Polycystic ovary syndrome: relationship between insulin sensitivity,sex hormone levels and ovarian stromal blood flow

Polycystic ovary syndrome (PCOS) is the most common cause of menstrual disorders ,and is characterized by chronic anovulation ,hyperandrogenism and infertility. In recent years ,it has become apparent that PCOS is also associated with hyperinsulinemia that is probably central to the pathogenesis of PCOS. As a peculiar vascular pattern has been reported to be present in PCOS ,the aim of this study was to investigate intraovarian stromal vascularization in PCOS patients and its possible correlation with sex hormones ,gonadotropins and insulin levels. Twenty-eight oligomenorrheic or amenorrheic patients with PCOS and 14 eumenorrheic women with a PCOS-like ovarian pattern undergoing endocrine screening and ultrasound color Doppler intraovarian blood flow were recruited to the study. Ten healthy women with regular menses represented the control group. Hormonal assays (follicle-stimulating hormone (FSH) ,luteinizing hormone (LH) ,androstenedione ,testosterone ,sex hormone-binding globulin (SHBG) and estradiol), oral glucose tolerance test (OGTT) ,baseline and glucose-induced insulin levels ,and transvaginal ultrasonographic and color Doppler analysis (pulsatility index (PI) ,resistance index (RI) and velocity (V_max) of ovarian stromal flow) were performed in all participants in the early proliferative phase. Endocrine values showed significant differences in PCOS patients compared with PCOS-like women and controls ,while PI and RI indices were significantly higher in controls. PCOS patients were divided into hyperinsulinemic (n = 16) and normoinsulinemic (n = 12). Androstenedione was significantly higher (p < 0.01) in the hyperinsulinemic than in the normoinsulinemic patients and controls ,while SHBG was significantly (p < 0.01) lower in the hyperinsulinemic group. Analysis of color Doppler intraovarian vascularization showed a significantly lower RI and a higher V_max in the hyperinsulinemic subjects than in the normoinsulinemic PCOS patients and controls. An increased stromal blood flow was observed in the PCOS and PCOS-like patients by transvaginal color Doppler evaluation ,but this technique is not able to differentiate these two similar ovarian patterns. However, hyperinsulinemic PCOS patients had an increased vascularity of the ovarian stroma. A strong correlation between hyperinsulinemia ,hyperandrogenism and low SHBG levels was evidenced ,and a hyperinsulinemia-induced mechanism for ovarian stromal angiogenesis is discussed.     

Effects of laparoscopic ovarian drilling on young adult women with polycystic ovarian syndrome

STUDY OBJECTIVE: To assess changes in serum hormone levels and ovarian stromal blood flow after laparoscopic ovarian drilling (LOD) in young adult women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, nonrandomized study (Canadian Task Force classification II-1). SETTING: Tertiary care, major teaching hospitals. PATIENTS: Anovulatory young women with PCOS who were resistant to clomiphene citrate. INTERVENTION: Laparoscopic ovarian drilling. MEASUREMENTS AND MAIN RESULTS: To evaluate the endocrinological effects of LOD, serum leptin, insulin-like growth factor-1, estrone (E1), and estradiol were measured before and after ovarian drilling in the early follicular phase. Three-dimensional transabdominal power Doppler examinations were performed to determine the effects of LOD. Serum leptin was correlated with body mass index (BMI) before LOD. Levels of BMI, fasting blood sugar, and leptin were higher and LH, LH/FSH, and the sugar/insulin ratio were lower in the obese group. There were significant decreases in the free androgen index, and total testosterone, luteinizing hormone (LH), and LH/follicle-stimulating hormone (FSH) levels, and a significant increase in sex hormonebinding globulin (SHBG) concentration in the 3 months after the operation. The vascularization index and vascularization flow index of the intraovarian stroma significantly decreased after treatment. Reversed correlations between leptin and LH, LH/FSH, E1, thyroid-stimulating hormone, and SHBG were noted 3 months after the operation compared with levels obtained before the operation. CONCLUSIONS: Treatment of young adult women with PCOS using LOD did not influence leptin levels but changed the ovarian stromal blood flow dynamics during short-term follow-up. The surgical procedure may be beneficial both to endocrine profiles and to intraovarian stromal flow in patients with PCOS.     

