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PubMed1995

The effect of sodium valproate on luteinizing hormone secretion in women with polycystic ovary disease.

The aim of this study was to examine whether modulation of the GABA-ergic system (with sodium valproate) affects gonadotropin secretory frequency and amplitude in women with polycystic ovarian syndrome (PCOS). Six women aged 25 +/- 2 years with diagnosed PCOS and six healthy women aged 26 +/- 2 years at day 7-11 of menstrual cycle were included in the study. Sodium valproate 1200 mg p.o./day (600 mg t.i.d.) was administered for five days in both groups. Efficacy of treatment was assessed in women with PCOS by measuring six hour LH pulsatility (every .10 min), and by GnRH tests before and after treatment. Basal serum steroids were assessed as well. Hormones were determined by radioimmunoassay and pulse detection was carried out by the program PULSAR. The administration of valproate did not change basal serum LH concentration (9.1 +/- 0.6 vs 9.0 +/- 0.8 IU/L p > 0.05) nor LH pulse frequency (7.3 +/- 0.5 vs 6.3 +/- 0.5 p > 0.05) or the LH pulse amplitude (3.0 +/- 0.5 vs 3.5 +/- 0.4 p > 0.05). LH response to GnRH (mean peak 43.6 +/- 5.2 vs 44.1 +/- 6.0 IU/L p > 0.05) did not change either. Valproate did not affect the LH secretory activity in women with PCOS. There was no change in FSH, and prolactin secretion. In five patients with PCOS valproate caused further increase in serum testosterone level but this did not reach significance in the group as a whole (5.6 +/- 1.0 vs 9.1 +/- 2.0 nmol/L p > 0.05).

Adult↗

PubMed1988

Plasma pro-opiomelanocortin fragments and adrenal steroids following administration of metyrapone to normal and hirsute women.

The present study was undertaken to characterize further the adrenal abnormalities in the polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH). We have previously reported the close association of elevated estrone levels with amenorrhea in hyperandrogenemic patients. In addition we have suggested that high estrone levels in PCOS occur as a consequence of the provision of excess substrate, androstenedione, for conversion to estrone. In the present study plasma estrone levels rose following endogenous adrenal stimulation induced using metyrapone; the highest plasma estrone levels achieved were seen in patients with PCOS and occurred later than peak androstenedione levels. These findings are consistent with the hypothesis that elevated estrone levels occurring in PCOS may arise as a consequence of increased adrenal androgen secretion. In addition, we have examined ACTH and other pro-opiomelanocortin (POMC) fragments in an attempt to identify a factor responsible for the excessive adrenal androgen secretion occurring in hirsute patients. Plasma levels of ACTH, and of immunoreactive beta-endorphin and h-lipotropin were not elevated when androgen levels were raised prior to therapy, although these POMC fragments, and also the 16K fragment, rose in response to metyrapone treatment as did androgen levels. Following treatment with dexamethasone there was more profound suppression of the 16K, beta-endorphin and h-lipotropin responses to metyrapone stimulation, than of the ACTH response, as indicated by decreased POMC-fragment/ACTH ratios; this parallels the dissociation of cortisol from androgens in hirsute patients under similar conditions. However, we have not identified a POMC fragment which consistently parallels changes in androgen levels in patients with idiopathic hirsutism or PCOS.

Administration, Oral↗

PubMed1998

The pathogenesis of polycystic ovary syndrome: lessons from ovarian stimulation studies.

In polycystic ovary syndrome (PCOS) the ovary produces markedly increased amounts of both androgens and estrogens in response to gonadotropin stimulation. Distinctive responses of 17-hydroxyprogesterone and androstenedione to ovarian stimulation testing suggest that ovarian hyperandrogenism is a result of dysregulation of theca cell androgen production which is intrinsic to the ovary. The occurrence of hyperestrogenism together with hyperandrogenism in PCOS suggests that whatever the abnormality of local regulatory factors of steroidogenesis, it affects granulosa as well as theca cells. Dysregulation is often associated with an increase in the number of follicles which evade atresia and reach the 2-8 mm stage of development. Autocrine/paracrine factors, especially those which are FSH-dependent, likely play an important role in the pathogenesis of the ovarian abnormality. Both LH and insulin hypersecretion probably play a secondary role in PCOS by amplifying the preexisting ovarian dysregulation. Because FSH secretion is under tight long-loop negative-feedback control and LH is not, hyperandrogenism is the primary clinical manifestation of dysregulation of steroid production in PCOS. However, anovulation in PCOS is most likely a result of excessive estrogen and inhibin production by multiple, small follicles which inhibit FSH secretory dynamics sufficiently to prevent selection of a dominant follicle.

