Immunohistochemical and hysteroscopic assessment of postmenopausal women with uterine bleeding whilst taking Tibolone

The gonadomimetic steroid Tibolone, is currently widely used for the treatment of menopausal symptoms. Up to 20% of women have been reported to have episodes of bleeding whilst on therapy. We investigated 37 cases who experienced bleeding episodes whilst on Tibolone and compared these to six cases who experienced no bleeding whilst on therapy and who underwent similar investigations in the course of a clinical study. All women underwent a diagnostic hysteroscopy and an endometrial biopsy, under a local anaesthetic. The endometrium was assessed by histology and with immunohistochemical markers for cellular proliferation (Ki67, PCNA), Heat Shock Protein 27 (HSP27) and bcl-2. There were 17 women with intracavitary lesions on hysteroscopy (including one in the control group), 10 with polyps, five with fibroids, two with congenital uterine anomalies. Histological diagnosis was not obtained in 16 cases, The high incidence of uterine polyps in the group who bled on Tibolone suggests an etiologic relation. The staining pattern with HSP27 demonstrated an oestrogenic effect. There were no differences in the bcl-2 immunoreactivity between those who bled and those who did not bleed on treatment which suggests absence of a link. Similarly, there were no differences in the expression of the proliferation markers. We conclude that episodes of bleeding in patients receiving Tibolone for hormone replacement therapy, whilst warranting investigation, should not cause undue concern.