ACTRIMS 2026 | Hormonal phases and sex hormone metabolite differences in women with MS

Given technological advances, we now have a pretty sensitive metabolomics platform that really is capable of quite sensitively measuring the level of metabolites in the serum of people with MS. So we were fortunate to use data from the Accelerated Cure Project cohort. This cohort was very clinically homogeneous. So all non-Hispanic white, all within early stage, within five years of disease onset, and all were either DMT-naive or free for 90 days. Luckily, the ACP data set also had pretty copious amounts of self-report data, so this also allowed us to identify and adjust for key confounders, including age, BMI, smoking status, statin use, hormonal replacement therapy, or OCP use, as well as steroid use.

So yeah, with that, we performed a linear regression model, adjusting for these confounders, among others, and looked specifically at the sex hormones in females with MS versus healthy controls. And we looked at overall differences as well as stratified by menopausal status, so pre versus post-menopausal. And interestingly, we did not find any differences. So, you know, we were kind of wanting to explore that further and take a little more nuanced approach rather than just stratifying by menopause status. We also wanted to look at menstrual phase. So kind of the hormonal phase throughout a woman’s cycle leading up into menopause. So with that, we repeated our linear regression model, and this time included a MS status versus menstrual phase interaction term, using the difference between the healthy controls and MS in the menopausal group as our reference. And when we performed that analysis, we did see some differences largely in the perimenopausal group. So that was defined as women with their last menstrual cycle between 60 days up to a year since their last cycle. And we surprisingly found elevations quite a few androgen metabolites, as well as a few progestin, there was also an anovulatory phase, so between 30 and 60 day timeframes from their last menstrual cycle, also had elevations in some of these progestin metabolites. So as far as kind of the relevance of these findings clinically, you know, we do think that, you know, this does provide insight into the fact that this perimenopausal phase is an important context for kind of understanding some of these sex hormone differences. And this is particularly of interest, given the aging MS population, and we’re going to be having a larger percentage of women with MS, approaching the perimenopausal stage.

So I think really kind of a missing piece from our study and, you know, should be the subject of future studies is really correlating some more functional outcomes with these sex hormone changes. Obviously, there’s kind of more mechanistic studies that have shown sex hormones can directly modulate immune activity, inflammation, neuroprotection. So it’s plausible that, you know, the consequence of these changes in sex hormones could, you know, shape disease progression, activity, and even treatment response. So I think really a big kind of next step would be to, again, kind of correlate some of these disability scores or even, you know, radiological progression to really, I guess, provide more context to the significance of these findings.

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