Rosiglitazone and Clomiphene for Ovulation Induction

罗格列酮和克罗米芬用于诱导排卵

• 批准号: 6526395
• 负责人: NICHOLAS A CATALDO
• 金额: $ 6.05万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6526395
• 关键词: assistive reproductive technique; blood glucose; clomiphene; combination chemotherapy; fertility promoting drug; glucose tolerance test; hormone binding protein; human subject; human therapy evaluation; hyperinsulinism; hypoglycemic agents; immunologic assay /test; insulin; insulinlike growth factor; luteinizing hormone; ovulation; patient oriented research; polycystic ovary syndrome; reproductive system disorder chemotherapy; serology /serodiagnosis; testosterone; thiazoles; ultrasound; urinalysis; women's health

This proposal will evaluate the effectiveness of a new drug combination, rosiglitazone and clomiphene, for the induction of ovulation in anovulatory women with polycystic ovary syndrome (PCOS). PCOS is a disorder affecting about 5% of women of reproductive age, characterized by anovulation with loss of menstrual cyclicity and hyperandrogenism, often resulting in hirsutism or acne. Anovulation leads to spontaneous infertility and poses a risk of endometrial carcinoma if untreated. A majority of women with PCOS have peripheral insulin resistance and compensatory hyperinsulinemia. These abnormalities may lead to a long-term increased rish of Type 2 diabetes mellitus, hypertension, and accelerated atherosclerosis. Induction of ovulation is necessary to restore fertility to women with PCOS. The standard initial treatment is oral clomiphene citrate, a selective estrogen-receptor modulator which increases endogenous FSH secretion. Clomiphene is successful in inducing ovulation in only about 70% of women with PCOS, and failure is associated with hyperinsulinemia. Women who fail clomiphene ovulation induction are usually treated with parenteral FSH, but this is associated with a greater risk than clomiphene of both multiple gestation and ovarian hyperstimulation syndrome, which in its severe form can be life- threatening. This study will examine whether clomiphene can be more effective in inducing ovulation in women with PCOS when given concomitantly with rosiglitazone, an insulin sensitizer which lowers circulating insulin levels. Women with PCOS selected for previous resistance to clomiphene ovulation induction will be randomized to receive either rosiglitazone or placebo in double-bind fashion for 6 weeks, and then will undergo attempted ovulation induction with clomiphene. If unsuccessful, the clomiphene dose will be increased in up to 2 subsequent cycles in standard fashion in an effort to achieve ovulation. Spontaneous and clomiphene-induced ovulatory outcomes, assessed by serum progesterone levels, will be compared between rosiglitazone and placebo groups and correlated with changes in hyperinsulinemia, assessed on oral glucose tolerance testing (OGTT), and with changes in baseline LH, total and free testosterone, sex hormone binding globulin (SHBG), and insulin-like growth factor binding protein-1 (IGFBP-1) levels. The effects of rosiglitazone on insulin secretion on OGTT will be correlated with its effects on the levels of the above hormones and binding proteins.

该建议将评估一种新的药物组合罗格列酮和克罗米酚对多囊卵巢综合征（PCOS）无排卵妇女诱导排卵的有效性。 多囊卵巢综合征是一种影响约5%的育龄妇女的疾病，其特征是无排卵伴月经周期丧失和高雄激素血症，通常导致多毛症或痤疮。无排卵导致自发性不孕，如果不治疗，有患子宫内膜癌的风险。 大多数PCOS患者存在外周胰岛素抵抗和代偿性高胰岛素血症。这些异常可能导致2型糖尿病、高血压和加速动脉粥样硬化的长期风险增加。诱导排卵对于恢复PCOS妇女的生育能力是必要的。 标准的初始治疗是口服克罗米芬，这是一种选择性雌激素受体调节剂，可增加内源性FSH分泌。 克罗米芬仅在70%的PCOS患者中成功诱导排卵，失败与高胰岛素血症有关。 克罗米酚诱导排卵失败的妇女通常用注射FSH治疗，但这与多胎妊娠和卵巢过度刺激综合征的风险比克罗米酚更大有关，严重时可危及生命。本研究将探讨克罗米酚与罗格列酮（一种降低循环胰岛素水平的胰岛素增敏剂）同时使用时，是否能更有效地诱导PCOS妇女排卵。 选择对克罗米酚诱导排卵有抵抗力的PCOS妇女，随机接受罗格列酮或安慰剂双重治疗6周，然后尝试用克罗米酚诱导排卵。 如果不成功，克罗米酚剂量将在随后的2个周期中以标准方式增加，以达到排卵。将比较罗格列酮组和安慰剂组的自发和克罗米酚诱导的排卵结局（通过血清孕酮水平评估），并与口服葡萄糖耐量试验（OGTT）评估的高胰岛素血症变化以及基线LH、总睾酮和游离睾酮、性激素结合球蛋白（SHBG）和胰岛素样生长因子结合蛋白-1（IGFBP-1）水平的变化相关。 罗格列酮对OGTT胰岛素分泌的影响与其对上述激素和结合蛋白水平的影响有关。