Hum. Reprod. Advance Access originally published online on October 20, 2005
Human Reproduction 2006 21(2):451-456; doi:10.1093/humrep/dei329
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Discontinuous low-dose flutamide–metformin plus an oral or a transdermal contraceptive in patients with hyperinsulinaemic hyperandrogenism: normalizing effects on CRP, TNF-
and the neutrophil/lymphocyte ratio
1 Endocrinology Unit and 2 Hormonal Laboratory, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain and 3 Department of Pediatrics, University of Leuven, Leuven, Belgium
4 To whom correspondence should be addressed: Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain. E-mail: libanez{at}hsjdbcn.org
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 
(TNF-) 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- 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-, and a normalization of the neutrophil/lymphocyte ratio.
Key words: contraception/CRP/flutamide–metformin treatment/hyperinsulinaemic hyperandrogenism/PCOS
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