Brachial artery conductance during reactive hyperemia is increased in women with polycystic ovary syndrome

Objective

To examine changes in brachial artery conductance (BAC) during reactive hyperemia in women with polycystic ovary syndrome (PCOS) compared to controls.

Study design

This is a pilot case-control study performed at a single academic medical center. Changes in BAC during reactive hyperemia were evaluated in 31 women with PCOS and 11 healthy control women. Fasting glucose, insulin, lipids and androgen levels were also determined. A mixed-effects model was used to compare the PCOS curve to the control curve for change in BAC from baseline during reactive hyperemia.

Results

Body mass index (BMI) and testosterone levels were significantly increased in the PCOS group compared to controls (P < 0.05). In addition, the PCOS group had higher total and LDL cholesterol levels (P = 0.05 and 0.09, respectively). Change in BAC from baseline during reactive hyperemia was significantly increased in the PCOS group compared to controls even after adjusting for age, BMI and LDL cholesterol levels (P < 0.0001). There were no significant differences between the two groups in age, blood pressure, or fasting glucose or insulin levels.

Conclusions

Brachial artery conductance during reactive hyperemia is significantly increased in women with PCOS compared to controls and may be a novel early indicator of increased cardiovascular risk in women with PCOS.     

Three-dimensional power Doppler imaging in the diagnosis of polycystic ovary syndrome

Objective

To determine the role of three-dimensional (3D) power Doppler imaging in the diagnosis of polycystic ovary syndrome (PCOS).

Methods

Pulsatility index (PI) and resistance index (RI) of the uterine artery and ovary were measured by two-dimensional (2D) Doppler imaging, while vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured by 3D power Doppler in 25 patients with PCOS and 25 women with normal menstrual cycles used as a control group.

Results

Uterine artery PI and RI were significantly higher (P < 0.001) and ovarian PI and RI were significantly lower (P < 0.001) in women with PCOS compared with controls. Ovarian VI and VFI were significantly higher in women with PCOS compared with the control group (P < 0.001).

Conclusion

3D power Doppler indices were higher in women with PCOS than in the control group and were positively correlated with 2D color Doppler indices, and clinical and hormonal parameters. High 3D power Doppler indices may be useful as one of the diagnostic criteria for PCOS.     

Bilateral uterine artery ligation plus B-Lynch procedure for atonic postpartum hemorrhage with placenta accreta

Objective

To assess the effectiveness of bilateral uterine artery ligation followed by B-Lynch compression suturing in women with atonic postpartum hemorrhage and placental site bleeding due to adherent placenta accreta.

Method

This protocol was followed in 26 women undergoing cesarean delivery for placenta accreta.

Results

Two women died from disseminated intravascular coagulopathy. In the remaining 24 women, placental remnants completely disappeared within 8 months and ovulation resumed after a mean ± SD of 51.6 ± 3.2 days. Moreover, 18 women (75%) became pregnant within 12 months.

Conclusion

Atonic postpartum hemorrhage and placental site bleeding due to adherent placenta accreta can be safely controlled by bilateral uterine artery ligation followed by B-Lynch compression suturing in women who desire to remain fertile.     

Modified Ferriman-Gallwey hirsutism score and androgen levels in Turkish women

Objective(s)

To evaluate a modified Ferriman-Gallwey (mFG) scoring system and serum total testosterone (tT) and dehydroepiandrosterone sulfate (DHEAS) levels, in women with polycystic ovary syndrome (PCOS) and in control subjects.

Study design

Women with any gynecological problem who presented to the Kahramanmaras Sutcuimam University Medical Faculty Gynecology and Obstetric Outpatient Clinic in the Mediterranean region of Turkey were assessed prospectively. Oligo-anovulation, clinical and biochemical hyperandrogenism, and PCO appearance on ultrasound that met the 2003 Rotterdam Consensus Criteria were used for PCOS diagnosis. Group 1 consisted of 43 cases with a diagnosis of PCOS and group 2 (control group) consisted of 75 age and BMI matched control subjects without PCOS.

