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PubMed2004

A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study.

OBJECTIVE: To obtain data from a pilot randomized trial on the effect of metformin therapy and lifestyle modification on ovulation and androgen concentrations in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, placebo-controlled pilot trial. SETTING: Academic medical center. PATIENT(S): Thirty-eight overweight or obese women with PCOS. INTERVENTION(S): All subjects were randomized to one of four 48-week interventions: metformin 850 mg two times per day, lifestyle modification plus metformin 850 mg two times per day, lifestyle modification plus placebo, or placebo alone. MAIN OUTCOME MEASURE(S): Recruitment, dropout, and compliance with a long-term lifestyle intervention in PCOS; preliminary estimates of treatment effect on ovulation, as measured by weekly urinary pregnanediol glucuronide, and on total T and free androgen index. RESULT(S): It was necessary to screen seven women to have one subject randomized. The dropout rate was 39%, with the majority of dropouts occurring within the first 24 weeks. Mean body mass index was >39 mg/kg(2). Modest weight reduction was found in all treatment groups, with the most significant reduction occurring with the combination of metformin and lifestyle intervention. Significant androgen reduction occurred in the combination group only. Ovulation rates did not differ significantly between groups. However, when data were analyzed by presence or absence of weight reduction in subjects, independent of treatment group, the estimated odds ratio for weight loss was 9.0 (95% confidence interval 1.2-64.7) with respect to regular ovulation. If weight loss occurred during metformin therapy, the odds ratio for regular ovulation was 16.2 (95% confidence interval 4.4-60.2). CONCLUSION(S): Key methodologic issues for a large-scale, randomized trial of lifestyle intervention in PCOS include minimizing early dropout from the lifestyle intervention and including a range of body mass index that is not skewed toward severe obesity. Weight reduction might play the most significant role in restoration of ovulation in obese women with PCOS.

Adipose Tissue↗

PubMed2005

Molecular profiling of polycystic ovaries for markers of cell invasion and matrix turnover.

OBJECTIVE: To study gene expression profiles of connective tissue components in polycystic ovaries using complementary deoxyribonucleic acid (cDNA) array technology. DESIGN: Descriptive study of normal and polycystic human ovarian biopsy samples analyzed by cDNA array hybridizations. SETTING: Experimental laboratory research. PATIENT(S): Eight women with polycystic ovary syndrome (PCOS) and two normally cycling women treated with electrocauterization and hysterectomy, respectively. INTERVENTIONS: Ovarian biopsy samples. MAIN OUTCOME MEASURE(S): Expression levels of 588 genes involved in cellular invasion, extracellular matrix (ECM) turnover, and cell-ECM interactions in polycystic ovaries. RESULT(S): A majority of the 30 genes down-regulated in PCOS ovaries represented those related to cell adhesion and motility, as well as angiogenesis, followed by regulators of cell cycle and growth. The 14 up-regulated genes represented those regulating cell fate and development, growth factors, cytokines, chemokines, and cell-cell interactions. Of the 44 transcripts exhibiting marked changes in the cDNA array analysis, only one - proliferating cell nuclear antigen messenger ribonucleic acid (PCNA mRNA) - was systematically down-regulated; 2 transcripts, for CDC27HS protein and CD9 antigen, were down-regulated in 7 out of 8 PCOS samples. CONCLUSION(S): The present data suggest that gene expression profiling may become a useful tool to classify PCOS patients into subgroups with different etiologies. Genome-wide expression profiling using microarrays should be performed to better understand the metabolic derangement(s) in PCOS.

Adult↗

PubMed2005

Ovarian size and blood flow in women with polycystic ovary syndrome and their correlations with endocrine parameters.

