The effects of norethisterone in postmenopausal women on oestrogen replacement therapy: a model for the premenstrual syndrome

Summary. The influence of norethisterone on mood and behaviour was investigated in prospective placebo‐controlled study in 58 postmenopausal hysterectomized women who were being treated with subcutaneous oestradiol and testosterone implants. Norethisterone, 2·5 or 5 mg daily, was given for 7 days and a placebo for two periods of 7 days. Psychological, behavioural and physical variables were assessed using the Menstrual Distress Questionnaire. There were widespread adverse effects which were dose‐related. Significant changes in five of the eight symptom complexes studied (pain, concentration, behavioural change, water retention and negative affect) were found with 5 mg/day of the progestogen. The symptoms were similar to the typical complaints of the premenstrual syndrome, such that a combination of oestradiol and testosterone implants with cyclical oral norethisterone appears to be a model for this condition. The dose of this progestogen should therefore be the minimum to achieve the desired therapeutic effect.