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

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.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.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 (P0.001). Lean body mass increased (P0.001) in both groups but, in contrast to earlier experience with continuous Flu-Met, fat mass failed to decrease in either group.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.