Except for the bone marrow, the most sensitive organs to radiation therapy in the body are the gonads, both the male testis and the female ovary. The extent of damage in the female and male gonads depends on the dose, fractionation schedule and irradiation field. Radiation therapy can be administered as teletherapy, which aims at treating a large volume of tissue. For small volumes of tissue, such as in the case of cervix cancer in the female, radiation therapy can be administered in encapsulated sources of radiation that can be implanted directly into or adjacent to tumor tissue. Whenever female reproductive organs are involved in the irradiated field, i.e., the ovaries, the uterus and the vagina may be compromised and damaged by direct irradiation. Scattered radiation may also damage reproductive organs.
In the female, radiation therapy results in dose-related damage of the gonads by the destruction of primordial follicles, which constitute the nonrenewable follicle pool. In women, the degree and persistence of the damage is also influenced by age at the time of exposure to radiotherapy and due to a reduced reserve of primordial follicles in older women, the number of follicles remaining may be also be reduced at older ages. Table 1 presents a compilation of current knowledge on the impact of radiation doses and age at radiotherapy in male and female gonadal function. In general, a dose of about 2 Gy (Gray - a derived unit of ionizing radiation) applied to the gonadal area destroys up to 50 % of the ovarian follicle reserve. In pediatric patients, failure in pubertal development may be the first sign of gonadal failure in both sexes. Total body irradiation (TBI) given in conjunction with myeloablative conditioning prior to bone marrow transplantation is one of the most toxic treatments for the gonads and it is highly related to gonadal failure in both sexes.
In men, the gonadal stem cells responsible for the continual differentiation and production of mature spermatozoa, the spermatogoniae, are extremely sensitive to radiation. The Leydig cells, which are responsible for the hormonal production of testosterone, are on the contrary more resistant to radiotherapy and adult patients may thus preserve hormonal production although becoming infertile. In prepubertal boys, the sensitivity to radiation therapy of Leydig cells is greater than that of older males at very high doses. Prepubertal patients may retain Leydig cell function after radiation therapy during childhood and in those cases they will present with normal pubertal development and well-preserved sexual function later in life. Nevertheless, most of those patients present at adulthood with reduced testicular size, impaired spermatogenesis and infertility.