|Rabe T et al.|
Intermittent Treatment with Ulipristal Acetate for Conservative Treatment of Uterine Leiomyoma and Bleeding control in Patients with Hypermenorrhoea caused by Uterine Leiomyoma
(Joint statement of the DGGEF e. V. and the BVF e. V.)
Journal für Reproduktionsmedizin und Endokrinologie - Journal of Reproductive Medicine and Endocrinology 2015; 12 (4): 380-387
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Keywords: amenorrhea, anaemia, hypermenorrhoea, progesterone receptor modulator, ulipristal acetate, Uterus myomatosus
Approximately 24 million women in Europe and more than 20 million women in North America mainly between the ages of 35 and 55 years suffer from uterine myomas; this is 40% of all women in this age group. Myoma-derived symptoms manifest themselves by strong uterine bleeding, anaemia, pain and infertility. Thereby, the quality of life of many women is impaired to a high extent and in many cases this ultimately leads to hysterectomy.
Two randomised double-blind studies published in 2012 demonstrated the efficacy of the progesterone receptor modulator ulipristal acetate in the treatment of uterine myomas in women who were eligible for surgery in order to control their hypermenorrhoea. Considerable side effects did not occur over the course of 3 months with dosages of 5 as well as 10 mg of UPA. A reduction of the uterine bleeding was already observed after 7 days, along with a volume reduction by 40% in the uterine myomas within 3 months, which also appeared to be sustained for 6 months after the end of treatment. Esmya®, a tablet with 5 mg ulipristal acetate, was approved by the EMA for the preoperative treatment of symptomatic leiomyoma in spring 2012.
The PEARL-III study examined the control of bleeding, volume reduction in myoma, quality of life and pain in symptomatic myoma patients after four 3-month courses of UPA treatment cycles (10 mg/day). Each 3-month treatment cycle was followed by 10 days of double-blind treatment with either 10 mg norethisterone acetate (NETA) or Placebo and a treatment-free period of two menstrual cycles. The follow-up period was three months after the end of the fourth treatment course. The NETA therapy had no effect on the primary and main secondary study parameters. During the study, a control of the bleeding could be achieved in 94% of the patients, and 90% were seen to develop amenorrhea. The total volume reduction (median) of the three largest myomas after 4 treatment cycles was about 72% and 82% of the patients demonstrated a reduction in volume of ≥ 25%. In 95% of the patients, an operation was no longer necessary during the entire study period. Drug-safety examinations did not reveal any particular risks and the profile of side-effects showed no differences to those found in the PEARL-I and PEARL-II studies. The good tolerance profile of UPA was maintained over repeated treatment courses.
In the PEARL-III study, women also reported on essential improvements in the quality of life including a reduction of pain, fear and depression during the treatment. The UFS QOL scores at the beginning of the study were slightly less severe than in some former studies. At the end of the UPA treatment cycles, the severity of the symptoms and the quality of life scores were comparable with those seen in follow-ups for patients who had been subjected to a hysterectomy, myomectomy, embolisation of the uterus or following a focused high-intensity ultrasonography (not recommended in infertility patients).
Since January 2014, there has been a change in the authorization for a further 3-month cycle of therapy in symptomatic patients with uterine myomas, who are eligible for surgery.
In May 2015, UPA has been approved for the long-term intermittent therapy of symptomatic patients with uterine fibroids. UPA now has two indications.