All symptomatic fibroid will eventually require treatment.
Absolute treatment is surgery consisting of removing the myoma or the
entire uterus, but there are patients in whom Hysterectomy is not a feasible option, or patients who refuse surgery.
These patients have a choice between radiological or medical
management. Radiological management consists of uterine artery embolization/
ultrasound ablation. All medical management offer short term relief and
consists of progestin, aromatase inhibitors, GnRH analogues, and selective
estrogen receptors modulators. All these
agents modify the hormonal milieu leading to shrinkage in size and decreasing
the severity of symptoms.
Ulipristal acetate (UPA) is a possible option for medical
therapy. It most common use is for preoperative shrinkage of fibroids in
reproductive age group women. It is a
steroid that reversibly binds to the progesterone (P) receptor in its target
tissue, acting as a potent orally active P receptor modulator. It belongs to
the class of drugs known as elective P receptor modulators (SPRMs).
This study aims to investigate the long term intermittent
use of UPA in relieving fibroid symptoms.
It was designed by the sponsor (PregLem S.A.)
makers of ESMYA, with
the involvement of academic investigators and a contract study statistician (CROS NT).
This is the first double blind RCT for UPA by Donnez J et al published in the January
issue of journal of Fertlity and Sterility.
Study subjects consist of premenopausal women with fibroid
size between 3-12 mm in diameter, menorrhagia and uterine size less than 16
weeks. All study participants were aged between 18 and 50 years inclusive,
with body mass index 18–40 (kg/m2) and regular menstrual cycles of
22–35 days with FSH ≤20 IU/L.
The subjects were assigned to receive UPA 5mg or 10 mg and
matching placebos for four 12-week courses. A drug holiday was held after each
course and the subsequent course was started on second menstruation during the
drug free period.
The primary endpoints were percentage of subjects with
amenorrhea at the end of four course treatments, the safety endpoint included
number of women withdrawing from the treatment due to the adverse effects.
At the end of completion of the study, it was seen that:
- 75% of the subjects remained in the study for 20 months, demonstrating a very good compliance.
- UPA 5 and 10 mg both resulted in amenorrhea, ≥70% of subjects achieved it in a week and the average post-treatment menstrual bleeding was markedly less comparing with pretreatment bleeding.
- 73% of all subjects ended in amenorrhea with ≥25% reduction in fibroid volume at the end of treatment period.
- The endometrial changes were benign and returned to pretreatment levels in 3 months post treatment.
- Levels of E2 remained well above postmenopausal levels, evading the fear of decreased bone mineral density.
It was concluded that treatment with four 12-week treatment
courses of UPA at doses of 5 and 10 mg was well tolerated. No differences were
observed between the 5 and 10 mg dosing groups. At the end of treatment
cycle more than three fourth women achieved amenorrhea and a reduction in
fibroid size.
This study also showed that UPA 5 mg as an intermittent
therapy can be a good medical alternative in those women with fibroid who wish
to avoid surgery or surgery is contraindicated.
References:
http://www.fertstert.org/article/S0015-0282%2815%2901960-3/fulltext