Androgens↗

PubMed1998

Polycystic ovary syndrome and insulin resistance: thrifty genes struggling with over-feeding and sedentary life style?

Almost two decades of research have greatly increased our knowledge in the complex field of metabolic aberrations in polycystic ovary syndrome, but still many problems remain unsolved. The statistical association between insulin levels and androgens originally put the focus on possible direct cause-and-effect relationships between these factors. Indeed there is evidence that insulin may affect ovarian functions in multiple ways, presumably in some cases causing anovulation and hyperandrogenism. Clearly, insulin may increase biologically active testosterone through reducing SHBG levels. Conversely, major increases in androgen levels may induce muscular changes leading to reduced insulin-mediated glucose uptake. There are suggestions of increased steroidogenesis in both ovarian and adrenal pathways, with the net result of increased androgen production. There are also findings supporting increased corticosteroid production, which could contribute to insulin resistance directly or through promoting accumulation of abdominal fat, a typical feature of over-weight women with PCOS. Free fatty acids, released in great amounts from abdominal fat, may induce insulin resistance. Insulin resistance may also be due to a primary aberration in the insulin receptor. Putatively increased serine phosphorylation may cause both impairment of the insulin signal and increased 17,20 lyase activity, thus suggesting a common cause for insulin resistance and increased androgen production. There are also findings supporting a high prevalence of beta-cell dysfunction in PCOS, ranging from increased insulin secretion, not explained by insulin resistance or BMI, to failing beta-cell function, mainly in obese women during progress to glucose intolerance and NIDDM. Recent genetic findings also support a multifactorial genesis to PCOS, notably with positive findings both in genes regulating steroidogenesis and insulin secretion. It is suggested that PCOS is the result of "thrifty" genes, providing advantages in times of shortage of nutrition such as muscular strength, moderate abdominal fatness and decreased insulin sensitivity, i.e. an anabolic, energy saving constitution. However, when this constitution is exposed to unlimited food supplies and modern sedentary life style a full-blown PCOS with insulin resistance and infertility is triggered, presumably via several mechanisms, which follow a logical amplification system between two basic anabolic hormones, insulin and testosterone.

Body Composition↗

PubMed2002

Prevalence of Type II diabetes mellitus and insulin resistance in parents of women with polycystic ovary syndrome.

AIMS/HYPOTHESIS: Insulin resistance with increased risk of Type II (non-insulin-dependent) diabetes is a common feature of polycystic ovary syndrome (PCOS). To investigate antecedents of metabolic disorders in family members of patients with PCOS, we evaluated glucose tolerance and insulin resistance in parents of patients with PCOS compared to parents of healthy women. METHODS: A total of 200 parents of women with clinical and hormonal evidence of PCOS (PCOSp) and 120 parents of healthy normally cycling women (HWp) were studied. A 75-g OGGT was performed and subjects were classified according to the World Health Organization (WHO) criteria (1999). Serum glucose and insulin were measured before the glucose load and 30, 60 and 120 min after. C-peptide and sex hormone-binding globulin were also determined before the glucose load. Insulin resistance was assessed by HOMA model and ISI composite. RESULTS: The prevalence of Type II diabetes was 1.89-(1.06-3.38)-fold higher in PCOSp compared to HWp. Insulin resistance, evaluated by HOMA(IR)and ISI composite was also significantly higher in the PCOSp group compared to the HWp group. After both study groups were distributed by sex, and adjusted by age and BMI, the metabolic parameters were still significantly different between PCOSp and HWp. CONCLUSIONS/INTERPRETATION: The data suggest that parents of PCOS women exhibit insulin resistance and Type II diabetes more frequently than those of healthy women, thus constituting a high-risk group but an ideal cohort to detect and prevent the development of Type II diabetes.

