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To investigate the influence of fetal sex on maternal testosterone levels throughout pregnancy, blood was sampled from 37 healthy pregnant women from week 14 until term and at 6 weeks postpartum. Testosterone concentrations were measured with a highly specific RIA after chromatographic purification. Mean (+/- SD) testosterone at the end of gestation was significantly higher compared to non-pregnant values (3.10 +/- 2.38 mM/l, n = 32 vs 1.14 +/- 1.06 nM/l, n = 35). It appeared that in women carrying a male fetus testosterone levels gradually increased during pregnancy up to 3.99 +/- 2.72 nM/l. In women carrying a female fetus the levels decreased after the first trimester from 2.44 nM/l to 1.80 nM/l. A statistically significant difference (P less than 0.01) existed in maternal testosterone concentrations between both groups during the second half of pregnancy.

The effect of oral contraceptives and of pregnancy on the daily rhythm of cortisol, and its metabolite cortisone in plasma and saliva has been investigated. In both conditions the total plasma cortisol levels were raised to the same extent, the mean values in saliva in the oral contraceptive users being intermediate between those in pregnancy and in the controls, particularly in the morning. Salivary cortisone levels were more related to salivary cortisol than to total plasma cortisone which exhibited a rather flat daily rhythm. There was a shift in peak values for salivary cortisol and cortisone towards late morning: this may be due to a delay in the daily activation of the hypothalamic-pituitary-adrenal axis in these patients.

We measured cortisol and cortisone in plasma--both total and free--and in saliva during the course of pregnancy and postpartum. Antepartum and postpartum concentrations and morning and afternoon concentrations of both steroids were compared. The mean concentrations of cortisol and cortisone increased towards term and were significantly greater at the end of pregnancy than postpartum, except for free cortisol in plasma in the afternoon. The daily rhythm of both steroids was maintained throughout pregnancy and postpartum. The correlations between salivary and plasma free concentrations of cortisol and cortisone as well as of the sum of cortisol + cortisone were highly significant. The mean concentrations of cortisone in saliva accurately reflected both total and free concentrations in plasma. For cortisol, however, the change of the concentrations in saliva, was somewhat different from that in plasma. Moreover, the mass ratio of plasma free cortisol to salivary cortisol was about 2, whereas for cortisone the ratio was only about 0.5, probably owing to the conversion of cortisol to cortisone by 11 beta-hydroxysteroid dehydrogenase in the salivary gland. Furthermore, the passage of cortisol and cortisone from plasma to saliva should not be regarded as simple diffusion, because in the first half of pregnancy the sum of the concentrations of cortisol + cortisone in saliva significantly exceeded the sum of their free concentrations in plasma.

The effect of oral contraceptives (OC) containing a combination of ethinyloestradiol (EE2) and either desogestrel (Dg/EE2) or levonorgestrel (Lg/EE2) on plasma concentrations of sex hormone binding globulin (SHBG), total testosterone (T), free T, total androstenedione (A), free A and on salivary T and A concentrations have been studied. SHBG concentrations were higher in the Dg/EE2 group than in the Lg/EE2 group. Total T, measured by RIA with prior extraction and chromatography, is also higher in the Dg/EE2 group. Per cent free T was lower in the Dg/EE2 group. Plasma free T and free A concentrations were the same in both groups. However, free T and free A were significantly lower in the OC-groups than in controls. In contrast, by direct assay, no difference in total T was observed between the OC-groups. Since the per cent free T was lower in the Dg/EE2 group, it would be concluded that free T in the Dg/EE2 group is lower than in the Lg/EE2 group. Salivary free T and free A concentrations did not differ between control and OC-groups. There was good correlation between salivary and free hormone concentrations within each group. We conclude that the concentrations of androgens in saliva do not necessarily directly reflect their free concentrations in plasma.

Postmenopausal patients with metastatic breast cancer were treated with aminoglutethimide (AG) and high-dose medroxyprogesterone acetate (MPA). Studying the interaction between the two drugs as far as plasma MPA and cortisol levels are concerned we observed a 50% decrease of plasma MPA levels after the addition of AG (P less than 0.005). With large interindividual differences in plasma MPA levels, a significant correlation with serum cortisol levels was found (P less than 0.001). It can be concluded that AG leads to a lowering of plasma MPA levels to such an extent that its adrenal suppressive effect may be diminished or even abrogated. In future trials of MPA with or without AG correlations between plasma MPA levels, serum cortisol levels and treatment response should be taken into account.

