Biomedical subjects
Publications and source records attributed to G C Lachelin.
Saliva specimens were collected approximately every 6 hours from day 280 to day 294 by 16 women who labored on day 294. There was a normal rise in the mean saliva estriol/progesterone ratio in the six who went into labor spontaneously but no change in the 10 whose labor was induced.
Two patients with severe ovarian hyperstimulation syndrome are described. Increased plasma concentrations of immunoradiometrically determined total renin are shown, together with greatly increased plasma levels of active renin and aldosterone. These very high values for total renin, renin activity and aldosterone were not suppressed when extracellular compartments were greatly expanded; the values subsequently declined to normal levels, despite the use of diuretics. This suggested that the renin was of non-renal origin since its production was apparently unaffected by influences which control juxtaglomerular secretion. The high concentrations of the renin-angiotensin-aldosterone system suggest that it contributes to the genesis of the ovarian hyperstimulation syndrome.
Twenty-one nulliparous oligomenorrheic women with polycystic ovaries, complaining of infertility (mean duration 6 years) refractory to medical treatment, underwent laparoscopic ovarian diathermy. Eleven had adhesions and/or endometriosis. Regular ovulatory cycles ensued in 17 women (81%). In 9 responders there was a transient rise in mean follicle-stimulating hormone from 5.0 +/- 0.4 (standard error of the mean [SEM]) to 6.7 +/- 0.5 mIU/mL on postoperative day 1 and a fall in testosterone from 2.6 +/- 0.2 to 1.9 +/- 0.2 nmol/L by day 8. Luteinizing hormone fell from 19 +/- 1.2 to 10.4 +/- 1.2 mIU/mL by the follicular phase of the next cycle. Eleven women have conceived 13 pregnancies; 3 miscarried, 7 were delivered at term and 3 are ongoing. Ovarian diathermy is a useful option in women with polycystic ovaries complaining of refractory anovulatory infertility.
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Total and free cortisol levels are significantly elevated in pregnancy, but the reasons for this are not clear. The relationships between the diurnal variation in saliva (free) cortisol and baseline levels of total cortisol, corticosterone-binding globulin (CBG), progesterone, and estrogens were studied in several groups of women (normal nonpregnant, taking a combined oral contraceptive pill, after superovulation therapy, during early and late pregnancy, and postpartum). Saliva cortisol levels were significantly elevated in late pregnancy throughout the day, with preservation of diurnal variation. Total cortisol and CBG levels were also significantly raised in pregnancy, but total cortisol levels were normal in women taking a combined oral contraceptive pill in spite of significantly elevated CBG. There was no relationship between saliva cortisol and progesterone levels, and it is unlikely that the increase in cortisol is due to displacement of cortisol from CBG by progesterone. Cortisol levels fell slowly postpartum over several days, making it improbable that the increase in cortisol is solely due to elevated CRH levels. It appears that increased free and total cortisol levels in pregnancy are related to resetting of the sensitivity of the hypothalamic-pituitary-adrenal axis and not merely to raised CBG, progesterone, or CRH levels.
Six serial ultrasound scans were performed on each of 12 healthy term babies on days 1, 3, 5, 11, 21, and 42 of extrauterine life in order to determine normal neonatal values for various adrenal parameters. Measurements were made of transverse and anteroposterior diameters, of circumference and area in the transverse plane, and of longitudinal length of the adrenals and kidneys. There was a significant decrease in all adrenal parameters of 22%, 25%, 25%, 44%, and 34%, respectively, between days 1 and 5 (p less than .002) and of 46%, 39%, 46%, 67%, and 55%, respectively, between days 1 and 42 (p less than .00005), whereas the kidneys increased in size over the same period.
The diurnal variation of plasma oestrone (E1), oestradiol (E2), oestriol (E3), progesterone (P), cortisol (F) and dehydroepiandrosterone sulphate (DHAS) and saliva E1, E2, E3, P and F was investigated in matched plasma, and saliva samples were obtained hourly from 08.00 to 24.00 h and at 04.00, 07.00 and 08.00 h from nine pregnant women (3 at 30, 3 at 34 and 3 at 38 weeks gestation). A diurnal variation in plasma and saliva cortisol levels was found in all subjects and in plasma DHAS in 8 out of 9 subjects. No consistent diurnal variation was found at any gestation in any of the other hormones in plasma or saliva. There was a significant correlation between saliva E3 and P levels at 30 weeks gestation but no other consistent correlations between hormone levels were found at any gestation.
Saliva oestriol, oestradiol, and progesterone concentrations were measured in 23 women who went into spontaneous preterm labour. The patients fell clinically and biochemically into two groups. The 13 who went into preterm labour with intact membranes had a saliva oestriol to progesterone ratio greater than one in every case and greater than the 95th centile for their length of gestation in 12 cases; by contrast, all those who went into spontaneous preterm labour after prolonged rupture of the membranes had an oestriol to progesterone ratio less than one and below the 50th centile for their period of gestation in the one to four days before delivery. Saliva oestradiol to progesterone ratios were randomly distributed throughout the normal range in both groups. It appears that preterm labour without prior prolonged rupture of the membranes is, like term labour, preceded by an increase in the saliva oestriol to progesterone ratio. It may therefore be possible to use this ratio to predict preterm labour.