Significance of Doppler ultrasonography in the diagnosis of polycystic ovary syndrome

OBJECTIVE: To investigate the importance of transvaginal color Doppler ultrasonography of uterine and intraovarian arteries in the clinical diagnosis of polycystic ovary syndrome (PCOS). MATERIAL & METHOD: This study was planned as a cohort, controlled, prospective study. A total of 80 participants (40 with PCOS and 40 as a control group) were enrolled in the study. A Doppler system with a 6.0 MHz transvaginal probe was used when performing ultrasonography (USG) and Doppler examinations. Ovarian size and volume, number of follicles and stromal echogenity were evaluated by USG. Doppler flow studies were targeted to uterine and intraovarian arteries and the pulsatility index (PI) was assessed. The concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (T) and dihydroepiandrostenedione sulphate (DHEAS) were measured by immunometric methods. RESULTS: The mean values of the number of follicles and the ovarian volume of both the right and left ovaries were higher in the group with PCOS than the control group (p < 0.05). The mean PI values of the right and left ovaries, respectively, were 0.84 +/- 0.23 and 1.09 +/- 1.17 in the group with PCOS, and 0.88 +/- 0.14 and 0.92 +/- 0.15 in the control group. The mean PI values of the right and left uterine arteries, respectively, were 3.25 +/- 0.98 and 3.33 +/- 1.12 in the group with PCOS, and 3.17 +/- 0.93 and 3.2 +/- 1.38 in the control group (p > 0.05). The correlation analysis of the ovarian volume, the number of follicles and Doppler parameters revealed that there was a positive correlation and statistically significant difference between the right ovarian volume and right uterine artery PI in the group with PCOS and the left ovarian volume and left uterine artery PI in the control group (p > 0.05). The mean stromal PI of the ovarian and uterine arteries were 0.96 +/- 0.61 and 3.29 +/- 1.02 in the group with PCOS and 0.9 +/- 0.12 and 3.19 +/- 1.14 in the control group, respectively (p > 0.05). In the group with PCOS, the mean ovarian volume and the mean number of follicles were 11.46 +/- 4.43 and 13.91 +/- 4.11, respectively, whereas they were 7.63 +/- 2.44 and 5.55 +/- 2.34 in the control group (p < 0.05). CONCLUSION: It is not beneficial to use color Doppler transvaginal ultrasonography in the clinical diagnosis of patients with PCOS.     

The effect of myoinositol on ovarian blood flows in women with polycystic ovary syndrome

To evaluate whether 4 gram myoinositol and 400?mcg folic acid(MYO) therapy has any effects on ovarian stromal blood flow by using pulsed and color Doppler at 3?months follow-up period in polycystic ovary syndrome (PCOS). One-hundred eighty patients were designed into six groups; Group 1: PCOS patients that received OCP containing 30?mcg ethinyl estradiol (EE) plus 3?mg drospirenone (DRP); Group 2: PCOS patients that received MYO; Group 3: PCOS patients that received no medication. Group 4: Healthy patients that received OCP; Group 5: Healthy patients that received MYO; Group 6: Healthy patients that received no medication. Resistance index (RI) and pulsatility index (PI) of both ovaries were assessed. There was a significant increase in RI and PI of both ovarian stromal blood flow women with PCOS who received OCP (Group 1, p?<?.001) and MYO (Group 2, p?<?.001). The rate of increment in both RI and PI values were similar for OCP users (Group 1) and MYO users(Group2) in PCOS patients. MYO therapy reduced ovarian vascularization in both PCOS and healthy users after 3?months and this decrease is especially noticeable in women with PCOS compared to healthy women. OCP therapy also reduced ovarian vascularization just like MYO therapy.     

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.     