OBJECTIVE: To determine how common polycystic ovarian morphology may be in women given the clinical diagnosis of polycystic ovary syndrome (PCOS) based on chronic anovulation and hyperandrogenism and whether certain hormonal factors correlate with ovarian morphology and blood flow. DESIGN: Prospective study. SETTING: Two academic endocrinology centers in Italy. PATIENT(S): Three hundred twenty-six women with PCOS and 50 age-matched and weight-matched ovulatory women. INTERVENTION(S): Ultrasound assessment of ovarian morphology in patients and controls and ovarian blood flow and fasting hormone levels in a subset of 50 patients and matched controls. MAIN OUTCOME MEASURE(S): Ovarian morphological assessments, ovarian blood flow by pulsatility index (PI) and resistance index (RI), and measurements of gonadotropins, estrogen, sex hormone-binding globulin, androgens, inhibin B, glucose, and insulin. RESULT(S): Using strict ultrasound criteria, 195 woman (60%) had enlarged ovaries, 135 (35%) had normal ovarian size but characteristic morphology, and 16 (5%) had normal size and morphology. Ovarian blood flow was increased (reduced PI and RI) in PCOS. All hormonal parameters were elevated in PCOS. Ovarian size correlated only with insulin and a measure of insulin resistance. Ovarian blood flow correlated positively with insulin, T, free T, and E2 but not with luteinizing hormone. Inhibin B showed a negative correlation with ovarian blood flow. CONCLUSION(S): When a clinical diagnosis of PCOS was made, virtually all women were found to have characteristic ovarian morphology. Insulin correlated with increased ovarian size as well as with increased blood flow. Blood flow also correlated positively with sex steroids but negatively with inhibin B.

Analysis of Variance↗

PubMed2005

Association of Gly972Arg variant of insulin receptor substrate-1 with metabolic features in women with polycystic ovary syndrome.

OBJECTIVE: To examine the prevalence and the effects of Gly972Arg (G972A) variant of insulin receptor substrate-1 (IRS-1) in women with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: An academic clinical research center. PATIENT(S): Sixty women with PCOS and 60 control women matched for age. INTERVENTION(S): Biometric measures, metabolic and hormonal measures, genetic analyses. MAIN OUTCOME MEASURE(S): Serum androgens, glucose, and insulin were measured. Blood leukocytes were used for genetic analyses. RESULT(S): The G972A variant was encountered more often in women with PCOS. The G972A carriers were more obese than their counterparts, had higher fasting insulin levels, and were more insulin-resistant. However, androgen levels did not differ on the basis of IRS-1 genotype. CONCLUSION(S): We observed that the G972A variant of IRS-1 was more prevalent in women with PCOS, and that it had important metabolic effects without having a direct effect on the androgen levels. However, the G972A variant of IRS-1 may modulate reproduction by lowering sex hormone-binding globulin in both healthy women and women with PCOS.

Analysis of Variance↗

PubMed2006

Increased luteinizing hormone pulse frequency in obese oligomenorrheic girls with no evidence of hyperandrogenism.

OBJECTIVE: To determine whether obese, nonhirsute adolescents with oligomenorrhea exhibit similar increased LH pulse secretion patterns compared with obese girls with polycystic ovary syndrome (PCOS). DESIGN: Prospective, observational study. SETTING: Tertiary university hospital. PATIENT(S): Nine obese girls with oligomenorrhea, 15 with PCOS, and 10 controls. INTERVENTION(S): Twenty-four-hour IV blood sampling for LH (every 10 minutes); measurement of steroid hormones (every 12 hours); and injection of leuprolide acetate (10 microgm/kg SC). MAIN OUTCOME MEASURE(S): Twenty-four-hour, wake, and sleep LH mean serum concentration, pulse frequency, amplitude; steroid hormones, including free androgen index (FAI); and pre- and post-leuprolide acetate 17-hydroxyprogesterone measurements. RESULT(S): Twenty-four-hour LH pulse frequency in oligomenorrheic girls (18.6 +/- 1.2) (mean +/- SE) was comparable to that in girls with PCOS (20.9 +/- 0.7) and greater than in normal girls (13.4 +/- 0.8). The pulse number during both sleep and wake was identical in oligomenorrheic and PCOS girls and significantly greater than that of normal girls. Mean 24-hour LH level, serum androgen levels, and FAI in oligomenorrheic girls were equivalent to those of normal controls and lower than those of PCOS girls. CONCLUSION(S): These preliminary results indicate that obese girls with oligomenorrhea exhibit increased LH pulse frequency in the absence of clinical and/or biochemical evidence of hyperandrogenism.

