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Reproductive Consequences of Steroid Hormone Administration

类固醇激素管理的生殖后果

基本信息

批准号：
9921444
负责人：
Molly Bennette Moravek
金额：
$ 50.04万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9921444
关键词：
Address Adolescent Adult Affect Agonist Androgens Animal Model Animals Architecture Assisted Reproductive Technology Breeding Caring Clinical Clinical Research Conflict (Psychology)Counseling Data Defect Development Estradiol Estrous Cycle Female Fertility Fertilization Fertilization in Vitro Foundations Future Gender Identity Goals Gonadal Steroid Hormones Gonadotropin Hormone Releasing Hormone Histologic Histology Hormones Human Infertility International Knowledge Lead Medical Modeling Mus Neurosecretory Systems Observational Study Oocytes Operative Surgical Procedures Outcome Ovarian Ovarian Stimulations Ovary Patients Phenotype Polycystic Ovary Syndrome Prevalence Puberty Recommendation Regimen Reproduction Reproductive Health Research Research Personnel Role Serum Sex Characteristics Superovulation Testing Testosterone Time Translational Research United States base body system clinical practice clinically relevant evidence base experimental study fertility preservation folliculogenesis gender transition hormone therapy implantation improved insight male mouse model offspring oocyte cryopreservation ovary transplantation peripubertal period prenatal prepuberty reproductive reproductive function reproductive tract response sex steroid hormone tool transgender transgender men translational study

项目摘要

Recent data estimates 1.4 million transgender adults and 150,000 transgender adolescents live in the United States, many of whom are on cross-sex hormone therapy with estradiol or testosterone (T). National and international medical organizations recommend fertility preservation counseling prior to initiation of cross-sex hormone therapy, based on an assumption of fertility loss. However, the impact of long-term cross-sex hormone therapy on reproductive health is largely unknown, particularly in transgender men (female-to- male or FTM). The available human studies suggest ovarian changes from cross-sex T therapy, but are observational studies, with conflicting results. Moreover, there is a lack of data on the fecundity of T-treated transgender men, and there have been no studies that address the reversibility of T-induced changes after cessation of T for reproductive purposes. There are also no studies on future reproductive consequences of the treatment paradigm for transgender adolescents, in which GnRHa is initiated in the early peripubertal period to suppress further pubertal progression prior to transitioning directly to T therapy (GnRHa-T). None of the existing animal models that address the effect of androgens on reproductive function in females are directly applicable to the clinical paradigm of cross-sex T therapy in transgender men or GnRHa-T therapy in transgender adolescents. To address this knowledge gap, we have developed a mouse model to mimic T treatment for FTM gender transition. These mice manifest defects in ovarian architecture and have altered folliculogenesis. This model provides a powerful tool to clarify the effects of T therapy on reproductive phenotype and function, in a manner not possible in humans. The objective of the proposed studies is to use the FTM mouse model to investigate the effects of cross-sex T treatment on reproductive phenotype and function, and determine the reversibility of these effects following cessation of T. Our central hypothesis is that T therapy will adversely affect ovarian architecture and fertility, but that fertility can be recovered with cessation of T, without adverse reproductive effects in offspring. To test this hypothesis, we will examine the reversibility of postpubertal T administration in female mice, mimicking FTM gender transition, on reproductive phenotype (AIM 1), and examine fertility during and after cessation of long-term testosterone therapy, including reproductive phenotype in offspring (AIM 2). In an exploratory aim, we will examine the reproductive consequences of testosterone administration after pretreatment with peripubertal GnRHa, mimicking FTM cross-sex hormone therapy in adolescents, on reproductive phenotype and fertility (AIM 3). This proposal challenges the status quo of recommending fertility preservation prior to cross-sex T therapy, and will lay the foundation for further translational studies. Our long-term goal is to provide the necessary data for evidence-based fertility counseling of transgender men. Clarifying the effects and reversibility of cross-sex T therapy on the reproductive tract could lead to future paradigm shifts in clinical fertility care of transgender men.

最近的数据估计，美国有140万变性成年人和15万变性青少年