三维及彩色多普勒超声对多囊卵巢综合征的辅助诊断价值

目的探讨三维及彩色多普勒超声对多囊卵巢综合征(PCOS)的辅助诊断价值。方法对中国医科大学附属盛京医院2005年2月至2007年6月收治的60例PCOS患者和60例健康育龄女性进行三维及彩色多普勒超声检查,检测卵泡数目、三维容积和血流动力学指标,并进行对比分析。结果PCOS组的卵泡数目、卵巢容积、卵巢间质容积、卵泡容积大于对照组[分别为(16.91±4.34)个、(12.56±3.96)cm3、(11.49±3.50)cm3、(1.07±0.61)cm3对(5.48±2.10)个、(4.76±1.78)cm3、(4.43±1.74)cm3、(0.32±0.21)cm3],差异均有统计学意义(P<0.01);卵巢间质内动脉阻力指数低于对照组(0.53±0.06对0.65±0.09),收缩期峰值血流速度高于对照组[(12.68±3.10)cm/s对(9.30±1.64)cm/s],差异具有统计学意义(分别P<0.01,P<0.05)。结论三维超声和彩色多普勒超声增加了鉴别PCOS的客观定量指标,对多囊卵巢综合征有较高的辅助诊断价值。     

Insulin-lowering medications in polycystic ovary syndrome

A growing body of evidence suggests that serum hyperinsulinemia contributes to the excess ovarian androgen secretion observed in women with PCOS. As a group, women with PCOS are hyperinsulinemic and insulin resistant when compared with weight-matched normal women, but not all PCOS subjects display clear metabolic defects. The small studies using insulin-sensitizing drugs have demonstrated conclusively that a reduction in serum insulin levels is associated with a reduction of ovarian androgen secretion in PCOS, providing further evidence that hyperinsulinemia contributes to hyperandrogenism by increasing ovarian androgen secretion and reducing SHBG. The improvement of serum androgen levels with multiple different drug classes with different mechanisms of actions suggests an effect mediated by reduction in circulating insulin levels rather than a direct ovarian effect of the drugs. Although the studies published to date have increased understanding of the pathophysiologic mechanisms of PCOS, before these drugs can be recommended as first-line therapy for women, longer term clinical trials are needed to compare their safety and efficacy with other established therapies, such as oral contraceptive pills and antiandrogens. Because of the potential direct and unique beneficial effects of these medications on metabolism, studies must be performed to evaluate their efficacy in combination with other therapies, especially oral contraceptives. It is likely that subsets of patients who cannot tolerate traditional medications will be better managed with insulin sensitizers as first-line therapy; however, to date, the optimal way to identify these subjects is unknown. Whether therapy should be limited to subjects with documented hyperinsulinemia also remains unknown.     

Predictive value of glucose–insulin ratio in PCOS and profile of women who will benefit from metformin therapy: Obese,lean, hyper or normoinsulinemic?

OBJECTIVE: The aim of the present study is to evaluate sub-groups of PCOS patients who will benefit from metformin therapy and to find out any predictors of ovulation in PCOS sub-groups. METHOD: In the current prospective-randomized, placebo-controlled, double-blind study, PCOS patients (n = 116) were divided into six main groups according to glucose to insulin ratio (G-I ratio mg/10(-4) U) and body mass index (BMI kg/m2) as: Group 1: normoinsulinemic (G-I ratio > or = 4.5 mg/10(-4) U), lean (BMI < 25) (n = 37); Group 2: normoinsulinemic, overweight (BMI: 25-29.9) (n = 19); Group 3: normoinsulinemic, obese (BMI > or = 30) (n = 18); Group 4: hyperinsulinemic (G-I ratio < 4.5 mg/10(-4) U), lean (n = 28); Group 5: hyperinsulinemic, overweight (n = 17); Group 6: hyperinsulinemic, obese (n = 20). Patients in each group were randomized onto placebo or metformin treatments (850 mg two to three times per day according to BMI). The rate of ovulation, biochemical profile, hormonal profile and clinical symptoms of hyperandrogenism were evaluated before and after 6 months of metformin and placebo treatments. RESULT(S): We observed a significant decrease in WHR following metformin therapy in the normoinsulinemic overweight sub-group (P < 0.05). The duration of the menstrual cycle significantly decreased in the normoinsulinemic obese sub-group on metformin therapy (P < 0.05). Metformin had a significant effect on hirsutism scores in hyperinsulinemic lean women (P < 0.05) and decreased DHEAS levels significantly in the lean hyperinsulinemic and normoinsulinemic groups (P < 0.05). Metformin had significant effects on ovulation in only lean hyperinsulinemic women (P < 0.05). CONCLUSIONS: Clinical outcomes of metformin therapy may be categorized on the basis of basal BMI and insulin levels in PCOS patients.     