The effect of a low estrogen oral contraceptive (OC) on glucocorticoid levels in plasma and saliva as well as glucocorticoid binding was studied in 23 healthy women using 30 micrograms ethinyl estradiol (EE2) + 150 micrograms desogestrel (Marvelon) (II). Fifteen healthy females with normal menses served as controls (I). Blood and salivary samples were taken between 9.00 and 9.30 a.m. on the 18th day of menstrual or pill cycle. Assay accuracy had been optimised by applying extraction and chromatographic purification before radioimmunoassay (RIA) of cortisol and cortisone in both plasma and salivary samples. Free steroid assays were performed by applying the same procedure to equilibrium dialysates obtained after dialysing plasma against an equal volume of buffer, instead of measuring tracer distribution. Corticosteroid Binding Globulin (CBG) was measured by a commercial RIA. As expected, CBG as well as plasma total cortisol were elevated in the pill group. Interestingly both plasma free and salivary cortisol were higher than in controls (free cortisol I: 18.0 +/- 7.95 nmol/l; II: 32.3 +/- 9.03 nmol/l; salivary cortisol I: 9.2 +/- 3.88 nmol/l; II: 18.8 +/- 6.92 nmol/l. Salivary cortisol closely parallelled plasma free cortisol both within and between the groups, though at a much lower level (about 50%). Free cortisone was slightly lower in the pill group (I: 10.8 +/- 2.55 nmol/l; II 8.5 +/- 1.86 nmol/l) whereas salivary cortisone was 2.3 (I) and 4.4 (II) times higher than plasma free cortisone and tended to follow the plasma free and salivary cortisol pattern, both within and between the study groups.(ABSTRACT TRUNCATED AT 250 WORDS)

To see if saliva is a valid substitute for plasma in assay of progesterone even when concentrations of hormone and binding proteins are fluctuating, we determined the concentrations of total and free progesterone in plasma and salivary progesterone in specimens from 36 women volunteers during the course of pregnancy and six weeks postpartum, using a highly specific RIA for total progesterone after extraction and chromatographic purification of the steroid. The free fraction in plasma was determined via equilibrium dialysis, followed by the same RIA analysis for progesterone in the dialysate. Despite the dramatic increases in concentrations of total progesterone and binding proteins in plasma during pregnancy, we found highly significant correlations between total and free progesterone in plasma and salivary progesterone in the group as a whole as well as individuals (P less than 0.001 in almost all cases). The proportion of free progesterone in plasma and of salivary progesterone relative to total progesterone in plasma remained constant at approximately 1% and 0.5%, respectively, whereas during the postpartum period there was much more variance. Evidently salivary progesterone is a very good alternative to plasma as a sample for use in follow-up during pregnancy.

Growth hormone (GH), prolactin (Prl) and cortisol secretion was studied in 5 ovariohysterectomized dogs before and after oestradiol implantation and medroxyprogesterone acetate (MPA) administration. MPA was given at regular intervals during a period of 10 months in a total of 12 injections. Short-term effects of oestradiol were restricted to significantly enhanced Prl responses to thyrotropin-releasing hormone (TRH). MPA treatment after oestradiol implantation resulted in significantly elevated basal GH levels in all dogs, with a continuing increase in one dog. Only in the latter dog was a significant decrease in basal Prl levels seen. MPA administration did not significantly change Prl responses to TRH. The GH responses to clonidine were significantly reduced at 9 and 16 weeks of oestradiol and MPA treatment. In the one dog which exhibited the greatest rise in basal GH levels, GH responses were completely abolished at 9, 16 and 43 weeks of oestradiol and MPA treatment. TRH never evoked significant GH responses. Both basal and lysine-vasopressin (LVP)-stimulated cortisol levels were significantly suppressed during combined oestradiol-MPA treatment. These findings denote that in the dog. Oestradiol rapidly induces an enhanced Prl response to TRH. The oestradiol-MPA induced GH overproduction is associated with a reduced responsiveness of GH to clonidine and is not accompanied by GH responsiveness to TRH. Oestradiol-MPA treatment suppresses both basal and LVP-stimulated cortisol secretion.