Short-term testosterone use in female mice does not impair fertilizability of eggs: implications for the fertility care of transgender males
Authors: Bartels C B , Uliasz T F , Lestz L , Mehlmann L M 
Published: September 2020

Abstract

STUDY QUESTION
Does testosterone use in females affect reproductive potential, particularly with regard to the production of fertilizable gametes?

SUMMARY ANSWER
Testosterone (T) injections given to post-pubertal female mice caused virilization and although the ovaries were smaller than controls they were still responsive and produced fertilizable eggs when superovulated.

WHAT IS KNOWN ALREADY
Studies to examine the effects of testosterone on reproductive potential in transgender males are lacking. Recently, a model was developed that simulates many aspects of testosterone use in transgender males in order to look at reproductive effects of testosterone in female mice. This study found masculinizing effects on the mice but did not find significant deficits on the number of ovarian follicles; however, effects of testosterone use on ovarian stimulation and fertilizability of oocytes were not investigated.

STUDY DESIGN, SIZE, DURATION
A total of 66, 6-week-old Hsd:NSA (CF-1) female mice and six Hsd:ICR (CD-1) male mice were used for this study. Mice were injected s.c. with 400 µg T or sesame oil once a week for 6 weeks and were either killed 1 week after the sixth injection (active exposure group), or 6–7 weeks after the final T injection (washout group).

PARTICIPANTS/MATERIALS, SETTING, METHODS
Both active exposure and washout groups were further subdivided into three groups: unstimulated, equine CG (eCG)-stimulated or eCG/hCG-stimulated. eCG-stimulated mice were killed 44–48 h after eCG injection. eCG/hCG-stimulated mice were injected with eCG, followed 48 h later with hCG. Mice were killed ∼13–18 h after the hCG injection. Data collected included daily vaginal cytology, terminal testosterone levels, ovary weights and histology, number of oocytes/eggs collected in each group, and cleavage to the two-cell stage following IVF.

MAIN RESULTS AND THE ROLE OF CHANCE
Testosterone-treated mice had testosterone levels elevated to the level of male mice and ceased cycling. Ovaries were significantly smaller in testosterone-treated mice, but they contained normal cohorts of follicles and responded to gonadotrophin stimulation by ovulating similar numbers of eggs as controls, that fertilized and cleaved in vitro.

LIMITATIONS, REASONS FOR CAUTION
Mice were treated for only 6 weeks, whereas many transgender men use testosterone for many years before considering biological children, and developmental competence was not assessed. Importantly, a mouse system may not perfectly simulate human reproductive physiology.

WIDER IMPLICATIONS OF THE FINDINGS
The current standard of care for transgender men who desire biological children is to cease testosterone therapy prior to ovarian stimulation, but the necessity for stopping testosterone is not known. Our model demonstrates that it is possible for testosterone-suppressed ovaries to respond to gonadotrophic stimulation by producing and ovulating fertilizable eggs, thereby obviating the need for testosterone cessation prior to ovarian stimulation. In time, these results may provide insights for future clinical trials of fertility treatment options for transgender men.

STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the Reproductive Endocrinology and Infertility fellowship program through UConn Health Graduate Medical Education (to C.B.B.). The authors have no competing interests.

TRIAL REGISTRATION NUMBER
N/A.