Maternal PCOS status and metformin in pregnancy: Steroid hormones in 5-10 years old children from the PregMet randomized controlled study.
Maternal PCOS status and metformin in pregnancy: Steroid hormones in 5-10 years old children from the PregMet randomized controlled study.
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DOI：
10.1371/journal.pone.0257186
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Ødegård R
中科院分区：
文献类型：
--
作者：
Hanem LGE;Salvesen Ø;Madsen A;Sagen JV;Mellgren G;Juliusson PB;Carlsen SM;Vanky E;Ødegård R
多囊卵巢综合征（PCOS）是一种常见的内分泌疾病，对后代的遗传和宫内环境的改变有潜在的影响。二甲双胍，改善非怀孕妇女与PCOS的激素紊乱越来越多地用于怀孕。它通过胎盘，对后代内分泌发育的潜在后果的证据是稀缺的。我们探讨了母亲PCOS状态和宫内二甲双胍暴露对后代类固醇激素水平的潜在影响。这是一项5-10岁儿童的随访研究，来自PregMet研究-一项比较PCOS妊娠期间二甲双胍（2000 mg/天）与安慰剂的随机对照试验。在被邀请的255名儿童中，有117名（46%）被包括在内。本随访研究未进行干预。结果是雄烯二酮，睾酮，SHBG，皮质醇，17-羟孕酮，11-脱氧皮质醇的血清水平和计算的游离睾酮转换为性别和年龄校正的z分数从挪威参考人群。通过i）单样本t检验的z评分偏差比较安慰剂暴露儿童与参考人群儿童（z评分为零），以及ii）通过双样本t检验比较二甲双胍与安慰剂暴露儿童。进行Holm-Bonferroni调整以考虑多个终点。PCOS母亲的女孩（n = 30）雄烯二酮的平均z评分较高（0.73（95%置信区间（CI）0.41至1.06），p<0.0001），睾酮（0.76（0.51至1.00），p<0.0001）和游离睾酮（0.99（0.67至1.32），p<0.0001）。二甲双胍暴露男孩（n = 31）的11-脱氧皮质醇z评分往往高于安慰剂暴露男孩（n = 24）（平均差异0.65（95% CI 0.14-1.17），p = 0.014）。母亲的PCOS状态与5- 10岁女儿的雄激素升高有关，这可能表明早熟和发展PCOS的风险增加。不能排除妊娠期二甲双胍对PCOS母亲所生儿童类固醇生成的影响。我们的发现需要在包括已进入青春期的参与者的研究中得到证实。
Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with potential effects on offspring both genetically and through altered intrauterine environment. Metformin, which ameliorate hormonal disturbances in non-pregnant women with PCOS is increasingly used in pregnancy. It passes the placenta, and the evidence on potential consequences for offspring endocrine development is scarce. We explore the potential effects of maternal PCOS status and intrauterine metformin exposure on offspring steroid hormone levels. This is a follow-up study of 5–10 years old children from the PregMet-study–a randomized controlled trial comparing metformin (2000 mg/day) to placebo during PCOS pregnancies. Of the 255 children invited, 117 (46%) were included. There was no intervention in this follow-up study. Outcomes were serum levels of androstenedione, testosterone, SHBG, cortisol, 17-hydroxyprogesterone, 11-deoxycortisol and calculated free testosterone converted to gender-and age adjusted z-scores from a Norwegian reference population. These were compared in i) placebo-exposed children versus children from the reference population (z-score zero) by the deviation in z-score by one-sample t-tests and ii) metformin versus placebo-exposed children by two-sample t-tests. Holm-Bonferroni adjustments were performed to account for multiple endpoints. Girls of mothers with PCOS (n = 30) had higher mean z-scores of androstenedione (0.73 (95% confidence interval (CI) 0.41 to 1.06), p<0.0001), testosterone (0.76 (0.51 to 1.00), p<0.0001), and free testosterone (0.99 (0.67 to 1.32), p<0.0001) than the reference population. Metformin-exposed boys (n = 31) tended to have higher 11-deoxycortisol z-score than placebo-exposed boys (n = 24) (mean difference 0.65 (95% CI 0.14–1.17), p = 0.014). Maternal PCOS status was associated with elevated androgens in 5- to 10-year-old daughters, which might indicate earlier maturation and increased risk of developing PCOS. An impact of metformin in pregnancy on steroidogenesis in children born to mothers with PCOS cannot be excluded. Our findings need confirmation in studies that include participants that have entered puberty.
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影响因子：
5.8
作者：
Courant, Frederique;Aksglaede, Lise;Le Bizec, Bruno
通讯作者：
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DOI：
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