Anti-Estrogens - A Potential Treatment for Bipolar Affective Disorder in Women?

双相情感障碍(BPAD)或躁郁症是一种严重的精神疾病，发病率和死亡率都很高。致病原因尚不清楚，躁狂期和抑郁期的潜在神经化学变化也不同。目前治疗BPAD的方法范围有限，在生化方面也没有得到很好的理解。BPAD的表现和结果存在性别差异，这增加了疾病的复杂性。我们正在提出一项研究，以开发一种新型的治疗BPAD躁狂期的方法，并正在探索抗雌激素在患有躁狂症的女性中的使用。我们拟议研究的背景来自一些病例报告，这些病例报告表明，黄体酮和他莫昔芬等抗雌激素药物可能是治疗的有用辅助药物。我们在10名患有躁狂症的女性中进行了一项小型先导性研究，比较了口服他莫昔芬与口服黄体酮和安慰剂的效果，发现在28天的试验中，服用他莫昔芬的女性躁狂症状的改善明显更好。我们现在提出的这项研究是一项规模更大的、三臂、双盲、安慰剂对照、为期28天的女性躁狂症辅助研究，以扩大和澄清我们的初步研究结果。在我们拟议的研究中，患者除了标准的锂药物外，还将接受每天40毫克的他莫昔芬或每天20毫克的黄体酮或安慰剂。我们将测量酶活性(蛋白激酶C)和雌孕激素水平，以更多地了解这些新激素治疗的作用机制。BPAD是一种致残性疾病，如果我们成功了，他莫昔芬治疗可能是一种重要的新疗法。这项拟议的研究还将为BPAD背后的一些神经化学机制提供新的线索，并开辟严重精神疾病的激素治疗的新领域。

Bipolar Affective Disorder (BPAD) or Manic-Depressive Illness is a serious mental illness with high morbidity and mortality. The cause of the illness is still unclear and the underlying neurochemical changes are different for the manic phase compared with the depressive phase. The current treatments for BPAD are limited in scope and not biochemically well understood. There are gender differences in the presentation and outcomes for BPAD which adds to the complexity of the illness. We are proposing a study to develop a new type of treatment for the manic phase of BPAD and are exploring the use of anti-estrogens in women with mania. The background to our proposed study comes from a few case reports suggesting that anti-estrogen agents such as progesterone and tamoxifen may be useful adjuncts to treatment. We conducted a small pilot study comparing the addition of oral tamoxifen with oral progesterone and placebo in 10 women with mania and found that the women who received tamoxifen made significantly better improvements in their manic symptoms over a 28-day trial. The research study we are now proposing is a larger, three-arm, double blind, placebo controlled, 28-day adjunctive study in women with mania to expand and clarify our pilot study findings. Patients in our proposed study would receive either 40mg per day tamoxifen or 20mg per day progesterone or placebo in addition to standardised lithium medication. We will measure enzyme activity (protein kinase C) and estrogen-progesterone levels to understand more about the mechanisms of action by these new hormone treatments. BPAD is a crippling disorder and if we are successful, then tamoxifen treatment may be an important new treatment. This proposed study will also shed new light on some of the neurochemical mechanisms underlying BPAD as well as opening up the new area of hormone treatments for serious mental illness.