Gonadotoxicity of cancer therapies in pediatric and reproductive-age females

Abstract

The natural depletion of the finite number of follicles present in the ovaries can be accelerated by cancer treatment, leading to acute ovarian failure or premature menopause. The negative impact of cancer therapy on ovarian follicular reserve, hypothalamic-pituitary-ovarian axis function, uterine function, and cardiac function can impact the ability of female cancer survivors to conceive or carry a biologic pregnancy to term. Chemotherapeutic agents that affect the cell cycle interfere with growing follicles, whereas alkylating agents have a non-cycle-specific mechanism of action leading to single- and double-strand DNA breaks, thereby potentially affecting both quiescent and dividing cells in the ovary. Chemotherapy can also lead to cortical fibrosis, blood vessel damage, and stromal damage in the ovary. The impact of cancer treatment on reproductive potential depends on the age of the patient, the chemotherapeutic agents used, the duration of treatment, the total cumulative dose administered, and patient-specific factors. Current efforts are focusing on determining the gonadotoxicity of specific chemotherapeutic regimens rather than single agents. Irradiation of the ovaries (in total body radiation; direct pelvic, abdominal, or spinal irradiation; or scatter irradiation) of 1–2 Gy in girls and 4–6 Gy in adults depletes the follicle population and permanently impacts ovarian function. Posttreatment, reproductive capacity should be monitored through the measurement of gonadotropins and markers of follicle health, such as anti-Müllerian hormone (AMH).