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

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.