Ulipristal Acetate: a novel medical therapy for uterine fibroids

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Fibroids are the most common tumors of women during their reproductive life and they are found in one out of every four women. They are symptomatic in 50% of the women who have them, with the peak incidence of symptoms occurring among women in their 30s and 40s. Fibroids can cause a variety of symptoms which include menstrual disturbances (commonly menorrhagia and dysmenorrhea), pressure symptoms such as increased urinary frequency, pelvic pain and constipation, they may also interfere with reproduction. Although it is usually assumed that problems associated with fibroids resolve with the onset of the menopause, in reality fibroids can cause symptoms (including abnormal bleeding) even in the menopause.

          Although the exact etiology of fibroids is not well established, it is known that these tumors depend on sex hormones for their growth and several risk factors have been identified such as early menarche, nulliparity and family history.majority of symptomatic uterine fibroids are currently treated by surgical interventions (myomectomy or hysterectomy) or radiological treatments (uterine artery embolization or focused ultrasound surgery). None of these treatments are a panacea for every woman, and what is conspicuous is the lack of an effective long-term medical therapy for a disorder so common among women of reproductive age.Although hysterectomy constitutes a ‘cure’, the operation remains unacceptable to the woman wishing to retain her fertility potential.

          Myomectomy is a major operation with associated morbidity and indeed mortality risks. It may also compromise the very same fertility that it seeks to preserve owing to the potential for adhesion formation, and there is a significant risk of recurrence of the fibroids.In recent years, a multitude of additional therapeutic choices have emerged, including laparoscopic and vaginal myomectomy, uterine artery embolization (UAE) and, more recently, magnetic resonance-guided focused ultrasound surgery (MRgFUS). 

The status of current medical treatments for uterine fibroids

         Gonadotropin-releasing hormone (GnRH) analogues have been the most widely used medical treatment; however, while they do cause fibroid regression, they can only be used in the short term, as temporizing measures in the perimenopausal woman, or preoperatively to reduce fibroid size and influence the type of surgery, restore hemoglobin levels and apparently reduce blood loss at operation. They are notorious for rebound growth of the fibroids upon cessation of therapy, and have major side-effects such as bone mineral density loss and vasomotor symptoms. They are also reasonably expensive and may make subsequent myomectomy more difficult because they can destroy tissue planes. Selective estrogen receptor modulators (SERMs) such as raloxifene have been shown to effectively induce fibroid regression in post-, but not premenopausal women, but experience with these drugs is limited and they are associated with significant side-effects. Progestational agents such as norethisterone (non-proprietary) 5 mg three times a day continuously have also been used in less resourced settings to induce amenorrhea while improving anemia. But side-effects include bloating, fluid retention, breast tenderness, weight change, nausea, headache, drowsiness and mood swings. There is no significant reduction in uterine or fibroid volume. T

What is ulipristal acetate and what is its mechanism of action on fibroids?

    Recent biochemical studies have suggested that progesterone and its receptors enhance proliferative activity in fibroids and this has, therefore, raised the possibility that anti-progestational agents and progesterone receptor modulators could be useful in the medical management of fibroids1,2. The first progesterone receptor antagonist, mifepristone (RU-486), emerged on the clinical horizon 25 years ago and since then hundreds of steroidal as well as non-steroidal compounds displaying progesterone antagonist (PA) or mixed agonist/antagonist activity have been synthesized. Ulipristal acetate (UA also known as CDB-2914) belongs to this group of compounds collectively known as selective progesterone receptor modulators (SPRMs). It reversibly blocks the progesterone receptor in its target tissues (uterus, cervix, ovaries, hypothalamus) and acts as a potent, orally active anti-progestational agent.

     Most gynecologists will be familiar with UA as it has been on the clinical scene for some while as an efficient emergency contraceptive. Recently, it has successfully completed phase III clinical trials for medical treatment of uterine fibroids.