Premature ovarian failure (POF) occurs in 1% of all women, and in 0.1% of women under the age of 30 years. The mechanisms that give rise to POF are largely unknown. Inhibin has a role in regulating the pituitary secretion of FSH, and is therefore a potential candidate gene for ovarian failure. Using single-stranded conformation polymorphism (SSCP) and DNA sequencing, DNA samples were screened from 43 women with POF for mutations in the three inhibin genes. Two variants were found: a 1032C-->T transition in the INHssA gene in one patient, and a 769G-->A transition in the INHalpha gene in three patients. The INHssA variant appears to be a polymorphism, as there was no change in the amino acid sequence of the gene product. The INHalpha variant resulted in a non-conservative amino acid change, with a substitution from alanine to threonine. This alanine is highly conserved across species, and has the potential to affect receptor binding. The INHalpha variant is significantly associated with POF (3/43 patients; 7%) compared with control samples (1/150 normal controls; 0.7%) (Fisher's exact test, P < 0.035). Further analysis of the inhibin gene in POF patients and matched controls will determine its role in the aetiology of POF.

The effect of ethnicity on the prevalence and presentation of polycystic ovarian syndrome (PCOS) was examined in a cross-sectional study of women with clinical - and ultrasound - diagnosed PCOS. European, Maori and Pacific Island women were seen in proportion to the general population, whereas Indian women were over-represented and Chinese women under-represented. European and Maori women were more likely to present with hirsutism than other ethnic groups (43% versus 25%, p < 0.05), while European women were less likely to present with infertility (46% versus 68%, p < 0.01). The Pacific Island women had little or no acne but other signs of PCOS were similar among ethnic groups. Although less than 10% of patients were referred with obesity, the majority of PCOS women were overweight on examination. Maori and Pacific Island women were more obese and had the highest rates of insulin resistance and lipid abnormalities. The adverse metabolic profile of many of these women, particularly the Maori and Pacific Islanders, is very likely to predispose them to early cardiovascular disease.

There is no evidence that adding metformin to 'standard care' is beneficial. Pregnancy and live birth rates are low in women with BMI > 32 kg/m(2) whatever treatment is used, with no evidence of benefit of metformin over placebo. For women with BMI < or = 32 kg/m(2) there is no evidence of significant differences in outcomes whether treated with metformin, CC or both. ClinicalTrials.gov number NCT00795808; trial protocol accepted for publication November 2005: Johnson, Aust N Z Journal Obstet Gynaecol 2006;46:141-145.

The plasma ACTH response to corticotrophin releasing factor (CRF) was studied in seven normal individuals. Five subjects were restudied following 4 d of salt restriction which resulted in raised endogenous plasma angiotensin II secretion. In a third experiment six subjects were given CRF following pre-infusion of hypertonic saline which significantly increased endogenous plasma vasopressin (AVP) levels. We were unable to demonstrate that high endogenous plasma AII levels were associated with a significant change in the plasma ACTH or cortisol responses to CRF. However there was an almost three-fold increase in the ACTH response when endogenous plasma AVP was elevated by hypertonic saline. It is concluded that AVP is likely to be of physiological importance in potentiating the ACTH response to CRF and that AVP and CRF together may provide a better test of pituitary ACTH secretion than either peptide alone.

A clinical test ofintestinal calcium absorption has been developed using non-radioactive stable strontium as a calcium tracer. In nine elderly subjects there was a close correlation between the fractional absorption of strontium and radioactive calcium (45Ca) during a five hour period after the simultaneous oral administration of the two tracers. Comparable precision was achieved with each tracer in six subjects in whom the test was repeated after two weeks. The effect of food on strontium absorption was examined in a further 33 normal subjects (age 21-60 years), and the administration ofthe strontium with a standard breakfast was shown to reduce the variance at individual time points. A simplified test in which serum strontium concentration was measured four hours after the oral dose given with a standard breakfast was adopted as the routine procedure. The normal range (mean (2 SD)), established over 97 tests in 53 patients, was 7*0-18-0% of the dose in the extracellular fluid. A further 30 patients with possible disorders of calcium absorption (10 with primary hyperparathyroidism and 20 with coeliac disease) were studied by this standard test. In both groups of patients the mean four hour strontium values were significantly different from normal.This standard strontium absorption test allows assessment of calcium absorption with sufficient sensitivity and precision to have a wide application in clinical practice. In an earlier study we showed a close correlation between serum 45Ca and stable strontium concentrations after an oral dose of the tracers given on consecutive days under fasting conditions in patients with various abnormalities of calcium metabolism.3 In this study we compared the simultaneous absorption of 45Ca and strontium in normal subjects and assessed the comparative precision of each test. To optimise and simplify the procedure we took serum samples for measurement at different times and studied the effect of a standard breakfast on the absorption oforal strontium. A modified strontium tracer test was then used to assess patients in whom intestinal calcium absorption was likely to be abnormal.

