AMENORRHOEA ASSOCIATED WITH INCREASED PRODUCTION OF GONADOTROPHINS AND A MORPHOLOGICALLY NORMAL OVARIAN FOLLICULAR APPARATUS

Abstract

ABSTRACT Three cases of amenorrhoea associated with increased production of gonadotrophins and a morphologically normal ovarian follicular apparatus are presented. The first patient was 23 years old and had primary amenorrhoea. The other 2 patients were 28 and 26 years old, and had secondary amenorrhoea of 26 and 12 months' duration, respectively. It was characteristic of all 3 patients that the secondary sexual characteristics were developed before they had received any substitution therapy. The urinary excretion of total gonadotrophins was markedly increased, and by selective assays it was shown that the excretion of both FSH and LH was increased. The excretion of total oestrogens and pregnanediol was low. Furthermore, histological examination of ovarian biopsies in all 3 patients revealed ovaries with a normal stroma without any luteinization or hyperplasia of the hilus cells and a follicular apparatus with numerous primordial follicles. Very few of these, however, showed progression to the antrum stage and practically none showed any further development. In an attempt to stimulate the development of the ovarian follicles and to induce ovulation 1 patient was treated with clomiphene, and in addition all 3 patients were treated with very high doses of human gonadotrophins, but all attempts were unsuccessful. The explanation is probably that the ovaries of these patients are resistant to stimulation with gonadotrophins. Unfortunately, the possibility of an autoimmune reaction in the ovaries with formation of antigonadotrophins was not investigated in the present study. The aetiology of this syndrome is not yet known, but it might be of interest that 2 out of our 3 patients had received long-term treatment with combined oestrogen-gestagen preparations during the years before the diagnosis was made.