IGF-1R Antagonism in Thyroid Eye Disease and Female Reproductive Function

PURPOSE: To examine our current understanding of insulin-like growth factor-1 receptor's (IGF-1R) role in female reproductive physiology and identify the mechanisms that underlie commonly reported new-onset menstrual abnormalities in premenopausal women following initiation of teprotumumab, an IGF-1R antagonist, for treatment of thyroid eye disease. METHODS: This is a narrative review. First, studies were identified that reported menstrual changes with the use of teprotumumab. Then, literature regarding IGF-1R signaling and female reproductive physiology was explored to generate a hypothesis on how IGF-1R antagonism may be causative of the menstrual abnormalities attributable to teprotumumab. RESULTS: Reported rates of menstrual abnormalities, predominantly amenorrhea, attributable to IGF-1R antagonism range from 5% to 50%. Cellular expression of IGF-1R is documented across the spectrum of tissues that are critical to the successful functioning of the female reproductive system, including the hypothalamus, pituitary, ovary, and the endometrium. CONCLUSIONS: The likely mechanisms through which menstrual abnormalities occur with IGF-1R antagonism are through disruption of ovarian processes of folliculogenesis, steroidogenesis, and ovulation. Ultimately, further basic and clinical research is warranted to better understand the mechanisms whereby IGF1-R antagonism disrupts female reproductive functioning, as well as to examine if there is any lasting detriment beyond cessation of exposure to IGF1-R antagonists such as teprotumumab.