The potential of selective progesterone receptor modulators for the treatment of uterine fibroids

Abstract

In addition to the estrogen receptor, the progesterone receptor plays an important role in the growth of uterine fibroids. Several selective progesterone receptor modulators (SPRMs) have been evaluated for medical treatment of uterine fibroids and, because of safety issues, some molecules were stopped during clinical development. However, in 2012, ulipristal acetate received the approval for a pre-surgical treatment of uterine fibroids. Clinical trials with ulipristal acetate for long-term medical treatment of uterine fibroids are ongoing. This review article describes the action of SPRMs at the progesterone receptor level and the mechanism of action on the fibroid tissue. A review of the published clinical trials is performed, including the current evidence of efficacy on uterine fibroid symptom management, size reduction and tolerability. The therapeutic potential of SPRMs for uterine fibroids is discussed.

Keywords::

• asoprisnil
• estrogen receptor
• GnRH-agonist
• mifepristone
• progesterone receptor
• progesterone receptor modulators
• SPRM
• telapristone acetate
• ulipristal acetate
• uterine fibroids

Acknowledgement

The authors thank J Nwachuku, PregLem SA for her review and editorial assistance.

Financial & competing interests disclosure

E Bestel is an employee of PregLem, held stock options related to Preglem’s acquisition by Gedeon Richter. No relation between stock payment and future commercial performance of ulipristal acetate. J Donnez is a member of the scientific advisory board for PregLem. He has held stock options related to Preglem’s acquisition by Gedeon Richter. No relation between stock payment and future commercial performance of ulipristal acetate. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Selective progesterone receptor modulators are becoming an interesting target for the medical treatment of uterine fibroids.

• Selective progesterone receptor modulators inhibit fibroid cell proliferation and induce apoptosis in fibroid cells.

• In clinical trials, selective progesterone receptor modulators were shown to provide an efficient bleeding control with frequent occurrence of amenorrhea due to anovulation and a suggested direct effect on the endometrium.

• Clinical studies with ulipristal acetate demonstrated that, despite a high rate of anovulation, endogenous estradiol concentrations remain at physiological levels under selective progesterone receptor modulator treatment which has a protective effect on bone mineral density and reduces the risk of occurrence of hot flashes.

• Under selective progesterone receptor modulator therapy, non-physiological appearances of the endometrium are observed, and these are named as Progesterone receptor modulator Associated Endometrial Changes (PAEC). It is judged as benign condition and is shown to be reversible.

• Ulipristal acetate received approval from the European Commission for the treatment of uterine fibroids prior to surgery for 3 months. Studies to evaluate extended use are currently ongoing.

• Tolerability data of ulipristal acetate indicate low occurrence of headache, fatigue, nausea and hot flashes, with hot flashes occurring significantly less frequently compared to gonadotropin-releasing hormone agonist therapy.

Notes