Ulipristal acetate delivers in Asian women with fibroids

In the treatment of symptomatic uterine fibroids (UFs) in Asian women, ulipristal acetate (UPA) relieves heavy bleeding as well as leuprorelin (LEU) without increasing the risk of adverse events (AEs), as shown in a phase III study.

“With regard to randomized controlled trials of UPA for UFs conducted to date, the PEARL studies were mainly conducted for whites and the VENUS studies mainly for blacks. This is the first confirmatory trial of UPA for UFs among Asians,” the investigators said. [New Engl J Med 2012;366:421-432; New Engl J Med 2012;366:409-420; Obstet Gynecol 2018;131:431-439]

“The efficacy of UPA in Asian patients with UFs was comparable to that of UPA in [the said] studies,” demonstrating its clinical utility for Asians, they added.

In total, 161 women (mean age, 43 years) recruited from 32 sites in Japan were randomized to treatment with UPA 10 mg (n=82), orally administered once a day for 12 weeks, or with LEU (n=79) 1.88 mg or 3.75 mg, given subcutaneously at weeks 0, 4, and 8. There were no significant between-group differences in patient characteristics, pictorial bleeding assessment chart (PBAC) score, and fibroid and uterine volumes.

The percentage of patients with amenorrhea for 35 days was 87.0 percent in the UPA group and 81.8 percent for the LEU group, confirming the noninferiority of UPA to LEU. [Fertil Steril 2021;doi:10.1016/j.fertnstert.2021.01.023]

Patients on UPA exhibited amenorrhea at a much shorter time than those on LEU (6 vs 9 days). There were no significant differences in the 56-day amenorrhea or uterine bleeding normalization rates between the groups. Likewise, symptom-related pain and quality of life improved with both drugs.

“No notable AEs occurred because of the UPA treatment, and the incidence of AEs in the UPA group was comparable with that in the LEU group (78.0 percent vs 88.8 percent),” according to the investigators.

The most common AEs recorded in either treatment group were nasopharyngitis (UPA, 23.2 percent; LEU, 15.0 percent), metrorrhagia (13.4 percent; 31.3 percent), genital haemorrhage (8.5 percent; 15.0 percent), and hot flash (6.1 percent; 22.5 percent).

“Both UPA and LEU have the effect of reducing UFs and inducing amenorrhea, but their mechanisms of action are different,” the investigators pointed out.

LEU binds to the GnRH receptor in the pituitary gland, reducing oestrogen levels as a result of decreased gonadotropin secretion. On the other hand, UPA induces amenorrhea by inhibiting ovulation and directly acting on the endometrium via progesterone receptors. [Endocr J 2005;52:131-137; J Clin Endocrinol Metab 2007;92:3582-3589]

“The results of this study were based on 12 weeks of 10-mg UPA administration, with a 12-week follow-up period. Because the efficacy and safety of long-term or repeated administration of UPA in Japanese patients are unknown, a further phase III study is currently underway,” the investigators said.