Gender-affirming interventions and prognosis in multiple sclerosis

Gender-affirming hormone therapy (GAHT) may increase multiple sclerosis (MS) risk, yet MS disease course among transgender and gender-diverse (TGD) individuals remains understudied. We aimed to evaluate the disease course in TGD individuals with MS (TGD-MS).

Seventeen TGD-MS were identified. Ten TGD-MS on GAHT (five transgender women with MS (TW-MS) and five transgender men with MS (TM-MS)) were investigated further for MS outcomes of symptomatic (clinical)/asymptomatic (radiological) disease activity and progressive MS (PMS) onset.

TW-MS (mean = 54.5 years, range = 35.1-66.3) were older than TM-MS (39.2 years, range = 29.6-47.2) at last follow-up. MS onset was later in TW-MS (31.5 years, range = 25.1-39.1) than in TM-MS (21.0 years, range = 15.0-29.8). Three patients (one TW-MS, two TM-MS) experienced symptomatic activity after GAHT initiation (8-10 months); in two patients (one TW-MS, one TM-MS), this marked symptomatic MS onset. Seven patients (four TW-MS, three TM-MS) had ⩾1 clinical/radiological disease activity. Four had PMS; all were TW-MS. In three, GAHT initiation preceded PMS onset (1-5 years). Disability was higher in TW-MS than in TM-MS.

MS disease course may be modified by GAHT and may differ between TW-MS and TM-MS, highlighting the need for larger long-term studies to overcome disparities in MS care. Comprehensive GAHT history, timely management, and closer follow-up are warranted in TGD-MS.