Ovarian function following targeted anti-angiogenic therapy with bevacizumab

Abstract

Improvements in cancer therapy have enabled further insight into the long-term effects of treatment, including the highly prevalent gonadal failure. The focus of treatment has been shifted to the preservation of fertility, which may be achieved by preventing ovarian toxicity. To this end, new molecular-targeted agents, including monoclonal antibodies, have been developed and used in a standard procedure for managing different cancers. However, the prolonged antitumor activity of these drugs may cause the emergence of new toxic effects. The aim of the present review was to discuss the leading toxic effect of the anti-angiogenic agent bevacizumab on ovarian function in female patients of reproductive age, which may be observed and expected during in clinical practice. The majority of bevacizumab-induced side effects are expected to be transient and eliminated within the anticipated drug clearance time frame; however, fundamental investigations on these effects are required for generating more evidence-based practice guidelines.

Keywords: anti-angiogenic chemotherapy; bevacizumab; female reproduction; ovarian damage.

Figure 1.

Follicular growth and VEGF. The oocyte is surrounded by granulosa cells, which are separated from an outer layer of theca cells by an intervening basal lamina. LH surge triggers maturation and ovulation of the oocyte and theca cell differentiation to corpus luteum. VEGF and its receptor are expressed in granulosa cells and theca cells in response to gonadotropins, namely FSH and LH. The expansion of the angiogenic networks during follicular development enhances oxygenation and diffusion of several substances important for follicle cells, promoting oocyte maturation. VEGF, vascular endothelial growth factor receptor; LH, luteinizing hormone; FSH, follicle-stimulating hormone.