Background: Male-to-female transsexual women or transwomen who undergo cross-sex hormone treatments experience increased health-related risks (e.g., increased rates of cardiovascular disease and premature death). Yet, the exact mechanism by which altering biochemistry leads to metabolic impairment remains unclear. While much attention has been paid to cross-sex hormone therapy, little is known about the metabolic risk associated with orchiectomy. Methods: To address the above limitation, we prospectively enrolled 12 transwomen: 4 who had undergone bi-lateral orchiectomy and 8 who had not. Both groups were using cross-sex hormones. Glucose tolerance was assessed using a standard 75g oral glucose tolerance test. Hepatic steatosis was assessed by 1H magnetic resonance spectroscopy. The amount of subcutaneous and visceral abdominal fat was determined from a single abdominal axial image at the level between the vertebral L2 and L3 bodies. Baseline venous fasting blood sampling was performed for measurement of hemoglobin A1c, glucose, insulin, sex hormones, and sex hormone binding globulin. Results: The major novel findings were: (1) orchiectomy and cross-sex hormone therapy is associated with less hepatic steatosis and insulin resistance; (2) orchiectomy may be metabolically protective, and (3) circulating concentrations of sex hormones may be a major determinant of metabolic health in transwomen. Conclusions: To our knowledge, this is the first study to suggest an independent and protective role of orchiectomy on the metabolic health of transwomen.
Keywords: androgens; estrogens; insulin resistance; metabolic syndrome; orchiectomy; steatosis; transwomen.