Circulating leptin concentrations and ovarian function in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction. Although the role of leptin in the control of reproduction is unclear, it may be involved in the control of ovulation. The aim of this cross-sectional study was to determine the relationship between circulating leptin concentrations, and anthropometric, metabolic and endocrine variables as well as to examine a possible role of leptin in ovarian dysfunction associated with PCOS. DESIGN: Prospective observational study. METHODS: Seventy-one subjects with PCOS and 23 body mass index (BMI)-matched control subjects were recruited from infertility clinics. The association between serum leptin concentrations and the above variables was measured outwith the luteal phase. A subgroup of 24 PCOS subjects underwent more frequent blood sampling to monitor follicular growth and ovulation. The association between variables was measured by univariate, multivariate and partial correlation analyses. RESULTS: Serum leptin concentrations were not different in subjects with PCOS and controls, and were strongly associated with BMI in both groups. Twelve patients ovulated during the study period. There was no significant difference in serum leptin concentrations between ovulatory and anovulatory subjects. The relationship between BMI and leptin was similar in both groups. CONCLUSION: The results indicated that circulating leptin concentrations relate principally to total body fat in subjects with PCOS and controls, and that this is not associated with the facility for follicular development and ovulation in these patients.

Lipids and lipoprotein subfractions in women with PCOS: relationship to metabolic and endocrine parameters.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) exhibit an abnormal lipoprotein profile, characterized by raised concentrations of plasma triglyceride, marginally elevated low density lipoprotein (LDL)-cholesterol, and reduced high density lipoprotein (HDL)-cholesterol. However, a normal LDL-cholesterol level may be misleading since LDL exists as subpopulations of particles differing in size and atherogenic potential. Smaller LDL particles are more atherogenic and high concentrations often occur in association with elevated circulating triglyceride concentrations (but frequently normal total LDL-cholesterol), increased hepatic lipase activity (HL) and insulin resistance. Information on LDL subclasses and HL activity in women with PCOS is sparse. The aim of this study was to determine the concentrations of small, dense LDL (LDL-III) in women with PCOS relative to body mass index (BMI)-matched controls. We also examined the association of lipoprotein subfraction concentrations with endogenous sex hormone concentrations, since existing literature suggested that androgens up-regulate and oestrogens down-regulate HL activity, a key determinant of LDL subfraction distribution. DESIGN: Cross sectional study. PATIENTS: Fifty-two women with oligomenorrhoea and polycystic ovaries determined by ultrasound and BMI matched women with normal menstrual rhythm (NMR) and normal ovarian appearances (n = 14) were recruited from gynaecology clinics. Anthropometric data and fasting blood samples were obtained for metabolic, hormonal and LDL subfraction estimation and a heparin provocation test was used to estimate HL activity. RESULTS: Subjects with PCOS demonstrated higher waist:hip ratio (WHR), testosterone, triglyceride, VLDL-cholesterol concentrations, and HL activity (P < 0.05), whereas SHBG concentrations were significantly lower than controls. PCOS women had higher concentrations (38.0 vs. 25.0 mg/l; P = 0.026) and proportions (12.8 vs. 8.2%; P = 0.006) of small, dense LDL (LDL III), relative to controls. Within the PCOS group, plasma triglyceride and HL activity were the strongest univariate predictors of LDL III mass. They remained as independent predictors in multivariate analysis, and together accounted for 37% of its variability (P = 0.0002). Independent predictors of plasma triglyceride and HL in turn, were measures of fat distribution (waist circumference or WHR) and fasting insulin concentration. Serum testosterone concentration was not associated either in univariate or multivariate analysis with any of the measured lipid, lipoprotein or subfraction parameters, nor with HL activity in the women with PCOS. CONCLUSION: We conclude that women with polycystic ovary syndrome have increased hepatic lipase activity and mass and percentage of small, dense low density lipoprotein relative to body mass index-matched controls with normal menstrual rhythm and normal ovaries. Further, these metabolic perturbances appear related more closely to adiposity/insulin metabolism than to circulating androgen levels.

Effects of the insulin sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea.

