Luteinizing hormone secretion in patients presenting with post-oral contraceptive amenorrhoea: evidence for a hypothalamic feedback abnormality.

Twenty-four patients who presented with amenorrhoea after discontinuing oral contraceptives were studied. In fourteen patients underlying conditions were present which could account for the amenorrhoea. Two patients were pregnant, two had premature ovarian failure and four polycystic ovarian disease. Pituitary tumours were present in three patients, and in another three radiological abnormalities of the pituitary fossa suggested the presence of an intrasellar tumour. Basal serum luteinizing hormone levels reliably differentiated ovarian from hypothalamic or pituitary lesions. Varied patterns of serum LH response to clomiphene were present in the patients with post-oral contraceptive amenorrhoea or pituitary lesions. Most patients showed normal hormone response patterns, with a secondary LH peak, but in others a partial response only was seen. In the latter group, who responded normally to exogenous gonadotrophin releasing hormone, no secondary LH peak occurred despite normal oestradiol responses. This suggests an abnormality of the positive feedback system for oestrogens. Subsequent stimulation with clomiphene produced normal LH responses in these patients showing that the abnormality was reversible. These findings are consistent with the hypothesis that post-oral contraceptive amenorrhoea is the result of continuing suppression of normal hypothalamic pituitary feedback systems after the sex steroids have been stopped. The different patterns of hormone response to clomiphene suggest varying degrees of feedback abnormality, and in some patients the positive feedback mechanism only is impaired.