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 mglday 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.

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Immunophenotyping of PBMC from SLE patients (n~40) indicated significantly reduced numbers of CD4+CD25hi Foxp3+ T cells and CD8+Foxp3+T cells (p<0.02) as compared to healthy matched controls (n ~20) and autoimmune disease control RA patients (n=30). Numbers of CD4+ and CD8+regulatory T cells are decreased in healthy females compared to healthy males (p<0.01). Both CD4+CD25hi and CD8+CD25hi subsets in males had 3-4-fold higher Foxp3 mRNA compared to females. Stimulation of PBMCs with b-estradiol (30pg/ml) decreases Foxp3 expression in healthy females but not in age matched healthy males. At higher doses (60,150 pg/ml) estrogen has little effect in either sex. Estrogen decreases Foxp3 mRNA and protein expression in both female and male SLE patients’ CD4+CD25- T cells (p<0.05). An Inhibitor of b estradiol (ERa) increased apoptosis in male SLE patients only. These data suggest that estrogen affects the T regulatory compartment.