Leptin, polycystic ovaries and polycystic ovary syndrome.

As soon as leptin was discovered four years ago, its potential as a player in the polycystic ovary syndrome (PCOS) was explored in a primitive way, though little light was shed on the enigma that is PCOS. As a second wave of leptin research is now available, we review how the expanded role of the cytokine in reproduction might yet impact upon our understanding of PCOS.     

Microvascular dysfunction in women with polycystic ovary syndrome

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with multiple cardiovascular risk factors and an increased prevalence of arterial dysfunction. However, microvascular dysfunction in PCOS has not been assessed. METHODS: Subjects comprised 12 women with PCOS and 12 age-matched controls with normal ovaries. Microvascular function was assessed by observing forearm skin microvascular erythrocyte flux responses, to cumulative iontophoretic doses of 1% (w/v) acetylcholine (ACh) and 1% (w/v) sodium nitroprusside (SNP), using laser Doppler imaging. RESULTS: Basal microvascular perfusion was comparable in PCOS and controls. The increase in skin microvascular perfusion in response to ACh was however generally blunted in PCOS women (P = 0.018). Peak ACh-induced erythrocyte flux was also less (p < 0.04) in PCOS women (125.1 +/- 21.7, i.e. 5.3-fold basal flux) than in controls (200.8 +/- 28.5, i.e. 8.3-fold basal flux). Analysis of covariance indicated this effect was unrelated to differences in body mass index or serum testosterone but serum insulin may be a weak confounder. No differences were noted between the PCOS and control groups in their response to SNP. CONCLUSION: Despite its limited sample size studied, this is the first demonstration that women with PCOS exhibit microvascular endothelial dysfunction, indicated by an inhibited vasodilatory response to ACh.     

Ovarian steroidogenic response to human chorionic gonadotrophin in obese women with polycystic ovary syndrome: effect of metformin.

BACKGROUND: The aim of the present study was to investigate the steroidogenic response pattern to HCG in obese women with polycystic ovary syndrome (PCOS) and the possible effects of metformin treatment on it. METHODS: A single injection of human chorionic gonadotrophin (HCG, 5000 IU) was given to 12 obese [body mass index (BMI) > or = 27 kg/m2] women with PCOS and to 27 control women. Blood samples for assays of 17alpha-hydroxyprogesterone (17-OHP), androstenedione, testosterone and oestradiol were collected at baseline and 1, 2 and 4 days after the injection. Responses to HCG were also assessed in the PCOS women after 2-month treatment with metformin (500 mg x 3 daily). RESULTS: Serum 17-OHP and oestradiol concentrations peaked at 24 h in the PCOS women and preceded the maximum testosterone concentration, which was seen at 48 h. In the control women the maximum concentrations of all these steroids were reached 96 h after HCG. After metformin treatment, the basal serum testosterone concentration and the areas under the androstenedione (AUC(A)) and testosterone (AUC(T)) response curves after HCG decreased significantly. CONCLUSIONS: The results demonstrate that obese PCOS women have a male-type steroidogenic response pattern to a single injection of HCG and a higher androgen secretory capacity than control women, which may be explained by the increased thecal cell activity in the polycystic ovary. The slight alleviation of hyperandrogenism brought about by metformin therapy appears to be due to its effect on ovarian steroidogenesis possibly mediated by decreased insulin action.     

Metabolic syndrome in young Czech women with polycystic ovary syndrome

METHODS: Sixty-nine young women with polycystic ovary syndrome (PCOS) [age 25.2+/- 4.7 years, with body mass index (BMI) 24.3 +/- 4.8 kg/m2; mean 6 SD] and 73 age-matched healthy females (BMI 22.3 +/- 3.3 kg/m2; mean +/- SD) were evaluated for the occurrence of features of metabolic syndrome according to the Adult Treatment Panel III. RESULTS: Overt metabolic syndrome (the presence of three and more risk factors) was not more common in PCOS women (1/64, 1.6%) than in healthy controls (0/73, 0%). On the other hand, in nearly 50% of PCOS women isolated features of metabolic syndrome, most often a decrease in high-density lipoprotein (HDL) cholesterol, were found. Women with at least one feature of metabolic syndrome were, in comparison with women without any of these features, significantly more obese (P = 0.0001), with lower insulin sensitivity (P = 0.05). When comparing PCOS women according to the degree of insulin sensitivity, as determined by euglycaemic clamp, isolated features of metabolic syndrome were found in 8/17 women above the upper quartile, compared with 11/16 women below the lower quartile of insulin sensitivity (P = 0.20). CONCLUSIONS: Overt metabolic syndrome is only rarely encountered in young Czech females affected by PCOS but its isolated features are relatively frequent, both in young PCOS patients and in age-matched control women.     