Results

In groups 1 and 2, clinical hyperandrogenism (hirsutism) appearance ratio was 86.0% (37/43) and 18.0% (15/75) (p < 0.001); while biochemical hyperandrogenism (high serum tT or DHEAS level) was 65.1% (28/43) and 36% (27/75) (p < 0.05), respectively. In groups 1 and 2, mean serum tT levels were 115.2 and 73.4 ng/dL (p < 0.001), mean serum DHEAS levels were 256.1 and 177.7 ng/dL (p < 0.001), and mean hirsutism scores were 11.2 and 5.5 (p < 0.001), respectively. Serum mean tT, DHEAS and hirsutism scores for group 1 were significantly higher than those of group 2 (<0.001). No correlation was observed between BMI and the hirsutism scores or the biochemical hyperandrogenism in both groups.

Conclusion(s)

In our study, mean serum androgen levels and hirsutism ratio in the PCOS group were higher than the control group. These values were also substantially higher than those previously published in the literature.     

Apnea-hypopnea index in nonobese women with polycystic ovary syndrome

Objective

To assess the influence of polycystic ovary syndrome (PCOS) on respiratory events during sleep in nonobese Taiwanese women.

Method

Overnight polysomnography was recorded in 18 nonobese women with PCOS who had not received treatment (body mass index [BMI] 21.7 ± 0.57, age 29.1 ± 1.43 years) and in 10 age- and BMI-matched women without PCOS (BMI 20.9 ± 0.58, age 31.6 ± 3.87 years).

Results

The nonobese women with PCOS had a higher total apnea-hypopnea index (AHI) especially during the non-rapid eye movement stage (AHI_NREM) than the women who did not have PCOS. The women with PCOS had higher serum levels of high-sensitivity C-reactive protein (hsCRP) and this was positively correlated with AHI_REM. Total testosterone level was positively correlated with AHI_NREM, and androstenedione was negatively correlated with AHI_NREM.

Conclusion

PCOS was directly linked to increased obstructive respiratory events during sleep in nonobese women in Taiwan.     

Flujo sanguíneo de las arterias renales fetales en preeclámpticas graves y embarazadas normotensas sanas

Objective

To compare the blood flow in fetal renal arteries in severe preeclamptic and healthy normotensive pregnant women.

Method

The sample consisted of 30 women with severe preeclampsia (group A) and 30 healthy normotensive pregnant women (group B) with single pregnancies of more than 30 weeks. The pulsatility and resistance indexes of the uterine, umbilical, fetal middle cerebral and fetal renal arteries were measured.

Results

There were no significant differences in maternal age, gestational age or newborn weight (p = ns). Pulsatility and resistance index values in the uterine and umbilical arteries were significantly higher and both measurements for the fetal middle cerebral artery were significantly lower in group A than in group B (p = 0.0001). Pulsatility and resistance index values in the fetal renal artery were significantly higher in group A than in group B (p = 0.0001). The fetal renal artery pulsatility index was significantly correlated with the pulsatility index of the uterine artery (p = 0.011) and the fetal middle cerebral artery (p < 0.007). The fetal renal artery resistance index was correlated with the resistance index of the three vessels (p < 0.05).

Conclusion

Women with severe preeclampsia show blood flow alterations in the fetal renal arteries compared with healthy normotensive pregnant women.     

Polycystic ovary syndrome and increased polyp numbers as risk factors for malignant transformation of endometrial polyps in premenopausal women

Objective

To determine the pre-malignant and malignant potential of endometrial polyps and to assess whether different clinical parameters are associated with malignancy in the polyps of premenopausal women.

Methods

The clinical records of operative office hysteroscopic and resectoscopic procedures for endometrial polyps in 417 premenopausal women who attended Baskent University were examined over a retrospective period of 30 months. Only premenopausal patients were included in the study.

Results

In 97.8% of women, histology showed benign endometrial pathology. In 2.2% of women, pre-malignant or malignant conditions were found in the polyp. Polycystic ovary syndrome (PCOS) and the presence of 2 or more polyps were associated with significant pre-malignant or malignant changes.

Conclusion

The presence of irregular vaginal bleeding was not a predictor of malignancy in the polyp. Premenopausal women with PCOS and those with 2 or more polyps had an increased prevalence of polyp malignancy. These groups of patients, whether symptomatic or not, should be evaluated by hysteroscopic resection of the polyps.     