Hyperinsulinaemic insulin resistance is commonly associated with hyperandrogenaemia, and menstrual dysfunction. The aim of this study was to examine the effects of the insulin sensitizing drug, metformin, on ovarian function, follicular growth, and ovulation rate in obese women with oligomenorrhoea. Twenty obese subjects with oligomenorrhoea [polycystic ovarian syndrome; (PCOS)] were observed longitudinally for 3 weeks prior to and for 8 weeks during treatment with metformin (850 mg twice per day). Fifteen patients completed the study. The frequency of ovulation was significantly higher during treatment than before treatment (P = 0.003). A significant decline in both testosterone and luteinizing hormone concentrations was recorded within 1 week of commencing treatment. Patients with elevated pretreatment testosterone concentrations showed the most marked increase in ovulation rate (P < 0.005), and significant reductions in circulating testosterone from 1.02 to 0.54 ng/ml (P < 0.005) after only 1 week of treatment. However, the sub-group with raised fasting insulin showed less marked changes, and the sub-group with normal testosterone concentrations showed no effect of treatment. Metformin had a rapid effect upon the abnormal ovarian function in hyperandrogenic women with PCOS, correcting the disordered ovarian steroid metabolism and ovulation rate; however, there appeared to be no effect in cases where the circulating androgen concentration was normal.

Audit of infective morbidity following caesarean section at a district general hospital.

This paper sets out to audit infectious morbidity before and after introduction of a policy of antibiotic prophylaxis following emergency and elective caesarean section in a district general hospital in Scotland with approximately 3800 deliveries a year. In the first 'loop of audit', case notes of 200 consecutive patients managed during 1992 were studied. Audit loop was completed by studying 224 patients prospectively in 1993-94 following the introduction of new guidelines, which required the intraoperative administration of a single dose of intravenous antibiotic, following delivery of the baby. A significantly greater proportion of women received prophylactic antibiotics in 1993 compared with 1992 (81% vs. 14%; Diff= 67%; 95% CI 60%, 74%). The incidence of infection related morbidity was significantly reduced after routine antibiotic prophylaxis (28,5% vs. 16%; Diff= 12.5%, 95% CI=(4.60%,20.4%). The incidence of wound infection was halved in 1993 (9% vs. 17.5% in 1992). None of the patients in 1993 had a serious postoperative infection. Postnatal stay was significantly shorter in 1993 compared with 1992 (P < 0.0001). Although the target of adherence to the guidelines of 90% coverage was not met, this audit demonstrates the benefits of antibiotic prophylaxis for emergency and elective caesarean sections. Further reduction in morbidity may be obtained by strictly implementing the guidelines, and also by considering the use of multiple doses of antibiotics.

Colocolic fistula caused by a previously inserted intrauterine device. Case report.

Uterine perforation remains the most serious complication of the intrauterine contraceptive device (IUD). It is more common in the puerperium, usually occurring at the time of insertion of a new device. Perforation may, however, also occur in the puerperium if a pre-existing device is not removed in early pregnancy or extruded at the time of delivery. The case is presented of a 30-year-old woman who became pregnant for the third time following insertion of an IUD in the puerperium of her second pregnancy. An uneventful pregnancy and delivery followed. Failure to detect the IUD at the time of delivery led to laparoscopy and laparotomy to locate the device. A colotomy was necessary to retrieve the device, which had formed a colocolic fistula. It is concluded that the puerperium remains the time of greatest risk of uterine perforation by an IUD. Although most occur at the time of insertion, this complication can also occur with a previously inserted device. Severe intra-abdominal complications may ensue if the device is not localized and removed. Laparotomy is justified if the laparoscopic removal is unsuccessful. A high degree of suspicion is necessary if serious consequences are to be avoided.

PIP: The incidence of uterine perforation following IUD insertion has been estimated as 1.2/1000 insertions. Presented is the case of a 30-year-old woman from Scotland who became pregnant for the third time following insertion of a Multiload Copper 250 device 6 weeks after the delivery of her second child, while she was still breast feeding. The IUD was not removed antenatally because the locator strings could not be visualized. The pregnancy was uncomplicated, with no gastrointestinal symptoms. Failure to detect the IUD at the time of delivery necessitated laparoscopy and laparotomy to locate the IUD and colotomy to retrieve the device. The IUD was located on the left side of the pelvis in the region of the descending colon. One arm had eroded through the full thickness of the sigmoid colon and the other had penetrated the adjacent loop of the colon, forming a colocolic fistula. This case confirms the observation that the puerperium is the time of greatest risk of IUD-caused uterine perforation. Although perforation is most common at the time of insertion, this complication also can occur with a previously placed device. Failure to localize and remove the IUD can result in severe intra-abdominal complications.