Some Biochemical and Behavioural Effects of Female Gonadal Hormones

Abstract

This thesis investigates some of the possible factors involved in the aetiology of the psychological syndromes seen at times of hormonal flux in human females. The thesis is split into two sections, firstly human clinical studies and secondly animal behavioural and biochemical studies. Putative aetiological factors of post partum ‘blues’ were investigated, however no relationship between this syndrome and either sociological factors such as marital status or age or biochemical factors such as plasma progesterone or oestradiol was seen. Significantly decreased plasma total tryptophan on the first day post partum was found amongst ‘blues’ cases. The incidence of ‘blues’ was significantly greater amongst primiparae than multiparae, although there were no consistent significant biochemical differences between these two parity groups. The same factors were investigated in relation to those subjects who exhibited depressed affect within 9 months of parturition. The incidence of such depressive symptoms was significantly greater amongst mothers of male infants than amongst mothers of female infants, although there were no consistent biochemical differences between these two groups. Puerperal plasma non esterified fatty acids were also significantly increased in those subjects who later exhibited depressed affect, there were no differences in any of the other biochemical variables measured. There was no relationship between the incidence of "blues’ and the incidence of depression post partum. Plasma total tryptophan and non esterified fatty acids were also studied in respect to menstrual mood changes. There was no relationship between these parameters and the psychological symptoms. Plasma tryptophan was also studied in relation to perimenopausal depression. There were no differences in plasma free or total tryptophan between depressed and non depressed subjects, although plasma free tryptophan was significantly decreased amongst post menopausal subjects. Studies of the sedative effects of progestational hormones in mice showed that both natural progesterone and synthetic progestogens were capable of prolonging thiopentone anaesthesia in female mice, however there was no such effect in male mice. Chronic administration of high doses of progestational hormones to female mice produced significantly increased plasma tryptophan, plasma non esterified fatty acids and brain indoleamines. There was no effect of this treatment in male mice. Acute withdrawal of the chronic progesterone treatment in female mice (as a simulation of parturition) had no effects on plasma tryptophan or non esterified fatty acids, brain indoleamines were all significantly decreased. There was no effect of this treatment in male mice. Behavioural studies performed during this hormone treatment suggested that the changes in brain indoleamines involved ‘non functional’ rather than ‘functional’ 5HT stores. The conclusions drawn were that variations in plasma progesterone concentrations were unlikely to be involved in the changes of plasma tryptophan seen during human pregnancy or puerperium, or to be involved in the mood changes frequently seen at these times.