Reproduction Abstracts

Introduction: Uterine fibroids cause pain, pressure symptoms and heavy menstrual bleeding (HMB). Fibroid growth is sex steroid dependent. The selective progesterone receptor (PR) modulator (SPRM), ulipristal acetate (UPA) reduces fibroid size and alleviates HMB in 90% of women. UPA has both agonist and antagonist properties and induces (S)PRM-associated endometrial changes (PAEC). The mechanism of UPA action and aetiology of PAEC are unknown. We propose that modulation of steroid receptor signalling is involved.

Materials and methods: Endometrium from women with fibroids was collected with ethical approval/consent after UPA treatment (5 mg od, up to 12 weeks) and from non-treated controls (n=9/18). Oestrogen receptor alpha (ERα), androgen receptor (AR) and progesterone receptors (PR(AB), PR(B)) mRNAs and protein were examined by q-rtPCR and immunohistochemistry. Steroid responsive genes, phosphatase and tensin homolog (PTEN), Indian hedgehog (IHH) and COUP transcription factor 2 (COUP-TFII) mRNA were examined by q-rtPCR. Ki67 immunohistochemistry was used to assess cell proliferation.

Results and discussion: AR, ERα, PR(AB) and PR(B) mRNA concentrations were significantly higher in UPA-treated endometrium compared to controls (P<0.5). UPA treatment reversed the normal pattern of glandular and stromal protein expression for ERα and both PR isoforms. UPA induced immunoexpression of AR in glandular epithelium and elevated IHH mRNA over controls (P<0.01). PTEN and COUP-TFII mRNAs were unaffected and Ki67 immunostaining was similar in UPA-treated and control endometrium.

In conclusion, UPA treatment altered steroid receptor expression and resulted in up-regulation of PR responsive genes. No effects on cell proliferation were demonstrated.