Low-Dose Pioglitazone-Flutamide-Metformin Combination Benefits Adolescent Girls With Androgen Excess: Presented at ENDO
By Cheryl Lathrop
BOSTON -- June 7, 2011 -- A low-dose combination of pioglitazone, flutamide, and metformin (PioFluMet) may become a first-choice therapy for adolescent girls and young women with androgen excess and without pregnancy risk, researchers stated here at the 93rd Annual Meeting of the Endocrine Society (ENDO).
The combination therapy has been found to normalise the endocrine-metabolic profile in young hyperandrogenic women concomitantly receiving an oestro-progestagen, stated Lourdes Ibanez, MD, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain, speaking at a poster session here on June 5.
The effects of PioFluMet include a decrease in visceral adiposity, a less pro-inflammatory state, and a more favourable adipokine profile than that seen with a commonly prescribed oral contraceptive containing an anti-androgenic progestagen such as ethinylestradiol-cyproterone acetate (EE-CA).
This study compared the effects of EE-CA (Diane 35 Diario, 35 mcg of ethinylestradiol plus 2 mg of cyproterone acetate) to those of a combination of pioglitazone (7.5 mg/d), flutamide (62.5 mg/d), and metformin (850 mg/d) in 34 adolescent girls with androgen excess and without pregnancy risk.
All subjects (mean age 16 years, body mass index 23 kg/m2) were randomised to receive EE-CA (n = 17) or low-dose PioFluMet (n = 17) for 6 months.
The following data were collected at 0 and 6 months:
· Anti-androgenic efficacy (hirsutism and acne scores; circulating testosterone, androstenedione, and 5-Dehydroepiandrosterone [5-DHEA]),
· Body composition (by absorptiometry and abdominal magnetic resonance imaging),
· Carotid intima-media thickness (cIMT), and
· High-sensitivity C-reactive protein (hsCRP).
Circulating levels of aspartate aminotransferase and alanine transaminase were measured at 0, 2, and 6 months.
Anti-androgenic benefits were similar between the 2 treatment groups. Most girls on PioFluMet developed regular menses within 6 months. All divergences between the treatment groups were to the advantage of low-dose PioFluMet, since it was associated with development of a leaner body composition, a lower cIMT, and lower hsCRP levels.
Divergent effects also were observed on measures of insulin resistance; circulating insulin-like growth factor 1, cholesterol, triglycerides, hsCRP, high molecular weight adiponectin, leptin, and follistatin, as well as on cIMT, lean mass, and abdominal, visceral, and hepatic fat.
Transient ALT elevations were observed in 2 girls on EE-CA and in none on low-dose PioFluMet.
Ovarian androgen excess is the most prevalent endocrinopathy of adolescent girls, often presenting with acne, hirsutism, or irregular menses.
[Presentation title: EthinylEstradiol-Cyproterone Acetate vs Pioglitazone-Flutamide-Metformin in Adolescent Girls With Androgen Excess. Abstract 247]