Endometrial Morphology After Treatment of Uterine Fibroids With the Selective Progesterone Receptor Modulator, Ulipristal Acetate

Abstract

Selective progesterone receptor modulators (SPRMs) have beneficial effects in reducing the size of uterine fibroids and the amount of bleeding, but their endometrial effects have not been seen with other agents. This report describes the morphology of the endometrium after 3 mo of treatment with the SPRM, ulipristal acetate (UPA). In 2 Phase III randomized double-blind controlled clinical trials, 546 patients with uterine myomas were treated with 5 or 10 mg of UPA daily for 13 wk or placebo or gonadotropin-releasing hormone agonist. Endometrial biopsies were taken at screening, end of treatment (13 wk), and after treatment-free follow-up (38 wk). Biopsies were assessed independently by 3 pathologists according to a preset morphologic scheme. After 13 wk, the UPA-treated endometrium showed altered architectural glandular features including extensive cystic dilatation. The glandular epithelium appeared inactive or contained abortive subnuclear vacuolization, occasional mitoses, and apoptosis. Abnormal stromal vessels were commonly seen. There was a high level of agreement between pathologists on the presence or the absence of nonphysiological changes. One case of hyperplasia without atypia and 4 polyps were seen at 13 wk of UPA treatment. Six months after treatment, the endometrium returned to normal histology in the majority of the patients, with 1 polyp and no cases of hyperplasia in the UPA-treated groups, and 2 hyperplasias (1 with and 1 without atypia) in the placebo or the gonadotropin-releasing hormone-agonist groups. Mild reversible thickening of the endometrium occurs in a minority of cases. It is important that pathologists are aware of the spectrum of changes induced by SPRMs to avoid misdiagnoses of endometrial hyperplasia or polyps.

Acetato de ulipristal en el diagnóstico diferencial de carcinoma de endometrio

“…Estos cambios específicos de clase se han denominado Cambios Endometriales Asociados a los MSRP o CEAP (PAEC en la terminología inglesa). Estos cambios endometriales tan representativos pueden aparecer hasta en un 60% de las pacientes y son reversibles tras la suspensión del tratamiento (6)(7)(8)(9)(10).…”

Medical Treatment of Leiomyomas

“…Ancak Pearl I, II ve III çalışmalarında bu endometrial değişikliklerin klinik endişe yaratmadığı ve tedavi kesildikten sonra regrese olduğu görülmüştür. Kadınların %10-12'sinde endometrial kalınlık 16 mm üzerinde saptanmış ve endometrial biyopsilerinde basit veya kompleks atipi izlenmemiştir (49). Bunun tedavi süresi ile ya da kümülatif doz ile iliş-kisi bulunmamıştır.…”

Medical Management of Symptomatic Fibroids: Worth It?

“…Most endometrial patterns were benign or resembled that seen in a normal endometrial cycle. However, some changes were unique and were termed progesterone receptor modulators-associated endometrial changes (PAECs) [21]. An annual ultrasound could be recommended in patients on prolonged therapy and endometrial biopsies obtained when deemed necessary.…”