Methods based upon the principles of radioimmunoassay have been developed and evaluated for the measurement of oestrone-3-glucuronide, LH and pregnanediol-3\g=a\-glucuronidein samples of unextracted urine. The procedures have been applied to daily urine (early morning fraction and combined 24 hour collections) from 6 women throughout one complete menstrual cycle and to serial samples from an additional 14 women who only collected early morning specimens. The results showed that there were characteristic, well-defined changes in the concentration of all 3 metabolites in both samples of urine and from all subjects. In addition, there was a reasonable correlation between the concentration of all 3 compounds in samples of early morning urine and the corresponding rates of excretion per 24 hours. These findings suggest that the procedures may be of value for monitoring ovarian function over long periods of time, without the problems of stress and inconvenience to the patient. Furthermore, the ratio of values for oestrone-3-glucuronide to pregnanediol-3\g=a\-glucuronidemay be used to indicate the start and finish of the fertile period.The study of factors which enhance or inhibit fertility often necessitates longterm monitoring of ovarian function. At the present time, the most accepted and useful approach has been to measure the concentrations of oestradiol

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The concentrations of oestrone-3-glucuronide, LH/hCG and pregnanediol-3\g=a\-glucuronide have been measured in daily samples of early morning urine from 6 women throughout the normal ovarian cycle and from 5 subjects, who conceived during the period of study. In addition, the ratio of oestrone to pregnanediol glucuronide was calculate as an additional index of ovarian function.The results showed that the ratio during the follicular phase of the cycle was similar in both groups of women. Moreover, there was no significant difference between the groups in either the duration or intensity of the LH peak. Seven days later, however, the women who conceived excreted significantly higher amounts of oestrone\x=req-\ 3-glucuronide (P<0.05) and 12 days after the LH peak the values for pregnanediol-3\g=a\-glucuronide and LH/hCG were also elevated (P<0.05). A defined increment, in the concentration of hCG (3 times the mean basal level) occurred 11 to 15 days after the peak of LH and appeared 3 to 5 days after the increased excretion of the steroid glucuronides.There is still a need for the development of simple, reliable methods to assess ovarian function in wo¬ men -particularly over long periods of time. One approach to this objective has been to measure the concentration of oestrone-3-glucuronide (Oei-3-G), LH/hCG and pregnanediol-3a-glucuronide (Pd-3a-G) in serial samples of early morning urine (Collins et al. 1979). The results from this study showed that the levels of the two glucuronides, could be used to monitor follicular development and luteal function in apparently healthy women. In addition, it was deduced that a defined rise in the concentration of LH might be used to predict ovulation.A limitation to this study, however, was the lack of direct evidence, that ovulation had occurred.Accordingly, it was decided to collect daily samples of early morning urine from a group of healthy women, who wished to become pregnant. The concentrations of Oei-3-G, LH/hCG and Pd-3a-G in urine from those women who conceived were compared with the corresponding values from a group of control cycles. Materials and MethodsSubjects A total of I 1 women (age 22 to 28 years) was studied.They had all experienced regular menstrual cycles (26 to 33 days) for at least 3 months prior to the investigation. Furthermore, all were in good general health and were not on a special diet or receiving any form of drug therapy. Particular care was taken to ensure that there was no evidence of liver or kidney disease or dysfunction. Six of the volunteers (Group 1) did not wish to become pregnant (2 had been sterilised by tubal ligation and 4 were using barrier methods of contraception). The other 5 women (Group 2) wanted a pregnancy and 4 conceived during the first cycle of study. The fifth became preg¬ nant during the 3rd cycle of urine collection. All 5 had an uneventful pregnancy and gave birth to a healthy baby at term.

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SUMMARY Non‐steroidal anti‐inflammatory drugs (NSAIDs) damage the gastric mucosa, and an important part of this effect is probably due to inhibition of prostaglandin synthesis. We have therefore studied various drugs for their ability to reduce prostaglandin and thromboxane formation by human isolated gastric mucosa. The overall relative potencies for inhibiting the endogenous production of PGE, 6‐keto‐PGF1α and thromboxane B2 by mucosal pieces was generally: indomethacin = naproxen > ibuprofen > piroxicam; diflunisal, the prodrug sulindac, and the analgesic paracetamol usually had small or variable effects. This rank order was mainly similar to the inhibition of gastric microsomal PGE2 formation from exogenous arachidonic acid, the relative potencies being: indomethacin > naproxen > ibuprofen = piroxicam = diflunisal; again sulindac and paracetamol had little or no effect. The relative propensity of NSAIDs to cause gastric mucosal damage is controversial, but aspirin and indomethacin may be worst, and ibuprofen seems to be among the safest. Potency as an inhibitor of prostaglandin synthesis correlates better with the reported propensity for damage than does potency dose. For reasons that are given in the discussion, this may indicate that gastric mucosal damage by NSAIDs with short or moderate half‐lives is due largely to locally absorbed drug. Whereas inhibition of prostaglandin synthesis is probably the major cause of the damage, the simultaneous reduction of thromboxane formation might be advantageous for gastric mucosal integrity. Various implications arise from our hypotheses concerning the design of anti‐inflammatory drugs.

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