Effect of a Selective Progesterone Receptor Modulator on Induction of Apoptosis in Uterine Fibroids In Vivo

Abstract

Aim. To determine if hormonal treatment induces apoptosis in uterine fibroids. Methods. Immunohistochemical examination of fibroid tissue, using avidin-biotin complex and cleaved caspase-3 antibody for detecting apoptosis, was performed in premenopausal women who underwent 12-week treatment with oral SPRM (6 patients with 5 mg and 5 patients with 10 mg of ulipristal acetate per day) or gonadoliberin agonist (GnRHa, 17 patients) and subsequent myomectomy or hysterectomy for symptomatic uterine fibroids. Ten patients with no presurgical hormonal treatment were used as controls. Results. Apoptosis was present in a significantly higher proportion of patients treated with ulipristal acetate compared to GnRHa (P = 0.01) and to patients with no hormonal treatment (P = 0.01). In contrast to an AI of 158.9 in SPRM patients, the mean AI was 27.5 and 2.0 in GnRHa and control groups, respectively. No statistical difference in the AI was observed between the two groups of patients treated with ulipristal acetate (5 mg or 10 mg). Conclusion. Treatment with ulipristal acetate induces apoptosis in uterine fibroid cells. This effect of SPRM may contribute to their positive clinical effect on uterine fibroids.

Changes in proliferating and apoptotic markers of leiomyoma following treatment with a selective progesterone receptor modulator or gonadotropin-releasing hormone agonist

“…PCNA protein was increased after SPRM treatment, in contrast to several previous reports of decreased PCNA levels in cultured leiomyoma cells after treatment with SPRM [21]. However, similar to previous reports [22], caspase-3 protein was increased by SPRM treatment. Eventually, proliferation and apoptosis were also observed after in vivo SPRM, although fibroid volume was reduced by approximately 30%, indicating that SPRM may precipitate fibroid reduction through an apoptotic rather than anti-proliferative effect.…”

Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids

“…Ulipristal acetate, a selective P receptor (PR) modulator with pharmacokinetic properties supporting once daily dosing (13) potently modulates PR activity without suppressing E 2 to postmenopausal levels, and shows proapoptotic/antiproliferative effects on fibroid cells (13)(14)(15)(16)(17). Several short-term (3 months) randomized clinical studies showed that ulipristal acetate effectively controls bleeding and shrinks fibroids (18)(19)(20)(21).…”

Hysteroscopic Myomectomy

“…UPA is a selective Progesterone receptor modulator (SPRM) that potently modulates P-receptor activity [ 23 ] with proapoptotic/ antiproliferative effects on fi broid cells [ 24 ] and with pharmacokinetic properties supporting once daily dosing [ 25 ]. Two short-term (3 months) randomized clinical trials showed that UPA effectively controls HMB and shrinks fi broids [ 26 , 27 ].…”