Adolescent↗

PubMed2006

Selecting controls is not selecting "normals": design and analysis issues for studying the etiology of polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a highly prevalent disorder among postmenarcheal premenopausal women, accounting for much of anovulatory infertility, and it is associated with several comorbidities. The natural history of PCOS, as well as hypotheses regarding its etiology, facilitates employment of the case-control study design. However, a review of the literature suggested that inconsistency of research findings in relation to the etiology of PCOS might be, in part, due to the different choice of controls for case-control design and application. DESIGN: Investigators have often employed "healthy" control groups and neglected to consider the tenability of the "rare disease" assumption in the analysis when instituting the case-control strategy. This might result in the introduction of a positive bias or overestimation of odds ratios, producing an effect estimate that is more extreme than that in the underlying population. Using several quantitative, though hypothetical, literature-driven examples, this bias is described and demonstrated. In addition, recommendations are provided with regard to case-sampling strategy when the rare disease assumption is untenable, as it may frequently be in studies of PCOS. CONCLUSION(S): It is hoped that more consistent case-control methodology, in concert with recent consensus on case definition, will more effectively facilitate the elucidation of the causes and consequences of PCOS.

Bias↗

PubMed2006

Serum soluble leptin receptor levels and free leptin index in women with polycystic ovary syndrome: relationship to insulin resistance and androgens.

OBJECTIVE: To evaluate levels of soluble receptor (sOB-R) and free leptin in women with polycystic ovarian syndrome (PCOS) and note any relationships with insulin resistance, adiposity, and androgens. Leptin is an adipokine that circulates in a free form and bound to an sOB-R. Only free leptin is biologically active. DESIGN: Prospective, case-control study. SETTING: University-based reproductive endocrinology practice. PATIENT(S): Forty women with PCOS and severe insulin resistance and 15 body mass index (BMI)-matched ovulatory controls. INTERVENTION(S): Measurements of serum insulin, leptin, sOB-R at fasting and during a standard oral glucose tolerance test (OGTT), and measurements before and after treatment with rosiglitazone. MAIN OUTCOME MEASURE(S): Fasting glucose, insulin, leptin, sOB-R, T, and DHEAS levels in women with PCOS and controls were measured to investigate the relationship of sOB-R and the free leptin index (FLI) to insulin, adipocity, and androgens and to investigate the effect of acute hyperinsulinemia during OGTT and the effect of improvement of insulin resistance with rosiglitazone on the leptin system. FLI was calculated by dividing leptin levels by sOB-R. RESULT(S): Total leptin and FLI correlated significantly with BMI in both patients with PCOS and in controls. There was a significant negative correlation between DHEAS and sOB-R in PCOS. Leptin, sOB-R, and FLI were not significantly different in the two groups, and neither sOB-R nor FLI correlated with insulin or glucose levels. The sOB-R levels increased significantly 3 hours after oral glucose ingestion, resulting in a significant decline in FLI. CONCLUSION(S): [1] Adiposity rather than insulin resistance appears to be the main determinant of leptin levels and FLI. [2] Acute increase in insulin levels during OGTT is associated with an increase in levels of sOB-R. [3] DHEAS may play a role in leptin bioavailability by modulating sOB-R levels.

Acanthosis Nigricans↗

PubMed2006

Two weeks of metformin improves clomiphene citrate-induced ovulation and metabolic profiles in women with polycystic ovary syndrome.

