Hypogonadism After Childhood Cancer Treatment

Long-term survival of children with cancer has greatly improved in the last decades due to effective treatment, especially multiagent chemotherapy (ChT). The chief concern is now being directed toward the late effects of treatment. Endocrine glands, gonads in particular, are very susceptible to damaging effects of anticancer therapy. The damaging effect of both ChT and radiotherapy (RT) on gonads is well known (Cohen 2003, Diamond et al. 2001, Spoudeas 2002). In a study of 2283 long-term survivors of childhood cancer Byrne and colleagues found that RT below the diaphragm depressed fertility in both sexes for about 25%, ChT with alkylating agents (AA) with or without RT below the diaphragm depressed fertility by 60% in men, in women, however, AA therapy administered alone had no apparent effect on fertility (Byrne et al. 1987). Hypogonadism is most often due to direct damage by ChT, RT and/or surgery, rarely is due to damage to the hypothalamus and/or pituitary gland (Cicognani et al. 2003, Muller 2003). The gonads have two main functions, the production of sex hormones (estrogens and testosterone) and germ cells (ova and sperm). Both of them depend on a normal function of the hypothalamic-pituitary-gonadal axis. Long term survivors of childhood cancer are at risk of hypogonadism related to gonadotropin secretion, but more frequently hypogonadism is caused by direct damage of testes or ovaries. In human testis two functions are combined: sex steroid production and sperm production. Germ cells form sperm, Sertoli cells support and nurture the developing germ cells and Leydig cells produce testosterone. These three cell types are organized into two functional compartments: germ cells and Sertoli cells form the seminiferous tubules where spermatogenesis takes place, and the network of Leydig cells are responsible for the production of testosterone, which is necessary for normal spermatogenesis. These two compartments are under separate controls and affected in different ways by cancer treatments (Meistrich 2009, Shalet 2009, Sklar 1999). In the ovary, follicle is the site where the production of sex hormones and germ cells takes place. As a result, when ovarian failure occurs, both sex hormone production and fertility are disrupted. Germ cells in the ovary unlike spermatogonial cells lack the ability of repopulation. Preliminary stages of oogenesis are completed shortly after birth, the dominant part of the cell population in ovary being oocytes in the stationary stage of prophase. Older age is an important risk factor for ovarian failure following childhood