Julia Jones

A COMPARISON OF FOLLICULAR FLUID LEVELS OF INSULIN‐LIKE GROWTH FACTOR‐1 IN NORMAL DOMINANT AND COHORT FOLLICLES, POLYCYSTIC AND MULTICYSTIC OVARIES

Fourteen ovulatory patients undergoing diagnostic laparoscopy had at least two samples of clear follicular fluid (FF) collected in the late follicular phase. The cohort concentrations of Insulin‐like Growth Factor‐1 (IGF1) were significantly correlated with serum IGF1 and dominant follicles contained significantly higher concentrations of IGF1 and oestradiol (E2) than their cohorts. After the LH surge, a further significant increase in dominant FF‐IGF1 occurred. FF‐(log)E2 was significantly correlated with both FF‐IGF1 and FF volume. Nine women with the polycystic ovary syndrome (PCOS) and one patient with multicystic ovaries (MCO) associated with weight‐loss related amenorrhoea also had follicular aspiration performed. The mean (SD) FF‐IGF1 in the PCOS group, 0.42 (0.15) U/ml, was not significantly different from that of the cohorts in the control group, 0.39 (0.13) U/ml. The patient with MCO had both serum and FF‐IGF1 concentrations < 10th centile. These results support the hypothesis that IGF1 has a paracrine (and possibly endocrine) role in the regulation of ovarian function in the human female.

The anomalous behaviour of exogenous 25-hydroxyvitamin D in competitive binding assays.

The Vitamin D International External Quality Assessment Scheme (DEQAS) was established in 1989 to monitor the performance of assays for 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (I,25(OH)(2)D). This is achieved through the quarterly distribution of five samples of human serum. Results are used to calculate an All-Laboratory Trimmed Mean and a Method Mean for each of the methods used by participants. In July 2005, participants were asked to assay serum to which 50.9 nmol of either 25-OHD(3) or 25-OHD(2) had been added as ethanolic solutions. The final concentration of ethanol in the serum was 0.7%. The distribution also included a sample of the original serum (OS) containing 0.7% pure ethanol. The percentage recoveries of exogenous 25-OHD(3) (R1) and 25-OHD(2) (R2) were calculated for each method. Results (OS nM, R1 and R2) were as follows: DiaSorin RIA (n=53); 39.2, 82.1%, 83.3%, DiaSorin Liason (n=16); 36.8, 81.4%, 88.6%, IDS RIA (n=21); 36.4, 54.2%, 29.1%, IDS OCTEIA (n=16); 47.3, 78.8%, 56.4%, Nichols Advantage (n=21); 58.9, 46.4%, 43.2%, HPLC (n=9); 42.6, 112.2%, 97.1%, LC-MS (n=4); 34.0, 111.5%, 118.1%. The IDS RIA and Nichols assays gave unexpectedly low recoveries. This does not appear to be a calibration problem or the effect of ethanol.

Captopril in essential hypertension; contrasting effects of adding hydrochlorothiazide or propranolol.

Twenty-four patients with moderate to severe hypertension were treated for four weeks with captopril, an oral inhibitor of angiotensin-converting enzyme. The fall in blood pressure with captopril alone correlated with pretreatment plasma renin activity. The effect of adding either hydrochlorothiazide or propranolol to the captopril treatment was then studied. The addition of hydrochlorothiazide to captopril produced a dose-dependent fall in blood pressure. At the higher dose of the diuretic this fall in blood pressure correlated with weight loss, suggesting that when the diuretic-induced compensatory rise in angiotensin II is prevented by captopril the fall in blood pressure becomes dependent on loss of sodium and water. In contrast, the addition of propranolol to captopril produced no further fall in blood pressure, suggesting that inhibition of angiotensin-converting enzyme prevents the blood pressure lowering effect of propranolol. This may have implications for the mechanism whereby beta-blockers alone lower blood pressure. These contrasting effects of hydrochlorothiazide and propranolol in the presence of captopril indicate that in patients whose hypertension is not controlled by captopril alone the addition of increasing doses of diuretic is likely to control the blood pressure. The addition of a beta-blocker, however, is less likely to be effective.

Essential hypertension: effect of an oral inhibitor of angiotensin-converting enzyme.

Captopril, a specific oral inhibitor of angiotensin-converting enzyme, was given to 18 unselected patients with moderate essential hypertension. Mean blood pressure fell by 14.5% at the maximum dose given, and this fall was significantly correlated with the initial plasma renin activity. The main fall in blood pressure occurred two hours after the first dose of captopril. These results suggest that captopril effectively lowers blood pressure in patients with essential hypertension and that the renin-angiotensin aldosterone system may maintain blood pressure in essential hypertension. This does not necessarily imply that the renin-angiotensin system is the cause of the high blood pressure.

Relation between arterial pressure, dietary sodium intake, and renin system in essential hypertension.