Comparison of ovarian stromal blood flow between fertile women with normal ovaries and infertile women with polycystic ovary syndrome

BACKGROUND: Conflicting information exists in the literature with respect to ovarian stromal blood flow in women with polycystic ovary syndrome (PCOS). We compared the ovarian stromal blood flow and serum vascular endothelial growth factor (VEGF) concentration between fertile women with normal ovaries and infertile women with PCOS. METHODS: In the second to fourth day of the menstrual period, they underwent transvaginal scanning with three-dimensional (3D) power Doppler to determine total antral follicle count (AFC), total ovarian volume, total ovarian vascularization index (VI), flow index (VFI) and vascularization flow index (VFI). Serum FSH, LH and VEGF concentrations were also checked. RESULTS: 107 fertile controls and 32 PCOS women were recruited. Fertile controls and PCOS women had similar total ovarian VI/FI/VFI after controlling for age of the woman, although PCOS women had significantly higher total AFC, total ovarian volume and serum LH concentration than fertile controls. Total ovarian VI/FI/VFI were significantly higher in normal weight (BMI < 25 kg/m2) PCOS women than their overweight (> or = 25 kg/m2) counterparts. CONCLUSIONS: Fertile controls and PCOS women had similar total ovarian 3D power Doppler flow indices. Normal weight PCOS women had significantly higher total ovarian 3D power Doppler flow indices than their overweight counterparts.     

Ovarian stromal echogenicity in women with normal and polycystic ovaries

Since the widespread use of transvaginal ultrasound to diagnose polycystic ovary syndrome (PCOS), a cardinal feature has been shown to be the presence of a bright, highly echogenic stroma. This is usually assessed subjectively. The objective of this study was to determine whether ovarian stromal echogenicity when measured objectively actually differed between women with polycystic ovaries and those with normal ovaries. A total of 67 women underwent a detailed ultrasound assessment before considering assisted conception treatment. Ovarian morphology was assessed and total ovarian volume, stromal volume, peak stromal blood flow velocity and mean stromal echogenicity were measured. The stromal index (ratio of mean stromal echogenicity to mean echogenicity of the entire ovary) and total stromal echogenicity were also calculated. Ovarian volume, stromal volume, and stromal peak blood flow velocity were all significantly higher in ovaries from women with PCOS. There was no difference in the mean stromal echogenicity, although the stromal index was significantly greater in women with polycystic ovaries. The apparent subjective increase in stromal echogenicity in women with polycystic ovaries, as exemplified by the greater stromal index, is due to a combination of the increased volume of ovarian stroma and the significantly lower mean echogenicity of the entire ovary in these women.     

Abnormal glucose tolerance in Chinese women with polycystic ovary syndrome

BACKGROUND: The aims of this study were to analyse the prevalence of impaired glucose tolerance (IGT) and diabetes mellitus (NIDDM) in Chinese polycystic ovary syndrome (PCOS) patients and to assess the ability of screening tests to predict these abnormalities within this population. METHODS: A total of 102 PCOS patients were evaluated. All patients underwent oral glucose tolerance tests (OGTTs) with blood samples taken at 0, 1 and 2 h. The 2-h plasma glucose level was used to categorize subjects as having IGT or NIDDM. RESULTS: The prevalence of IGT was 20.5% and that of NIDDM was 1.9%. There was no significant relationship between BMI and 2-h plasma glucose levels. The areas under the receiver operating characteristic (ROC) curve for glucose to insulin ratio (G:I), homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were 0.702, 0.734 and 0.733 respectively. ROC analysis suggested a threshold value of 10.7 in G:I ratio (73.9% sensitivity and 59.5% specificity), a value of 2.14 in HOMA (73.9% sensitivity and 73.4% specificity) and a value of 0.34 in QUICKI (73.9% sensitivity and 73.4% specificity) for the prediction of abnormal glucose tolerance (IGT and NIDDM). CONCLUSIONS: Chinese women with PCOS are at increased risk of IGT and NIDDM. Even though G:I, HOMA and QUICKI are easier than OGTT, they could not replace the role of 2-h post-challenge plasma glucose level in the screening of IGT and NIDDM in PCOS women.     

