低剂量睾酮增强治疗女性抗抑郁药难治性重度抑郁症：一项 8 周随机安慰剂对照研究。
Low-Dose Testosterone Augmentation for Antidepressant-Resistant Major Depressive Disorder in Women: An 8-Week Randomized Placebo-Controlled Study.
机构信息
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (Dichtel, Kimball, Miller); Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston (Nyer, Mischoulon, Deckersbach, Dougherty, Yeung, Cassano, Hahn, Farabaugh, Pedrelli, Trinh, Dording, Cusin, Papakostas, Chang, Fisher, Shapero, Chen, Fava); Department of Psychiatry, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston (Brady); Biostatistics Center, Massachusetts General Hospital, Boston (Schoenfeld); Butler Hospital and Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Medicine, Brown University, Providence, R.I. (Carpenter, Tyrka, Price); Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston (Rao); Mayo Clinic Endocrine Laboratory, Rochester, Minn. (Singh).
出版信息
Am J Psychiatry. 2020 Oct 1;177(10):965-973. doi: 10.1176/appi.ajp.2020.19080844. Epub 2020 Jul 14.
OBJECTIVE
Low-dose testosterone has been shown to improve depression symptom severity, fatigue, and sexual function in small studies in women not formally diagnosed with major depressive disorder. The authors sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with antidepressant-resistant major depression. A functional MRI (fMRI) substudy examined effects on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation.
METHODS
The authors conducted an 8-week randomized double-blind placebo-controlled trial of adjunctive testosterone cream in 101 women, ages 21-70, with antidepressant-resistant major depression. The primary outcome measure was depression symptom severity as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. The primary outcome of the fMRI substudy (N=20) was change in ACC activity.
RESULTS
The participants' mean age was 47 years (SD=14) and their mean baseline MADRS score was 26.6 (SD=5.9). Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS scores decreased in both study arms from baseline to week 8 (testosterone arm: from 26.8 [SD=6.3] to 15.3 [SD=9.6]; placebo arm: from 26.3 [SD=5.4] to 14.4 [SD=9.3]), with no significant difference between groups. Improvement in fatigue and sexual function did not differ between groups, nor did side effects. fMRI results showed a relationship between ACC activation and androgen levels before treatment but no difference in ACC activation with testosterone compared with placebo.
CONCLUSIONS
Adjunctive transdermal testosterone, although well tolerated, was not more effective than placebo in improving symptoms of depression, fatigue, or sexual dysfunction. Imaging in a subset of participants demonstrated that testosterone did not result in greater activation of the ACC.
目的
在非典型性重度抑郁症女性患者中，小样本研究表明低剂量睾丸酮可以改善抑郁症状严重程度、疲劳和性功能。作者旨在确定辅助低剂量经皮睾丸酮是否可以改善抗抑郁药治疗抵抗性重度抑郁症女性患者的抑郁症状严重程度、疲劳和性功能。一项功能磁共振成像（fMRI）子研究检验了其对前扣带回皮层（ACC）活性的影响，该脑区对情绪调节很重要。
方法
作者对 101 名年龄在 21-70 岁之间、患有抗抑郁药治疗抵抗性重度抑郁症的女性进行了为期 8 周的随机、双盲、安慰剂对照试验，研究辅助睾丸酮乳膏的效果。主要结局评估指标是蒙哥马利-阿斯伯格抑郁评定量表（MADRS）评估的抑郁症状严重程度。次要结局指标包括疲劳、性功能和安全性指标。fMRI 子研究（N=20）的主要结局是 ACC 活性的变化。
结果
参与者的平均年龄为 47 岁（标准差=14），平均基线 MADRS 评分为 26.6（标准差=5.9）。87（86%）名参与者完成了 8 周的治疗。两组患者的 MADRS 评分均从基线到第 8 周下降（睾丸酮组：从 26.8[标准差=6.3]降至 15.3[标准差=9.6]；安慰剂组：从 26.3[标准差=5.4]降至 14.4[标准差=9.3]），两组间无显著差异。两组间的疲劳和性功能改善无差异，副作用也无差异。fMRI 结果显示，治疗前 ACC 激活与雄激素水平之间存在相关性，但与安慰剂相比，睾丸酮并未导致 ACC 激活增加。
结论
辅助经皮睾丸酮虽然耐受良好，但在改善抑郁、疲劳或性功能障碍症状方面并不优于安慰剂。亚组参与者的影像学检查表明，睾丸酮并未导致前扣带回皮层（ACC）活性增加。
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