Forty-one patients with mild essential hypertension, 36 patients with severe hypertension, and 28 normotensive subjects were studied on a high sodium intake of 350 mmol/day for five days and low sodium intake of 10 mmol/day for five days. The fall in mean arterial pressure on changing from the high-sodium to the low-sodium diet was 0.7 +/- 1.7 mm Hg in normotensive subjects, 8 +/- 1.4 mm Hg in patients with mild hypertension, and 14.5 +/- 1.4 mm Hg in patients with severe hypertension. The fall in blood pressure was not correlated with age. Highly significant correlations were obtained for all subjects between the ratio of the fall in mean arterial pressure to the fall in urinary sodium excretion on changing from a high- to a low-sodium diet and (a) the level of supine blood pressure on normal diet, (b) the rise in plasma renin activity, and (c) the rise in plasma aldosterone. In patients with essential hypertension the blood pressure is sensitive to alterations in sodium intake. This may be partly due to some change either produced by or associated directly with the hypertension. A decreased responsiveness of the renin-angiotensin-aldosterone system shown in the patients with essential hypertension could partly account for the results.

A Longitudinal Study of the Effect of Subcutaneous Estrogen Replacement on Bone in Young Women With Turner's Syndrome

It is desirable that young women with primary ovarian failure achieve normal peak bone mass to reduce the subsequent risk of osteoporosis, and that there are management strategies to replace bone that is already lost. While estrogen (E2) is generally considered to prevent bone loss by suppressing bone resorption, it is now recognized that estrogen also exerts an anabolic effect on the human skeleton. In this study, we tested whether estrogen could increase bone mass in women with primary ovarian failure. We studied the mechanism underlying this by analyzing biochemical markers of bone turnover and iliac crest biopsy specimens obtained before and 3 years after E2 replacement. Twenty‐one women with Turners syndrome, aged 20‐40 years, were studied. The T scores of bone mineral density at lumbar spine and proximal femur at baseline were −1.4 and ‐1.1, respectively. Hormone replacement was given as subcutaneous E2 implants (50 mg every 6 months) with oral medroxy progesterone. Serum E2 levels increased incrementally from 87.5 pM at baseline to 323, 506, 647, and 713 pM after 6 months and 1, 2, and 3 years of hormone replacement therapy (HRT), respectively. The bone mineral density at the lumbar spine and proximal femur increased after 3 years to T scores of ‐0.2 and ‐0.4, respectively. The cancellous bone volume increased significantly from 13.4% to 18.8%. There was a decrease in activation frequency, but the active formation period was increased by HRT. There was a significant increase in the wall thickness from 33.4 μm at baseline to 40.9 μm after 3 years of HRT, reflecting an increase in bone formed at individual remodeling units. Although there was an early increase in biochemical markers of bone formation, these declined thereafter. Our results show that estrogen is capable of exerting an anabolic effect in the skeleton of young women with Turners syndrome and low bone mass.

Changes in bone density and biochemical markers of bone turnover in pregnancy‐associated osteoporosis

* Gautam Khastgir Research Fellow (Wellbeing Grant), * John W. W. Studd Consultant Gynaecologist, * Hilary King Senior Radiographer, * Hossam Abdaila Consultant Gynaecologist, ** Julia Jones Senior Scientist, ** Graham Carter Consultant Biochemist, ** Jamshid Alaghband-Zadeh Consultant Endocrinologist * Fertility and Endocrinology Centre, Lister Hospital and Academic Department of Obstetrics and Gynaecology, Chelsea & Westminster Hospital, London ; ** Endocrine Laboratory, Charing Cross Hospital, London

Elevated free androgen index as an indicator of polycystic ovaries in oligomenorrhoea without obesity or hirsuties

A group of oligomenorrhoeic women without obesity or hirsuties was investigated with high-resolution ultrasound, laparoscopy and biochemical parameters. In this series, polycystic ovaries (PCO), as defined by ultrasound and laparoscopy, are a common cause of oligomenorrhoea in women without the classic symptoms, and were strongly associated with an elevated free androgen index (FAI). Despite an elevated FAI, these women were not hirsute, It would seem reasonable to include a FAI in the investigation of the oligomenorrhoeic woman, along with the more ‘standard’ tests, such as thyroid function and a prolactin level.

The diagnosis of polycystic ovaries in subfertile women.

Summary. Laparoscopy was used to identify the polycystic ovary (PCO) in a group of subfertile women. A third were found to have PCO. These patients had higher levels of luteinizing hormone (LH), testosterone (T) and a higher free androgen index (FAI) than those with normal ovaries. Only 15% of patients with laparoscopic evidence of PCO were obese, hirsute and oligomenorrhoeic. Within the PCO group, hirsutism was strongly associated with obesity and a high FAI. A group of subfertile women with PCO and regular cycles was found who had no other identifiable cause for their infertility. These women had higher follicular phase concentrations of LH and higher FAI than ovulatory women with normal ovaries.

Interference by polar metabolites in a direct radioimmunoassay for plasma aldosterone.

The CIS Aldoctk-125 kit, a direct radioimmunoassay for plasma aldosterone, has been compared with a conventional technique involving solvent extraction. Results given by these two methods were poorly correlated (r = 0·445, n = 103), the direct assay giving higher values, particularly in patients being dialysed for renal failure. When the kit was modified to include an extraction step, results correlated well with those of the standard method (r = 0·952, n = 60). These observations suggested interference from polar metabolites. The possibility that glucuronides were responsible was investigated by measuring plasma aldosterone before and after hydrolysis with β-glucuronidase. Higher post-hydrolysis values confirmed the presence of glucuronides in plasma from normal subjects and patients with renal failure. Preliminary chromatographic studies on plasma from nine dialysis patients indicated the presence of tetrahydroaldosterone 3-glucuronide, and it is thought that this metabolite might contribute to the high values obtained with the direct assay.