COMMENTARY

Another Option for Fibroid Management

Peter Kovacs, MD, PhD

Disclosures

February 05, 2016

Long-term Medical Management of Uterine Fibroids With Ulipristal Acetate

Donnez J, Donnez O, Matule D, et al.
Fertil Steril. 2016;105:165-173

Background

Fibroids are benign tumors that originate from the uterine smooth muscles and can be found in up to around 50% of women. Most are asymptomatic, but symptoms may be associated with size or location. Submucous and intramural fibroids are typically associated with bleeding abnormalities (menorrhagia and menometrorrhagia). Submucous fibroids especially are often associated with pregnancy-related complications, such as infertility, miscarriage, preterm delivery, and abnormal placentation.[1]

This study evaluated results of long-term treatment of uterine fibroids with ulipristal acetate, a selective progesterone receptor modulator.

The Study

Ulipristal acetate is a steroid that reversibly binds to the progesterone receptor and selectively modulates its activity. It was shown in previous studies to successfully control fibroid-related symptoms preoperatively in women scheduled to undergo surgical treatment.[2]

This study evaluated the benefits of long-term ulipristal acetate administration as medical management of fibroid symptoms. Premenopausal women with fibroids between 3 and 12 cm and menorrhagia were randomly assigned to receive ulipristal acetate 5 mg, ulipristal acetate 10 mg, or placebo for four 12-week courses. After each 12-week course, a drug-free period was held, and the new course started with the second menstruation during the pill-free period.

Fibroid size, endometrial thickness, endometrial histology, and the amount of menstrual blood loss (as measured using the pictorial blood-loss assessment chart) were evaluated. Baseline characteristics were well balanced among the groups.

The researchers reported:

  • 75% of women completed all four treatment cycles.

  • Significantly more women achieved amenorrhea after the first treatment cycle in the 10-mg vs 5-mg ulipristal acetate group (82.6% vs 71.8%).

  • Amenorrhea rates were in the 70%-80% range in both active drug groups from the second cycle onward and were observed with similar frequency.

  • 48.7% in the 5-mg group vs 60.5% in the 10-mg group reached amenorrhea by the end of the four cycles.

  • The proportion of women who reported control of bleeding in the last 8 weeks of each treatment cycle was similar with the 5-mg and 10-mg dose (73.3% vs 93.4%).

A significant reduction in the amount of bleeding was seen in both active drug groups, and the magnitude of decrease was similar with 5 mg and 10 mg of ulipristal acetate. The proportion of women with a significant reduction in fibroid size increased in each subsequent treatment cycle, and by the fourth cycle, close to three fourths of women had a reduction in myoma volume of at least 25%.

Pain scores and quality of life improved in both groups. Hemoglobin and hematocrit values increased in both groups, whereas estradiol levels remained stable.

In summary, this study found good compliance with the extended treatment of symptomatic fibroids using both 5 and 10 mg ulipristal acetate. The majority of participants achieved good control of menorrhagia and a significant reduction in fibroid size.

Viewpoint

Symptomatic fibroids eventually will require treatment. Definitive therapy is surgery in which the myoma itself or, more often, the entire uterus is removed. There are patients, however, for whom hysterectomy is not a viable option. For such patients, radiologic treatment (uterine artery embolization or ultrasound destruction) or one of the several medical options can be offered.

Various medical treatments (progestins, aromatase inhibitors, selective estrogen receptor modulators, gonadotropin-releasing hormone analogues) offer short-term symptom relief. They typically modify the hormonal milieu to result in fibroid shrinkage and, therefore, alleviate the severity of symptoms. Long-term use of these agents, however, is associated with side effects, and they therefore are usually offered for a relatively short period.

Ulipristal acetate is a steroid compound with selective progesterone receptor-modulating activity. A 13-week randomized controlled trial showed significant bleeding control with both 5 mg and 10 mg ulipristal acetate (amenorrhea in 63.1% and 71.3% of women) compared with placebo.[2]

The current study showed that treatment efficacy can be maintained over a longer period as well. Women who completed the four treatment cycles stayed in the study for an average of 20 months. Most achieved significant bleeding control and reduction in fibroid size. Estradiol levels remained greater than the menopausal range; therefore, one does not have to be concerned about bone loss.

Hematologic variables improved with both the 5- and 10-mg dose; other laboratory changes that were observed were clinically nonsignificant. Endometrial increased thickness only transiently. There were six cases of hyperplasia among the 451 women receiving ulipristal, and all reverted to benign endometrium.

This study showed that intermittent administration of ulipristal acetate is an option for women who need treatment but wish to avoid surgery.

Abstract

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