Adolescent↗

PubMed2006

Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling.

AIMS/HYPOTHESIS: Polycystic ovary syndrome (PCOS) is a risk factor of type 2 diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been recommended, but this is relatively time-consuming and inconvenient. Thus, a strategy that could minimise the need for an OGTT would be beneficial. MATERIALS AND METHODS: Consecutive PCOS patients (n=118) with fasting glucose <6.1 mmol/l were included in the study. Parameters derived from medical history, clinical examination and fasting blood samples were assessed by decision tree modelling for their ability to discriminate women with IGM (2-h OGTT value >/=7.8 mmol/l) from those with NGT. RESULTS: According to the OGTT results, 93 PCOS women had NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of luteinising hormone:follicle-stimulating hormone. This tree identified 69 women with NGT. The remaining 49 women included all women with IGM (100% sensitivity, 74% specificity to detect IGM). Pruning this tree to three levels still identified 53 women with NGT (100% sensitivity, 57% specificity to detect IGM). Restricting the data matrix used for tree modelling to medical history and clinical parameters produced a tree using BMI, waist circumference and WHR. Pruning this tree to two levels separated 27 women with NGT (100% sensitivity, 29% specificity to detect IGM). The validity of both trees was tested by a leave-10%-out cross-validation. CONCLUSIONS/INTERPRETATION: Decision trees are useful tools for separating PCOS women with NGT from those with IGM. They can be used for stratifying the metabolic screening of PCOS women, whereby the number of OGTTs can be markedly reduced.

Adult↗

PubMed2006

Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metalloproteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats.

One of the characteristics of polycystic ovary syndrome (PCOS) is the presence of cystic follicles in various stages of growth and atresia, the latter of which is known to be the result of apoptosis and tissue remodeling. To further investigate the process of follicular atresia, we compared ovarian expression and localization of Fas, Fas ligand (FasL), casapse-8 and membrane-type1 matrix metalloproteinase (MT1-MMP) in rats treated with dehydroepiandrosterone (DHEA) as a model of PCOS, and in control rats. We found that the numbers of TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive follicles were significantly higher in ovaries from PCOS rats than in those from control rats (P < 0.05), as were ovarian levels of FasL mRNA and protein, processed caspase-8 protein and MT1-MMP mRNA. Correspondingly, we also observed an increase in the level of MTI-MMP catalytic activity and a decrease in the level of pro-caspase-8 protein. In addition, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TUNEL-positive apoptotic granulosa cells within atretic follicles of PCOS ovaries. Our results suggest that under the PCOS-like conditions induced by DHEA, the Fas/FasL/Caspase-8 (death receptor dependent) pathway is pivotal for follicular atresia, and that increased levels of MT1-MMP likely play an important role in tissue remodeling during structural luteolysis.

Animals↗

PubMed1996

Epithelial ovarian cancer risk among women with polycystic ovary syndrome.

OBJECTIVE: To investigate the relationship between polycystic ovary syndrome (PCOS) and ovarian cancer, and to present three hypotheses regarding hormonal factors and the risk of ovarian cancer in women. METHODS: Data were analyzed from a population-based, case-control study, the Cancer and Steroid Hormone Study, to test the hypotheses. Four hundred seventy-six subjects with histologically confirmed epithelial ovarian cancer were identified from eight tumor registries of the Surveillance Epidemiology and End Results program. The study included 4081 controls ascertained via random-digit telephone dialing. All subjects and controls were aged 20-54 years. RESULTS: Seven subjects with ovarian cancer and 24 controls reported that they had been diagnosed with PCOS before the study period. Ovarian cancer risk was found to increase 2.5-fold (95% confidence interval [CI] 1.1-5.9) among women with PCOS. This association is found to be stronger among women who never used oral contraceptives (odds ratio [OR] 10.5, 95% CI 2.5-44.2) and women who were in the first quartile of body mass index (13.3-18.5 kg/m2) at age 18 (OR 15.6, 95% CI 3.4-71.0). CONCLUSION: The data suggest that the hormonal status of women with PCOS featuring abnormal patterns of gonadotropic secretion (enhanced levels of LH) in lean women may be a mitigating factor for the observed association between PCOS and ovarian cancer. We hope that our preliminary data stimulate further investigation of the testable hypotheses.

