Ovarian Morphometric Changes following Cyclophosphamide Treatment

Abstract

Cyclophosphamide (CP) is a bifunctional alkylating agent routinely used in the treatment of a wide variety of malignancies and immunological disorders. Although CP can be quite effective in the management of these diseases, it also causes several adverse side effects. Observations by a number of investigators show that CP acts as a potent toxicant in the female reproductive system, capable of producing transient amenorrhea or complete ovarian failure (1–3). These side effects are accompanied by a reduction in serum estrogen and progesterone levels and an increase in FSH and LH, suggesting toxicity at the level of the ovary and not at the level of the hypothalamus or pituitary (4). Indeed, many animal studies demonstrate that CP produces a time-, dose-, strain-, and species-dependent destruction of oocytes and follicles (5–7). These data, collected in rodents, suggest that primordial follicles are most sensitive to CP insult, followed by growing and antral follicles. Although such changes in follicle pools are well defined, quicker and more sensitive assays are needed to assess earlier changes occurring in the follicle complex itself and other ovarian components that may be indicative signs of ovarian toxicity. Given the dynamic nature of follicle growth and replacement, it is possible that growing and antral follicles are equally or more sensitive than primordial folheies.