Martin Vincent, Wernke Suzanne, Mandell Karen, Zoma Willie, Bean Judy, Pinney Susan, Liu James, Ramadan Nabih, Rebar Robert
Department of Internal Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 6003, Cincinnati, OH 45267-4217, USA.
Headache. 2003 Apr;43(4):309-21. doi: 10.1046/j.1526-4610.2003.03065.x.
To determine the preventive benefit of "medical oophorectomy" and transdermal estradiol in women with migraine.
Epidemiological studies have demonstrated that declines in serum estrogen levels occurring during normal menstrual cycles can trigger headache in women with migraine. Prior to this study, no randomized controlled trials have evaluated whether minimizing these hormonal changes pharmacologically can prevent headache.
Twenty-one women with regular menstrual cycles and a diagnosis of migraine headache were enrolled. After a 2.5-month placebo run-in phase, all patients received a subcutaneous goserelin implant (a gonadotropin-releasing hormone agonist) to induce a medical oophorectomy. One month later, while continuing goserelin, participants were randomized to receive a transdermal patch containing 100 microg of estradiol-17beta (gonadotropin-releasing hormone agonist/estradiol group, n = 9) or a placebo patch (gonadotropin-releasing hormone agonist/placebo group, n = 12) during a 2-month treatment phase. The primary outcome measure was the headache index, which was defined as the mean of pain severity ratings (0 to 10 scale) recorded three times per day by daily diary. Secondary outcome measures included headache disability, headache severity, headache frequency, and the percentage of headaches with a pain severity rating of 7 or greater.
The headache index was significantly lower during the treatment period in the gonadotropin-releasing hormone agonist/estradiol group than in the gonadotropin-releasing hormone agonist/placebo group (P =.025). Similar improvements were observed in the gonadotropin-releasing hormone agonist/estradiol group for all secondary outcome measures with the exception of headache frequency, which was unchanged between the groups. Within the gonadotropin-releasing hormone agonist/estradiol group, there was a 33.7% reduction (95% confidence interval, -64.4 to -3.0) in the headache index during the treatment phase when compared with the placebo run-in phase; no difference was seen between those phases within the gonadotropin-releasing hormone agonist/placebo group.
Minimization of hormonal fluctuations with gonadotropin-releasing hormone agonist therapy alone is inadequate to prevent headache in women who are premenopausal with migraine. The addition of transdermal estradiol to existing gonadotropin-releasing hormone agonist therapy provides a modest preventive benefit.
确定“药物性卵巢切除术”及经皮雌二醇对偏头痛女性的预防益处。
流行病学研究表明，正常月经周期中血清雌激素水平下降可引发偏头痛女性的头痛。在本研究之前，尚无随机对照试验评估通过药物手段减少这些激素变化是否可预防头痛。
纳入21名月经周期规律且诊断为偏头痛的女性。经过2.5个月的安慰剂导入期后，所有患者接受皮下戈舍瑞林植入剂（一种促性腺激素释放激素激动剂）以诱导药物性卵巢切除术。1个月后，在继续使用戈舍瑞林的同时，参与者在2个月的治疗期内被随机分为接受含100μg 17β-雌二醇的经皮贴片（促性腺激素释放激素激动剂/雌二醇组，n = 9）或安慰剂贴片（促性腺激素释放激素激动剂/安慰剂组，n = 12）。主要结局指标为头痛指数，其定义为通过每日日记每天记录3次的疼痛严重程度评分（0至10分）的平均值。次要结局指标包括头痛致残率、头痛严重程度、头痛频率以及疼痛严重程度评分为7或更高的头痛百分比。
促性腺激素释放激素激动剂/雌二醇组治疗期间的头痛指数显著低于促性腺激素释放激素激动剂/安慰剂组（P = 0.025）。促性腺激素释放激素激动剂/雌二醇组在所有次要结局指标上均观察到类似改善，但头痛频率除外，两组间该指标无变化。在促性腺激素释放激素激动剂/雌二醇组内，与安慰剂导入期相比，治疗期头痛指数降低了33.7%（95%置信区间，-64.4至-3.0）；促性腺激素释放激素激动剂/安慰剂组在这两个阶段之间未观察到差异。
单独使用促性腺激素释放激素激动剂疗法使激素波动最小化不足以预防绝经前偏头痛女性的头痛。在现有的促性腺激素释放激素激动剂疗法基础上加用经皮雌二醇可提供一定的预防益处。