Adult↗

PubMed2004

Intima-media thickness of elastic and muscular arteries of young women with polycystic ovaries.

BACKGROUND: Polycystic ovary syndrome (PCOS) occurs in around 10% women of reproductive age and is characterised by obesity, hyperandrogenism, insulin resistance and adverse lipid profile. This suggests that these women may be at an increased risk of coronary artery disease at a young age. The objective of this study was to measure the intima-media thickness (IMT) in the carotid bulb (CB), common carotid (CCA) and common femoral (CFA) arteries in young women aged less than 35 years. METHODS: A total of 43 age-matched women were recruited; 19 symptomatic women with PCOS, 12 asymptomatic women with polycystic ovaries (PCO) and 12 staff volunteers with normal ovaries on transvaginal scan. All subjects were examined with ultrasound wall tracking system for IMT measurements. Their age, body mass index, heart rate, systolic and diastolic blood pressures, fasting endocrine and biochemical parameters were also measured. RESULTS: The IMT measurements were significantly higher in both the CFA and the CCA in young women with PCOS compared with controls (CFA, 0.74 +/- 0.30 mm versus 0.42 +/- 0.078 mm, P < 0.001 and CCA, 0.54 +/- 0.11 mm versus 0.40 +/- 0.01 mm, respectively, P < 0.006). After adjustment for known risk factors, the IMT in both the femoral and carotid arteries remained highly significant. CONCLUSIONS: The results of this study suggest that PCOS affects femoral and carotid wall mechanics leading to premature sub-clinical atherosclerosis in young women with PCOS and may lead to the development of new strategies for screening.

Adolescent↗

PubMed2005

Laparoscopic ovarian drilling in polycystic ovary syndrome.

BACKGROUND AND OBJECTIVE: Patients with polycystic ovary syndrome (PCOS) treated with gonadotrophins often have a polyfollicular response and are exposed to the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. The aim of the present study was to evaluate the efficacy of laparoscopic ovarian drilling (LOD) on the endocrinologic, clinical parameters and reproductive outcome of clomiphene-resistant anovulatory infertile patients with PCOS using monopolar diathermy. MATERIAL AND METHODS: Forty-five clomiphene-resistant anovulatory women with PCOS have participated in the study. Serum testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH), fasting insulin and glucose levels, body mass indexes, modified Ferriman Gallwey (FG) hirsutism scores of the subjects are recorded before and after the procedure. Endocrinologic and clinical profile and reproductive outcome of the patients were analysed. RESULTS: Ovarian drilling was successfully employed without any surgical complications and mean +/- S.D. duration of follow-up time was 29.73 +/- 10.64 months. In the follow-up period 93.3% of the subjects were recorded to have regular cycles and 64.4% pregnancy rate was achieved, spontaneously. The serum levels of T, free T, LH, LH:FSH ratio, insulin and FG scores were significantly reduced after LOD, although glucose levels and glucose/insulin ratio remained unchanged. CONCLUSION: In choosing ovulation induction method in clomiphene resistant PCOS patients, LOD may avoid or reduce the risk of OHSS and multiple pregnancy than gonadotrophins with the same success rate of conception. The high pregnancy rate, and economic aspect of the procedure offer an attractive management for patients with PCOS.

Adult↗

PubMed2005

A polymorphism of the plasminogen activator inhibitor-1 gene promoter and the polycystic ovary syndrome.

