Reversibility of Testosterone-Induced Acyclicity after Testosterone Cessation in a Transgender Mouse Model

ABSTRACT Objective CTo establish if cessation of testosterone (T) therapy reverses T-induced acyclicity in a transgender mouse model that allows for well-defined T cessation timing. Design Experimental laboratory study using a mouse model. Setting University-based basic science research laboratory. Animals A total of 10 C57BL/6NHsd female mice were used for this study. Intervention(s) Postpubertal C57BL/6NHsd female mice received subcutaneously implanted T enanthate (n = 5 mice) or control (n = 5 mice) pellets. Pellets were surgically removed after 6 weeks to ensure T cessation, after which mice were followed 4 cycles after resumption of cyclicity. Main Outcome Measure(s) Primary outcomes included daily vaginal cytology and weekly T levels before, during, and after T enanthate or placebo pellet implantation and removal. Additional secondary outcomes included ovarian follicle distribution and corpora lutea numbers, body metrics, and terminal diestrus hormone levels. Result(s) T-treated mice (100%) resumed cycling within one week of T pellet removal after 6 weeks of T therapy. T levels were significantly elevated during T therapy (p Conclusion(s) Our results demonstrate a close temporal relationship between estrous cycle return and T levels dropping to control levels following T pellet removal. The return of regular cyclic ovulatory function is also supported by the formation of corpora lutea and the lack of detectable differences in key reproductive parameters as compared to controls four cycles after T cessation. These results may be relevant to understanding the reversibility of T-induced amenorrhea and possible anovulation in transgender men interested in pausing T to pursue pregnancy or oocyte donation. Results may be limited by duration of T treatment, lack of functional testing, and physiological differences between mice and humans.