Letrozole for Treatment of Uterine Fibroids: A randomized, placebo-controlled trial

来曲唑治疗子宫肌瘤：一项随机、安慰剂对照试验

• 批准号: 10718036
• 负责人: Alison Huang
• 金额: $ 69.49万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10718036
• 关键词: Accounting; Adverse effects; Adverse event; Age; Aromatase; Aromatase Inhibitors; Back; Biological; Blinded; Caring; Cells; Clinical; Clinical Data; Clinical Research; Clinical Trials; Control Groups; Data; Development; Disease; Dose; Drug usage; Economics; Enrollment; Enzymes; Estrogens; FDA approved; Fibroid Tumor; Follow-Up Studies; Functional disorder; Goals; Gonadotropin Hormone Releasing Hormone; Gonadotropins; Growth; Hemorrhage; Hormonal; Hormone Antagonists; Hormone use; Hormones; Hot flushes; Hypertension; Hysterectomy; Infertility; Intestines; Letrozole; Long-Term Effects; Mediating; Medical; Menopause; Operative Surgical Procedures; Oral; Outcome; Ovarian; Ovarian hormone; Ovary; Participant; Patients; Pelvic Pain; Pelvis; Pharmaceutical Preparations; Phase; Placebos; Population; Population Heterogeneity; Postoperative Period; Premenopause; Procedures; Production; Progestins; Quality of life; Questionnaires; Randomized; Recovery; Reporting; Risk; Safety; Serum; Smooth Muscle Tumor; Source; Symptoms; Testing; Time; Uncontrolled Study; Uterine Fibroids; Uterine myomectomy; Uterus; Woman; Work; adverse pregnancy outcome; autocrine; black women; care costs; clinical outcome assessment; disability; efficacy evaluation; ethnic diversity; follow-up; hormone therapy; improved; novel; novel therapeutics; open label; paracrine; placebo controlled trial; preference; pressure; racial diversity; randomized placebo controlled trial; reduce symptoms; safety assessment; side effect; social; symptomatic improvement; tumor; ultrasound; urinary

PROJECT SUMMARY Uterine fibroids are smooth muscle tumors that occur in >80% of Black women and 70% of white women by age 50 years. Fibroids cause heavy menstrual bleeding, pelvic pain or pressure, urinary and bowel dysfunction, infertility, and adverse pregnancy outcomes. Major surgery with hysterectomy and myomectomy is the most common fibroid treatment, but surgery generally requires 2-6 weeks of recovery with substantial time off work and the inability to perform usual activities. To avoid surgery, many women prefer medical therapy for fibroids, but few options are available. There are only two FDA approved oral medications to treat fibroids, GnRH antagonists that block gonadotropins and diminish ovarian estrogen production akin to menopause. These medications require concomitant use of estrogen and progestin “add-back” therapy to mitigate hot flashes and other side effects and risks of low serum estrogen. Many women aim to avoid this long-term hormone therapy or have contraindications to hormone use. New medications that alleviate fibroid symptoms but avoid low serum estrogen are needed to improve care for women with fibroids. Fibroids are hormonally responsive tumors that decrease in volume when deprived of estrogen. The ovary is the primary source of estrogen in premenopausal women, but fibroid cells also produce local estrogen through activity of the aromatase enzyme. Through both autocrine and paracrine action, estrogen produced by fibroids demonstrates local control over fibroid growth. Letrozole is an aromatase inhibitor (AI) that blocks estrogen synthesis within fibroid cells. Therefore, letrozole may decrease fibroid volume and improve symptoms. Low doses of letrozole will inhibit the modest aromatase activity within fibroids, but not significantly block the robust aromatase activity in the ovaries of premenopausal women. Letrozole may serve as a novel therapy that improves fibroid symptoms without adverse effects of low serum estrogen. Despite a biologic mechanism to support AIs as a fibroid treatment, clinical data is very limited. In a few small uncontrolled studies, fibroid volume decreased 35-55% during 8-12 weeks of treatment. We recently completed a pilot, randomized, placebo-controlled trial of letrozole. The letrozole group had greater improvement in fibroid symptoms and quality of life compared with the placebo during 2 months of treatment and reported few side effects. Building on this preliminary data, we propose a full scale randomized, blinded, placebo-controlled trial that is powered to detect clinically meaningful changes in fibroid symptoms and fibroid volume. We will enroll 140 racially and ethnically diverse premenopausal women randomly assigned to oral letrozole 2.5mg/day or an identical placebo for 3 months and assess clinical outcomes and the development of adverse events. We will also evaluate long-term letrozole use with an open-label follow-up phase for up to 6 months of letrozole therapy. This trial will provide gold standard evidence to evaluate the efficacy of a novel treatment for uterine fibroids that has significant advantages over existing medication.

项目总结