OBJECTIVE: To investigate the association of a common 5G/4G polymorphism of the plasminogen activator inhibitor-1 gene (PAI1) with occurrence and clinical characteristics of the polycystic ovary syndrome (PCOS). STUDY DESIGN: In a case-control study, we evaluated a series of 106 Caucasian women with PCOS and 102 healthy controls. Women completed a detailed questionnaire and underwent a peripheral venous puncture, ultrasonography, and a standardized oral glucose tolerance test (OGTT). The PAI1 gene promoter polymorphism was evaluated using PCR. RESULTS: Allele and genotype frequencies were not significantly different among women with PCOS and controls (P=0.3 and 0.6, respectively). In women with PCOS, presence of the 5G/4G polymorphism of PAI1 was not associated with changes in serum hormone levels or with clinical characteristics. CONCLUSIONS: The 5G/4G polymorphism of the PAI1 promoter is not associated with occurrence and phenotype of the PCOS.

Adult↗

PubMed2005

Are there differences in ultrasound parameters between Chinese women with polycystic ovaries only and with polycystic ovary syndrome?

OBJECTIVE: We aimed to compare antral follicle count (AFC), ovarian volume, ovarian stromal blood flow between Chinese women with polycystic ovary (PCO) only and polycystic ovary syndrome (PCOS) and to evaluate the effect of age on these ultrasound parameters in these women. STUDY DESIGN: In the second to fourth day of the period, they underwent a transvaginal three-dimensional scanning with power Doppler to determine total AFC, total ovarian volume, total ovarian vascularization index (VI), flow index (FI) and vascularization flow index (VFI). Hormonal profile was also measured. RESULTS: A total of 71 Chinese women were recruited in the study: 39 women with PCO only and 32 women with PCOS. Women with PCO only had significantly lower AFC, ovarian volume, ovarian VI, serum LH, testosterone and DHEAS concentrations but higher serum SHBG concentration when compared with PCOS women. When women with PCO only and PCOS were considered together, the rate of decline of AFC over age was 0.905 follicle per year (95% CI=0.008-1.803, p=0.048) and there was no significant decline of ovarian volume and total ovarian VI, FI and VFI over age. CONCLUSION: PCO only represents a milder end of the PCOS spectrum.

Adult↗

PubMed2005

The association of serum androgens and insulin resistance with fat distribution in polycystic ovary syndrome.

OBJECTIVE: The aim of the study was to compare the body fat distribution of women with polycystic ovary syndrome (PCOS) with age and body mass index matched healthy controls and to investigate if androgens and insulin resistance associated with fat distribution. STUDY DESIGN: Thirty-three PCOS and 21 age and body mass index (BMI) matched healthy control women were evaluated in terms of body fat distribution with dual X-ray absorpsiometry (DEXA). Blood samples were obtained for follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, thyroid stimulating hormone (TSH), dehydroepiandrosterone-sulfate (DHEA-S), free testosterone, sex hormone binding globulin (SHBG), insulin and glucose levels. A 75 g 2 h glucose tolerance test was performed for each woman. Insulin resistance was estimated by fasting insulin level, fasting glucose/insulin ratio and 75 g 2 h glucose tolerance test. The Student's t-test and Mann-Whitney U-test were used to compare the groups. Pearson and Spearman rank correlation coefficients were calculated for normally and nonnormally distributed variables, respectively. Partial correlation coefficients were calculated using age and BMI as covariates. RESULTS: Fat mass in trunk and arms were significantly higher in patients with PCOS (p < 0.043 and 0.036, respectively). The ratio of fat mass in trunk to fat mass in legs were significantly higher in patients with PCOS (p < 0.011). Free testosterone was found to be positively correlated with fat mass in arms (r = 0.401, p < 0.05). There was still significant correlation between free testosterone and fat mass in arms (r = 0.5964, p < 0.05) after controlling for age and BMI. CONCLUSION: Free testosterone level is positively correlated with the fat mass in arms in women with PCOS.

Absorptiometry, Photon↗

PubMed2006

Indices of insulin sensitivity, beta cell function and serum proinsulin levels in the polycystic ovary syndrome.

