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.