Color Doppler analysis of pelvic arteries following bilateral internal iliac artery ligation for severe postpartum hemorrhage

Objective

To compare Doppler blood flow characteristics of the uterine, arcuate, and ovarian arteries of women who underwent bilateral internal iliac artery ligation with those of controls.

Methods

Thirteen women who underwent bilateral internal iliac artery ligation for severe postpartum hemorrhage (PPH) were matched with 15 healthy women of reproductive age. Transvaginal color and pulsed (duplex) Doppler modes were used to visualize the pelvic arteries. The pulsatility index, the resistance index, the systolic/diastolic blood flow ratio, the peak systolic velocity, and the end-diastolic velocity were measured.

Results

The mean age was 26.1 ± 5.2 years in the study group and 27.0 ± 5.4 years in the control group. All participants had regular menstrual periods. There were no significant differences between the groups regarding each of the vascular indices for the uterine, arcuate, and ovarian arteries.

Conclusion

These findings are consistent with published data demonstrating that pelvic circulation is not compromised after bilateral internal iliac artery ligation.     

Preliminary uterine artery ligation versus pericervical mechanical tourniquet in reducing hemorrhage during abdominal myomectomy

Objective

To compare the effectiveness of preliminary uterine artery ligation versus pericervical mechanical tourniquet in reducing hemorrhage during myomectomy.

Methods

A total of 103 patients undergoing myomectomy were randomly allocated to undergo preliminary uterine artery ligation (52 patients) or pericervical tourniquet (51 patients). The primary outcome measure was estimated blood loss. Secondary outcomes included duration of the operation, duration of hospital stay, postoperative hemoglobin, and the need for postoperative analgesia.

Results

Operative blood loss was significantly less with uterine artery ligation compared with tourniquet (433.80 ± 285.21 vs 823.23 ± 237.33 mL, P < 0.001). The mean duration of the operation was lower in the uterine artery ligation group compared with the tourniquet group (50.5 ± 8.7 vs 76.3 ± 9.4 minutes, P < 0.001). Postoperative hospital stay was significantly shorter in the uterine artery ligation group compared with the tourniquet group (4.1 ± 0.1 vs 5.1 ± 0.2 days; P < 0.001). Postoperative hemoglobin concentrations and the need for postoperative analgesia were higher in the uterine artery ligation group (P = 0.012 and P < 0.001, respectively).

Conclusion

Uterine artery ligation was more effective than pericervical tourniquet as a preliminary step in reducing blood loss during abdominal myomectomy.     

Polycystic ovary syndrome and abnormalities in glucose tolerance

Objectives

To compare the prevalence of abnormal glucose tolerance (AGT) among women with polycystic ovary syndrome (PCOS) and controls, and assess risk factors associated with PCOS.

Method

A fasting oral glucose tolerance test after ingestion of 75 g of glucose was administered to 264 women with and 116 without PCOS. Moreover, fasting glucose, insulin, and testosterone levels were measured in the women with PCOS. Body mass index (BMI), waist-to-hip ratio (WHR), and homeostasis model assessment-insulin resistance (HOMA-IR) were calculated for each woman with PCOS.

Results

The AGT prevalence was 14.4% in the PCOS group and 11.2% in the control group (P = 0.17). The women with both PCOS and AGT had significantly higher BMIs, WHRs, testosterone levels, and HOMA-IR values than those with normal glucose tolerance.

Conclusion

While AGT was not associated with PCOS, the women with both PCOS and AGT were significantly more obese, hyperandrogenic, and insulin resistant than those with PCOS and normal glucose tolerance.     

Uterine artery embolization versus laparoscopic occlusion of uterine vessels for management of symptomatic uterine fibroids

Objective

To evaluate the efficacy and complications of uterine artery embolization (UAE) versus laparoscopic occlusion of uterine vessels (LOUV) in the management of symptomatic fibroids.

Methods

A pilot randomized clinical trial in which 20 patients with symptomatic fibroids were randomly allocated into two groups. Ten women underwent UAE, and 10 women underwent LOUV. Symptomatic improvement in menorrhagia and reduction in the volumes of the uterus and the fibroid were assessed at 3 and 6 months.

Results

The patients were comparable with regard to age and parity. At 6 months, there was no significant difference in the mean reduction in menstrual blood loss, uterine volume, and volume of the dominant fibroid between the two groups (P = 0.436, P = 0.796, P = 1.00, respectively). However, higher pain scores were recorded on day 1 in the UAE group compared with the LOUV group (P = 0.0002).

