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.
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