The Effects of Puberty Blocking Treatment (Gonadotropin Releasing Hormone Agonist) on Reproductive Function in Young Female Rats

The number of adolescents identifying as transgender has been increasing with many transgender youth receiving treatment with a gonadotropin releasing hormone agonist (GnRHa) that suppresses sex hormone production (i.e., puberty blocker). Transgender individuals taking a GnRHa to block puberty have reported improved mental wellbeing, but the physiological impact on reproductive function needs to be examined. Objective: To investigate the effects of puberty blocking treatment using GnRHa on reproductive morphology and function in young female rats. It was hypothesized that puberty blocking treatment would decrease fertility. Methods: Four-week old female Sprague Dawley rats were given daily subcutaneous injections of the GnRHa triptorelin or saline as control. After four weeks of treatment a group of rats were euthanized and the uterus and ovaries were removed for H&E staining to assess morphology. An additional group was taken off GnRHa treatment for 4-weeks to examine recovery of reproductive organ morphology. The final group was taken off GnRHa treatment and housed with fertile males to determine reproductive performance. Results: GnRHa treatment led to a reduction in the mass of uteri and ovaries which recovered after 4-weeks of drug withdrawal. The myometrial and endometrial thickness of the uterus was reduced in GnRHa treated animals. The ovaries of puberty blocked animals exhibited a disruption in follicle development and corpora lutea health. The morphology of the uterus and ovaries recuperated after 4-weeks of drug withdrawal. No significant difference in pregnancy rate was detected; however, both the number of days until pregnancy detection and number of days until giving birth were considerably longer in GnRHa rats following withdrawal. The number of pups per litter was also significantly reduced by puberty blocking treatment but no abnormalities were observed in the pups. Conclusion: Young female rats treated with a GnRHa had significantly delayed development of the reproductive organs. After 4 weeks of GnRHa withdrawal reproductive organ mass and morphology recovered. A minor disruption in reproductive function was detected immediately following GnRHa withdrawal. These physiological effects on reproductive health should be considered when administering a GnRHa to block puberty. No external funding was used to support this research. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.