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Reversibility of testosterone-induced acyclicity after testosterone cessation in a transgender mouse model

Kinnear HM, Hashim PH, Dela Cruz C, Rubenstein G, Chang AL, Nimmagadda L, Brunette MA, Padmanabhan V et al.

F&S science, 2021

Abstract

OBJECTIVE: To establish if the 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 in this study.

INTERVENTION(S): Postpubertal C57BL/6NHsd female mice were subcutaneously implanted with T enanthate (n = 5 mice) or placebo (n = 5 mice) pellets. Pellets were surgically removed after 6 weeks to ensure T cessation, after which the mice were followed for four estrous cycles after the 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. 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 six weeks of T therapy. T levels were significantly elevated during T therapy and decreased to control levels after surgical pellet removal. No detectable differences were observed in the follicle count, corpora lutea formation, diestrus hormone levels, or body metrics after four estrous cycles, with the exception of persistent increased clitoral area between T-treated mice and controls. One T-treated mouse was…

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