Pioglitazone and metformin in obese women with polycystic ovary syndrome not optimally responsive to metformin

BACKGROUND: In an observational study of 13 women with polycystic ovary syndrome (PCOS) not optimally responsive to metformin diet, we assessed the efficacy and safety of addition of pioglitazone. We also compared these 13 women to 26 women with PCOS, who were responsive to metformin diet, matched by age and by pre- treatment menstrual history and not different by obesity categories. METHODS: Prospectively, as outpatients, with diet constant [1500-2000 calorie (depending on entry body mass index), 26% protein, 44% carbohydrate, 30% fat], metformin (2.55 g/day) was given for 12 months to 39 women, 13 not optimally responsive, 26 responsive to metformin diet, followed by addition of pioglitazone (45 mg/day) for 10 months in the 13 non-responders. Outcome measures included changes in sex hormones, insulin, insulin resistance (IR), insulin secretion, high density lipoprotein cholesterol, weight, and menstrual status. RESULTS: In 13 non-responders, on metformin diet, median serum insulin fell (21 to 16 microIU/ml, P<0.05) and insulin secretion fell from 251 to 200 (P<0.01); weight, dehydroepiandrosterone sulphate (DHEAS), testosterone and IR were unchanged (P> or =0.07). Compared with 14% pre- treatment, on metformin diet, expected menses occurred 46% of the time at 3 months (P=0.05), 38% at 6 months (P=0.07), 27% at 9 months, and 24% at 12 months. In 26 responders, on metformin diet, median weight fell (93 to 87 kg), testosterone fell (50 to 32 ng/dl), insulin fell (26 to 16 microIU/ml), IR fell (5.32 to 3.45) and insulin secretion fell (351 to 271) (P< or =0.017 for all). The occurrence of expected menses in the 26 responders was 2.5-fold higher than in the 13 non-responders (P<0.0001). In 11 non-responders, on pioglitazone + metformin diet over 10 months versus antecedent metformin diet, DHEAS fell (211 to 171 microg/dl, P=0.02), insulin fell (16 to 10 microIU/ml, P= 0.001), IR fell (3.37 to 1.73, P=0.002), insulin secretion fell (217 to 124, P=0.004), sex hormone-binding globulin rose (31 to 43 nmol/l, P=0.006), and HDL cholesterol rose (38 to 42 mg/dl, P=0.003). On pioglitazone + metformin diet, the occurrence of expected menses was 2-fold higher than on metformin diet (P<0.0001). CONCLUSIONS: In women with PCOS who failed to respond optimally to metformin, when pioglitazone was added, insulin, glucose, IR, insulin secretion, and DHEAS fell, HDL cholesterol and sex hormone-binding globulin rose, and menstrual regularity improved, without adverse side-effects.     

Endocrinology: Normal serum uric acid concentrations in women with polycystic ovary syndrome

Recently, an inverse correlation between serum uric acid concentrationsand insulin sensitivity has been described in subjects withvarying degrees of metabolic syndrome, suggesting that measurementof serum uric acid may provide a simple marker of insulin resistance.Several biochemical and clinical features of polycystic ovarysyndrome (PCOS) resemble those of metabolic syndrome: womenwith PCOS are often obese; they are also at increased risk forthe development of coronary artery disease, hypertension anddiabetes mellitus. The objective of the present study was toanalyse the usefulness of serum uric acid measurement in screeningfor the metabolic syndrome in women with PCOS. For that purposeserum concentrations of uric acid, insulin and triglycerideswere measured in 38 women with PCOS and 20 weight-matched controlwomen with regular menstrual cycles. No differences were foundin the uric acid concentrations between the PCOS and controlgroups. The mean concentrations of triglycerides and fastinginsulin were higher in the women with PCOS than in the healthycontrols. Serum uric acid concentrations were inversely relatedto serum hormone-binding globulin (SHBG) concentrations, andpositively with body mass index (BMI), insulin concentrationsand testosterone:SHBG ratio in the PCOS group. Our results suggestthat measurement of serum uric acid does not provide new meansfor identification of metabolic syndrome in patients with PCOS.     

