Hormone Therapy May Help With Menopause, But Safety a Concern

Eight weeks of hormone therapy was tolerable, and its use may ease the hot flashes and greater disease-related disability this life transition can cause in menopausal women with multiple sclerosis (MS), according to results of a small Phase 1b/2a trial of Duavee, an approved therapy.

Public concerns over the safety of hormone therapy, however, were seen to be a significant barrier to enrollment and could impede larger trials.

“Despite perceived benefits in MS, estrogens [hormone therapy] have perceived risks that represent a hurdle to enrollment,” the researchers wrote.

“With appropriate education and screening of participants,” they added, “the favorable study retention (87%) and treatment satisfaction observed in the current study support the feasibility of a longer, powered trial to evaluate whether a proven treatment for menopausal symptoms, Duavee, could also improve MS-related function in menopausal women with MS.”

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The study, “A Hormonal therapy for menopausal women with MS: A Phase Ib/IIa Randomized Controlled Trial,” was published in Multiple Sclerosis and Related Disorders. 

Menopause is characterized by a significant drop in sex hormones, namely estrogen and progesterone, leading to vasomotor symptoms that can range from hot flashes and sleep disturbances to mood swings and a loss of bone density.

MS is generally established in women before menopause’s onset, known to naturally occur in female patients at a median age of 51.5. Whether the fluctuations in hormone levels that it causes could exacerbate disease symptoms and promote MS progression is an area of interest.

“Women’s experience during this transition may be compounded by coincident age-related increases in disability and conversion to a progressive course … as well as decline in levels of potentially neuroprotective ovarian hormones, leading to further disability progression,” the scientists wrote.

Hormone therapy in the general population has been shown to ease menopause symptoms, and evidence suggests it may also have neuroprotective effects for women with MS, but its potential needs to be better investigated. Hormone therapy’s use, the researchers noted, “has not been tested in women with MS outside the childbearing window.”

Duavee is a therapy marketed by Pfizer that contains a mixture of estrogens and an estrogen receptor modulator called bazedoxifine. It is thought to offer several advantages over other types of hormone therapy, including beneficial effects on breast and bone health.

Researchers at the University of California at San Francisco conducted a single-site, Phase 1b/2a pilot study (NCT02710214) to evaluate the overall feasibility, safety, and efficacy of Duavee in menopausal women with MS between the ages of 40 and 62.

A major goal was to determine the feasibility of a larger trial in this patient population, needed to determine effectiveness. A total of 41 eligible women were screened for this study, with 24 ultimately choosing to take part over a 34-month enrollment period.

A major obstacle to recruitment centered on women’s concerns about the safety of hormone therapy, the researchers wrote, adding that this may be a significant barrier to larger-scale studies. Safety concerns were “voiced by many” of the “women approached but not interested in participating,” they noted.

They suggested that educational materials given to patients and clinicians, as well as future studies enrolling across multiple sites, might encourage better participation.

Enrolled patients had a median age was 51.2 and median disease duration of 10 years; most (22) had relapsing-remitting MS and “moderate” disability (an Expanded Disability Status Scale or EDSS score of three). They were randomized in equal numbers  to eight weeks of oral Duavee (12 people) or a placebo (12 people) given daily.

Of these 24 women, 21 finished the study. One left due to hot flashes, one was lost during follow-up, and one died of causes determined to be unrelated to the study.

The treatment was generally well tolerated, with side effects reported by 20% of those on Duavee and 13% of those on placebo. They included  breast tenderness in two women receiving Duavee, and a torso rash in one placebo arm patient. Liver function was normal for all participants.

No one experienced an MS relapse during the study, and none of the eight treated women who underwent MRI scans showed evidence of new MS-associated brain lesions. New lesions were found in one of four placebo-group women who underwent MRI scans.

Although not to a statistically significant degree, those randomized to Duavee reported fewer menopausal symptoms interfering with daily life by the study’s end.

All women treated with Duavee reported a significant decline in the number of hot flashes experienced each day, as did eight of 10 in the placebo arm, with no differences between the two groups observed.

Likewise, no statistically significant differences were seen between these groups with regard to MS symptoms. However, those given Duavee had a greater median decrease from the study’s start in EDSS severity, indicating a potentially beneficial effect of the treatment on MS-related disability.

Cognitive, quality of life, and neuropsychological functions tests similarly suggested a trend toward improvement with Duavee’s use.

The researchers noted that while promising, these results are preliminary. The therapy’s efficacy needs to be evaluated in larger trials, they said.

“Our preliminary findings with Duavee suggest that clinical trials in women with MS merit further pursuit,” the researchers wrote.