Clinical and endocrinological effects of 6 months of metformin treatment in young hyperinsulinemic patients affected by polycystic ovary syndrome.

Most patients with polycystic ovary syndrome (PCOS) have hyperinsulinemia; thus it has been postulated that insulin-lowering drugs, such as metformin, might be a useful long-term choice. We evaluated the effects of 6 months' administration of metformin on clinical and endocrine indices in PCOS patients. Forty-two hyperinsulinemic women with PCOS were continuously treated with metformin for 6 months. Gonadotropins, androgens (testosterone and androstenedione), insulin, sex hormone binding globulin (SHBG), lipid profile and clinical indices (menstrual length, body mass index (BMI), Ferriman-Gallwey score and waist/hip ratio (WHR)) were studied before and after metformin treatment. All women experienced a normalization of menstrual cycle length (reduction rate, 36.9%), a significant decrease in luteinizing hormone, insulin and androgen levels and an increase in SHBG plasma concentrations, with a concomitant decrease in cycle length and WHR. Significant changes were observed in the lipid profile. According to baseline androgen levels, patients were divided into two groups: 20 normoandrogenic and 17 hyperandrogenic women. The greatest decline of androgens, BMI and Ferriman-Gallwey score was observed in hyperandrogenic patients. Lowering of androgenicity was independent of BMI. Significant changes in lipid profile were observed in both groups after metformin treatment. These results suggest that metformin is effective in decreasing hyperandrogenism, mainly by reducing insulin levels. This leads to an improvement of clinical manifestations of PCOS and, in particular, of hyperandrogenism.     

Implications of polycystic ovary syndrome on oocyte development

Human follicle development requires the recruitment of primordial follicles into a cohort of growing follicles from which one follicle is selected to ovulate a mature oocyte. During this developmental process, complex endocrine and intraovarian paracrine signals create a changing intrafollicular hormonal milieu. With this microenvironment, appropriate cumulus cell-oocyte signaling governs oocyte developmental competence, defined as the ability of the oocyte to complete meiosis and undergo fertilization, embryogenesis, and term development. Many of these mechanisms are perturbed in polycystic ovary syndrome (PCOS), a heterogeneous syndrome characterized by ovarian hyperandrogenism, hyperinsulinemia from insulin resistance, and reduced fecundity. In addition to these endocrinopathies, PCOS also is characterized by paracrine dysregulation of follicle development by intraovarian proteins of the transforming growth factor-beta family. Consequently, PCOS patients undergoing ovarian stimulation for in vitro fertilization are at increased risks of impaired oocyte developmental competence, implantation failure, and pregnancy loss. Recent data demonstrate links between endocrine/paracrine factors and oocyte gene expression in PCOS and suggest that new clinical strategies to optimize developmental competence of PCOS oocytes should target correction of the entire follicle growth and oocyte development process.     

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.     

Increased frequency of the G972R variant of the insulin receptor substrate-1 (irs-1) gene among girls with a history of precocious pubarche

