A low-dose combination of
flutamide-
metformin and ethinylestradiol-
drospirenone was recently found to reduce the excess of total and abdominal fat, to diminish the deficit in lean mass, and to attenuate the dysadipocytokinemia of young women with ovarian
hyperandrogenism, a variant of
polycystic ovary syndrome. We questioned the need to give
flutamide, an
androgen receptor blocker, together with an
oral contraceptive that contains
drospirenone, a
progestin claimed to have
antiandrogen properties. The additive effects of low-dose
flutamide (62.5 mg/d) were assessed over 3 months in young patients with hyperinsulinemic ovarian
hyperandrogenism (n = 40; age, approximately 17 yr; body mass index, approximately 22 kg/m(2)); all participants started on
metformin (850 mg/d) and a fourth-generation
contraceptive (ethinylestradiol 30 microg plus
drospirenone 3 mg, 21 d/month), and they were randomized to receive
flutamide in addition (n = 20) or not (n = 20). Fasting
blood glucose, serum
insulin,
lipid profile,
testosterone,
adiponectin, and
IL-6 were determined at baseline and after 3 months, together with body composition (by dual x-ray absorptiometry) and with Doppler assessment of ovarian arterial resistance. At start, the pulsatility and resistance indices of ovarian arteries were elevated. By comparison of 3-month changes between randomized subgroups, the addition of low-dose
flutamide was found to have consistently (more) normalizing effects on
low-density lipoprotein cholesterol,
IL-6, and
adiponectin, lean body mass, total and abdominal fat mass, and arterial flow in the ovaries. In conclusion, low-dose
flutamide is herewith identified as a pivotal component within a first
contraceptive combination
therapy that has been shown to attenuate the
hypoadiponectinemia, ovarian vascular hyperresistance, lean mass deficit, and central adiposity of young women with
polycystic ovary syndrome. Finally, these data challenge any claim that
drospirenone, as currently used in a
contraceptive, is a clinically significant
antiandrogen.