BACKGROUND: The study aim was to investigate the relationship between insulin resistance (IR), beta-cell function (betaF), hyperandrogenism and proinsulin levels during an oral glucose tolerance test (OGTT) in women with polycystic ovary syndrome (PCOS). METHODS: One hundred and twenty-six selected women were classified as follows: PCOS, BMI > 25 kg/m2 (n = 39); PCOS, BMI < 25 kg/m2 (n = 54); controls, BMI > 25 kg/m2 (n = 14); controls, BMI < 25 kg/m2 (n = 19). Blood samples were collected between the third and sixth day of a spontaneous menstrual cycle, at 9:00 a.m., after an overnight fast. Serum levels of FSH, LH, PRL, 17alpha-OH-progesterone, SHBG, testosterone, delta4-androstenedione, insulin, proinsulin and glucose were measured. A 75 g OGTT was performed, and concentrations of glucose, insulin and proinsulin were also measured at t = 30, 60, 90, and 120 min. RESULTS: The markers of insulin secretion and the AUC for proinsulin were higher in obese and overweight women and in women with PCOS, respectively. The AUC for proinsulin was positively correlated with markers of IR, betaF and androgen levels. An inverse relationship between PI/I values and indices of IR and betaF was observed. CONCLUSIONS: Increased proinsulin levels reflect, most probably, insulin resistance, which is the key disorder in PCOS-associated metabolic abnormalities. Beta-cell function, pre-proinsulin mRNA processing and proinsulin conversion to insulin could be initially increased as a result of IR. An interaction between circulating proinsulin and androgen biosynthesis or action might also exist.

Adolescent↗

PubMed2006

Serum levels of 3alpha-androstanediol glucuronide in young women with polycystic ovary syndrome, idiopathic hirsutism and in normal subjects.

OBJECTIVE: The study objective was to assess the role of 3alpha-androstanediol glucuronide (3alpha-diolG) as the marker of peripheral androgen action in the young women with hirsutism diagnosed as polycystic ovary syndrome (PCOS), in patients with idiopathic hirsutism (IH) and in normal non-hirsute women. STUDY DESIGN: Fifty-nine young women with mean age 21.90+/-3.52 years suffered from hirsutism were included in the study. Among these 59 hirsute women 31 women with mean age 21.60+/-3.56 years were diagnosed as PCOS and 28 women with mean age 22.20+/-3.59 years were classified as idiopathic hirsutism patients. Twenty-seven normal women, age-matched (mean age 22.60+/-2.90 years), without signs of hirsutism and with normal menstrual cycle served as control for this study. Serum was collected from women with hirsutism (due to PCOS or idiopathic hirsutism) and from non-hirsute women. Serum levels of 3alpha-androstanediol glucuronide (3alpha-diolG), main androgens such as: testosterone, free testosterone, dehydroepiandrosterone (DHEAS) and also others hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and sex hormone-binding globuline (SHBG) were measured using radioimmunoassay (RIA) method in the study and control group. Hirutism was assessed using modified Ferriman-Gallwey method. Serum 3alpha-diolG levels in PCOS women were significantly higher than in controls. RESULTS: There were no significant differences between serum 3alpha-diolG levels in PCOS group and IH group. Similarly, there were significant differences between serum 3alpha-diolG levels in IH group and control subjects. CONCLUSION: We conclude that 3alpha-diolG is not useful as the marker for peripheral androgen metabolism and for differentiation between idiopathic hirsutism and PCO-related hirsutism.

Adolescent↗

PubMed2006

Nitric oxide and fibrinogen in polycystic ovary syndrome: associations with insulin resistance and obesity.

OBJECTIVE: Nitric oxide (NO) and fibrinogen levels, two markers of vascular disease, are associated with insulin resistance, a common trait in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Case-control study including 31 women with PCOS and 21 age-matched women with regular, ovulatory cycles, normal androgen levels and idiopathic hirsutism (control group). Nitrite/nitrate concentration (index of endothelium-derived NO) and fibrinogen plasma levels were assessed and analysed in association with anthropometric, metabolic and hormonal variables. RESULTS: The groups were similar in terms of age, positive family history of diabetes and Ferriman-Gallwey hirsutism score. Nitrite/nitrate and fibrinogen levels were also similar in the two groups. In contrast, in PCOS patients, insulin levels and the homeostatic model assessment were negatively correlated with NO production (r=-0.39, p=0.03 and r=-0.41, p=0.02, respectively). Age, BMI, waist circumference and waist-to-hip ratio were positively correlated with fibrinogen in both groups. CONCLUSION: The present data indicate a negative, BMI-independent association between NO levels and insulin resistance in PCOS patients. Further studies are required to clarify the role of androgens on the pathogenesis of endothelial dysfunction in PCOS and investigate androgen action and/or the gene receptor modulating NO secretion.