To test the hypothesis that lower sex hormone-binding globulin (SHBG) concentrations are associated with heterozygosity for the G972R variant of the IRS-1 gene among adolescent girls with a history of precocious pubarche (PP) and hyperinsulinemic ovarian hyperandrogenism.Association study.Academic research environment.Adolescent girls with a history of PP and healthy adolescent female control subjects.Determine body mass index; measure serum androgen, insulin-like growth factor (IGF)-binding protein 1, lipids, IGF-1, and SHBG concentrations; perform glucose tolerance tests; and assay for G972R variant of the IRS-1 gene.Serum androgen, IGFBP-1, and SHBG concentrations; IRS-1 genotypes.Twenty-five of 54 (45%) girls with a history of PP developed hyperinsulinemic ovarian hyperandrogenism at adolescence. Frequency of heterozygosity for G972 was 31% among girls with a history of PP, 40% among girls with hyperinsulinemic ovarian hyperandrogenism, and 19% among healthy control subjects. Sex hormone-binding globulin concentrations were lower among girls heterozygous for G972R variant. Predictors of progression from PP to hyperinsulinemic ovarian hyperandrogenism included chronological age, insulin, low-density lipoprotein cholesterol, and IGFBP-1 concentrations.The low mean SHBG concentration found among G972R carriers suggests that this variant may be a minor locus associated with development of hyperinsulinemic insulin resistance and ovarian androgen excess in girls with a history of PP.     

Diagnosis and treatment of polycystic ovary syndrome

Obesity, ultrasonic ovarian morphology, serum LH levels and LH/FSH ratio are inconstant symptoms of the polycystic ovary syndrome (PCOS) and are thus no longer essential for diagnosis. PCOS is diagnosed today by the finding of chronic anovulation and hyperandrogenism characterized by a high serum level of "free" testoterone. The other causes of hyperandrogenism, as well as anovulations due to hyperprolactinemia, high levels of FSH and abnormal thyroid function have to be ruled out. PCOS is very often associated with insulin resistance (IR) and hyperinsulinemia (hyper I). From in vitro and vivo studies and treatment of hyper I, it has been shown that the hyper I of PCOS stimulates androgen production. Hyper I of PCOS increases the activity of androgens: by first provoking an important decrease of the sex hormone binding globulin (SHBG) thus increasing the "free", bioactive testosterone level. and then by activating the cytochrome P 450 c 17 alpha enzymatic system that controls androgen production. Subsequent to metformin administration, the reduction of hyper I and androgen serum levels creates a favorable condition for the resumption of ovarian function and clomiphene citrate action. This explains the high percentage of ovulations and pregnancies.     

Predictive value of ovarian stroma measurement for cardiovascular risk in polycyctic ovary syndrome: a case control study

Background

To verify the feasibility of ovarian stromal evaluation and correlate ovarian parameteres (echogenicity and volume) with hyperandrogenism, and both cardiovascular and metabolic risk factors in PCOS.

Methods

Twenty four young PCOS patients and twelve age-matched control women were enrolled. Diagnosis of PCOS was based on the Rotterdam criteria. Ultrasound ovarian study included ovarian volume, stromal volume, stromal area and stromal area/total ovarian area ratio (S/A). Concerning hormones, insulin, LH, FSH, estradiol, androstenedione, testosterone, DHEAS, 17-hydroxy-progesterone, and SHBG were measured during the early follicular phase (days 2-5). Cardiovascular risk factors were represented by fasting plasma levels of glucose, lipids (total and HDL-cholesterol), plasminogen activator inhibitor 1 (PAI-1), von-Willebrand factor (vWF), and adiponectin. Carotid intima-media thickness (C-IMT) was measured as a parameter of cardiovascular risk.

Results

A positive correlation between the S/A ratio and plasma levels of testosterone (p < 0.05) and androstenedione (p < 0.05) was found. The stromal volume, stromal area and S/A ratio were also significantly and positively correlated with PAI-1, and vWF levels, and with IMT in PCOS women (P < 0.05).

Conclusions

This study shows that the ultrasound measurement of ovarian stroma is a predicting factor of hyperandrogenism degree, prothrombotic factors and cardiovascular risk in patients with PCOS.     

