INDIANAPOLIS – About 50% of women with multiple sclerosis are postmenopausal, but objective data about the impact of menopause on the course of multiple sclerosis are lacking.
“We don’t know anything about the impact of menopause on the MS course; there is wide variability in patient-reported outcomes, but nothing written about comorbidities or symptom management,” Dr. Riley Bove, a neurologist at Brigham and Women’s Hospital, Boston, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “We’ve been working on this. A lot of it is unknown.”
Dr. Riley Bove
She described menopause is “an opportunity for providers to tackle symptoms and improve well-being and discuss meaningful quality of life and priorities with patients. It can be a good time to talk about these things.”
In a study that Dr. Bove conducted with the online patient-powered research platform PatientsLikeMe, female MS patients were asked to describe the impact of menopause on their disease. Among the themes that emerged were an occasional perimenopausal onset of MS (“menopause and MS symptoms were pretty much simultaneous,” one 58-year-old respondent said); the effect of hot flashes on MS symptoms (“I confused the two, especially hot flashes,” said a 53-year-old woman); and worsening of MS-related disability after menopause, particularly surgical (“Before I stopped taking birth control pills I was working and able to walk and house clean , etc.,” a 53-year-old respondent said. “I had the surgery, and I started to progress toward being completely wheelchair bound.”)
When it comes to solid recommendations for how to manage MS symptoms that overlap with menopause, “we’re in an evidence-free zone,” Dr. Bove said. “Symptoms in MS are kind of like dominoes: You have difficulty sleeping and then your day is off, fatigue is up and your mood is off, and everything can spiral. In the clinic, perimenopausal women often say things like, ‘I feel like I’m falling apart’ or ‘something has to give’ or ‘I need a change.’ ”
Common overlapping symptoms include vasomotor manifestations such as hot flashes, cold flashes, vascular instability, and rapid heartbeat. “The leading mechanistic explanation for the vasomotor symptoms is that abrupt hormone deprivation will result in the loss of negative feedback over hypothalamic NA [noradrenaline] synthesis,” Dr. Bove explained. “The proximity of the hypothalamic thermoregulatory center to luteinizing hormone–releasing hormone-producing areas may also be involved.”
Sleep disturbances and insomnia in menopausal MS patients can impact fatigue and mood. Also, hot flashes can directly exacerbate the MS symptoms, fluctuating over the day or the week.
According to recommendations from the North American Menopause Society, estradiol is the most effective therapy for treating vasomotor symptoms. Other options include selective serotonin reuptake inhibitors (SSRIs) and selective noradrenergic reuptake inhibitors (SNRIs). “Probably the best studied SNRI is venlafaxine,” Dr. Bove said. “It seems to have modest effects on sleep quality and insomnia perimenopausally, as well as on hot flashes.”
Other alternatives include clonidine and gabapentin.
“If a patient wants to use [hormone therapy] for menopausal symptoms, it has to be an individualized approach,” Dr. Bove said. “You have to communicate with the primary care physician to understand what else is going on in this woman’s medical history. The current recommendations are to treat the symptoms with as low a dose as possible for as short a duration as possible. Our MS patients are also at risk for neurodegeneration, for brain volume loss, for cognitive decline, and for worsening function over time.”
With respect to cognition, observational studies have demonstrated that during a certain window of opportunity – defined as within 5 years of the last menstrual period – hormone therapy (HT) may have protective effects against Alzheimer’s disease and against cognitive decline in general. “Beyond this window of time, perhaps due to estrogen receptor down regulation, HT can be harmful, with an increased risk of stroke and dementia reported later on,” she said.
Against this, the Women’s Health Initiative Memory Study (WHIMS) looked at unopposed estrogen, and estrogen and progestin combination, compared with placebo. It found that in women who initiated HT at the age of 65 or older faced an increased risk of dementia from any cause, and of cognitive decline. “This study really put the kibosh on HT as a form of neuroprotection,” Dr. Bove said. “But perhaps it’s unfair to the many patients who are at risk for cognitive decline and neurodegeneration, because the WHIMS did not find an increased risk of adverse cognitive events in women in whom HT was started perimenopausally. Longitudinal, placebo-controlled trials of the effects of HT within the window of opportunity are required to either prove or refute the observational studies that already exist that suggest HT may be neuroprotective. This is an important point to discuss with patients.”