Mechanism and management of ovulatory failure in women with polycystic ovary syndrome

Polycystic ovary syndrome is the most important cause of chronicanovulation. In women who fail to respond to clomiphene, low-doseFSH given in a step-wise fashion can induce normal folliculargrowth and ovulation. The failure of the action of endogenousFSH in these women may be related to reduced biological activityof circulating FSH, but may also involve inhibition of its actionat follicular level by polypeptide growth factors such as EGF.     

Endocrinology: Subjects with polycystic ovaries without hyperandrogenaemia exhibit similar disturbances in insulin and lipid profiles as those with polycystic ovary syndrome

Polycystic ovaries (PCO) are detected using ultrasonographyin a proportion of women who do not have clinical symptoms ofthe polycystic ovary syndrome (PCOS). The aim of this studywas to compare the metabolic and endocrine differences betweenwomen with such ultrasound-detected PCO and women with PCOS,and to relate these changes to clinical presentation with particularreference to cycle irregularity. A group of 118 women showingPCO on vaginal ultrasound scan was divided into those who hadno hyperandrogenaemia (n = 21) and those who had increased androgensand a clinical presentation normally associated with PCOS (n= 97). These were compared with a reference group of 26 normalsubjects. Glucose tolerance, lipid concentrations and endocrineprofiles were compared between groups. Apart from higher concentrationsof androgens in the PCOS group, there were no significant differencesbetween the PCO and PCOS groups in either fasting and stimulatedinsulin and glucose or in concentrations of sex hormone-bindingglobulin, gonadotrophins and blood lipids or in ovarian volume.Both PCO and PCOS subjects with cycle irregularity had significantlyhigher concentrations of serum fasting and stimulated insulinindependent of androgens and body mass index than those withnormal cycles. It was concluded that: (i) PCO and PCOS patientshave equivalent disturbances in relation to insulin and glucosemetabolism as well as lipid and lipoprotein disturbances comparedto reference subjects; (ii) higher serum insulin values areassociated with menstrual irregularity in both groups; (iii)ultrasound evidence for PCO predicts similar metabolic sequelaeto PCOS and can therefore be used for studies of the geneticsand long term risks for this condition.     

Comparative study of plasma ghrelin levels in women with polycystic ovary syndrome, in hyperandrogenic women and in normal controls

BACKGROUND: Ghrelin is a novel peptide associated with energy balance, obesity, and perhaps gonadal function. The present study was designed in order: (i) to compare plasma ghrelin levels between women with PCOS, women who presented only with hyperandrogenaemia and healthy controls; and (ii) to investigate the relationship between circulating ghrelin and the heterogeneity of clinical and biochemical manifestations of PCOS. METHODS: Two hundred and fifty-nine women with PCOS, 25 women who had only hyperandrogenaemia and 46 controls, were studied. Women with PCOS were further divided, based on the presence of chronic anovulation, biochemical hyperandrogenaemia, clinical hyperandrogenism, and polycystic ovary morphology on ultrasound evaluation. In all women, the basal levels of gonadotrophins, androgens, 17-OH-progesterone, sex hormone-binding globulin, glucose, insulin and ghrelin were measured. RESULTS: Women with PCOS had lower ghrelin levels, compared to both women with hyperandrogenaemia and controls; women with hyperandrogenaemia had lower ghrelin levels, compared to controls, but not significantly so. While PCOS-associated hyperandrogenaemia was inversely related to ghrelin levels, anovulation and polycystic ovary morphology were associated with higher concentrations. Ghrelin levels were negatively correlated with 17-OH-progesterone levels. CONCLUSIONS: In PCOS, circulating ghrelin and androgens are inversely related and it is possible that this peptide is involved in steroidal synthesis and/or action. It is also likely that different clinical and biochemical manifestations of the syndrome are also associated with different ghrelin concentrations.     

