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Eleven healthy women were examined three times a week during the third trimester. The possibility of monthly cyclical changes in the serum concentrations of cortisol, placental hCG and fetoplacental estradiol was tested because of previous findings of highly significant monthly cycles in aldosterone and progesterone. A semiparametric statistical model was used and a highly significant monthly cycle in serum cortisol was found, whereas the amplitude for a cycle in hCG was barely significant and non-significant for estradiol. The previous findings of monthly cycles in aldosterone and progesterone, using a parametric multivariate model, were retested by the semiparametric method employed for the present publication. The findings of highly significant cycles in aldosterone and progesterone were corroborated. We think that the results indicate the existence of an adrenocortical cycle. We think that the monthly ovarian cycle in the non-pregnant state is paralleled by an adrenocortical cycle, where changes in aldosterone are "linked" with changes in progesterone and changes in cortisol with changes in estrogens. During pregnancy the adrenocortical cycle persists, probably controlled by the maternal hypothalamus. The physiological background for this monthly endocrine cycle during pregnancy is enigmatic.

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Eleven healthy women were examined three times a week during the third trimester. A mathematical model (parabolas overlaid with a cosine curve and containing parameters for cycle length, cycle amplitude and phase) was used in a multivariate analysis of changes in serum progesterone, serum aldosterone, serum osmolality and urinary potassium. A highly significant monthly cycle in progesterone and aldosterone and a significant cycle in the urinary excretion rate of potassium were found. The individual rates of increase in serum progesterone and serum aldosterone were different and uncorrelated, and in the monthly cycle there was a phase difference between them. We think that the changes in serum progesterone and serum aldosterone are controlled by different stimuli and that the control of the cyclical component originates in the maternal neuro-endocrine system.

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To investigate the pattern of change in endogenous overnight creatinine clearance during the third trimester, 12 healthy women with uncomplicated pregnancies were examined three times a week. Urine was collected overnight from 22.00 to 08.00 hours and analysed for creatinine. Serum was sampled in the morning and analysed for creatinine, beta 2-microglobulin, progesterone and estradiol. The general trend of creatinine clearance was parabolic with a declining level during the last month before term. A sinusoid pattern with minimum values around the time when the women would have had menstruation had they not become pregnant was superimposed on the parabolic trend. A mathematical model (parabolas overlaid with a cosine curve) was constructed and fitted to the data. The cyclical pattern was significant. Serum creatinine showed a pattern with increasing values during the last 4-6 weeks before term and cyclical changes which were also significant. In the individual case the monthly and preterm clearance decrement sometimes was over 50%. Monthly and preterm decreases in creatinine clearance may be quite normal and serial measurements of creatinine clearance are therefore necessary to determine if declining values indicate pathological falls in the glomerular filtration rate.

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Renal haemodynamics and extracellular homeostasis during the menstrual cycle were studied in 14 healthy women (age 21-41 years) who were not taking oral contraceptives in the follicular (Period I) and luteal phase (Period II). The glomerular filtration rate [( 51Cr] EDTA clearance) and the effective renal plasma flow ([125I] hippuran clearance) increased from Period I to II by a median of 6.3% (95% confidence interval (CI): 0.6-9.2%) and 7.3% (95% CI: -0.4-22%) respectively. Serum sodium decreased from period I to II (p less than 0.01) by a median of 1 mmol/l (95% CI: -2.0 to -0.5 mmol/l) and the urinary excretion rate of potassium increased (p less than 0.02) from a median value of 35 mumol/min in Period I to 45 mumol/min in Period II. The extracellular fluid volume did not change between the two periods but the concentration of water in serum increased (p less than 0.05) from a median value of 91.7-92.0 g/100 g in Period II. Serum total protein and serum albumin both showed a borderline statistically significant decrease from Period I to II. The investigation demonstrated a number of physiological and biochemical changes from the follicular to the luteal phase, most of which in a lower scale mimic well known changes that occur during pregnancy.

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Endogenous overnight (22.00-08.00 hours) creatinine clearance and serum concentrations of beta 2-microglobulin and water were measured three times a week during 11 ovulatory menstrual cycles. In some of the women creatinine clearance changed more than 100% within a week from values below reference range to high normal levels. In all the women the creatinine clearance was higher during the luteal than during the follicular phase and correlated with the production of ovarian hormones. The urinary excretion rate of creatinine was highest during the luteal phase. Urinary volume, serum creatinine and serum water were not significantly influenced by the menstrual phases. An unexplained finding was a parallel change in the individual creatinine clearance and serum beta 2-microglobulin during the luteal, but not during the follicular phase. Our results suggest that ovarian hormones influence creatinine clearance during the menstrual cycle. One must therefore accept even considerable short-time variations in creatinine clearance in fertile women. It remains to be settled if these changes reflect true alterations in glomerular filtration rate or mainly changes in the urinary (tubular) excretion rate of creatinine.

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Fourteen healthy women aged 21-41 years, who did not take oral contraceptives and who all had ovulatory cycles, were examined once in the follicular phase and once in the luteal phase of a single menstrual cycle. The glomerular filtration rate (51Cr-EDTA clearance) increased from the follicular to the luteal phase by a median of 7.0% (95% confidence interval: 0.7-10.3%). Endogenous overnight (22.00-08.00 hours) creatinine clearance increased by a median of 7.3% (95% confidence interval: 1.0-14.6%). The urinary creatinine excretion rate also increased with a median of 7.3% (95% confidence interval: 1.5-11.9%) whereas the serum concentrations of creatinine and beta 2-microglobulin, urine flow and urinary excretion rate of urea did not change. The results confirm previous observations of an increase in creatinine clearance in the luteal phase of the menstrual cycle and indicate that the increase in overnight creatinine clearance reflects a true change in glomerular filtration rate.

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