SUN-121 - Effects of IGF-1 Receptor Antagonists on Female Reproductive Function

Thyroid eye disease (TED) often accompanies autoimmune thyroid dysfunction; prevalence of TED is disproportionately higher in biological females. Insulin like growth factor-1 receptor antagonist (IGF-1R-Ant) is an increasingly utilized treatment for TED since FDA approval in 2020.1 An unanticipated emerging effect of real life use of IGF-1R-Ant in premenopausal (Pre-M) women is new- onset menstrual dysfunction.2 However, to date, it is unknown if menstrual cyclicity resumes after discontinuation of IGF-1R-Ant, nor is there clarity on treatment effects on symptomatology of reproductive aging.

Methods: TED patients (Pre-M and postmenopausal [Post-M]) previously treated with IGF-1R-Ant were surveyed to gain clarity on occurrence of menstrual changes (in Pre-M) and/or vasomotor symptoms (VMS) during IGF-1R-Ant treatment, on timing of symptom onset during treatment, and if symptom resolution followed treatment completion. Study was IRB approved and participants provided informed consent.

Results: Questionnaires were completed by 7 Pre-M and 11 Post-M women, (mean ages 42.8 [SD 6.6] & 65.5 [SD 7.2] years respectively). Mean time (in months) since IGF-1R-Ant treatment completion was 34.0 [SD 11.8] for Pre-M, and 22.1 [SD 16.5] for Post-M patients. Of Pre-M group, 3/7 (43%) noted a change in menstrual cycle pattern, 5/7 (71%) experienced VMS and 1/7 (14%) noted a change in libido; cycles normalized following treatment completion in only 1/3 (33%), after 3 months of IGF-1R-Ant discontinuation. Of Post-M women, 2/11 (18%) endorsed experiencing worsening daytime VMS, 1/11 (9%) endorsed improvement in daytime VMS, and 2/11 (18%) reported worsening nightly VMS during treatment, with no resolution in these symptoms after treatment discontinuation.

Conclusions: This is the first study to investigate persistence of effects of IGF-1R-Ant treatment for TED on menstrual function following treatment discontinuation, and the first to examine for occurrence of VMS in both Pre-M and Post-M women in relation to IGF-1R-Ant use for TED. A majority of Pre-M women noted VMS and nearing half (43%) experienced menstrual cycle changes during treatment; these symptoms persisted after treatment discontinuation in the majority (in 2/3rd). Of Post-M women, nearly 1/4th reported experiencing VMS which persisted beyond treatment discontinuation. Our findings can help TED patient counseling towards guiding treatment related patient expectations and improving patient experience.


1. Ugradar, Shoaib et al. “Teprotumumab for the Treatment of Thyroid Eye Disease.” Endocrine reviews
2. Terrarosa, Anna K et al. “Menstrual Irregularities and Amenorrhea in Thyroid Eye Disease Patients Treated With Teprotumumab.” Ophthalmic plastic and reconstructive surgery

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