Vascular dysfunction during pregnancy in women with polycystic ovary syndrome

BACKGROUND: An association has been proposed between polycystic ovary syndrome (PCOS) and pregnancy-induced hypertensive disorders. Ambulatory blood pressure and carotid artery elasticity were therefore prospectively investigated in matched PCOS and control pregnancies. METHODS: Twenty-two PCOS-control subject pairs with singleton pregnancies, matched for age, body mass index, parity and ethnicity, were recruited in the first trimester (T1, 11-13 weeks). Ambulatory blood pressure recording for 24 h and carotid artery ultrasound for elasticity estimation were performed in T1 and in the second (T2, 22-24 weeks) and third (T3, 32-34 weeks) trimesters. RESULTS: At nearly all time points during gestation, ambulatory systolic, diastolic and mean arterial pressures were elevated in PCOS versus control pregnancies. Carotid artery stiffness index was greater and compliance was less in PCOS pregnancies compared with controls. Differences in night-time systolic pressure and carotid artery elasticity were greatest in T3. PCOS also increased the incidence of pregnancy-induced hypertension (6 of 22 cases versus 0 of 22 in controls; P = 0.011). CONCLUSIONS: Pregnant women with PCOS have higher baseline ambulatory blood pressure and impaired arterial elasticity, suggestive of disturbed vascular adaptation to pregnancy.     

Difference in body weight between American and Italian women with polycystic ovary syndrome: influence of the diet

BACKGROUND: The study aim was to determine differences in body mass in two populations of women (USA and Italy) with polycystic ovary syndrome (PCOS), and to assess the effect of diet on body mass and cardiovascular risk factors. METHODS: Pools of women with PCOS from the USA (n = 343) and Italy (n = 301), seen between 1993 and 2001, were available for assessment. From these populations, 20 women who were seen consecutively in 2001 at each site had detailed analyses of diet and cardiovascular risk factors. RESULTS: In the entire group, American women had a significantly higher body mass compared with Italian women (P < 0.01). Also, the 20 women consecutively evaluated in the USA had a significantly higher mean (+/- SD) body mass index (40.3 +/- 1.0 kg/m(2)) than in Italy (29.7 +/- 1.0 kg/m(2)). US women had worse insulin resistance, lower levels of high-density lipoprotein-cholesterol (HDL-C) (P < 0.01) and higher levels of triglycerides (P < 0.01). Dietary analysis in the two groups indicated that the total daily calorific intake was similar (USA 2277 +/- 109; Italy 2325 +/- 68 Kcal), with no appreciable differences in dietary content of protein, carbohydrate and fat. However, the dietary saturated fat content was significantly higher in US women (31.9 +/- 3 versus 18.2 +/- 2 g/day, P < 0.01). Saturated fat intake correlated negatively with HDL-C (P < 0.01). CONCLUSIONS: Among women with PCOS, body mass was significantly higher in US women compared with Italian women. However, total calorie intake and dietary constituents were similar, except for a higher saturated fat in US women. It is hypothesized that diet alone does not explain differences in body mass; genetic and lifestyle factors likely contribute. An increased saturated fat intake may worsen the cardiovascular risk profile.     

High ovulatory rates with use of troglitazone in clomiphene-resistant women with polycystic ovary syndrome.

This preliminary report reviews our experience with 18 infertile patients with clomiphene-resistant polycystic ovary syndrome (PCOS). In the first treatment cycle, troglitazone was administered alone. During cycles 2-5, clomiphene was added with increments of 50 mg (up to 200 mg/day) if the previous cycle was anovulatory. Basal body temperature charts and serum progesterone were obtained to confirm ovulation. In a total of 66 treatment cycles, ovulation occurred in 44 (67%) and pregnancy in seven (11%). There were no significant changes in body weight, waist:hip ratio or liver enzymes during treatment. Troglitazone, alone or with clomiphene, induced ovulation in 15 of 18 patients (83%) and seven (39%) of them achieved pregnancy. This is the first report on ovulatory rates in clomiphene-resistant women with PCOS when troglitazone was used alone or with clomiphene. Recently, metformin and clomiphene were successfully used in women with PCOS. However, our patients represent a more resistant population of women with PCOS, with each patient serving as her own historical control by previous resistance to clomiphene. Although the pregnancy rate (39%) was promising for clomiphene-resistant women with polycystic ovary syndrome, it does not seem to have a definite advantage over gonadotrophins.     

