Gonadal dysfunction and fertility problems in cancer survivors

Abstract

Gonadal dysfunction and fertility problems are adverse effects of cancer treatment or may be associated with specific malignancies. This review focuses on these problems in the young cancer survivors, where methods of protecting or restoring endocrine function and fertility need to be considered. In females, treatment adverse effects can result in infertility, but premature ovarian failure (POF) is probably relevant for more female cancer survivors, affecting also those who do not wish post-treatment parenthood. POF affects present and future health, especially through oestrogen deficiency symptoms and an increased risk of developing osteoporosis. A lower risk of developing POF has been considered in young females than in older due to a larger pool of oocytes. However, a recent long-term follow-up study reported a prevalence of POF in young females with Hodgkin's lymphoma of 37% showing that young age at time of treatment only delays the development of POF. In male gonads, germ cells are much more sensitive to irradiation and chemotherapy than Leydig cells. Thus, infertility is a more common adverse effect than hypogonadism. Some malignancies are particular relevant. Persistent azoospermia was formerly common after treatment for Hodgkin's lymphoma, but currently, most patients recover spermatogenesis. Modern treatment of childhood acute lymphoblastic leukemia is also unlikely to cause infertility. Norwegian testicular cancer survivors diagnosed in 1980–1994 who attempted conception had an overall 15-year actuarial post-treatment paternity rate of 71% (range 48–92% depending on the treatment). However, the rate was significantly higher among men diagnosed in1989–1994 (over 80%) than in 1980–1988 (about 63%). Patients at risk for hypogonadism and infertility should be defined prior to treatment, and available methods for gonadal preservation should maximally be utilised. During follow-up, oncologists should routinely address these issues.