Fig. 1.

Consequences of gonadotoxic treatment in reproductive-aged women. (A) The primordial follicle population—the ovarian reserve—can be represented by a parabolic curve across the female lifespan in which activation or death of primordial ovarian follicles occurs progressively with each menstrual cycle, from puberty to the menopause. Reprinted from Wallace and Kelsey [4]. (B–D) The growth of follicles with each cycle maintains hormonal balance necessary for overall women’s health. Gonadotoxic stress or treatment, such as chemotherapy or radiation therapy (red bar across all panels), induces a rapid decrease in the highly sensitive primordial follicles of the ovarian reserve (A, C), resulting in a follicle-depleted ovary (B) and premature ovarian failure (POF). Depletion of the ovarian reserve disrupts normal endocrine function and the production of hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, inhibin B, and inhibin A (D), leading to hormonal imbalance similar to that seen in postmenopausal women.