How do chemotherapeutic agents damage the ovary?

Hum Reprod Update. 2012 Sep-Oct;18(5):525-35. doi: 10.1093/humupd/dms022. Epub 2012 May 30.

Abstract

Background: Chemotherapy treatment in premenopausal women is associated with an increased risk of premature ovarian failure (POF) but the exact mechanism through which this occurs is uncertain. In this review we examine the current evidence for the direct action of chemotherapeutic agents on the ovary and discuss possible molecular pathways through which follicle loss may occur.

Methods: A systemic search of the databases, PubMed and Google Scholar, was made for all English language articles through to 2011 in each subject area discussed.

Results: POF results from the loss of primordial follicles but this is not necessarily a direct effect of the chemotherapeutic agents. Instead, the disappearance of primordial follicles could be due to an increased rate of growth initiation to replace damaged developing follicles. Likewise, the loss of oocytes need not necessarily be a direct result of damage: evidence suggests that chemotherapy drugs can also induce oocyte death indirectly via damage to somatic cells. Specific molecular mechanisms and likely ovarian targets are discussed for some of the anti-cancer drugs most commonly used to treat premenopausal women. Finally, we consider current and prospective methods of preserving fertility.

Conclusions: It is likely that different chemotherapeutic drugs act through a range of mechanisms and on different target cells. More research into the cellular mechanisms underpinning chemotherapy-induced follicle loss could lead to the generation of treatments specifically designed to prevent POF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Female
  • Fertility Preservation / methods
  • Gonadotropin-Releasing Hormone / agonists
  • Humans
  • Oocytes / drug effects
  • Oocytes / pathology
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / pathology
  • Ovary / drug effects*
  • Ovary / pathology
  • Pregnancy
  • Primary Ovarian Insufficiency / chemically induced*
  • Primary Ovarian Insufficiency / prevention & control*
  • Prospective Studies

Substances

  • Antineoplastic Agents
  • Gonadotropin-Releasing Hormone