Hormonal Therapies in Multiple Sclerosis: a Review of Clinical Data

Abstract

Purpose of review: Given the potential for exogenous hormones to influence risk and course of MS, this narrative review aims to summarize current knowledge from observational and interventional studies of exogenous hormones in humans with MS.

Recent findings: Large randomized clinical trials for combined oral contraceptives and estriol both show modest effect on inflammatory activity, with the latter showing potential neuroprotective effect. After fertility treatment, large actively treated cohorts have not confirmed any elevated risk of relapse. Preclinical data suggest that androgens, selective estrogen receptor modulators (SERMs), and selective androgen receptor modulators (SARMs) may be neuroprotective but clinical data are lacking. Gender affirming treatment, particularly estrogen in trans-women, could possibly be associated with elevated risk of inflammation. For women with MS entering menopause, hormone therapy appears safe during the appropriate menopausal window, but its long-term effects on neuroprotection are unknown. Exogenous hormones, used in varied doses and for diverse indications, have variable effects on MS risk, inflammatory activity, and neuroprotection. Large randomized trials are needed before it is possible to determine the true effect of exogenous hormones in a condition as complex as MS.

Keywords: Contraceptives; Exogenous hormone therapy; Fertility treatments; Gender affirming therapy; Menopausal hormone therapy; Multiple sclerosis.

Fig. 1

Stages of reproductive aging. Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. The Journal of clinical endocrinology and metabolism. 2012;97(4):1159–68. https://doi.org/10.1210/jc.2011-3362. [18]

Fig. 2

Overview of benefits and risks of systemic menopausal hormone therapy in women aged 50–59 years in the Women’s Health Initiative. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause (New York, NY). 2022;29(7):767–94. https://doi.org/10.1097/gme.0000000000002028 [19]

Fig. 3

Overview of common fertility treatments, organized based on hypothetical risk of MS inflammatory activity. Graham EL, Bakkensen JB, Anderson A, Lancki N, Davidson A, Perez Giraldo G, et al. Inflammatory Activity After Diverse Fertility Treatments: A Multicenter Analysis in the Modern Multiple Sclerosis Treatment Era. Neurology(R) neuroimmunology & neuroinflammation. 2023;10(3). https://doi.org/10.1212/nxi.0000000000200106. [71]