Is valproate pharmacotherapy associated with polycystic ovaries?

To review and evaluate the published data associating the use of valproate with the development of polycystic ovaries.

A computerized search of MEDLINE (1966-May 1999) and Current Contents was performed. Also, bibliographies were cross-referenced to yield additional pertinent publications. All articles written in English were considered for review.

All pertinent clinical studies and review articles associating valproate with polycystic ovaries and other endocrinologic disorders were evaluated.

Valproate is among the most commonly used medications today effective in the treatment of a variety of neurologic and psychiatric disorders. An accumulating body of literature has suggested an increase in the incidence of polycystic ovarian syndrome among women treated with valproate. The syndrome is characterized as hyperandrogenism and chronic anovulation in the absence of identifiable adrenal or pituitary pathology. It is a highly prevalent syndrome, affecting 2-22% of women in the general population.

Although a number of studies have found clear evidence of neuroendocrine perturbations in patients treated with valproate, there are presently limited data from large controlled studies involving valproate monotherapy. Nonetheless, there appears to be a greater incidence of polycystic ovaries associated with valproate use in comparison with other anticonvulsants. The mechanism by which valproate may induce polycystic ovarian syndrome is unknown, but could possibly be secondary to valproate-induced weight gain or direct interference with steroid metabolism. Further study of the potential association of valproate treatment with the development of polycystic ovarian syndrome is warranted. Until the issue is clarified, clinicians should at least be aware of the possibility of valproate-induced polycystic ovarian syndrome and monitor patients accordingly.