Hot flushes during Gn-RH analogue administration despite normal serum oestradiol levels

Five out of 6 normally-menstruating women who were treated with a potent gonadotropin-releasing hormone (Gn-RH) agonist in order to achieve medical hypophysectomy developed hot flushes despite having normal oestradiol (E₂) levels. The Gn-RH agonist was administered subcutaneously for 6 days and then intranasally for a further 14 days. A dose of 2 mg of E₂ benzoate was injected intramuscularly once a week for 2 consecutive weeks. This combined treatment resulted in low peripheral gonadotropin levels but normal serum E₂ concentrations. Four (4) women developed mild to moderate hot flushes and there was 1 case of flushes severe enough to necessitate cessation of treatment. The flushes occurred in the second week of Gn-RH analogue treatment when the level of serum luteinizing hormone (LH) was low and the pituitary was unresponsive to provocative tests, despite the fact that the patients' E₂ levels were normal (mean 250 ± 25 pg/ml). It is suggested that neither LH pulsatility nor low peripheral E₂ levels are mainly responsible for the development of hot flushes. It is possible that Gn-RH, a hypothalamic decapeptide, may play a major role or act as a mediator in the aetiology of hot flushes.