Clinical and endocrinological effects of 6 months of metformin treatment in young hyperinsulinemic patients affected by polycystic ovary syndrome

Most patients with polycystic ovary syndrome (PCOS) have hyperinsulinemia; thus it has been postulated that insulin-lowering drugs, such as metformin, might be a useful long-term choice. We evaluated the effects of 6 months' administration of metformin on clinical and endocrine indices in PCOS patients. Forty-two hyperinsulinemic women with PCOS were countinuously treated with metformin for 6 months. Gonadotropins, androgens (testosterone and androstenedione), insulin, sex hormone binding globulin (SHBG), lipid profile and clinical indices (menstrual length, body mass index (BMI), Ferriman-Gallwey score and waist/hip ratio (WHR)) were studied before and after metformin treatment. All women experienced a normalization of menstrual cycle length (reduction rate, 36.9%), a significant decrease in luteinizing hormone, insulin and androgen levels and an increase in SHBG plasma concentrations, with a concomitant decrease in cycle length and WHR. Significant changes were observed in the lipid profile. According to baseline androgen levels, patients were divided into two groups: 20 normoandrogenic and 17 hyperandrogenic women. The greatest decline of androgens, BMI and Ferriman-Gallwey score was observed in hyperandrogenic patients. Lowering of androgenicity was independent of BMI. Significant changes in lipid profile were observed in both groups after metformin treatment. These results suggest that metformin is effective in decreasing hyperandrogenism, mainly by reducing insulin levels. This leads to an improvement of clinical manifestations of PCOS and, in particular, of hyperandrogenism.     

Doppler, ultrasonographic and endocrinological environment with regard to the number of small subcapsular follicles in polycystic ovary syndrome.

The aim of this study was to evaluate how, in patients with polycystic ovary syndrome, the number of small subcapsular follicles correlates with uterine and ovarian blood flow and with specific hormonal parameters. At an ultrasonographic evaluation, 30 patients with polycystic ovary syndrome showed 5-10 (group I; n = 14) or > 10 (group II; n = 16) small follicles. These patients underwent ultrasonographic (ovarian volume and stroma echodensity; number, diameter and distribution of follicles) and color Doppler (uterine and intraovarian vessels) analyses, and hormonal assay. In group II, significantly lower pulsatility index values than in group I were observed in the ovarian stromal arteries. The Ferriman-Gallwey score, plasma androstenedione level and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio results were significantly higher in group II than in group I. Androstenedione plasma levels correlated with the number of small follicles. Furthermore, the LH/FSH ratio correlated with both the number of small follicles and the stromal artery pulsatility index. The combined assessment of ovarian morphology by transvaginal ultrasound and color Doppler may provide insight into the pathological state of polycystic ovary syndrome.     

Endocrine-metabolic effects of the treatment with pioglitazone in obese patients with polycystic ovary syndrome.

The hyperandrogenism found in polycystic ovary syndrome (PCOS) can be a consequence of hyperinsulinemia as a result of peripheral insulin resistance. Metformin and insulin sensitizers have become a potential therapeutic tool for treating these patients; however, there are few studies with pioglitazone in PCOS. Elevated luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratios and LH hyper-responsivity to stimulation with gonadotropin-releasing hormone (GnRH) are common findings in PCOS. The reason why hyperinsulinemia produces hyperandrogenism and whether insulin action on the pituitary alters gonadotropin liberation remain unknown. In the present study, we evaluated the effect of pioglitazone (30 mg/day for 2 months) on insulin response to an oral glucose tolerance test (OGTT), serum levels of androgens and sex hormone-binding globulin (SHBG), and pituitary gonadotropin response to GnRH stimulation in 15 obese PCOS women. We found a significant decrease in insulin response to the OGTT and also in total and free testosterone levels, an increase in SHBG and a reduction in the LH response to GnRH stimulation after pioglitazone treatment. In conclusion, this short-term treatment with pioglitazone decreased hyperinsulinemia and hyperandrogenemia in obese PCOS patients, and there was a significant reduction in LH response to GnRH stimulation. Further research should be carried out to establish the risks and benefits of pioglitazone, which would assist in the physiopathologic comprehension of PCOS.     

