JCEM：青少年胰岛素增敏治疗可预防成年雄激素过多的表型

EE-CA和PioFluMet治疗中和治疗后CRP、CIMT、内脏脂肪和MSI变化

口服雌孕激素是少女雄激素过多的标准治疗，即使当这些女孩没有妊娠的风险。为了比较口服避孕药与胰岛素增敏治疗干预非肥胖青少年，在治疗中和治疗后对雄激素过多的影响，来自巴萨罗那大学Sant Joan de Deu医院内分泌科的Lourdes Ibanez教授及其团队进行了一项研究，该研究发现青少年胰岛素增敏治疗干预有可能预防成年部分雄激素过多表型。该研究结果在线发表在2012年4月1日的美国《临床内分泌代谢杂志》（The journal of clinical endocrinology & metabolism）上。
该研究是一项随机非盲试验，受试者是高胰岛素血症和雄激素过多的非肥胖少女，且没有妊娠的风险（34例；平均年龄16岁；体重指数：23kg/m2）。研究比较炔雌醇醋酸环丙孕酮（EE-CA）与小剂量吡咯列酮（7.5mg/d）、氟他米特（62.5mg/d）和二甲双胍（850mg/d）联合（PioFluMet）治疗18个月的疗效。治疗后随访6月。测量雄激素过多（多毛症、痤疮分数和血清睾酮），葡萄糖刺激后胰岛素，循环C反应蛋白，颈动脉内膜中层厚度，身体组成（吸收测量法），腹部脂肪分区（磁共振成像）和月经周期。
该研究结果表明，EE-CA和PioFluMet同样缓解雄激素过多，但有差异，以致影响其他结果。治疗后6个月，PioFluMet治疗的女孩比EE-CA治疗的女孩有更低的葡萄糖刺激后胰岛素，更低的C反应蛋白水平和更薄的内膜中层，并且他们的内脏脂肪较少，具有更高的瘦体重，以及更有可能有规律的月经周期。
该研究发现，在非肥胖的雄激素过多的青少年，PioFluMet治疗中和治疗后的疗效比口服避孕药的好。干预依靠青少年雄激素过多的降低影响治疗后的表型。在青少年，PioFluMet相似的干预有可能预防成年部分雄激素过多的表型，包括肥胖和生育能力低下。
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Oral Contraception vs Insulin Sensitization for 18 Months in Nonobese Adolescents With Androgen Excess: Posttreatment Differences in C-Reactive Protein, Intima-Media Thickness, Visceral Adiposity, Insulin Sensitivity, and Menstrual Regularity
Background
An oral estro-progestagen is the standard medication given to adolescent girls with androgen excess, even when those girls are not at risk of pregnancy.
Aim
The aim of this study was to compare on-treatment and post-treatment effects of intervention with an oral contraceptive vs an insulin-sensitizing treatment for androgen excess in nonobese adolescents.
Design
This was a randomized, open-label trial.
Study Population
Subjects were nonobese adolescent girls with hyperinsulinemic androgen excess and without risk of pregnancy (mean age, 16 years; body mass index, 23 kg/m2; n = 34).
Interventions
The effects of treatment with ethinylestradiol-cyproteroneacetate (EE-CA) vs a low-dose combination of pioglitazone (7.5 mg/d), flutamide (62.5 mg/d), and metformin (850 mg/d) (PioFluMet) for 18 months were studied. Posttreatment follow-up was for 6 months.
Main Outcome Measures
Androgen excess (hirsutism and acne scores and serum testosterone), glucose-stimulated insulinemia, circulating C-reactive protein, carotid intima media thickness, body composition (absorptiometry), abdominal fat partitioning (magnetic resonance imaging), and menstrual regularity were measured.
Results
EE-CA and PioFluMet attenuated androgen excess similarly but had divergent, and even opposing, effects on other outcomes. Six months posttreatment, the PioFluMet-treated girls had a lower glucose-induced insulinemia, a lower C-reactive protein level, and a thinner intima media than the EE-CA–treated girls, and they were viscerally less adipose, had a higher lean mass, and were more likely to have regular cycles.
Conclusions
The on-treatment and post-treatment effects of PioFluMet compared favorably with those of oral contraception in nonobese adolescents with androgen excess. The intervention whereby androgen excess is reduced in adolescence influences the post-treatment phenotype. PioFluMet-like interventions in adolescence may thus hold the potential to prevent part of the androgen-excess phenotype in adulthood, including adiposity and subfertility.