J. H. Evans

THE INVESTIGATION OF OVARIAN FUNCTION BY MEASUREMENT OF URINARY OESTROGEN AND PREGNANEDIOL EXCRETION

Urinary oestrogen and pregnanediol excretion was measured daily (“daily monitoring”) for a complete cycle in 20 normally menstruating women, in one patient with an anovulatory cycle and for 28 days in a patient with secondary amenorrhoea. The measurements were also performed on urine specimens collected at weekly intervals for 4 to 6 weeks (“weekly tracking”) from 506 patients with evidence of abnormal ovarian function. These included 9 patients with primary amenorrhoea, 132 patients with secondary amenorrhoea, 138 patients with oligomenorrhoea and 227 patients with evidence of ovarian dysfunction and cycle lengths of 25 to 42 days. The results were subjected to statistical analysis. In the normal cycles, ovulation could be identified on the criteria of a rising pregnanediol value reaching or exceeding 2.0 mg. per 24 hours for a period of 7 days or more. Valid conclusions on the overall mean oestrogen and pregnanediol values for a complete cycle could be made from the results of weekly tracking, irrespective of which day the tracking commenced. Correlations were obtained by comparing the mean and maximum urinary oestrogen values and the variability of the values with the evidence of ovarian function indicated by the clinical classifications of the patients, the duration of the disorders and the subsequent occurrence of uterine bleeding. Mean oestrogen values of 10μ g. per 24 hours or less were associated with lack of ovarian function. For values higher than this a discriminant function based on both the mean oestrogen value and the variability of the oestrogen values was useful in predicting onset of spontaneous menstruation. A single urine specimen collected 4 to 8 days before onset of menstruation showing a raised pregnanediol value of 2.0mg. per 24 hours or more provided a valid test for ovulation in women with regular cycles, and a single urine specimen giving an oestrogen value of 10 pg. per 24 hours or less gave a valid indication of absent ovarian function in women with amenorrhoea for two years or more. In all other circumstances serial sampling at weekly intervals provided a valid assessment of ovarian activity. Application of these principles allows the greatest amount of information on ovarian function to be obtained with the greatest economy of effort.

SERUM PROLACTIN LEVELS AND THE VALUE OF BROMOCRIPTINE IN THE TREATMENT OF ANOVULATORY INFERTILITY

Basal serum levels of prolactin were measured in 37 infertile anovulatory patients who had failed to conceive on therapy with clomiphene citrate. Twenty of these patients, 16 of whom had galactorrhoea, had elevated basal serum prolactin values which were suppressed to normal or subnormal values during therapy with bromocriptine, the most commonly effective dose being 2·5 mg twice daily. Ovulation, as assessed by urinary oestrogen and pregnanediol measurements, was induced in 17 of these patients with pregnancy in 14. Ovarian responses short of defined criteria for ovulation were induced initially in eight patients, but these progressed to full ovulatory responses in five patients, either on the same or increased doses of bromocriptine. In all the patients who ovulated, the prolactin levels had been reduced below the mean value for normal women (10·6 ng‐ml). The three patients who failed to ovulate all had values higher than this at a dose of bromocriptine reaching 5·0 mg thrice daily. There seemed to be no value in increasing the dose of bromocriptine once ovulation had been achieved. Of the 17 patients with normal basal prolactin values, only one had an unequivocal response to bromocriptine with ovulation and conception, even though the prolactin values in the majority were suppressed to below normal.

A STUDY OF THE EFFECTS OF BROMOCRIPTINE ON SERUM PROLACTIN, FOLLICLE STIMULATING HORMONE AND LUTEINIZING HORMONE AND ON OVARIAN RESPONSIVENESS TO EXOGENOUS GONADOTROPHINS IN ANOVULATORY WOMEN

Twelve anovulatory patients with normal serum prolactin values and six with elevated values were treated with bromocriptine and the effects on serum prolactin, FSH and LH levels were recorded. Ovulation resulted in one patient who had normal prolactin values and in all six who had raised values. No patient with normal basal prolactin values showed an increase in serum FSH during therapy with bromocriptine, whereas 5 of the 6 patients with elevated values showed significant increases. Similar results were obtained for LH. Although these differences were highly significant (P<0·005) the majority of the serum FSH and LH values remained within the normal ranges. Five patients with normal basal prolactin values and one with elevated values were also treated with human pituitary gonadotrophin (HPG). An increase in ovarian responsiveness to HPG during therapy with bromocriptine was recorded in the one patient with initially elevated prolactin values. It was concluded that bromocriptine acts by allowing FSH to rise above threshold requirements for follicular stimulation.

Gonadotrophin Stimulation for Oocyte Recovery and in Vitro Fertilization in Infertile Women

Summary: The effects of gonadotrophin stimulation were investigated by urinary oestrogen and pregnanediol analyses and by timed laparoscopic examination in 14 infertile ovulatory women with total tubal destruction who were candidates for in vitro oocyte fertilisation.

Induction of Ovuiation With Human Pituitary Gonadotrophin (HPG): The Australian Experience

Following the report of successful induction of ovulation by human pituitary follicle stimulating hormone (FSH), by Gemzell in 1959 (l), the Commonwealth Department of Health established the Human Pituitary Advisory Committee in 1967. The Commonwealth Serum Laboratories undertook the extraction and packaging of the hormone and its distribution was controlled by the Follicle Stimulating Hormone Subcommittee. Arrangements were made for suitable patients to be issued with the hormone free of charge through approved practitioners. This project was unique in the world where expensive therapy was dispensed with caution, both with regard to patient safety and also governmental economy. Other requirements included the association of the clinician with a specialized laboratory which had the facilities to monitor the hormonal response, and the ongoing reporting of treatment regimen and laboratory results from treatment cycles. The principle behind treatment was that daily injections of FSH were administered, monitoring the follicular development on the basis of levels of circulating oestrogens as measured in blood or urine. In the 198Os, the use of diagnostic ultrasound further refined monitoring of follicular development. Human chorionic gonadotrophin (HCG) was then administered when 1 or 2 mature follicles were identified and when the oestrogen assays revealed appropriate levels were present.

A Review of 50 Cases of Primary Amenorrhoea

Summary: Fifty cases of primary amenorrhoea are reviewed with reference to the aetiology. In all patients the buccal smear chromatin complement was measured and chromosomal study proceeded to if this revealed less than 25% of cells to be chromatin positive. Total urinary gonadotrophin and oestrogen assays were performed in all patients and the spectrum of values seen is presented.

Hirsutism in a Gynaecological Context

Summary: Investigation of patients presenting with hirsutism to a gynaecological endocrine clinic revealed a high incidence of anovulation, obesity and elevated androgen levels. The underlying abnormality was polycystic ovarian syndrome (PCOS) in the majority of patients. Low levels of sex hormone binding globulin were common; these increased with oestrogen treatment. Treatment with a combined oral contraceptive pill and low dose spironolactone was often effective in reducing symptoms.

Analysis of Results of Answers to Journal Questionnaire of Readers' Preferences

The response rate to the questionnaire circulated in the August, 1993 issue of the Journal was 13.3% with completed questionnaires being received from 527 subscribers. This compared favourably with the response rate to the previous questionnaire of slightly less than 10% (1).