TORONTO — Hormone replacement therapy (HRT) for menopausal symptoms in women with multiple sclerosis (MS) appears safe and hints at an additional, unexpected benefit.

In the first study to investigate the impact of HRT in women with MS after the introduction of highly effective disease-modifying therapy (DMT), investigators found the treatment is not only safe but may also have a positive impact on disability progression, although this signal requires further investigation.

“The most important goal of the study was met, and that was to provide reasonably high-quality evidence that it’s safe to use hormone replacement therapy for women with MS,” said study investigator, Timothy P. Copeland, PhD, postdoctoral researcher, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

The findings were presented on October 23 at the 10th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2026.

An Ongoing Debate

Evidence suggests women with MS may experience accelerated disability after menopause, possibly because of declining ovarian estrogen. HRT replaces estrogen, but whether it should be routinely recommended for women with MS is under debate.

The nationwide Swedish MS Registry study included 7390 women, accounting for 86% of patients with MS in the Swedish MS Registry. As of a 2025 report, the MS registry included 86% of all MS patients in the country.

Researchers linked the MS registry data with prescription and health registers for women aged 40-60 years at study entry between 2006 and 2023, with follow-up through 2024. During a median follow-up of 13 years, 1015 women (13.7%) initiated HRT.

The three study outcomes were the Expanded Disability Status Scale (EDSS) 4, EDSS 6, and recurring relapse. The EDSS scale is an indication of mobility impairment; EDSS 4 indicates that walking is limited or impaired, whereas EDSS 6 indicates a need for a mobility aid.

Copeland noted that the EDSS is an indication of the degree of disease progression. “It’s very much a proxy measure in terms of the biological state of the brain — the extent of the damage to the structure of the brain.”

Researchers looked at the time-varying variable of HRT exposed/unexposed. They converted all medications into oral estrogen equivalents and investigated doses over 90-day windows.

After adjusting for age, DMT class, disease phenotype, disease duration, year of study entry, education, region, and country of birth, results showed HRT use was associated with a lower hazard of sustained EDSS 4 (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.51-0.99; P = .043).

“I was surprised to see that there was an association with a lower risk of reaching EDSS 4 that’s attributable to, or associated with, hormone replacement therapy use,” said Copeland.

These results suggest that HRT may have neuroprotective qualities beyond the anti-inflammatory pathway, he added.

Don’t Hesitate to Prescribe HRT

HRT use was not associated with sustained EDSS 6 (aHR, 0.88; 95% CI, 0.61-1.29), a disability milestone indicating the need for walking assistance. Copeland suggested that HRT may have less influence once MS has reached a more advanced stage.

There was also no association between HRT use and recurring relapses (aHR, 0.99; 95% CI, 0.72-1.36).

In addition, a dose-category analysis showed no consistent gradient across HRT dose levels.

“Pretty much everyone was on the same average dose so there was no dose-response signal, and I think that’s just a limitation of the distribution of doses,” Copeland said.

The study period spanned the introduction of newer DMTs but also an earlier treatment era, making it difficult to assess how individual DMTs might influence the findings, he noted.

In a sensitivity analysis, researchers looked at an older cohort (50 years or older at entry vs 40 years) which yielded a consistent EDSS 4 estimate (aHR, 0.63; 95% CI, 0.40-1.00; P = .049).

“We got essentially the same findings,” said Copeland, adding the median age of menopause in Sweden is 51 years.

However, the MS registry does not record menopausal status. Copeland said the researchers plan to repeat the study when those data become available.

A separate sensitivity analysis looking only at women with relapsing-remitting MS subgroup produced similar results (aHR, 0.72; 95% CI, 0.51-1.00; P = .049).

Copeland’s message to physicians is to not hesitate to prescribe HRT “simply because your patient has MS.”

Healthy user bias was a study limitation, so it is possible that women taking HRT may have healthier lifestyles that could partly explain the findings.

Nevertheless, he believes the results “are strong enough to say that at the very least, it appears to be safe,” he said. “If I had a family member with MS who asked me if they should take HRT, I would say not to worry any more than you would if you didn’t have MS.”

However, because multiple factors can influence MS progression, Copeland cautioned that the study cannot establish whether HRT itself slows disability progression.

Filling an Important Research Gap

The study’s findings help fill an important gap in understanding HRT use during menopause among women taking the newer generation of DMTs, said Alise Carlson, MD, a staff neurologist at the Cleveland Clinic in Ohio, who was not involved in the research.

Carlson described the study as “really exciting” as it adds to mounting supporting HRT use in this patient population and suggests a possible protective effect against disability progression.

Previous research on HRT in MS was scarce and some predated widespread use of highly effective DMTs, leaving uncertainty about its use for menopausal symptoms, Carlson noted.

“This is the first large contemporary real-world study that looked at systemic HRT and showed that it’s safe and possibly modestly protective against disability progression in women with MS,” she said.

Many women receiving these therapies are now entering menopause, when biologic aging and hormonal changes may have compounding effects, she noted.

The study also addressed “a big evidence gap” as little work has been done in patients taking the newer DMTs.

The study received funding from the Swedish Research Council. Copeland and Carlson reported having no relevant disclosures.