Adult↗

PubMed2004

Glucose action and adrenocortical biosynthesis in women with polycystic ovary syndrome.

OBJECTIVE: To determine if insulin or glucose action plays a role in adrenocortical steroidogenesis in the polycystic ovary syndrome (PCOS). DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENT(S): Nine reproductive-aged patients with PCOS and nine age-, race-, and body mass index-matched controls. MAIN OUTCOME MEASURE(S): Insulin-modified frequently sampled intravenous glucose tolerance testing and an acute 60-minute ACTH-(1-24) stimulation test. From the glucose tolerance test, glucose and insulin were measured and the insulin sensitivity index, glucose effectiveness, and acute insulin response to glucose were determined. Dehydroepiandrosterone sulfate (DHEAS) basally and 17-hydroxypregnenolone, 17-hydroxyprogesterone, DHEA, androstenedione, and cortisol during ACTH testing at 0 and 60 minute (steroid(0) and steroid(60)) were determined. The net change in steroid during the ACTH test was calculated. RESULT(S): The insulin sensitivity index had limited correlation with adrenocortical variables in both groups. In patients with PCOS, glucose effectiveness was positively associated with DHEAS, cortisol(0), cortisol(60), change in cortisol, DHEA(0), DHEA(60), change in DHEA, 17-hydroxyprenenolone(60), change in 17-hydroxypregnenolone, DHEA(0), androstenedione(0), 17-hydroxyprenenolone(0), 17-hydroxyprogesterone(0), 17-hydroxyprenenolone(60), and 17-hydroxyprogesterone(60). CONCLUSION(S): Adrenocortical biosynthesis, basally and in response to ACTH, appears to be closely associated with glucose effectiveness in PCOS. A common factor determining both the effectiveness of glucose to control its own production or uptake and adrenocortical biosynthesis may be aberrant in PCOS.

17-alpha-Hydroxypregnenolone↗

PubMed2004

A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome.

OBJECTIVE: We performed this study as a pilot experiment to investigate the short term effects of two diets of varying composition on weight loss as the primary outcome in obese women with polycystic ovary syndrome (PCOS) seeking fertility. DESIGN: Randomized clinical trial. SETTING: Academic medical center. PATIENT(S): Thirty-five obese women with PCOS. INTERVENTION(S): We examined the effects of a 1-month dietary intervention on the PCOS phenotype. Participants were randomized to one of two energy-restricted diets; high protein (HP: 30% protein, 40% carbohydrate, and 30% fat) or high carbohydrate (HC: 15% protein, 55% carbohydrate, and 30% fat). The fat content was held constant in both diets. MAIN OUTCOME MEASURE(S): Primary - change in body weight; Secondary - biometric, hormonal, lipid and lipoprotein, and markers of glucose homeostasis and energy metabolism. RESULT(S): Twenty-six women completed the study. Both the HP (-3.7 +/- 1.9 kg) and HC (-4.4 +/- 1.5 kg) diets resulted in significant weight loss, but there was no significant difference in mean weight loss between the two groups. There were also no differences between diets on a variety of measures including circulating androgens, measures of glucose metabolism, and leptin. However, the effects of a hypocaloric diet per se on improving metabolic and reproductive abnormalities in a group of PCOS women were marked by a decline in circulating androgens (P=.03), fasting and area under the curve (AUC) insulins (P<.05) on a 3-hour oral glucose tolerance test (OGTT), and fasting and AUC leptin levels (P<.0001). There was a high prevalence of menstrual bleeding during the trial (14 out of 26 patients). CONCLUSION(S): Those who completed the short-term hypocaloric diet had a significant weight loss and a significant improvement in their reproductive and metabolic abnormalities. There was no increased benefit to a high-protein diet. Future diet studies evaluating the ideal composition of a hypocaloric diet in women with PCOS will require a large study population, and will most likely require a multicenter trial.

Adult↗