Conclusions

The effects of UAE and LOUV in the management of symptomatic fibroids are comparable. The main advantage of LOUV is less postoperative pain compared with UAE.     

Determinants of fertility and reproductive success after hysteroscopic septoplasty for women with unexplained primary infertility: a prospective analysis of 88 cases

Objective

To evaluate prospectively the effect of hysteroscopic septoplasty as therapy for unexplained primary infertility in women with uterine septum as a sole cause for reproductive failure and to define the factors influencing reproductive success.

Study design

In a prospective comparative study, we enrolled 103 infertile women with uterine septum as a sole cause for reproductive failure. They had had unexplained primary infertility >2 years and a follow-up >12 months. Uterine anomalies were diagnosed by means of hysterosalpingography (HSG) and 2D-transvaginal sonography (TVS) with intrauterine saline infusion. Hysteroscopic septoplasty was performed in the early follicular phase. Pregnancy rates (PR) according to patient and septum characteristics (septum size) were the main outcome measures.

Results

Follow-up was complete for 88 patients. The mean (±SD) age of the patients was 36.1 ± 2.1 years. Forty-two patients became pregnant (40.7%). The mean (±SD) delay in conception was 7.5 ± 2.6 months. Nearly 80% of the pregnant women conceived spontaneously. Of 44 pregnancies in 42 women, 36 live newborns were delivered. The PR was significantly higher in women <35 years of age or with <3 years of unexplained primary infertility. Moreover, in women with a septum size larger than one-half of their uterine length the PR was significantly higher than those with septum size <1/2 of their uterus (P = .12).

Conclusion

Fertility and pregnancy after hysteroscopic septoplasty in women with unexplained primary infertility and uterine septum as a sole cause for reproductive failure seems to depend on patient age, duration of infertility before septoplasty, and septum size. Women with a septum size larger than one-half of their uterine length have a higher chance of successful pregnancy after hysteroscopic septoplasty.     

Influence of LH and high-density lipoprotein cholesterol (HDL-C) on metformin response in women with polycystic ovary syndrome

Objective

To search for predictors of metformin response in women with polycystic ovary syndrome (PCOS) through a detailed analysis of clinical and laboratory parameters.

Study design

We designed a prospective study to investigate clinical and laboratory parameters to search for predictors of metformin response in women with PCOS. A total of 53 PCOS patients were given metformin 850 mg twice a day for 6 months, after which patients were classified as responders or non-responders. Parameters analyzed for comparison between the two groups were: plasma fasting insulin glucose/insulin ratio; oral glucose tolerance test (OGTT) with insulin (120 min); HOMA and QUICKI tests; total cholesterol and fractions, triglycerides; LH, FSH, estradiol, progesterone, testosterone, androstenedione, 17-OH progesterone, and DHEAS.

Results

From all patients, 30 (56.6%) were responders and 23 (43.3%) were non-responders. Multinomial analysis showed that the positive response to metformin was associated with higher levels of basal LH (p = 0.038) and lower levels of high-density lipoprotein cholesterol (HDL-C) (p = 0.015).

Conclusion

In weight-matched PCOS subjects, laboratory markers might predict the metformin response. Higher levels of basal LH and lower levels of HDL-C are correlated with a positive response to metformin treatment in PCOS subjects.     

Association of biochemical hyperandrogenism with type 2 diabetes and obesity in Chinese women with polycystic ovary syndrome

Objective

To evaluate the effect of hyperandrogenism on metabolic disorders among patients with polycystic ovary syndrome (PCOS) diagnosed using the Rotterdam criteria.

Methods

A retrospective analysis of the clinical records of 883 women with PCOS and 717 premenopausal controls identified from the general population.

Results

A total of 686 (77.7%) patients were classified with PCOS based on National Institutes of Health (NIH) criteria, and 164 out of 197 (83.2%) additional patients had no hyperandrogenism. Women with normal androgen levels exhibited lower frequencies of obesity, type 2 diabetes, acanthosis nigricans, genetic history of diabetes, and elevated Matsuda index compared with hyperandrogenic patients. Hyperandrogenemia, but not hirsutism, was independently associated with the risk for type 2 diabetes (odds ratio [OR] 5.7; P = 0.028) and obesity (OR 1.7; P = 0.005) among Chinese patients with PCOS.

