Studies on the pathophysiology of gynaecological endocrine disorders

Abstract

The functional organisation of the hypothalamic-pituitaryovarian axis is reviewed.A description is given of two newly developed radioimmunoassays for the measurement of 17p -oestradiol and 1 7^-ethinyloestradiol in peripheral plasma. The characteristics of these assay methods qua sensitivity, specificity, accuracy and reproducibility are described.The effects of exogenous oestrogen administration on pituitary gonadotrophin and gonadal steroid secretion have been studied in normal women during the early-mid follicular phase of the cycle, in intact adult men and in male pseudohermaphrodites (testicular feminization, U pure gonadal dysgenesis). Unlike in normal women and XY pure gonadal dysgenesis, oestrogen treatment did not stimulate LH release in intact adult men or patients with testicular feminization. Evidence is presented which suggests that oestrogen may directly inhibit testicular testosterone secretion in normal men.In adolescents with anovulatory dysfunctional uterine bleeding it was demonstrated that the failure to ovulate in this condition may be attributed to an inability of these patients to release an adequate amount of LH in response to oestrogen.Long-term serial measurements of pituitary gonadotrophins and ovarian steroid hormones in perimenopausal women indicated that dysfunctional uterine bleeding in this age group may have a variety of causes. Several abnormalities in pituitary gonadotrophin secretion were found including failure to release LH in response to endogenous or exogenous oestrogen, monotropic elevation of FSH during ovulatory cycles with short follicular phase, and increases in both FSH and LH during anovulatory cycles with long intermenstrual intervals. It is suggested that these endocrine abnormalities during the menopausal transition may arise from a change in hypothalamic-pituitary sensitivity to steroid feedback or from a progressive decline in the ovarian secretion of a hypothetical FSH-release inhibiting substance (FRIS) produced by the growing follicle.In patients with polycystic ovary syndrome it was demonstrated that positive and negative feedback are intact in this condition and that pituitary EH secretion under basal conditions and in response to ERF was influenced by the pattern of ovarian activity during the U to 6 week period which preceded the measurement of this hormonal parameter.In patients with secondary amenorrhoea elevated basal 17-fluorogenic corticosteroid and androstenedione levels were found. In addition, underweight patients had elevated basal growth hormone levels, markedly suppressed basal gonadotrophin levels and impaired pituitary FSH and EH release after ERF-injection. Growth hormone and prolactin secretion in response to insulin-induced hypoglycaemia were also impaired in these patients. Low basal 17Β-oestradiol levels were found in patients with low FSH and EH but also in women with elevated prolactin levels who had normal peripheral gonadotrophin levels. Clomiphene responsiveness was related to the basal gonadotrophin and prolactin concentrations. It is hypothesised that the abnormalities in hypothalamic-pituitary function in women with secondary amenorrhoea may be a result of selective neurotransmitter deficiencies.