
during ART cycles have not consistently shown that GNRH
agonists have increased rates of MS relapse compared with
other hormonal treatments. For example, retrospective case
series in Germany did not find a higher rate of relapse in
GNRH-agonist ART cycles vs the use of other hormonal
treatments,
20,22
whereas reproductive case series performed in
France showed increased rates of relapse in the 3 months
following ART in patients with MS treated with GNRHagonists.
21,23
There is no consensus among ART providers and neurologists
as to what hormonal treatments to use and what diseasemodifying therapies should be employed or stopped during
fertility treatment. Patients with MS should be thoroughly
counseled about the risk of relapse with ART treatment, and as
with most chronic medical illnesses, disease stabilization
before initiating fertility treatment is advisable.
12
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Preconception Management of
Medications
As of June 2015, the US Food and Drug Administration
(FDA) has removed the categorization of medications in
pregnancy and instituted a system of prescription labeling that
includes more about the evidenced-based risks of the
medication (FDA). Most studies about the safety of diseasemodifying treatments in pregnancy are animal studies that use
higher doses of medications than are typically used in humans.
Medications that have positive safety profiles in pregnancy are
interferon beta and glatiramer, which are immunomodulators
that are used to prevent the occurrence of relapses and to delay
disability.
3,12
These medications, if used before pregnancy,
may be continued in pregnancy; however, owing to lack of
data with regards their safety in pregnancy, these medications
are only used up until the time of conception and then stopped
once the patient is pregnant. Natalizumab is a monoclonal
antibody that is often used for the treatment of relapsing forms
of MS. Current recommendations are that it be discontinued
before pregnancy, although it has been used to treat patients
during pregnancy in special circumstances.
3,12
Although there are several disease-modifying drugs for MS,
most clinicians recommend discontinuing these medications, if
possible, when planning for pregnancy. These medications are
discussed in the next section.
MS and Pregnancy
Hormonal Changes in Pregnancy
It is not surprising that the marked hormonal transition and
transient immunological tolerance of pregnancy modifies the
course and disease activity of MS.
Many animal studies have evaluated the hormonal effects of
estrogens (17β-estradiol-E2 and estriol-E3), progesterone, and
testosterone in MS. These hormones are thought to provide
anti-inflammatory and neuroprotective effects on experimental
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