OBJECTIVE: To determine if short courses of metformin (MET) administration in patients with polycystic ovary syndrome (PCOS) would reduce fasting insulin and improve the efficacy of clomiphene citrate (CC) to induce ovulation. DESIGN: A randomized prospective trial involving 31 subjects with PCOS and infertility. SETTING: University-based medical center. PATIENT(S): Obese patients (body mass index > 29 kg/m2) with PCOS. INTERVENTION(S): Patients with PCOS were treated either with CC or CC+MET for 2 weeks. MAIN OUTCOME MEASURE(S): Ovulation as determined by serum P, serum insulin, and total and free T. RESULT(S): In the CC/MET group, a significant increase in sex hormone-binding globulin (SHBG) levels, a decrease in fasting insulin, and an increase in fasting glucose/fasting insulin was detected on day 21 of the cycle. Of these parameters, only SHBG levels increased significantly in the CC group. In the CC/MET group, a significant increase in day 21 progesterone occurred, with 44% of subjects ovulating in the CC+MET group as compared with 6.7% in the CC group. Five subjects in the CC+MET group and none in the CC group conceived. Total and free testosterone levels did not change significantly for either group. CONCLUSION(S): In obese PCOS patients, 2 weeks of MET significantly reduces serum insulin and insulin resistance and increases SHBG levels, resulting in an improved response to CC. This regimen may be beneficial in noncompliant patients or those with intolerance to the side effects of MET.

Adult↗

PubMed2006

The Pregnancy in Polycystic Ovary Syndrome study: baseline characteristics of the randomized cohort including racial effects.

OBJECTIVE: To report the baseline characteristics and racial differences in the polycystic ovary syndrome (PCOS) phenotype from a large multicenter clinical trial (PPCOS). DESIGN: Double-blind, randomized trial of three treatment regimens (with extended release metformin or clomiphene citrate). SETTING: Academic medical centers. PATIENT(S): Six hundred twenty-six infertile women with PCOS, aged 18-39 years, with elevated T levels and oligomenorrhea (exclusion of secondary causes), seeking pregnancy, with > or = 1 patent fallopian tube, normal uterine cavity, and a partner with sperm concentration > or = 20 x 10(6)/mL in > or = 1 ejaculate. INTERVENTION(S): Baseline characterization. MAIN OUTCOME MEASURE(S): Historical, biometric, and biochemical measures of PCOS. RESULT(S): There were no significant differences in baseline variables between treatment groups. The overall mean (+/-SD) age of the subjects was 28.1 +/- 4.0 years, and the mean body mass index was 35.2 kg/m2 (+/-8.7). Polycystic ovaries (PCOs) were present in 90.3% of the subjects, and the mean volume of each ovary was 10 cm3 or more. Of the subjects, 7% had ovaries that were discordant for PCO morphology. At baseline, 18.3% of the subjects had an abnormal fasting glucose level (> 100 mg/dL). Asians tended to have a milder phenotype, and whites and African Americans were similar in these measures. CONCLUSION(S): The treatment groups were well matched for baseline parameters, and we have added further information to the PCOS phenotype.

Adolescent↗

PubMed2006

Sex hormone-binding globulin expression in the endometria of women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the protein and messenger RNA expression of sex hormone-binding globulin (SHBG) in endometria from women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Hospital research unit. PATIENT(S): Thirty-three women with PCOS, and 17 fertile, healthy women of similar age to those with PCOS. INTERVENTION(S): Endometrial and blood samples were obtained from women with PCOS (PCOSEs) and from control women (CEs) during the proliferative phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Expression studies for SHBG (immunohistochemistry and reverse transcription-polymerase chain reaction). Hormonal studies for determining sex steroids (T, P, and E(2)) and SHBG concentration. Insulin sensitivity was assessed by composite insulin sensitivity index (ISI(composite)). RESULT(S): In stroma, the protein expression of SHBG was lower in PCOSEs than in CEs. Epithelial cells had a similar expression of SHBG protein in both groups. Messenger RNA of variant 548 base pairs (wild-type) tended to be lower in PCOSEs compared to CEs. When PCOSEs were classified by insulin resistance, the PCOSEs with normal insulin sensitivity showed an expression of stromal SHBG similar to that observed in CEs. CONCLUSION(S): The low SHBG expression in the stromal compartment of endometria from women with PCOS with insulin resistance may contribute to generate an abnormal steroid milieu in the endometria of these women.

