How do chemotherapeutic agents damage the ovary?
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.
Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh EH8 9XD, UK.
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Morgan
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Anderson
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Gourley
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Wallace
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Spears
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D059247:Fertility Preservation / Q000379:methods; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D009865:Oocytes / Q000187:drug effects / Q000473:pathology; D006080:Ovarian Follicle / Q000187:drug effects / Q000473:pathology; D010053:Ovary / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced* / Q000517:prevention & control*; D011446:Prospective Studies
D000970:Antineoplastic Agents; D007987:Gonadotropin-Releasing Hormone