Neurosteroids

神经类固醇
  • 文章类型: Journal Article
    未经证实:慢性压力是早产的危险因素;然而,孕期压力的客观测量是有限的。母体压力生物标志物可以填补这一空白。类固醇激素和神经类固醇如异孕烷醇酮(ALLO)在应激生理和妊娠维持中起重要作用,因此可能有希望用于早产预测。
    未经批准:我们评估了母体血清ALLO,黄体酮,皮质醇,可的松,孕烷醇酮,和孕孕孕酮两次评估与早产的关系。
    UNASSIGNED:我们进行了一项巢式病例对照研究,使用了HealthyStart早产队列中生物样本的空腹血清样本。我们纳入了单胎妊娠的健康女性和足月对照的早产病例(1:1;每组N=27)。我们使用了一种新的HPLC-串联质谱测定法来定量ALLO和五种相关的类固醇。我们用方差分析,费希尔确切,χ2,t检验,以及线性和逻辑回归作为统计检验。
    UNASSIGNED:孕妇血清ALLO与早产无关,组间也无差异。妊娠早期早产组的平均皮质醇水平显着升高(13w0d-18w0d;P<0.05),并且妊娠早期皮质醇升高与早产几率增加有关(在13w0d;比值比,1.007;95%CI,1.0002-1.014)。孕酮,可的松,孕烷醇酮,和表孕烷酮与早产无关。
    UNASSIGNED:我们的初步研究结果表明,皮质醇作为孕妇血清生物标志物在妊娠早期早产风险评估中的潜在用途。对于ALLO和其他分析物,使用更大的群组和额外的妊娠时间点的进一步评估可能是有益的。
    UNASSIGNED: Chronic stress is a risk factor for preterm birth; however, objective measures of stress in pregnancy are limited. Maternal stress biomarkers may fill this gap. Steroid hormones and neurosteroids such as allopregnanolone (ALLO) play important roles in stress physiology and pregnancy maintenance and therefore may be promising for preterm birth prediction.
    UNASSIGNED: We evaluated maternal serum ALLO, progesterone, cortisol, cortisone, pregnanolone, and epipregnanolone twice in gestation to evaluate associations with preterm birth.
    UNASSIGNED: We performed a nested case-control study using biobanked fasting serum samples from the Healthy Start prebirth cohort. We included healthy women with a singleton pregnancy and matched preterm cases with term controls (1:1; N = 27 per group). We used a new HPLC-tandem mass spectrometry assay to quantify ALLO and five related steroids. We used ANOVA, Fisher exact, χ2, t test, and linear and logistic regression as statistical tests.
    UNASSIGNED: Maternal serum ALLO did not associate with preterm birth nor differ between groups. Mean cortisol levels were significantly higher in the preterm group early in pregnancy (13w0d-18w0d; P < 0.05) and higher early pregnancy cortisol associated with increased odds of preterm birth (at 13w0d; odds ratio, 1.007; 95% CI, 1.0002-1.014). Progesterone, cortisone, pregnanolone, and epipregnanolone did not associate with preterm birth.
    UNASSIGNED: The findings from our pilot study suggest potential utility of cortisol as a maternal serum biomarker for preterm birth risk assessment in early pregnancy. Further evaluation using larger cohorts and additional gestational timepoints for ALLO and the other analytes may be informative.
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  • 文章类型: Journal Article
    Objective No single drug is broadly efficacious in the long-term treatment of fibromyalgia syndrome (FMS). Spironolactone is known to ameliorate mood and tension headache or migraine in women with premenstrual syndrome or clinical signs of hyperandrogenism. In a case series of women with treatment resistant FMS spironolactone was therefore added to their medication, and they were observed for at least 12 months. Methods 31 women with treatment-resistant FMS received spironolactone as add-on medication to various pain modulating drugs. 15 women responded to spironolactone and baseline data were compared with assessments over 12-14 months on treatment with spironolactone (ALDACTONE®) in dose range 100-200 mg/day. The efficacy was evaluated by the fibromyalgia impact questionnaire (FIQ) total score and 8 FIQ subtests, a German mood inventory (BSKE-EWL), and further assessments of changes in relevant psychological and physical complaints. 16 women had no effect and stopped the treatment early. Results The subsequent data refer to the 15 responders. The FIQ total score (maximal score = 80) decreased from 56.6 ± 10.0 at baseline to 17.1 ± 11.9 (mean ± SD) 12-14 months later, and pain intensity on an 11 point numeric rating scale (NRS) decreased from 8.8 ± 1.6 to 2.6 ± 1.9 (mean ± SD). Similar changes in FIQ subscores were found for fatigue, morning tiredness, stiffness, anxiety, and depression. Emotional functioning consistently improved: positive mood from 20.0 ± 5.4 to 37.7 ± 5.4 (maximal score = 48), and negative mood from 35.4 ± 5.3 to 10.0 ± 4.4 (maximal score = 60) (each mean ± SD) as well as other mental and physical dysfunctions including non-restorative sleep. All these changes at 4-6 weeks remained on this level for 11-13 months. The drug was well-tolerated and safe, no serious adverse effects were observed. Regular monitoring of serum potassium did not reveal hyperkalemia. All 15 women were able to reduce or discontinue concomitant drugs. Conclusion Fifteen of 31 women with otherwise treatment-resistant FMS experienced a number of prolonged beneficial effects from spironolactone on their complex pain-condition. Implications and discussion We hypothesise that spironolactone affects several central and peripheral neurotransmitter systems such as γ-aminobutyric acid (GABA) activity and dopaminergic transmission. The high rate of non-responsive patients underlines that FMS may represent several subgroups. Pain relief and improvement of associated FHS-symptoms and positive effects on additional diseases or dysfunctions give reasons for marked and sustained improvement in the quality of life. Well-controlled, double-blind, and randomised trials are necessary to confirm our potentially very important observations.
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