An association between gender identity disorders (GIDs) and subsequent multiple sclerosis (MS) in males was found in an analysis of linked English Hospital Episode Statistics and mortality data from January 1999 to March 2012.

The findings “suggest that low testosterone levels and/or feminising gonadal hormones might influence MS risk in some men and highlight a need for further work to explore any potential role for gonadal hormones in management and/or prevention strategies,” wrote Dr. Julia Pakpoor of the Unit of Health-Care Epidemiology, Nuffield Department of Population Health, at University of Oxford (England).

She and her colleagues used the patient data to construct male and female cohorts (1,157 patients and 2,390 patients, respectively) of patients with GIDs. A patient was included in one of the two GID cohorts if he or she had an episode of care or hospital admission in which a GID or sexual transformation procedure was coded in any diagnostic position.

For males with GIDs transitioning to females, the most studied treatment regimen involves using feminizing hormones and anti-androgens, which reduce testosterone secretion or neutralize testosterone activity, the researchers noted.

They also used the database to construct male and female cohorts (4.6 million patients and 3.4 million patients, respectively) to serve as two control groups. For patients to be included in the control groups, they needed to have been first admitted to a hospital for a minor condition and to never have been admitted to a hospital for MS. Patients who had been admitted to a hospital for MS either before or at the same time they were admitted for GIDs were excluded from the GID cohorts. A patient stopped being followed upon diagnosis with MS.

“Our study design cannot give insights into mechanisms that might explain the association [between males with GIDs and MS]. However, there is evidence suggesting an association between gonadal hormones and MS, including animal models suggesting anti-inflammatory and/or neuroprotective actions of testosterone, studies indicating a high prevalence of hypogonadism in male MS patients, and improved cognitive function and slowed brain atrophy in a small pilot trial of testosterone,” the researchers noted.

The adjusted rate ratio of MS following GID in males was 6.63 (P = .0002), compared with 1.44 in females (P = .58). The adjusted rate ratios were based on 4 observed cases and 0.6 expected cases of MS in males and 5 observed cases and 3.5 expected cases of MS in females.

The authors reported no conflicts of interest.

Read the study in Multiple Sclerosis Journal ( doi: 10.1177/1352458515627205 ).