Pioglitazone (7.5 mg/day) added to flutamide-metformin in women with androgen excess: additional increments of visfatin and high molecular weight adiponectin.
OBJECTIVE
Low-dose pioglitazone (Pio), flutamide (Flu), metformin (Met) plus an oestro-progestagen is a novel polytherapy lowering total and visceral adiposity, and reducing carotid intima media thickness (IMT) in hyperinsulinaemic women with androgen excess, without changing their body mass index (BMI). In a search for mediators of PioFluMet's actions, we measured serum levels of visfatin and high molecular weight (HMW) adiponectin.


METHODS
In a double-blind study, we enrolled 38 young women with hyperinsulinaemic androgen excess [mean BMI: 23.7 kg/m(2)], all of whom started on Flu (62.5 mg/day), Met (850 mg/day) and a transdermal oestro-progestagen, each for 21/28 days over 1 year. Patients were randomly assigned to receive, in addition, placebo (n = 19) or Pio (7.5 mg/day; n = 19) on the same 21/28 days.


METHODS
Serum concentrations of visfatin and HMW adiponectin, visceral fat by magnetic resonance imaging, carotid IMT by ultrasound, all carried out during study start and after 1 year.


RESULTS
PioFluMet raised visfatin by a mean 84% and HMW adiponectin by 157% (P < 0.001), and reduced visceral fat and IMT by a mean 22% and 31% (both P < 0.001). Low-dose Pio accounted for about half of the PioFluMet effects on IMT, visfatin and HMW adiponectin.


CONCLUSIONS
In hyperinsulinaemic women with androgen excess, low-dose polytherapy with PioFluMet evoked striking rises in both circulating visfatin and HMW adiponectin, while lowering IMT and reducing visceral adiposity within 1 year.
Ibáñez
Lourdes
L
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain. libanez@hsjdbcn.org
López-Bermejo
Abel
A
Díaz
Marta
M
Enríquez
Goya
G
Valls
Carme
C
de Zegher
Francis
F
D052242:Adiponectin / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005485:Flutamide / Q000627:therapeutic use*; D006801:Humans; D017588:Hyperandrogenism / Q000097:blood / Q000188:drug therapy*; D006946:Hyperinsulinism / Q000188:drug therapy*; D008687:Metformin / Q000627:therapeutic use*; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood / Q000627:therapeutic use*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D055815:Young Adult
D052242:Adiponectin; D045162:Thiazolidinediones; D005485:Flutamide; D008687:Metformin; D054409:Nicotinamide Phosphoribosyltransferase; D000077205:Pioglitazone