Vascular endothelial growth factor and insulin-like growth factor-1 in polycystic ovary syndrome and their relation to ovarian blood flow

OBJECTIVES: (1) To determine the serum levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) in women with polycystic ovary syndrome (PCOS). (2) To study Doppler blood flow changes within the ovarian stroma of women with PCOS. (3) To evaluate the relationship between VEGF and IGF-1 and Doppler indices as well as hormonal profile. SETTING: Department of Obstetrics and Gynecology, and Department of Biochemistry, Faculty of Medicine, Assiut University, Egypt. DESIGN: Cross-sectional study. PATIENTS AND METHODS: Fifty infertile women with PCOS diagnosed by ultrasound examination and a history of oligomenorrhea, hirsutism and obesity were studied. Serum levels of vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1) and hormonal profile were measured. Doppler blood flow velocity waveforms analysis in both right and left intraovarian arteries was done. Twenty healthy and fertile women with regular menstrual cycles served as a comparison group were similarly studied at the third day of the cycle. RESULTS: The serum levels of VEGF, IGF-1 (4.79 +/- 0.91, 253.15 +/- 70.07 versus 2.39 +/- 0.42, 186.65 +/- 42.7) were significantly elevated (P <0.001 and P <0.01, respectively) in women with PCOS compared with control. Doppler indices, PI (2.01 +/- 0.77, 2.66 +/- 1.00 versus 2.98 +/- 0.77, 3.75 +/- 0.98) and RI (0.77 +/- 0.12, 0.82 +/- 0.09 versus 0.87 +/- 0.09, 0.89 +/- 0.09) in both right and left intraovarian vessels were significantly lower in the patients than controls. The VEGF and IGF-1 levels were negatively correlated with RI and PI in the uterine and intraovarian arteries. VEGF level was positively correlated with IGF-1 (r=0.41, P <0.05) in women with PCOS. CONCLUSIONS: Higher serum levels of VEGF and IGF-1 in PCOS women may be related to the increased vascularity that underlies the increased blood flow demonstrated by Doppler blood flow measurements in these women.     

Effect of laparoscopic ovarian drilling on vascular endothelial growth factor and ovarian stromal blood flow using 3-dimensional power Doppler

Objective

To determine, by using 3-dimensional power Doppler ultrasonography, the effect of laparoscopic ovarian drilling (LOD) on the serum level of vascular endothelial growth factor (VEGF) and ovarian stromal blood flow changes in polycystic ovary syndrome (PCOS).

Methods

A prospective controlled clinical study was conducted on 26 clomiphene-resistant women with PCOS who were scheduled for LOD and a control group of 22 fertile regularly menstruating women. VEGF and 3 ovarian Doppler indices—vascularization index, flow index, and vascularization flow index—were measured and compared between the 2 groups, and before and after LOD in the PCOS group.

Results

Serum VEGF and the Doppler indices of ovarian stromal blood flow were significantly higher in the PCOS group than in the control group. Serum VEGF and the ovarian stromal blood flow Doppler indices were significantly reduced in the PCOS group after LOD.

Conclusion

Increased vascularity in PCOS demonstrated by Doppler blood flow measurements might be explained by the high level of VEGF. LOD reduced ovarian vascularization and serum VEGF.     

Polycystic ovary syndrome: a new ultrasonographic and color Doppler pattern.

The aim of this study was to evaluate whether patients with partial bilateral polycystic ovaries show different ovarian and uterine blood flow to those with complete bilateral polycystic ovaries, and to investigate whether there is a correlation between ultrasonographic and hormonal parameters. Fifteen patients with partial polycystic ovaries and eighteen patients with complete bilateral polycystic ovaries underwent clinical, biochemical, gray-scale and color Doppler ultrasonographic evaluation. Hormonal (luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH concentration ratio, estradiol, prolactin, androstenedione, testosterone), clinical (body mass index, Ferriman-Gallwey score), ultrasonographic (ovarian volume, number and distribution of subcapsular follicles, stromal score) and Doppler (uterine artery and intraparenchymal vessels pulsatility index, ovarian stromal vascularization) parameters were evaluated, in the early follicular phase (cycle day 3-5) in oligomenorrheic patients, or at random in amenorrheic patients. Significantly higher androstenedione plasma levels and LH/FSH concentration ratios were observed in complete bilateral polycystic ovaries. In partial polycystic ovaries, gray-scale and color Doppler ultrasonography showed different features in affected and unaffected areas of the ovary, similar to polycystic and normal ovary appearance respectively. In conclusion, PCOS does not predetermine a single ultrasonographic or Doppler pattern.