Hormone Therapy May Increase Multiple Sclerosis Risk in Some Transgender Patients

Researchers hypothesized that an altered balance of sex hormones in men with gender identity disorder would increase the risk of MS.

Researchers from the United Kingdom have identified that men with gender identity disorder (GID) who took sex hormones to undergo a male-to-female conversion had a nearly 7-fold higher risk of developing multiple sclerosis (MS). The researchers presented their findings at the 2016 annual meeting of the American Academy of Neurology (AAN).

“Sex hormones may be important in mediating gender differences in MS, but their influence on MS risk remains largely uncharacterized,” wrote Julia Pakpoor, BA, BM BCh (Oxon), academic clinician and researcher from the University of Oxford, and colleagues. “We hypothesize[d] that an altered balance of sex hormones in males with GID [would] both inherently, and secondary to treatment in undergoing male-to-female conversion (which typically involves taking feminizing hormones, anti-androgens and/or sex reassignment surgery), increase MS risk.”

“MS is thought to be 3 times more common in females compared to males (and rising), but men tend to experience more rapid progression of the disease. This renders the notion that sex hormones may be important in mediating gender differences in MS, both as they pertain to disease risk and clinical course,” Dr Pakpoor told Neurology Advisor. “We previously reported a strong positive association between testicular hypofunction and MS risk in males. The study of gender identity disorders was thought to be a valuable way to decipher the impact sex hormones may have on MS risk, and whether this may be modifiable.” 

To investigate a possible association between GIDs and subsequent MS risk, the researchers analyzed 1157 men and 2390 women with GID from English National Hospital Episode Statistics between 1999 and 2011, and compared their data with a control group of 4.6 million men and 3.4 million women without GID. The investigators searched for incidences of MS admission or death from MS and calculated the rates of MS in each group, then stratified and standardized by age, calendar year of first recorded admission, region of residence, and socio-economic status.

The researchers found an adjusted rate ratio of MS in men who transitioned to women of 6.63 (95% confidence interval [CI], 1.81-17.01, P=.0002) and an adjusted rate ratio of MS in women who transitioned to men of 1.44 (95% CI, 0.47-3.37, P=.58).

“We report a positive association (a near 7-fold elevation of rates) between GID and subsequent MS in [men]. Our findings support a postulated [link] between low testosterone and MS risk, and highlight a need for further exploration of the influence of feminizing sex hormones on MS risk,” the authors wrote.

“We hope that this epidemiological study will highlight a need for further work to more directly explore the potential incorporation of gonadal hormones in future management and/or prevention strategies of MS,” said Dr Pakpoor. 

Click here for more coverage from the 68th Annual Meeting of the American Academy of Neurology, April 15-21, 2016, in Vancouver, British Columbia, Canada.


  1. Pakpoor J, Wotton CJ, Schmierer K, Giovannoni G, Goldacre M. Gender identity disorders and multiple sclerosis risk: a national record-linkage study. Presented at: The 68th Annual Meeting of the American Academy of Neurology. April 15-21, 2016; Vancouver, British Columbia, Canada. Presentation I5.008.

This article originally appeared on Neurology Advisor