Fibroid management in premenopausal women

Abstract

Uterine fibroids are the most common tumors affecting premenopausal women, responsible for bleeding, pain, and reduced quality of life. When symptomatic, their management mainly involves surgery, which is all too often radical (hysterectomy). While surgical options sparing the uterus (hysteroscopic and laparoscopic myomectomy) and other non-surgical approaches do indeed exist, drug-based therapies are associated with lower costs and morbidity rates. Since progesterone is required for fibroid growth, gonadotropin agonists have been used to control bleeding and decrease fibroid volume, but they only represent a temporary remedy due to adverse events.

Ulipristal acetate (UPA), a selective progesterone receptor modulator, is indicated for fibroid management. It is safe, provides fast control of bleeding, and causes sustained fibroid volume reduction in the vast majority of cases (80%). Indeed, UPA-treated fibroids shrink by a combination of inhibition of cell proliferation, stimulation of cell death, and fibrosis resorption. In the case of symptom recurrence, repeated intermittent 3-month courses of daily UPA considerably maximize the impact of treatment, sometimes resulting in complete disappearance of treated fibroids. Despite the therapeutic dose of UPA being very well tolerated, patients with liver anomalies or disorders should be excluded at screening according to European Medicines Agency–Pharmacovigilance Risk Assessment Committee (PRAC) recommendations. We therefore propose new algorithms for fibroid management in premenopausal women with symptomatic fibroids, depending on their localization, the patient’s wishes, and clinical response, while monitoring liver enzymes and bilirubin, as recommended by the PRAC, in order to minimize the risks of possible liver toxicity.

Chinese abstract

子宫肌瘤是影响绝经前妇女最常见的肿瘤, 导致出血、疼痛和生活质量降低。当有症状出现时, 其管理主要包括手术, 通常为根治性的（子宫切除术）。虽然确实存在保留子宫的手术选择（宫腔镜和腹腔镜子宫肌瘤切除术）和其他非手术方法, 但基于药物的治疗与低成本和低发病率相关。由于孕酮是肌瘤生长所必须的, 促性腺激素激动剂已被用于控制出血和缩小肌瘤体积, 但由于不良事件的发生, 它们仅能用于短暂治疗。

醋酸乌利司他（UPA）, 一种选择性孕酮受体调节剂, 适用于肌瘤的管理。它是安全的, 可快速控制出血, 并在绝大多数情况下（80%）导致持续的瘤体体积缩小。事实上, 经UPA治疗的肌瘤由于抑制细胞增殖、刺激细胞死亡和纤维化吸收而缩小。在症状复发的情况下, 每天服UPA并间歇性重复3个月疗程, 可很大程度上使治疗效果最大化, 有时可使治疗的肌瘤完全消失。尽管UPA的治疗剂量具有良好的耐受性, 根据欧洲药品管理局——药物警戒风险评估委员会（PRAC）建议, 有肝脏异常或疾病的患者应在筛选时被排除。因此, 我们建议, 对于绝经前妇女有肌瘤症状者, 根据她们的地点、患者意愿和临床反应, 根据PRAC的建议, 在监测肝酶和胆红素的同时, 提出新的管理方法, 以便尽量减少可能的肝脏毒性风险。

Keywords:

• Uterine fibroids
• myomas
• medical therapy
• myomectomy
• surgery
• selective progesterone receptor modulators
• ulipristal acetate

Acknowledgement

The authors thank Mira Hryniuk, BA, for reviewing the English language of the manuscript.

Conflict of interest

J. Donnez has been a member of the Scientific Advisory Board of PregLem S.A. since 2007. He receives grants and fees from lectures and coverage of travel expenses to investigator meetings of PEARL studies from the Gideon Richter Group. G. E. Courtoy and M.-M. Dolmans have no conflict of interest in relation to the article to disclose.

Additional information

Funding

No funding was received for this study.