PROSPECTIVE RANDOMIZED STUDY OF THE EFFECT OF ADD-BACK HORMONE REPLACEMENT ON VASCULAR FUNCTION DURING TREATMENT WITH GONADOTROPIN-RELEASING-HORMONE AGONISTS

Background-Gonadotropin-releasing hormone agonists (GnRHas) are a grou p of drugs that with long-term use induce a pseudomenopausal state in which estrogen production is suppressed. They are commonly used in the treatment of sex steroid-dependent conditions. ''Add-back'' hormone r eplacement therapy is used to prevent menopause-like symptoms and bone loss during GnRHa treatment, but it is also recognized that hypoestro genism adversely affects vascular function. The aim of this study was to examine the effect of GnRHa and add-back therapy on vascular reacti vity. This model serves as a paradigm for the effect of hormone replac ement therapy in postmenopausal women. Methods and Results-Measurement s of endothelium-dependent and endothelium-independent vascular reacti vity were compared in 2 groups of women treated with a GnRHa for 6 mon ths. One group received estrogen/progestogen add-back therapy during t he second 3 months of GnRHa treatment. Vascular reactivity was examine d by use of ultrasound measurements of changes in brachial artery diam eter. Endothelium-dependent changes were assessed during reactive hype remia, whereas endothelium-independent changes were measured after the administration of glyceryl trinitrate sublingual spray. Treatment wit h the GnRHa alone had an inhibitory effect on endothelium-dependent re laxation. However, endothelium-dependent relaxation significantly impr oved in the group receiving add-back therapy (14.6%) compared with the group treated with GnRHa alone (8.6%) (P<0.01). There were no signifi cant endothelium-independent changes in either group. Conclusions-Thes e results suggest that the administration of add-back therapy has a pr otective effect on vascular function in GnRHa-induced hypoestrogenism. As a model for the menopause, these results also suggest that the lon g-term administration of hormone replacement therapy would result in e ndothelium-dependent arterial relaxation, an observation previously at tributed only to the acute administration of estrogen.