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Human Reproduction Update Advance Access published online on January 11, 2006
Human Reproduction Update, doi:10.1093/humupd/dmi054
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 13, 2005
Revised October 31, 2005
Accepted November 30, 2005

Article

Low-dose flutamide-metformin therapy for hyperinsulinemic hyperandrogenism in non-obese adolescents and women

Lourdes Ibáñez 1 * and Francis de Zegher 2

1 Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
2 Department of Woman and Child, University of Leuven, Leuven, Belgium

* To whom correspondence should be addressed.
Lourdes Ibáñez, E-mail: libanez{at}hsjdbcn.org


  Abstract

Polycystic ovary syndrome (PCOS) is a variable disorder that is characterized in adolescents and young women by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity and low-grade inflammation. At present, there is no approved therapy for PCOS. Recent studies indicate that a low-dose combination of flutamide (Flu; a generic androgen-receptor blocker) and metformin (Met; a generic insulin-sensitizer) normalizes the adolescent PCOS spectrum more than an oral contraceptive (OC); in young women, the PCOS spectrum was found to be more normalized by OC plus Flu-Met than by OC alone. Within the pathophysiological cascade of PCOS, Flu-Met seems to counter upstream anomalies like hyperinsulinemia or hyperandrogenism, thereby preventing or reversing downstream effects. In contrast, an OC essentially masks downstream symptoms like hirsutism, acne or irregular menses, whereas the upstream aberrations remain unaltered or may even be worsened. The available experience with Flu-Met is limited but promising. We emphasize that Flu-Met may (as part of its efficacy) induce ovulation but is contra-indicated post-conception because of potential embryotoxicity; therefore, it seems wise to combine Flu-Met with an oral or a transdermal oestro-progestagen or with a non-endocrine method of contraception. May this update prompt further research into Flu-Met’s therapeutic potential in patients with PCOS. Until the abovementioned effects have been broadly confirmed, Flu-Met should not be regarded as a standard therapy for widespread clinical practice.

Keywords: drospirenone/flutamide/metformin/oral contraception/polycystic ovary syndrome.
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