Is oestrogen therapy justified in the treatment of hereditary haemorrhagic telangiectasia: a biochemical evaluation

Abstract

INTRODUCTION: Systemic and topical oestrogen can provoke squamous metaplasia of epithelium. In Hereditary Haemorrhagic Telangiectasia (HTT) the underlying telangiectasia may be protected from trauma and epistaxis reduced. Oestrogens have been advocated but their efficacy is unclear.1 Recent advances have now identified two oestrogen and one progesterone receptors. The aim of this study is to analyse the sex receptor status of HHT nasal mucosa to determine if oestrogen therapy is biochemically justified. METHOD: Five HHT patients (three men, two women) and eight controls (four men, four women) underwent nasal mucosa biopsy. Samples were fixed in formalin and paraffin embedded. Alpha oestrogen (ERalpha ), beta oestrogen (Erbeta) and progesterone receptors (PgR) receptors wre identified using mouse monoclonal antibodies by the Streptavidin-biotin peroxidase method. RESULTS: Erbeta was detected in two HHT patients (one man, one woman) and two control patients. ERalpha and PgR was absent in HHT patients. CONCLUSION: This pilot study demonstrated that a subgroup of HHT patients is Erbeta positive. Oestrogen theraphy therefore has a potential therapeutic role on a biochemical basis in these patients. Erbeta status should be determined before considering oestrogen therapy.

Antiestrogen therapy for hereditary hemorrhagic telangiectasia: A double‐blind placebo‐controlled clinical trial

“…However, a positive finding on DNA sequencing has not yet been included among the accepted diagnostic criteria 26. In our series, all patients had at least three of the four established criteria for diagnosis,23 and all had grade 2 or 3 epistaxis 24…”

“…At present, estrogen is the most popular pharmacologic treatment for HHT‐associated telangiectasis, with favorable results reported in several studies 13–17, 19. The rationale for its use is based on estrogen's ability to provoke squamous epithelial metaplasia, which protects superficial telangiectacic vessels from breaking down and bleeding 23. In addition, studies have reported the detection of two estrogen receptors (alpha and beta) in patients with HHT 23.…”

“…The group included 11 men and 14 women aged 28 to 75 years (mean 51). HHT was diagnosed according to the clinical criteria established by the Scientific Advisory Board of the HHT International Foundation 23. The presence of three of the four criteria, namely spontaneous recurrent epistaxis, cutaneous telangiectases, visceral involvement, and family history, was considered diagnostic.…”

Lack of significant estrogen and progesterone receptor expression in nasal telangiectasias in hereditary hemorrhagic telangiectasia: An immunohistochemical analysis

“…Richtsmeier et al [17] examined a small sample of three biopsies using a ligandbinding assay and found progesterone receptors in three of three nasal mucosa specimens, two of which also contained estrogen receptors. In 2000, Pau et al presented their study after using the more sensitive immunohistochemistry [18]. Their results contradicted those reported by Richtsmeier et al, since they reported that only two of six samples were positive for estrogen receptor subtype b, estrogena and progesterone receptor were not detected.…”

“…Reviewing the related literature, only two articles were found that addressed the detection of estrogen and progesterone receptors in tissue specimens of HHT patients [17,18]. Richtsmeier et al [17] examined a small sample of three biopsies using a ligandbinding assay and found progesterone receptors in three of three nasal mucosa specimens, two of which also contained estrogen receptors.…”