Neuroscience Division, University Medical Center Utrecht (UMCU) & Rudolf Magnus Institute for Neuroscience, Heidelberglaan 100, 3485CX Utrecht, Netherlands.
Schizophr Res. 2012 Nov;141(2-3):179-84. doi: 10.1016/j.schres.2012.08.016. Epub 2012 Sep 19.
Sex differences in the incidence, onset and course of schizophrenia have led to the hypothesis that estrogens play a protective role in the pathophysiology of this disorder. Several trials have assessed the potential of estrogens in reducing schizophrenia symptoms, showing inconsistent results. This quantitative review summarizes available evidence on the efficacy of estrogens in the treatment of schizophrenia.
Only double-blind, placebo-controlled, randomized studies were included. Primary outcome measure was total symptom severity, secondary outcome measures were subscores for positive and negative symptoms. Effect sizes were calculated for individual studies and, if possible, pooled in meta-analyses to obtain combined, weighted effect sizes (Hedges's g).
Superior efficacy was found for estrogen treatment in female patients (four RCTs, 214 patients) on total symptom severity (Hedges's g=0.66), although heterogeneity was moderate to high. Estrogens were also superior in reducing positive (Hedges's g=0.54) and negative symptoms (Hedges's g=0.34), with low heterogeneity. As the included studies applied different forms of estrogens, a separate analysis was conducted on the trials applying estradiol (three RCTs, 170 patients). Even larger effect sizes were found for total symptom severity (Hedges's g=0.79), positive (Hedges's g=0.57) and negative symptoms (Hedges's g=0.45), with reduced heterogeneity. Estrogen treatment in male patients (one study, 53 patients) was not superior to placebo.
Our results suggest that estrogens, especially estradiol, could be an effective augmentation strategy in the treatment of women with schizophrenia. However, future larger trials are needed before recommendations on clinical applications can be made.
精神分裂症的发病率、发病和病程存在性别差异，这导致了雌激素在该疾病病理生理学中发挥保护作用的假说。多项试验评估了雌激素在减轻精神分裂症症状方面的潜力，结果不一致。本定量综述总结了雌激素治疗精神分裂症的疗效的现有证据。
仅纳入了双盲、安慰剂对照、随机试验。主要结局测量指标是总症状严重程度，次要结局测量指标是阳性和阴性症状的亚量表评分。为个别研究计算了效应量，如果可能，将其汇总进行荟萃分析以获得合并的、加权的效应量（Hedges 的 g）。
发现雌激素治疗对女性患者（四项 RCT，214 名患者）的总症状严重程度更有效（Hedges 的 g=0.66），尽管异质性为中度至高度。雌激素在降低阳性症状（Hedges 的 g=0.54）和阴性症状（Hedges 的 g=0.34）方面也更有效，异质性较低。由于纳入的研究应用了不同形式的雌激素，因此对应用雌二醇的试验进行了单独分析（三项 RCT，170 名患者）。甚至发现总症状严重程度（Hedges 的 g=0.79）、阳性症状（Hedges 的 g=0.57）和阴性症状（Hedges 的 g=0.45）的效应量更大，异质性降低。雌激素治疗男性患者（一项研究，53 名患者）并不优于安慰剂。
我们的结果表明，雌激素，特别是雌二醇，可能是治疗女性精神分裂症的有效增效策略。然而，在提出临床应用建议之前，需要进行更大规模的未来试验。