Saliva steroid levels reflect the unbound unconjugated (free, biologically active) plasma hormone levels. Saliva oestriol (E3), oestradiol (E2), oestrone (E1) and progesterone levels were estimated by radioimmunoassay in saliva samples obtained twice a week from 18 weeks gestation until 38 days before delivery and then daily until the spontaneous onset of labour at term from 20 normal pregnant women. The overall percentage increases in the median concentrations of E3, E2, E1 and progesterone were 718, 370, 80 and 214%, respectively, in the last 20 weeks and 149, 82, 24 and 41%, respectively, in the last 6 weeks of pregnancy. The median E3:progesterone ratio rose slowly from 0.65 at 20 weeks before delivery to 1.0 at 5 weeks before delivery and then rapidly to 1.65 one day before the spontaneous onset of labour. There was an increase in the E3:progesterone ratio from less than 1 to greater than 1 before labour in every subject.
Oestriol and progesterone concentrations were measured in samples of saliva obtained daily from six normal women during the final four weeks before the spontaneous onset of labour. Progesterone concentrations were found to plateau whereas oestriol concentrations continued to rise so that the mean ratio of saliva oestriol to progesterone increased from 0.80 to 1.43 between 29 days and one day before labour. Saliva oestriol concentrations were 15 times higher than saliva oestradiol concentrations. As saliva steroid concentrations reflect the unbound unconjugated (free) plasma steroid concentrations these data suggest that a changing ratio of oestriol to progesterone may play a part in initiating spontaneous labour in man.
Saliva unconjugated, plasma unconjugated and plasma total oestriol (E3) levels were measured longitudinally, by radioimmunoassay, in 25 normal women from 13 weeks gestation until delivery. The increase in salivary unconjugated oestriol closely paralleled that of plasma unconjugated oestriol and to a lesser extent that of plasma total oestriol. In each patient the percentage value of salivary E3/plasma unconjugated E3 x 100 was virtually constant throughout pregnancy but this percentage varied from one patient to another (mean 14.4%). The overall correlation coefficient (r) for salivary and plasma unconjugated E3 was 0.90. The variability in salivary levels in samples collected at daily, hourly, 15 min and 5 min intervals (12.7, 13.4, 10.1 and 9.3%) was similar to that previously described for plasma unconjugated E3. There was no distinct pattern in diurnal variation. It seems probable that measurement of salivary E3 could adequately replace that of plasma unconjugated E3 in the assessment of fetoplacental function.
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Conjugated and unconjugated oestrone, oestradiol and oestriol were measured in simultaneous milk and plasma samples obtained from 21 women in the early post-partum period. Conjugated oestrogens comprised more than 90% of the total oestrogen content of both milk and plasma. Oestrone glucosiduronate was the major oestrogen metabolite in milk (33%), the levels being significantly higher (P less than 0.01) than in plasma. Oestriol glucosiduronates were the predominant oestrogen metabolites (63%) in plasma.
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Reduced circulating sex hormone binding globulin (SHBG) levels were found in 54% of a group of women with moderate to severe acne and in 60% of another group of twenty-three women who had acne complicated by hirsutism and/or irregular menstrual cycles. The concentrations of SHBG for the women with acne alone (mean 48 +/- 24 nmol/l) and for those with acne and hirsutes (mean 39 +/- 18 nmol/l) were compared with the SHBG concentrations of fifteen unaffected women with normal menstrual cycles (mean 70 +/- 19 nmol/l). The differences in mean SHBG values for both groups of women with acne were significant (P less than 0.001) on comparison with the mean for the unaffected women. Twenty-nine per cent of the women with acne had elevated testosterone values (mean testosterone concentration for the group 1.5 +/- 0.3 nmol/l) and 41% had elevated 'derived' free testosterone levels (mean 21 +/- 6 pmol/l). Of the women with acne and hirsutes 65% had elevated plasma testosterone levels (mean 2.1 +/- 0.6 nmol/l) and 89% had elevated free testosterone concentrations (mean 31 +/- 10 pmol/l). The mean values for testosterone and free testosterone in the plasma of unaffected women (mean testosterone concentration 1.1 +/- 0.3 nmol/l and free testosterone 13 +/- 4 pmol/l) were significantly lower than in women with acne alone (P less than 0.01 and P less than 0.001) and in women with acne and hirsutism (P less than 0.001). This study indicates that a deficiency in SHBG and an elevation in 'derived' free testosterone is a frequent finding in women with severe acne and may be a significant factor in the aetiology and/or perpetuation of this condition.
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