Conclusions

Hyperandrogenemia is associated with type 2 diabetes and obesity in Chinese women with PCOS and should be considered at first-line management of hyperandrogenism and infertility due to PCOS.     

Metabolic and endocrine effects of metformin and metformin plus cyclic medroxyprogesterone acetate in women with polycystic ovary syndrome

Objective

To evaluate the metabolic and endocrine effects of treatment with cyclic medroxyprogesterone acetate (MPA) plus metformin compared with metformin alone in women with PCOS.

Methods

In this prospective randomized study of women with PCOS, 20 women received 850 mg of metformin twice a day, and 20 women received 850 mg of metformin plus 5 mg of MPA twice a day. Body mass index, hormonal and lipid blood profiles, homocysteine blood level, and insulin sensitivities assessed by homeostasis model assessment (HOMA) were recorded at baseline and at 3 months.

Results

Total cholesterol levels decreased in the metformin plus MPA group (P = 0.002) but did not change significantly in the metformin group (P = 0.159). While homocysteine levels remained unchanged in the metformin plus MPA group, they increased significantly in the metformin group (P = 0.002).

Conclusion

There were no adverse effects of short-term cyclic MPA plus metformin treatment on metabolic parameters or insulin resistance in patients with PCOS over a 3-month treatment period.     

Phenotypic expression, body mass index and insulin resistance in relation to LH levels in women with polycystic ovary syndrome

Objective

To evaluate LH levels in women with the classic (1990 criteria) and the newer (2003 criteria) PCOS phenotypes, and to examine the impact of BMI and insulin resistance indices on hormone levels.

Study design

In this controlled clinical study 936 women with PCOS, classified as classic (n = 729) and newer (n = 207), and 204 controls were included. All women were divided into normal-weight (BMI < 25 kg/m²) and overweight plus obese (BMI ≥ 25 kg/m²). Serum LH, FSH, anthropometrics, androgens, fasting insulin and glucose, HoMA-IR, number of follicles, and ovarian volume were assessed.

Results

Women with classic PCOS presented significantly higher LH and LH/FSH ratios, and lower glucose/insulin levels than those with the newer phenotype and controls. Overweight plus obese women of all groups had lower LH levels than normal-weight women. Independent positive correlations between LH and androgens and negative correlation between LH and BMI were found.

Conclusions

The higher LH concentrations of the classic phenotypes of PCOS could be attributed to the higher androgen levels, which desensitize the hypothalamus to the negative feedback regulation by progesterone. Moreover, the lower LH levels of overweight plus obese women of all groups could be attributed to the increased peripheral aromatization of androgens to estrogens in adipose tissue leading to suppression of LH secretion.

Condensation

Both normal-weight and overweight women with classic PCOS phenotypes present higher LH levels and LH-to-FSH ratios than women with similar BMI but the newer phenotypes.     

Bilateral uterine artery ligation via minilaparotomy for heavy menstrual bleeding

Objective

To assess the safety and short-term efficacy of bilateral uterine artery ligation (UAL) via minilaparotomy for the management of heavy menstrual bleeding (HMB).

Methods

A prospective study of 30 women with HMB who underwent UAL. The primary outcome was cumulative treatment failure 12 months after the procedure. Treatment failure was defined as the need for hysterectomy during the follow-up period.

Results

At 12 months, 6 women had undergone hysterectomy for bleeding, for a cumulative failure rate of 20% (95% CI, 9%-38%). The number of bleeding days was significantly reduced by 11.9 ± 1.5 days (P < 0.001) and hemoglobin level significantly increased by 1.3 ± 0.15 g/dL (P < 0.001). Of the 30 women, 24 (80%) were satisfied with the results. No major complications were reported during the procedure or median follow-up period of 13.2 months.

Conclusion

Bilateral UAL is a safe and effective minimally invasive procedure that can provide an alternative treatment for HMB.     

Circulating ghrelin levels and the polycystic ovary syndrome: correlation with the clinical, hormonal and metabolic features

Objectives

Dysregulation of ghrelin levels may lead to physiological problems including obesity and polycystic ovary syndrome (PCOS). The aim of the study was to compare ghrelin levels in women with and without PCOS.

