CCTN - CONTRACEPTIVE EFFICACY AND SAFETY OF DAILY ORAL ULIPRISTAL ACETATE

为了减少静脉血栓栓塞症(VTE)的风险，特别是对肥胖女性来说，需要无雌激素的避孕措施。一种新的口服避孕药已经开发出来，它由孕激素受体调节剂组成，不影响内源性雌激素水平。醋酸利普利酯(UPA)已被用于紧急避孕的单次大剂量使用，并已连续使用长达6个月用于治疗子宫肌瘤。小剂量连续口服uPA有望抑制排卵，并提供一种无雌激素、无出血的避孕方法。 尤尼斯·肯尼迪·施莱弗国家儿童健康和人类发展研究所(NICHD)的使命是为包括肥胖妇女在内的妇女开发安全有效的避孕药具。肥胖是美国民众面临的头号公共健康问题，也是静脉血栓栓塞症(VTE)的独立风险。因此，有一种公共卫生需要为妇女开发有效的避孕措施，而不增加VTE的风险。美国食品和药物管理局(FDA)批准的一种避孕方法是仅限孕激素的避孕药(POP)。这种方法需要严格遵守每天同一时间服用POP。这种方法与不规则出血有关，这往往会导致该方法的中断。每天小剂量口服孕激素受体调节剂(PRMs)，如uPA，已被证明抑制排卵和导致闭经。内源性雌激素水平不受PRM的影响。因此，该方法将提供一种比POP方案更容易遵循的方案，并且理论上患VTE的风险更低，特别是对肥胖女性来说。此外，有体外证据表明，uPA可能对乳腺癌具有保护作用。为了提供每日小剂量uPA可以有效避孕的初步证据，NICHD避孕临床试验网络(CCTN)将进行一项临床试验。拟议的研究将按顺序进行评估。最初，月经周期正常的育龄妇女将接受为期12周(三个28天周期)的治疗，以评估这种新避孕药的避孕效果、安全性和可接受性的机制。

There is a demand for estrogen-free contraception in order to reduce the risk of venous thromboembolism (VTE), particularly for obese women. A new oral contraceptive agent consisting of a progesterone receptor modulator, which does not affect endogenous estrogen levels, has been developed. Ulipristal acetate (UPA) has been used in a single high dose for emergency contraception and has been used continuously for up to six months for treatment of uterine fibroids. Low dose continuous usage of oral UPA is anticipated to inhibit ovulation and provide an estrogen free, bleed free method of contraception. The Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD) has a mission to develop safe and effective contraceptives for women, including obese women. Obesity is the number one public health issue facing the US population and is an independent risk for venous thromboembolism (VTE). Therefore, there is a public health need to develop effective contraception for woman that does not increase the risk of VTE. One Food and Drug Administration (FDA)-approved contraceptive method is the progestin-only pill (POP). This method requires strict adherence to taking the POP at the same time every day. The method is associated with irregular bleeding which often leads to discontinuation of the method. Daily low dose oral progesterone receptor modulators (PRMs), such as UPA, have been shown to inhibit ovulation and cause amenorrhea. The endogenous estrogen level is not affected by the PRM. Thus, the method will provide a regimen that is easier to follow than POP regimen and have a theoretically lower risk of VTE, especially for obese women. In addition, there is in vitro evidence that UPA may have protective activity against breast cancer. In order to provide preliminary evidence that daily, low dose UPA could be effective for contraception, a clinical trial will be conducted in the NICHD Contraceptive Clinical Trials Network (CCTN). The proposed study will be evaluated sequentially. Initially, women of reproductive age, with normal menstrual cycles, will receive treatment for 12 weeks (three 28-day cycles) in order to evaluate the mechanisms of contraceptive efficacy, safety and acceptability of this new contraceptive.