Differential effects of exogenous oestradiol and progesterone on mood in post-menopausal women: individual dose/effect relationship.

This study reports on 56 women who volunteered for consultation at a gynaecological hospital for their climacteric symptoms. The stability of their low oestradiol and high gonadotrophin plasma levels was controlled first. Afterwards they were treated for 3 mth with natural oestradiol (percutaneously). Once the plasma oestradiol levels were proved to be stable during the treatment, natural progesterone was also administered (orally) the last 10 days of treatment. As observed with all steroid administration, the same therapeutic regimen induced different individual plasma levels of the natural steroids. The relationship between mood and plasma levels was as follows. Moderate depressive symptoms were correlated to the lowest plasma oestradiol level, before and after treatment. Only when a moderate increase in oestradiol level was induced did the oestradiol treatment itself lead to a pleasant feeling of well-being. When an excessive increase was induced by the treatment, most of the women complained of unpleasant side effects, mostly irritability and aggressiveness. Progesterone had very few psychological effects if oestradiol levels were low or slightly increased. When plasma oestradiol was high, a moderate elevation of plasma progesterone induced a pleasant tranquillizing effect. A massive elevation of plasma progesterone levels immediately induced an inadequate hypnotic effect, sometimes with dizziness. Therefore, therapeutic administrations of natural steroids appear to strongly influence the mood and behaviour of post-menopausal women. However, the expected pleasant effect could not be successfully achieved without a careful adaptation of the correct dosage to each individual patient.