Uterine leiomyomas are common among women of reproductive age in the United States, occurring in up to 70% of white women and more than 80% of black women. Approximately 25% to 50% of women with leiomyomas have abnormal bleeding and other clinical symptoms that interfere with daily activities and negatively affect their quality of life. Severe abnormal bleeding requires intervention (mostly surgical and invasive) leading to costly medical care and time lost from work The most common treatment for symptomatic uterine leiomyomas is hysterectomy, but long-term health effects are poorly understood, and it is not an option for women wishing to preserve fertility. Commonly used off-label pharmacologic treatments include gonadotropin-releasing hormone agonists and tranexamic acid, which are prescribed for short-term use only. Although chronic use of nonsteroidal anti-inflammatory drugs, levonorgestrel intrauterine devices, and oral and nonoral combination contraceptives is common, data supporting their use for management of symptomatic uterine leiomyomas are limited. An orally administered selective progesterone receptor modulator, ulipristal acetate (UPA), given at daily doses of 5 to 10 mg decreases bleeding and reduces leiomyoma size. Several trials have demonstrated the maintenance of efficacy and safety of ulipristal. These trials were conducted in a predominantly white population. However, the onset of leiomyomas occurs at an earlier age in black women and with greater disease severity compared with white women. The present study-a phase 3, multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group trial-assessed the efficacy and tolerability of UPA for treatment of symptomatic uterine leiomyomas. Results are reported from a 12-week trial of once-daily 5 and 10 mg ulipristal in a diverse (nearly 70% black and largely overweight) population. Participants were premenopausal women aged 18 to 50 years with abnormal uterine bleeding, 1 or more discrete leiomyomas, and uterine size 20 weeks of gestation or less. The trial was conducted at 25 study centers in the United States. Subjects were randomized 1:1:1 to once daily oral 5 mg ulipristal, 10 mg ulipristal, or placebo for 12 weeks followed by 12-week drug-free follow-up. Coprimary efficacy end points were the proportion of patients who achieved amenorrhea (defined as no bleeding) during the last 35 consecutive days of treatment and time to amenorrhea during treatment. Secondary end points were the proportion of patients who achieved amenorrhea by day 11 and the change from baseline to end of treatment on the Revised Activities subscale of the Uterine Fibroid Symptomand Health-RelatedQuality of Life questionnaire (that included questions pertaining to physical and social activities). Safety assessments included monitoring of adverse events and endometrial biopsies. To provide greater than 90% power, a sample size of 150 was planned. Efficacy end points were analyzed according to the intent-totreat principle. A total of 157 patients were randomized from March 2014 to March 2016. Demographic and baseline clinical characteristics were similar across treatment groups. Responder rates for amenorrhea were significantly greater for ulipristal-treated patients (47.2% [25/53]; 97.5% confidence interval [CI], 18.104.22.168; and 58.3% [28/48]; 97.5% CI, 22.214.171.124) for the 5- A nd 10-mg groups, respectively, compared with placebo-treated patients (1.8% [1/56]; 97.5% CI, 0.0.10.9; P < 0.001 for both comparisons). Compared with placebo, time to amenorrhea was shorter for both ulipristal doses (P < 0.001), and both doses of the drug improved quality of life (P < 0.001). The most common treatment-emergent adverse events (.5% in either ulipristal arm during treatment) were hypertension, blood creatinine phosphokinase elevation, and hot flushes. Four patients had serious adverse events; none was considered related to treatment. The endometrial biopsies were benign. These data show that 5- A nd 10-mg doses of ulipristal in women with symptomatic uterine leiomyomas are well tolerated and superior to placebo in rate of and time to amenorrhea. This and other studies suggest that ulipristal may be useful for the medical management of abnormal uterine bleeding in patients with leiomyomas, especially for those desiring uterine- A nd fertility-sparing treatment.
ASJC Scopus subject areas
- Obstetrics and Gynecology