Adult↗

PubMed2007

Acute effects of metformin therapy include improvement of insulin resistance and ovarian morphology.

OBJECTIVE: To evaluate the acute effects of metformin therapy on biochemical markers and polycystic ovarian morphology among insulin-resistant (IR) and noninsulin-resistant (NIR) patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective interventional study. SETTING: Reproductive endocrinology clinic in a university hospital. PATIENT(S): Five IR and five NIR patients with PCOS. The mean age of patients was 29.5 +/- 4.8 years (range, 23-36 years). INTERVENTION: Metformin therapy, using 850 mg orally per day for 1 week. MAIN OUTCOME MEASURE(S): Serum levels of T, FSH, and LH, fasting glucose/insulin ratio, levels of anti-Müllerian hormone (AMH) and inhibin B, and antral follicle count. RESULT(S): Levels of AMH and inhibin B were statistically significantly higher in patients with PCOS compared to controls (2.81 +/- 1.79 ng/mL versus 0.95 +/- 1.17 ng/mL, and 56.24 +/- 29.39 pg/mL versus 17.89 +/- 12.87 pg/mL, respectively). Levels of AMH and inhibin B were similar among IR and NIR patients with PCOS (2.77 +/- 1.92 ng/mL versus 2.85 +/- 1.89 ng/mL, and 53.96 +/- 28.58 pg/mL versus 58.51 +/- 33.28 pg/mL, respectively). One week of metformin therapy did not alter either AMH or inhibin B levels. However, there was a statistically significant increase in glucose/insulin ratios (4.59 +/- 1.57 versus 6.35 +/- 3.6), and a significant decrease in the number of antral follicles after 1 week of metformin therapy (38.8 +/- 19.3 versus 23.1 +/- 7.4). CONCLUSION(S): Levels of AMH and inhibin B are significantly increased in patients with PCOS compared to controls, but are not associated with insulin resistance. Low-dose metformin therapy improves IR and polycystic ovary morphology, even though levels of T, AMH, and inhibin B remain unchanged.

Adult↗

PubMed2004

[Polycystic ovary syndrome in pubertal period: clinical, biological, metabolic and genetic polymorphism].

Polycystic ovary syndrome (PCOS) is a common cause of hyperandrogenism in adolescent girls. In its complete post menarchal expression, the syndrome is characterized by the association of typical clinical, biological, and ultrasonographic findings. Many factors have contributed to our knowledge of different clinical forms of PCOS in adolescent girls. They are helpful for clarifying misleading situations in a period of life when diagnosis of PCOS implies a treatment for many years and may interfere with gynecological outcome. During the last 3 years, we had the opportunity to manage in our unit 45 adolescent girls with ovarian hyperandrogenism: 32 of them had PCOS and the other 13 functional ovarian hyperandrogenism defined by clinical and biological hyperandrogenism without ultrasonographic abnormality. In this review, we report, from our personal experience as well as from recent literature data, the different clinical expressions of PCOS in the pubertal period: the classical post menarchal form, the exceptional pre menarchal form, the post precocious pubarche and the post precocious puberty forms, the familial expression as well as the dominant metabolic expression.

Adolescent↗

PubMed2004

Aromatase inhibition reduces the dose of gonadotropin required for controlled ovarian hyperstimulation.