Patterns of hormonal response to the GnRH agonist leuprolide in brothers of women with polycystic ovary syndrome: a pilot study

BACKGROUND: The aim of this study was to evaluate the effect of a single dose of leuprolide acetate on gonadotrophin and gonadal steroid secretion in brothers of women with polycystic ovary syndrome (PCOS), in order to assess P450c17alpha activity. An oral glucose tolerance test (OGTT) and a lipid profile were also performed. METHODS: Twenty-two unrelated brothers of women with PCOS (PCOS(b)) and 14 brothers of normal cycling women (C(b)), matched for age, underwent a leuprolide acetate test (10 microg/kg s.c.) and an OGTT with measurement of circulating concentrations of gonadotrophins, steroid hormones, glucose, insulin and lipids. RESULTS: Clinical and basal hormonal parameters were similar in both groups. After leuprolide administration, PCOS(b) exhibited a significant increase of 17alpha-hydroxyprogesterone (17-OHP) compared to C(b) (P<0.05). However, only 45% of PCOS(b) showed a supranormal increase of 17-OHP (2 SD above the respective control group mean values, P<0.003) with a normal gonadotrophin response (group 1). The other 55% of the PCOS(b) exhibited a normal 17-OHP response to the analogue (group 2). However, in group 2, basal steroid concentrations did not show a uniform pattern: six of the PCOS(b) exhibited high basal androstenedione (2 SD above the respective control group mean values), three were very similar to C(b), and the other three presented lower basal testosterone concentrations (2 SD below the respective control group mean values) than those observed in C(b). CONCLUSIONS: This study shows that different responses to leuprolide in PCOS brothers make evident the heterogeneity of this syndrome in which P450c17alpha activity could be involved.     

Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome

BACKGROUND: Visfatin, a protein secreted by adipose tissue, is suggested to play a role in pathogenesis of insulin resistance. In polycystic ovary syndrome (PCOS), insulin resistance might be involved in the development of endocrine and metabolic abnormalities. The aim of the study was to asses the relation between serum visfatin concentration and insulin sensitivity and markers of hyperandrogenism in lean and obese PCOS patients. METHODS: The study group consisted of 70 women with PCOS (23 lean and 47 obese) and 45 healthy women (25 lean and 20 obese). Euglycemic hyperinsulinemic clamp and the measurements of serum visfatin, sex hormones were performed. RESULTS: The PCOS group had lower insulin sensitivity (P=0.00049) and higher serum visfatin (P=0.047) in comparison to the control group. The decrease in insulin sensitivity was present in both the lean (P=0.019) and obese (P=0.0077) PCOS subjects, whereas increase in serum visfatin was observed only in lean PCOS subjects (P=0.012). In the whole group, serum visfatin was negatively correlated with insulin sensitivity (r=-0.27, P=0.004). This relationship was also observed in the subgroup of lean (r=-0.30, P=0.038), but not obese women. Additionally, in lean women, visfatin was associated with serum testosterone (r=0.47, P=0.002) and free androgen index (r=0.48, P=0.002), independently of other potential confounding factors. CONCLUSIONS: Visfatin is associated with insulin resistance and markers of hyperandrogenism in lean PCOS patients.     

