CLINICAL TRIAL OF HUMAN GONADOTROPHINS

ABSTRACT Thirteen patients with prolonged secondary amenorrhoea and 5 with anovular cycles each provided sufficient data to establish their individual sensitivity to FSH. The parameters used were based on the rise in excretion of oestriol and of pregnanediol. The sensitivity expressed as the ED 50 (that dose which is effective in 50 per cent of times it is given) varied between patients over at least a sevenfold range but the difference between the 2 groups of patients was not significant. After adjusting for differences between patients a dose-response relationship was established and it was found that a dose equal to half the ED 50 would be expected to produce a response in less than Io per cent of the times it is given while a dose equal to twice the ED 50 would be expected to produce a response in more than go per cent of the times it is given. Such a dose would be likely to produce an excessive response. An excessive response occurred three times in 140 months of treatment. Sixteen of the I8 patients became pregnant. The 2 who failed gave up treatment prematurely. A test of individual patient's sensitivity to FSH was established which depended on single injections of the hormone mixed with HCG. The test was repeated at 2 to 3 weekly intervals with increasing dosages until a positive response was obtained as judged by an increase in excretion of oestriol. The rate at which the dose should be increased was investigated and a 30 per cent rate was selected. When the effective test dose was established a standard schedule of dosages was recommended for treatment using 3 equal doses of FSH in 8 days and HCG on the tenth.