Low-dose pioglitazone, flutamide, metformin plus an estro-progestagen for non-obese young women with polycystic ovary syndrome: increasing efficacy and persistent safety over 30 months.
BACKGROUND
Therapy of androgen excess should not only confer cosmetic benefit, but also improve long-term markers of endocrine-metabolic and cardiovascular health. Here we report on our pilot experience with a low-dose polytherapy for 30 months. DESIGN, PATIENTS, INTERVENTION: Unblinded extension (24-30 months) of a double-placebo study exploring low-dose polytherapy over 24 months. Between 24 and 30 months, women with hyperinsulinemic androgen excess (N = 36; mean age: 19.4 year; BMI: 23.7 kg/m(2)) received metformin (850 mg/day), flutamide (62.5 mg/day), pioglitazone (7.5 mg/day), ethinylestradiol (20 μg/day) plus drospirenone (3 mg/day) for 24/28 days.


RESULTS
Carotid IMT, body composition (by absorptiometry), abdominal fat (by magnetic resonance), hirsutism score, fasting glycaemia, insulin, androgens, HDL cholesterol, C-reactive protein and hepatic safety indices.


RESULTS
Low-dose polytherapy for 30 months was not accompanied by a change in body weight or bone mineral density, but it was associated with a marked rise of insulin sensitivity (p < 0.00001), with a loss of visceral fat (mean: -27%; p < 0.00001) and with a lowering of IMT (-0.16 mm; p < 0.00001). Aspartate aminotransferase, gamma-glutamyl transferase and lactate dehydrogenase levels decreased slightly over 30 months.


CONCLUSIONS
Low-dose polytherapy (24/28 day) with pioglitazone, flutamide, metformin and estro-progestagen was found to improve, without changing weight, a spectrum of long-term health markers in young women with hyperinsulinemic androgen excess.
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
Del Río
Luis
L
De Zegher
Francis
F
D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D000728:Androgens / Q000097:blood; D000736:Androstenes / Q000008:administration & dosage*; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D005485:Flutamide / Q000008:administration & dosage*; D006801:Humans; D006836:Hydro-Lyases / Q000097:blood; D007328:Insulin / Q000097:blood; D008137:Longitudinal Studies; D008687:Metformin / Q000008:administration & dosage*; D000077205:Pioglitazone; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D045162:Thiazolidinediones / Q000008:administration & dosage*; D017539:Tunica Intima / Q000502:physiology; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood
D000728:Androgens; D000736:Androstenes; D001786:Blood Glucose; D007328:Insulin; D045162:Thiazolidinediones; C534342:drospirenone and ethinyl estradiol combination; D004997:Ethinyl Estradiol; D005485:Flutamide; D002097:C-Reactive Protein; D008687:Metformin; D002784:Cholesterol; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006836:Hydro-Lyases; C045581:lactate dehydratase; D000077205:Pioglitazone