Long-Term Follow-Up of Chemotherapy-Induced Ovarian Failure in Young Breast Cancer Patients: The Role of Vascular Toxicity

Abstract

Background. We previously reported that chemotherapy-induced ovarian toxicity may result from acute vascular insult, demon- strated by decreased ovarian blood flow and diminished post- treatment anti-Müllerian hormone (AMH) levels. In the present study, we report the continuous prospective evaluation of ovarian function in that cohort. Methods. Patients (aged,43 years) with localized breast cancer were evaluated by transvaginal ultrasound prior to initiation of chemotherapy, immediately at treatment completion, and at 6 and 12 months after treatment cessation. Doppler flow velocity indices of the ovarian vasculature (resistance index [RI], pulsatility index [PI]) were visualized. Hormone markers of ovarian reserve were assessed at the same time points. Results. Twenty patients were enrolled in the study. Median age was 34 6 5.24 years. Ovarian blood flow was significantly reduced immediately following chemotherapy (both RI and PI; p 5.01).These parameterswerepartially recovered at later points of assessment (6 and 12 months after treatment); patients aged,35 years significantly regained ovarian blood flow compared with patients aged.35 years (p,.05). AMH dropped dramatically in all patients following treatment (p,.001) and recovered in only 10 patients. Hormone markers of ovarian reserve shortly after chemotherapy depicted a postmenopausal profile for most patients, accompanied by related symptoms. Follicle-stimulating hormone (FSH) levels recovered in 14 of 20 patients and significantly returned to the premenopausal range in patients aged,35 years (p 5.04); 10 of 20 resumed menses at 12 months. The pattern of vascular impairment was lessened in patients treated with a trastuzumab-based protocol, although results did not reach statistical significance (p 5.068). Conclusion. Continuous prospective evaluation of ovarian vasculature and function in a cohort of young patients during and after chemotherapy indicated that ovarian toxicity may derive from acute vascular insult. Age may affect whether patients regain ovarian function, whereas recovery of blood flow and premenopausal FSH levels at later assessment was notable in patients aged,35 years.