These data indicate that moderate weight loss during long-term calorie restriction is associated with a marked clinical improvement which reflects the reduction in insulin concentrations and reciprocal changes in SHBG. The improvement in menstrual function and fertility may therefore be consequent upon an increase in insulin sensitivity which, directly or indirectly, affects ovarian function.

Two hundred and sixty-three women with ultrasound-diagnosed polycystic ovary syndrome were studied of whom 91 (35%) were obese (BMI greater than 25 kg/m2). Obese women with PCOS had a greater prevalence of hirsutism (73% compared with 56%) and menstrual disorders than non-obese subjects. Total testosterone and androstenedione concentrations in serum were similar in the two subgroups but SHBG concentrations were significantly lower, and free testosterone levels higher, in obese compared with lean subjects. In addition, concentrations of androsterone glucuronide, a marker of peripheral 5 alpha-reductase activity, were higher in obese than in non-obese women with PCOS. There were no significant correlations of either SHBG or free testosterone with androsterone glucuronide suggesting that obesity has independent effects on transport and on metabolism of androgen. There were no significant differences between the subgroups in either baseline gonadotrophin concentrations or the pulsatile pattern of LH and FSH secretion studied over an 8-h period. There was, however, an inverse correlation of FSH with BMI, but only in the obese subgroup. In conclusion, the increased frequency of hirsutism in obese compared with lean women with PCOS is associated with increased bio-availability of androgens to peripheral tissues and enhanced activity of 5 alpha-reductase in obese subjects. The mechanism underlying the higher prevalence of anovulation in obese women remains unexplained.

Objective To assess the effect of moderate obesity on the outcome of induction of ovulation with low dose gonadotrophin in women with polycystic ovary syndrome (PCOS). Design Retrospective analysis of women with PCOS treated consecutively. An analysis of the impact of obesity on outcome of pregnancy using data from the North West Thames Regional (NWTR) obstetric database was included for comparison. Setting Induction of ovulation clinic at the Samaritan Hospital for Women (St. Mary's Hospital Group). Subjects 100 women with clomiphene‐resistant anovulation associated with PCOS. 75 were of normal weight (BMI 19–24. 9 kg/m2, lean group) and 25 were moderately overweight (BMI 25–27.9 kg/m2, obese group). Interventions Induction of ovulation using low doses of gonadotrophins with small, stepwise increments in dosage as required. Main outcome measures Rates of ovulation, pregnancy and miscarriage; daily and total doses of gonadotrophin required for induction of ovulation. Results The proportion of ovulatory cycles was significantly greater in the lean group (77%) compared with the obese group (57%) (χ2 9.8, P<0.001). Obese women required larger doses of gonadotrophin to achieve ovulation (P <0.001). The proportion of women who achieved at least one pregnancy was similar in the two groups (39%vs 48%) but miscarriage was more frequent in the obese group (60%vs 27%; P<0.05). This difference was independent of the baseline and/or mid‐follicular luteinizing hormone (LH) concentration either before or during treatment. Analysis of data from the North West Thames Health Region obstetric database confirmed an increased risk of miscarriage in moderately obese women which was independent of maternal age. Conclusions Moderate obesity in women with PCOS, treated with low dose gonadotrophin, is associated with an increased risk of miscarriage. This is reflected in the results of analysis of the effect of obesity on outcome of pregnancy in the general population. It is therefore important to encourage weight reduction in obese women with PCOS before considering therapy to induce ovulation.

Insulin insensitivity in polycystic ovary syndrome occurs when there is oligo/amenorrhoea but not when the menstrual cycle is regular. This is consistent with PCO and insulin insensitivity being separate abnormalities which when combined are associated with anovulation.

Polycystic ovary syndrome is associated with biochemical risk factors for premature vascular disease, which cannot be explained by obesity alone.

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The purpose of this study was to investigate the effect of calorie restriction on serum concentrations of sex hormone binding globulin (SHBG) in women with normal or polycystic ovaries (PCO) and to examine the possible role of insulin and insulin-like growth factor-I (IGF-I) in mediating changes in SHBG levels. Six normal subjects with mean (SD) body mass index (BMI) 25.5 (2.2) and five subjects with PCO (BMI 36.1 (3.7)) were studied before and after 2 or (PCO only) 4 weeks of a very low calorie diet (330 kcal/day; Cambridge Diet). In both normal women and patients with PCO there was a twofold increase in SHBG concentrations after 2 weeks and this was sustained in the PCO subjects for a further 2 weeks. The rise in SHBG was accompanied by a fall in free testosterone concentrations. There were parallel changes in serum insulin and IGF-I concentrations which decreased during the diet and there were significant negative correlations of SHBG with insulin in both normal subjects (r = -0.62) and women with PCO (r = -0.60). In addition, serum concentrations of an insulin-dependent small molecular weight (34 kDa) binding protein for IGF-I (IGF-BPI) increased significantly during dieting in both groups and were negatively correlated with serum insulin (controls, r = -0.56; PCO, r = -0.68) and positively correlated with serum SHBG levels (controls, r = 0.69; PCO, r = 0.63). In summary, these data indicate that in both normal subjects and those subjects with PCO, calorie restriction results in a highly significant increase in SHBG concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

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