Insulin-like growth factors and their binding proteins in plasma and milk after growth hormone-stimulated galactopoiesis in normally lactating women. Acta Endocrinol 1993:129:427-35. ISSN 0001-5598 We performed a double-blind randomized placebo-controlled trial of recombinant human growth hormone (hGH) in normally lactating women (N = 8 per group) to investgate the endocrine mode of action of the galactopoietic effect of this hormone. Insulin-like growth factors I (IGF-I) and II (IGF-II) and their binding proteins (IGFBP-1, IGFBP-2 and IGFBP-3) were measured by radioimmunoassay in plasma and milk samples collected throughout the study. All assays were validated for human plasma and milk. Human GH treatment (0.1 IU\m=.\kg\m=-\1body wt\m=.\day\m=-\1 for 7 days) increased plasma concentrations of IGF-I from 22.1 \m=+-\1.3nmol/l (mean\m=+-\sem) to 59.7\m=+-\2.5nmol/l (p<0.01). At the end of the study the increase in plasma IGF-I correlated significantly with the increase in milk volume (r=0.67, p<0.005, N=16). The IGF-I levels were considerably lower in milk, with 0.14\m=+-\0.03 nmol/l before and 0.31 \m=+-\0.04nmol/l after hGH treatment. The increase in milk IGF-I levels (134.0\m=+-\14.5%)with hGH treatment was significant (p<0.01) and plasma and milk IGF-I concentrations correlated significantly when considering all samples of the study (r=0.45, p<0.001, N= 56). The concentrations of IGF-II were not changed significantly with hGH treatment in plasma (52.5 \m=+-\2.5 nmol/l before and 42.6 \m=+-\3.9nmol/l after treatment) or milk (2.1 \m=+-\0.29 nmol/l before and 2.3\m=+-\0.49nmol/l after hGH treatment). The IGFBP-1 levels were not changed with hGH treatment in plasma (approximately 1.3 nmol/l) or milk (approximately 0.2 nmol/l). Although IGFBP-2 concentrations in plasma were reduced significantly (p<0.05) after hGH treatment (11.1\m=+-\1.5 before and 8.4\m=+-\0.9nmol/l after hGH treatment), milk IGFBP-2 levels did not respond to hGH treatment. Milk levels were markedly higher (sevenfold) in comparison to plasma levels. Plasma IGFBP-3 showed a delayed and smaller rise with hGH treatment in comparison to the rise observed in IGF-I. However, at the end of the study the response (38.6\m=+-\4.9%) to hGH was significant (p<0.01) and a significant correlation was observed also between the increase in IGFBP-3 and the increase in milk volume (r=0.55, p =0.03, N=16). Plasma IGF-I and IGFBP-3 concentrations correlated significantly when considering all samples of the study (r=0.61, p<0.001, N=63). Milk IGFBP-3 levels were approximately 100-fold lower in comparison to plasma levels and did not correlate with any other measurements. Our data show that hGH-stimulated galactopoiesis in normally lactating women is mediated by significant elevations of plasma and milk IGF-I and plasma IGFBP-3. While IGF-I may be a principal mediator of the galactopoietic effect of hGH, we cannot simply attribute the action of hGH solely to a systemic rise in IGF-I. The increase in plasma IGFBP-3 with hGH treatment suggests that IGFBP-3 could facilit...

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Background:In women with prolactinoma medical treatment with dopamine agonists (DA) can restore fertility. A number of studies have established the safety of DA during pregnancy and the impact of pregnancy and lactation on remission of prolactinoma. However, the total number of reported cases remains modest and further evidence is needed. Aims:To evaluate the safety of DA during pregnancy and remission of prolactinoma after pregnancy and lactation. Materials and Methods: Retrospective cohort study (2002-2014) of 57 pregnancies in 47 women with prolactinoma who received DA. Neonatal and pregnancy complications were recorded. Prolactin levels and treatment data were collected at the time of diagnosis, pre-conception, during pregnancy and lactation, and postpartum (up to 114 months).Results: DA treatment was stopped a median of 4.5 weeks after conception in 49 pregnancies (86%). There were 49 live births (86% of pregnancies) and six miscarriages. Six pregnancies had an adverse neonatal outcome including two with congenital malformations. Following 26% of pregnancies women achieved remission after birth or lactation, and 25% of women were in remission at last follow-up.Remission was associated with older maternal age (P = 0.036), a lower prolactin level at diagnosis (P = 0.037), and a smaller adenoma at diagnosis (P = 0.045). Conclusions:Successful pregnancy and lactation is common after DA treatment for prolactinoma. Fetal exposure in the first four weeks of pregnancy appears to be generally safe. Encouragingly, post-partum and after lactation a quarter of women had a normal prolactin level without medical treatment. K E Y W O R D Sbromocriptine, cabergoline, lactation, pregnancy, prolactinoma