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Hum. Reprod. Advance Access published online on October 20, 2005
Human Reproduction, doi:10.1093/humrep/dei329
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© The Author 2005. 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 July 22, 2005
Revised September 6, 2005
Accepted September 7, 2005

Article

Discontinuous low-dose flutamide-metformin plus an oral or a transdermal contraceptive in patients with hyperinsulinaemic hyperandrogenism: normalizing effects on CRP, TNF-{alpha} and the neutrophil/lymphocyte ratio

Lourdes Ibáñez 1*, Carme Valls 2, and Francis de Zegher 3

1 Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
2 Hormonal Laboratory, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
3 Department of Pediatrics, University of Leuven, Leuven, Belgium

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


  Abstract

BACKGROUND: Low-dose flutamide-metformin (Flu-Met) with an oral contraceptive is a therapeutic option for women with hyperinsulinaemic hyperandrogenism. We questioned (i) whether Flu-Met maintains efficacy if given discontinuously; (ii) how the efficacy of discontinuous Flu-Met plus a transdermal contraceptive compares with Flu-Met plus oral contraceptive; and (iii) whether these treatments also lower circulating C-reactive protein (CRP) and tumour necrosis factor {alpha} (TNF-{alpha}) and the high neutrophil/lymphocyte ratio. METHODS: Non-obese, young patients (n = 31) with hyperinsulinaemic hyperandrogenism were started on Flu-Met (21/28 days) and randomized to receive in addition either a drospirenone oral contraceptive or a transdermal contraceptive for 6 months. RESULTS: The effects of Flu-Met were similar whether combined with oral or transdermal contraceptive. In both groups, CRP and TNF-{alpha} levels fell and the high neutrophil/lymphocyte ratio normalized (P < 0.001). Lean body mass increased (P < 0.001) in both groups but, in contrast to earlier experience with continuous Flu-Met, fat mass failed to decrease in either group. CONCLUSIONS: Flu-Met seems less lipolytic, if given for only 21 days in every 28-day period. The efficacy of Flu-Met is comparable when combined with an oral contraceptive or a transdermal contraceptive. The range of Flu-Met effects may henceforth include lower levels of CRP and TNF-{alpha}, and a normalization of the neutrophil/lymphocyte ratio.

Keywords: contraception/CRP/flutamide--metformin treatment/hyperinsulinaemic hyperandrogenism/PCOS.
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