OBJECTIVE: To compare the use of the aromatase inhibitor, letrozole, in conjunction with follicle-stimulating hormone (FSH) injection, and FSH alone for controlled ovarian hyperstimulation (COH) in patients with polycystic ovarian syndrome (PCOS) or ovulatory infertility. METHODS: This nonrandomized study included two study groups: 26 patients with PCOS and 63 with ovulatory infertility (unexplained infertility [41 patients], male factor infertility [17 patients], and endometriosis [5 patients]), who received letrozole in addition to FSH; and two control groups: 46 PCOS patients and 308 with ovulatory infertility (unexplained infertility [250 patients], male factor infertility [42 patients], and endometriosis [16 patients], who received FSH only. All patients had intrauterine insemination (IUI). Main outcome measures included dose of FSH used per cycle, number of preovulatory follicles greater than 16 mm in diameter, cancellation rate, and pregnancy rate. RESULTS: The FSH dose required for ovarian stimulation was significantly lower when letrozole was used in both study groups compared to the control groups without a significant difference in number of follicles greater than 16 mm. IUI cancellation rate was significantly lower with letrozole treatment in PCOS patients. In women with PCOS, clinical pregnancy rate per completed IUI cycle was 26.5% in the letrozole plus FSH group versus 18.5% in the FSH-only group. In ovulatory infertility patients, the pregnancy rate was similar in both study and control groups (11%). CONCLUSION: We believe that inhibition of estrogen synthesis by aromatase inhibition will release the estrogenic negative feedback, resulting in an increase in endogenous FSH secretion. Moreover, by inhibiting conversion of androgens into estrogens, accumulating androgens may increase follicular sensitivity to FSH. Such a protocol has the potential to lower FSH treatment cost and may improve response for low responders who require high FSH doses during ovarian stimulation.

Adult↗

PubMedDate not supplied

Effective treatment of polycystic ovarian syndrome with Roux-en-Y gastric bypass.

PURPOSE: Many women with polycystic ovarian syndrome (PCOS) are overweight. This study investigated the impact of weight loss surgery on the clinical manifestations of this disorder in morbidly obese women with PCOS-a major risk factor for the development of heart disease, stroke, and type II diabetes. METHODS: We reviewed the outcomes of women diagnosed with PCOS who had undergone weight loss surgery at the University of Pittsburgh between July 1997 and November 2001. We evaluated the changes in menstrual cycles, hirsutism, infertility, and type II diabetes. RESULTS: A total of 24 women with PCOS were included in the study. Their mean age was 34 +/- 9.7 years. The mean preoperative body weight was 306 +/- 44 lb, with a body mass index of 50 +/- 7.5. All patients were oligomenorrheic. Of the 24 patients, 23 were hirsute. All women underwent elective laparoscopic gastric bypass surgery. The mean follow-up period was 27.5 +/- 16 months. The mean excess weight loss at 1 year of follow-up was 56.7% +/- 21.2%. All women resumed normal menstrual cycles after a mean of 3.4 +/- 2.1 months postoperatively. Of the 23 women with hirsutism, 12 (52%) had complete resolution at a mean follow-up of 8 +/- 2.3 months, 6 (25%) had moderate resolution at a mean of 21 +/- 18 months, and 3 had minimal resolution at 34 +/- 14 months. Two women reported no change in their hirsutism at 32 +/- 7 months. Five women were able to conceive after surgery without the use of clomiphene. CONCLUSION: Gastric bypass surgery and its consequent weight loss results in significant improvement of multiple clinical problems related to PCOS.

Adult↗

PubMed2006

Androgen and estrogen receptors and co-regulators levels in endometria from patients with polycystic ovarian syndrome with and without endometrial hyperplasia.