Study design

Serum ghrelin levels (pre- and post-prandial) were compared between 30 Saudi women suffering from PCOS and 30 healthy controls. The relationship between circulating ghrelin levels and other hormones was investigated. Anthropometric measurements were made for all subjects. Biochemical and hormonal investigations included plasma glucose, insulin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17β-estradiol (E2), progesterone, testosterone and sex hormone binding globulin (SHGB), and serum ghrelin levels. The data were statistically analyzed using independent T-test and ANOVA. Correlation studies were performed between ghrelin levels and other variables.

Results

No differences were observed in the levels of ghrelin during fasting and the postprandial period in the PCOS (p = 0.487) and control groups (p = 0.378). A significant inverse correlation was observed in ghrelin levels (fasting and postprandial) levels and BMI (PCOS: r = −0.529; p = 0.009, controls: r = −0.670; p = 0.005); PCOS: r = −0.421; p = 0.007, controls: r = −0.491; p = 0.004 respectively). No correlations between ghrelin levels and other parameters were observed.

Conclusion

The findings of the study suggest that circulating plasma ghrelin levels were found to be normal and were inversely related to BMI in women with PCOS. No relationship between circulating ghrelin levels and the abnormal hormonal pattern of the PCOS were observed.     

Uterine artery embolization for fibroids does not have adverse effects on ovarian reserve in regularly cycling women younger than 40 years

Objective

To evaluate the impact of uterine artery embolization (UAE) for fibroids on ovarian reserve in women younger than 40 years.

Design

Prospective study.

Setting

University-based reproductive endocrinology unit.

Patient(s)

Twenty regularly cycling women aged 33-39 years undergoing UAE for fibroids. All had cycle day 3 FSH levels <10 mIU/mL.

Intervention(s)

Measurements of serum FSH and E₂ levels and of the total ovarian volume and antral follicle number by transvaginal ultrasonography on day 3 of the menstrual cycle preceding UAE and on day 3 of the cycles occurring in months 3, 6, and 12 after UAE.

Main outcome measure(s)

Preprocedural and postprocedural hormone levels, ovarian volumes, and antral follicle numbers.

Result(s)

There were no significant changes from baseline in the mean day 3 FSH and E₂ levels, ovarian volume measurements, and antral follicle numbers measured at 3, 6, and 12 months after UAE.

Conclusion(s)

Although this study might be not sensitive enough to conclude that UAE for fibroids does not interfere with a woman's ovarian status, these data indicate that in this series of reproductive-aged women UAE did not have short- or mid-term effects on ovarian reserve as assessed by hormonal and sonographic parameters.     

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

Objectives

It seems that adipokines participate in disturbances of the function of the hypothalamus-pituitary-ovary axis. The aim of the study was to assess the relationship between plasma adiponectin and resistin levels and insulin resistance and markers of hyperandrogenism in lean and obese PCOS women.

Study design

Forty-one women with PCOS (22 lean and 19 obese) and 16 healthy lean women were enrolled. Body mass and height were measured and body mass index was calculated. In addition to serum glucose, lipids, androgens and insulin, adiponectin and resistin concentration were assessed in the fasting state. The insulin resistance was calculated based on the HOMA-IR.

Results

Similar serum resistin concentrations were found in both PCOS subgroups and controls. The obese PCOS subgroup was characterized by the lowest serum adiponectin level (10.8 ± 8.3, compared with 21.0 ± 15.1 in the normal weight PCOS subgroup and 26.7 ± 12.5 μg/ml in controls). There were no correlations between resistin and adiponectin levels and HOMA-IR values and serum androgen concentrations. Significant positive correlations between adiponectin to resistin ratio and plasma FSH (r = 0.49; p = 0.001) and LH (r = 0.45; p = 0.003) concentrations, and a negative correlation with free androgen index (r = −0.34; p = 0.03) in PCOS group were found.

Conclusions

Obese but not normal weight PCOS women have lower adiponectin levels whereas resistin concentration did not differ in normal weight and obese PCOS compared to control subjects. We hypothesize that changes of the relative proportion of adiponectin to resistin, but not circulating adiponectin and resistin levels themselves, may play a role in hormonal disturbances but not in insulin resistance in PCOS.