Influence of hypo- and hyperglycaemia on plasma leptin concentrations in healthy women and in women with polycystic ovary syndrome

BACKGROUND: Insulin resistance and obesity play an important role in the pathogenesis of polycystic ovary syndrome (PCOS). It is known that experimentally induced insulin resistance diminishes the stimulatory effect of insulin on leptin secretion. It is not yet known whether the long-term insulin resistance as found in PCOS patients alters the leptin response to hypo- and hyperglycaemia. METHODS: We induced hyper- and hypoglycaemia by glucose clamp technique in 7 patients with PCOS and 20 healthy controls. After a plasma glucose level of 8.8 mmol/l was reached, the plasma glucose level was reduced stepwise to 6.8, 4.8 and 2.8 mmol/l. RESULTS: The PCOS patients required lower glucose infusion rates to reach the glycaemic targets (P < 0.05). Serum insulin and C-peptide concentrations increased significantly during the clamp compared with the baseline in both groups (P < 0.001 for insulin, and P < 0.001, P < 0.005 for C-peptide control and PCOS, respectively) and increased significantly more in PCOS patients compared with the control group (both P < 0.05). Basal leptin levels were significantly higher in the PCOS group than in the control group (P = 0.005). In the controls, the leptin concentration increased significantly during the clamp (P < 0.001 for each glycaemic target), whereas in the PCOS group, leptin secretion increased only during hypoglycaemia (P = 0.04). CONCLUSIONS: Compared with the healthy controls, the response of leptin secretion to hyper- and hypoglycaemia was diminished in PCOS patients. Changes in leptin secretion seem not to be caused by hyper- and hypoglycaemia, but rather by hyperinsulinaemia. Reduced insulin sensitivity seems to be responsible for the diminished leptin response, which might contribute to the obesity found in PCOS patients.     

Women with polycystic ovary syndrome gain regular menstrual cycles when ageing

The aim of this study was to investigate if previously oligo- or amenorrhoeic polycystic ovary syndrome (PCOS) patients gain regular menstrual cycles when ageing. Women registered as having PCOS, based on the combination of oligo- or amenorrhoea and an increased LH concentration, were invited by letter to participate in a questionnaire by telephone. In this questionnaire we asked for the prevalent menstrual cycle pattern, which we scored in regular cycles (persistently shorter than 6 weeks) or irregular cycles (longer than 6 weeks). We interviewed 346 patients of 30 years and older, and excluded 141 from analysis mainly because of the use of oral contraceptives. The remaining 205 patients showed a highly significant linear trend (P < 0.001) for a shorter menstrual cycle length with increasing age. Logistic regression analysis for body mass index, weight loss, hirsutism, previous treatment with clomiphene citrate or gonadotrophins, previous pregnancy, ethnic origin and smoking showed no influence on the effect of age on the regularity of the menstrual cycle. We conclude that the development of a new balance in the polycystic ovary, solely caused by follicle loss through the process of ovarian ageing, can explain the occurrence of regular cycles in older patients with PCOS.     

The effects of the somatostatin analogue octreotide on ovulatory performance in women with polycystic ovaries

The elevated luteinizing hormone (LH) and androgen concentrationscharacteristic of women with polycystic ovaries (PCO) are consideredcrucial factors in their infertility. The somatostatin analogueoctreotide lowers LH and androgen concentrations in women withPCO. The effects of octreotide given concurrently with humanmenopausal gonadotrophin (HMG) were therefore compared withthat of HMG alone in 28 infertile women with PCO resistant toclomiphene. In 56 cycles of combined HMG and octreotide therapythere was more orderly follicular growth compared with the multiplefollicular development observed in 29 cycles in which HMG wasgiven alone (mean number of follicles > 15 mm diameter onthe day of human chorionic gonadotrophin (HCG) administration:2.5 ± 0.2 and 3.6 ± 0.4 respectively; P = 0.026).There was a significantly reduced number of cycles abandoned(>4 follicles > 15 mm diameter on day of HCG) in patientstreated with octreotide + HMG, so that HCG had to be withheldin only 5.4% of cycles compared to 24.1% with HMG alone (P <0.05). The incidence of hyperstimulation was also lower on combinedtreatment. Octreotide therapy resulted in a more ‘appropriate’hormonal milieu at the time of HCG injection, with lower LH,oestradiol, androstenedione and insulin concentrations. Althoughgrowth hormone concentration was similar on both regimens, significantlyhigher insulin growth factor-I concentrations were observedon the day of HCG in women on combined therapy than on HMG alone.