Kamel E M, Maurer S A, Hochler M G, Hoffman D I, Rebar R W
Department of Obstetrics and Gynecology, Northwestern University Medical School, Northwestern Memorial Hospital, Chicago, Illinois.
Obstet Gynecol. 1991 Jul;78(1):98-102.
A prospective study was performed in 24 premenopausal women to evaluate the gonadotropin dynamics of pharmacologic doses of transdermal estradiol-17 beta (E2) administered after bilateral oophorectomy. Patients were given 0.2-mg transdermal E2 patches for 2 weeks, followed by 0.1-mg patches for 4 weeks either immediately postoperatively (immediate estrogen replacement therapy [ERT]) or beginning 12-14 days after surgery (delayed ERT). Serum gonadotropins and E2 levels were measured serially, and postmenopausal symptoms were prospectively recorded. Administration of 0.2 mg transdermal E2 immediately after surgery suppressed the post-castration rise in gonadotropins for at least 4 days, but LH and FSH levels did increase to the menopausal range after 2 weeks despite continued therapy. Sustained circulating levels of E2 with transdermal E2 therapy were comparable to follicular phase values. Vasomotor symptoms were well controlled by 0.2 mg of transdermal E2 in the majority of patients during the clinical trial. There was no significant estrogen-related morbidity despite the large doses used. Two patients had skin irritation at the patch site causing discontinuation of therapy. These data suggest that large doses of transdermal E2 can suppress gonadotropin levels only for a brief interval. We were unable to demonstrate any long-term alteration in the hypothalamic-pituitary set point for sensitivity to exogenous E2.
对24名绝经前女性进行了一项前瞻性研究,以评估双侧卵巢切除术后给予药理剂量的经皮17β-雌二醇(E2)时的促性腺激素动态变化。患者术后立即(立即雌激素替代疗法[ERT])或术后12 - 14天开始(延迟ERT)给予0.2毫克经皮E2贴片2周,随后给予0.1毫克贴片4周。连续测量血清促性腺激素和E2水平,并前瞻性记录绝经后症状。术后立即给予0.2毫克经皮E2可抑制去势后促性腺激素的升高至少4天,但尽管持续治疗,2周后LH和FSH水平仍升至绝经范围。经皮E2治疗使E2持续循环水平与卵泡期值相当。在临床试验期间,大多数患者中0.2毫克经皮E2能很好地控制血管舒缩症状。尽管使用了大剂量药物,但未出现明显的雌激素相关并发症。两名患者贴片部位出现皮肤刺激,导致治疗中断。这些数据表明,大剂量经皮E2仅能在短时间内抑制促性腺激素水平。我们未能证明下丘脑 - 垂体对外源性E2敏感性设定点有任何长期改变。