在使用地塞米松抑制肾上腺类固醇生成之前进行 GnRH 激动剂刺激试验后,高雄激素性多囊卵巢综合症非 PCOS 妇女与多囊卵巢综合症妇女的对比情况

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM Journal of Clinical and Translational Endocrinology Pub Date : 2024-09-01 DOI:10.1016/j.jcte.2024.100368
Salvatore Benvenga , Michele Russo , Gianpiero Forte , Vittorio Unfer
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引用次数: 0

摘要

多囊卵巢综合症(PCOS)这一主题在文献中已有大量论述,但有关无超声波显示 PCO 形态的高雄激素和/或高雄激素血症(EuHyperA)的无月经妇女的数据却很少,而有关 PCOS 和 EuHyperA 受试者之间的比较数据就更少了。以前的研究表明,约有一半的多囊卵巢综合症妇女在 GnRH 激动剂的刺激下会出现血清 17- 羟孕酮(17-OHP)的高反应,这也被称为功能性卵巢高雄激素症(FOH)。通常,在进行这种刺激试验之前,先用口服地塞米松(Dex)抑制肾上腺类固醇的生成。FOH 与胰岛素水平升高导致卵巢中 P450c17 活性增加有关。在这项回顾性研究中,我们纳入了 15 名高反应者(HR)EuHyperA、34 名正常反应者(NR)EuHyperA、62 名 HR-PCOS 和 45 名 NR-PCOS。分析了人口统计学特征、糖代谢指数以及对地塞米松或丁螺环酮的激素反应,并进行了组内和组间比较。与HR-PCOS相比,HR-EuHyperA的[i.]观察年龄明显较大;[ii.]皮质醇、17-OHP、Δ4-雄烯二酮(Δ4-ASD)、总睾酮(TT)、LH以及丁螺环酮刺激的硫酸脱氢表雄酮(DHEAS)、17-OHP、Δ4-ASD和TT的整体曲线均较低。与 NR-PCOS 相比,NR-EuHyperA 的[i.]FSH 和 buserelin 刺激的 DHEAS 整条曲线明显增加;[ii.]HD 后 Dex Δ4-ASD、TT、buserelin 刺激的 17-OHP、Δ4-ASD 和 TT 整条曲线明显减少。与 NR-PCOS 相比,HR-PCOS 的 [i.胰岛素抵抗的稳态模型评估(HOMA-IR)、皮质醇、DHEAS、Δ4-ASD、TT、FT、FAI、E2 和口服葡萄糖耐量试验(OGTT)中的胰岛素 AUC0-120min(曲线下面积)均明显增加;[ii]LD后和HD后Dex 17-OHP、Δ4-ASD、TT、HD后Dex DHEAS(水平越高表明肾上腺抑制越弱)、DHEAS、17-OHP、Δ4-ASD、TT和LH的整体曲线水平越高;[iii]性激素结合球蛋白(SHBG)显著降低。尽管在两组比较中评估的大多数参数在统计学上相似,但还是观察到了有趣的差异。患有多囊卵巢综合症的妇女在基线、肾上腺素抑制后和丁螺环酮试验中都表现出较高的雄激素水平,进一步导致卵巢体积增大。值得注意的是,与 EuHyperA 妇女相比,多囊卵巢综合症妇女组中 HOMA-IR≥2.5 的百分比和血清胰岛素水平更高。此外,在多囊卵巢综合症妇女中,与 NR 亚组相比,在进行 OGTT 时,HR 亚组的胰岛素水平更高。葡萄糖-胰岛素平衡的改变和循环雄激素的升高在多囊卵巢综合征中更为明显,这表明[i.]代谢改变可能是多囊卵巢综合征发病的关键因素,[ii]EuHyperA 可能代表了一种较轻的多囊卵巢综合征。
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Hyperandrogenic eumenorrheic NON-PCOS women versus women with PCOS after the GnRH-agonist stimulation test preceded by suppression of adrenal steroidogenesis with dexamethasone

The subject of polycystic ovary syndrome (PCOS) has been extensively covered in the literature; however, there is a paucity of data regarding eumenorrheic women with hyperandrogenism and/or hyperandrogenemia without ultrasound evidence of PCO morphology (EuHyperA), and even less data on the comparison between PCOS and EuHyperA subjects. It has previously been shown that around half of PCOS women exhibit a hyper-response of serum 17-hydroxy-progesterone (17-OHP) to the stimulation by GnRH-agonists, also indicated as functional ovarian hyperandrogenism (FOH). Often, this stimulation test is preceded by suppression of the adrenal steroidogenesis with oral dexamethasone (Dex). FOH has been associated with an increase of the P450c17 activity in the ovaries driven by elevated insulin levels. Interestingly, treatment of women with PCOS with Dex suppression and GnRH-agonist stimulation (buserelin) highlighted the possible existence of two clusters of patients: hyper-responders (HR) and normal responders (NR).

In this retrospective study, we included 15 hyper-responders (HR) EuHyperA, 34 normal responders (NR) EuHyperA, 62 HR-PCOS and 45 NR-PCOS. The demographic characteristics, glucose-metabolism indices, and the hormonal response to Dex or buserelin were analyzed, with both intra-group and inter-group comparisons performed.

The rate of FOH was significantly greater in PCOS than EuHyperA women. Compared to HR-PCOS, HR-EuHyperA had [i.] significantly greater age at observation; [ii.] lower cortisol, 17-OHP, Δ4-androstenedione (Δ4-ASD), total testosterone (TT), LH, and buserelin-stimulated whole curve of dehydroepiandrosterone sulfate (DHEAS), 17-OHP, Δ4-ASD and TT. Compared to NR-PCOS, NR-EuHyperA had [i.] significantly greater FSH, and buserelin-stimulated whole curve of DHEAS; [ii.] significantly lower post-HD Dex Δ4-ASD, TT, buserelin-stimulated whole curve of 17-OHP, Δ4-ASD and TT. Compared to NR-PCOS, HR-PCOS had [i.] significantly greater body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA-IR), cortisol, DHEAS, Δ4-ASD, TT, FT, FAI, E2, and insulin AUC0-120min (area under the curve) at oral glucose tolerance test (OGTT); [ii] higher levels of post-LD and post-HD Dex 17-OHP, Δ4-ASD, TT, post-HD Dex DHEAS (with greater levels indicating weaker adrenal suppression), whole curve of DHEAS, 17-OHP, Δ4-ASD, TT and LH; [iii] significantly lower sex-hormone binding globulin (SHBG).

Even if most of the parameters evaluated were statistically similar in the two sets of comparisons, interesting differences were observed. Women with PCOS exhibit higher androgen levels at baseline, after adrenal suppression and at the buserelin test, further to a higher ovarian volume. Of note, the percentage of women with HOMA-IR≥2.5 and serum insulin levels were greater in PCOS group compared to EuHyperA women. Moreover, within women with PCOS, the HR subgroup has higher insulin levels compared to the NR subgroup, when OGTT is performed. The alteration of the glucose-insulin balance and elevation of circulating androgens were more pronounced in PCOS, thus indicating that [i.] metabolic alterations might be crucial in the onset of PCOS itself and, [ii] EuHyperA might represent a milder form of PCOS.

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