Treatment of Endometriosis-Related Chronic Pelvic Pain with Ulipristal Acetate and Associated Endometrial Changes

Abstract

Background: Aberrant progesterone signaling has been demonstrated in mechanistic studies to be a shared common pathway in fibroids and endometriosis. Progesterone receptor modulation with the selective progesterone receptor modulator (SPRM) ulipristal may decrease pain associated with endometriosis. Case: A 25-year-old nulligravidae with endometriosis-related pelvic pain refractory to medical and surgical intervention was administered 15mg ulipristal every other day for 3 months. Daily pain scores and bleeding diary were recorded and serum chemistries and hormone levels were checked prior to, during, and after treatment. Pre-treatment and surveillance endometrial biopsy specimens were examined for histology and stained for estrogen and progesterone receptor status. During therapy, pain scores decreased to a median of 0 (P<0.05) and the patient became amenorrheic. Surveillance endometrial biopsy demonstrated SPRM-associated endometrial changes that appeared strikingly similar to simple hyperplasia and resolved with ulipristal discontinuation. Immunohistochemical evaluation demonstrated the presence of estrogen and progesterone receptors before and during ulipristal treatment. Conclusions: Progesterone receptor modulation with ulipristal substantially improved pain symptoms in a patient with treatment-refractory endometriosis. SPRM-associated changes in the endometrium closely mimicked hyperplasia, developed after less than three months of treatment, and resolved after discontinuation of ulipristal and induction of withdrawal bleed.

Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment

“…Ulipristal entails rare but severe risks such as endometrial hyperplasia 14 , endometrial carcinoma 15 , and hepatic damage. As recently as August 2018, the US Food and Drug Administration (FDA) had not approved the use of this drug for the treatment of myomas (and endometriosis as well).…”

90 YEARS OF PROGESTERONE: Selective progesterone receptor modulators in gynaecological therapies

“…This was accompanied by upregulation of proapoptotic markers, reduced cell proliferation and inflammatory markers (Huniadi et al 2013). A case report by Bressler et al described a significant reduction in endometriosis related refractory chronic pelvic pain, when treated with high dose UPA for 3 months (Bressler et al 2017). In contrast, Donnez et al described excellent response to UPA treatment when administered for two 3-month courses with regards to reduction in fibroid size; however, no effect on an ovarian endometrioma, with both conditions co-existing in the same patient (Donnez & Dolmans 2016).…”

“…A case report by Bressler et al . described a significant reduction in endometriosis related refractory chronic pelvic pain, when treated with high dose UPA for 3 months ( Bressler et al . 2017 ).…”

Phytoprogestins: Unexplored Food Compounds with Potential Preventive and Therapeutic Effects in Female Diseases

“…SPRMs have been developed for clinical applications, considering their tissue selectivity and low rate of side effects [59]. Their application is principally for the treatment of uterine fibroids [60], endometriosis [61], and breast cancer [62].…”