Flutamide-metformin plus ethinylestradiol-drospirenone for lipolysis and antiatherogenesis in young women with ovarian hyperandrogenism: the key role of metformin at the start and after more than one year of therapy.
Flutamide (Flu)-metformin (Met) with ethinylestradiol-drospirenone is a combination therapy that reduces the total and abdominal fat excess, diminishes the lean mass deficit, and attenuates the dysadipocytokinemia of young and nonobese women with ovarian hyperandrogenism, a variant of polycystic ovary syndrome. We have now questioned the need: 1) to add Met at the start of Flu plus ethinylestradiol-drospirenone; and 2) to maintain Met after more than 1 yr on full combination therapy. The additive effects of Met (850 mg/d) were assessed in studies A and B, over 3 months, in young patients with hyperinsulinemic hyperandrogenism. In study A, all participants [n = 31; age approximately 16 yr; body mass index approximately 22 kg/m(2)] started on Flu (62.5 mg/d) and an oral contraceptive (ethinyl-estradiol + drospirenone), and they were randomized to receive Met in addition or not. In study B, all participants (n = 42; age approximately 19 yr; body mass index approximately 22 kg/m(2)) had been treated with Flu-Met plus the same contraceptive for a mean duration of 17 months, and they were randomized for discontinuation of Met or not. Fasting blood glucose, serum insulin, testosterone, lipid profile, adiponectin, and IL-6 were determined at the start and after 3 months, together with body composition, by dual energy x-ray absorptiometry. The results of studies A and B complemented each other; the addition of Met was found to have consistently (more) normalizing effects on IL-6 and adiponectin, on lean mass (mean Met benefit of +1.2 kg in study A and +0.6 kg in study B), and in particular on abdominal fat excess [Met benefit of -0.7 kg (A) and -0.3 kg (B)]. In conclusion, Met proved to be a pivotal component of a prime combination therapy that attenuates the dysadipocytokinemia, the lean mass deficit, and the central adiposity of young patients with polycystic ovary syndrome.
Ibáñez
Lourdes
L
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain. libanez@hsjdbcn.org
de Zegher
Francis
F
D000293:Adolescent; D000328:Adult; D000736:Androstenes / Q000008:administration & dosage*; D001161:Arteriosclerosis / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D005485:Flutamide / Q000008:administration & dosage*; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy*; D008066:Lipolysis / Q000187:drug effects*; D008687:Metformin / Q000008:administration & dosage*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy*; D013997:Time Factors
D000736:Androstenes; D004997:Ethinyl Estradiol; D005485:Flutamide; D008687:Metformin; C035144:drospirenone