Ovarian, breast, and metabolic changes induced by androgen treatment in transgender men

Gender-affirming hormone therapy (GAHT) is often provided to transgender people. In this review of the literature, the current knowledge of ovarian, breast, and metabolic changes (body composition, insulin resistance, bone density, cardiovascular risk factors such as lipids, blood pressure, and hematocrit) observed following GAHT in adult transgender men is discussed. A body of literature concurs to describe that long-term androgen therapy in transgender men exerts atrophic effects on the breast. There is currently no evidence of an increased risk of breast cancer. Long-term testosterone treatment induces ovarian effects that become visible after 6 months of therapy. These changes consist of both macroscopic and microscopic alterations of ovarian morphology that mimic the typical ovarian aspect encountered in women with polycystic ovary syndrome but without an effect on antral follicle count. Metabolic effects of long-term androgen treatment in transgender men put them at par with cisgender men in terms of lipid profile, insulin resistance, and overall mortality. Body composition changes as desired after testosterone administration in most transgender men, and insulin resistance decreases with virilization. There are no detrimental effects on bone mineral density. Cardiometabolic risk and morbidity data are currently reassuring, even if certain studies show conflicting results. An increase in blood pressure and a decrease in high-density lipoprotein cholesterol have been reported as risk factors, whereas polycythemia is rare and treatable. Most available data are observational and based on biochemical markers instead of the more direct measures of cardiovascular damage. An explanation for these observed changes is mostly lacking. Psychological stress and lifestyle factors are often forgotten in a much needed integrated approach.