OBJECTIVE: To study if the endocrinological status of PCOS women affects the endometrial sensitivity to steroids by evaluating the expression of androgen receptor (AR), estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), co-activators AIB1 and ARA70, and co-repressor NCoR. METHODS: Gene and/or protein expression of steroid receptors and co-regulators was measured in 17 samples of normal endometrium (NE), 23 PCOS endometrium without treatment (PCOSE), 11 endometria from PCOS women and with endometrial hyperplasia (HPCOSE), and 10 endometria from patients with endometrial hyperplasia (HE), using RT-PCR and/or immunohistochemistry and Western blot. RESULTS: Gene and protein expression of AR was relatively elevated in PCOSE and HPCOSE compared with NE. A significant increase in ERalpha protein expression was observed in PCOSE, preferentially in the nucleus of endometrial cells, whereas ERbeta gene and protein expression increased gradually from PCOSE to HPCOSE and HE, mainly in the epithelial compartment. Importantly, we found a gradual increase in the ERbeta/ERalpha gene and protein expression ratio in endometria from the four groups of women. AIB1 showed increased nuclear protein expression in PCOSE compared to NE, in the presence of a high expression of ARA70 in all groups. High expression of ARA70 together with a normal expression level of AIB1 was observed in HPCOSE. The cytoplasmic immunostaining of NCoR was similar between the four groups of patients. CONCLUSION: The PCOS endometrium exhibits a higher sensitivity to steroid action. We can inferred that these alterations could deregulate the transcription of genes involved in the cell cycle, which may lead to the development of endometrial hyperplasia in PCOS women.

Adult↗

PubMed2006

Deregulation of tissue homeostasis in endometria from patients with polycystic ovarian syndrome with and without endometrial hyperplasia.

OBJECTIVE: To study the proteins involved in endometrial homeostasis in PCOS women. METHODS: Protein expression of Ki67, Bcl-2, Bax, Pro-Caspase-3 and Caspase-3 by immunohistochemistry and/or Western blot, and DNA fragmentation using in situ 3'-end labeling of apoptotic cells, was measured in 9 samples of normal endometrium (NE), 12 PCOS endometria without treatment (PCOSE), 7 endometria from PCOS women with endometrial hyperplasia (HPCOSE) and 9 endometria from patients with endometrial hyperplasia (HE). RESULTS: Cell proliferation was higher in epithelium from PCOSE (P<0.05), HPCOSE and HE vs NE. A higher Bcl-2/Bax relative ratio in PCOSE and HPCOSE was observed, in absence of active Caspase-3 and scarce DNA fragmentation in the four groups of endometria studied. CONCLUSION: As the apoptosis was scarce in all of the groups studied, endometrial homeostasis deregulation in PCOS could be a result of increased proliferation. Therefore, the onset of endometrial hyperplasia in PCOS endometrium could be linked to inadequate cell proliferation, and concomitantly to inadequate cell survival.

Adult↗

PubMed2005

Adiponectin and resistin serum levels in women with polycystic ovary syndrome during oral glucose tolerance test: a significant reciprocal correlation between adiponectin and resistin independent of insulin resistance indices.

Polycystic ovary syndrome (PCOS) is associated with an increased incidence of insulin resistance (IR), obesity, and type 2 diabetes. Resistin, an adipocytokine, may represent a link between obesity, and these metabolic disorders. There is also evidence that inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states. In contrast, adiponectin, increases insulin sensitivity, improves glucose tolerance, inhibits inflammatory pathways, while adenovirus-expressed adiponectin reduces atherosclerotic lesions in a mouse model of atherosclerosis. We aimed to assess, in women with PCOS, whether there is a relationship between adiponectin and resistin and the indices of IR, and whether serum levels of these adipocytokines are altered by glucose-induced hyperinsulinaemia. Serum levels of resistin and adiponectin were measured at 0, 60, and 120 min during 75 g oral glucose tolerance test (OGTT), in 19 women with PCOS, age 36.3+/-11.4 years (mean+/-SD), body mass index (BMI) 29.3+/-7.7 kg/m2, and correlated with the indices of IR, such as HOMA-IR, QUICKI, and the insulin resistance index calculated from glucose and insulin levels obtained during OGTT. There was no change in resistin concentrations (7.31+/-4.58, 7.47+/-5.40, 7.22+/-5.12 pg/ml, at 0, 60, and 120 min of OGTT, respectively, P = 0.77), but there was an increase in adiponectin from 11.32+/-4.64 microg/ml at baseline to 14.78+/-7.41 microg/ml, at 120 min of OGTT (P < 0.01). The magnitude of the overall rise in adiponectin was greater from 60 to 120 min (from 12.31+/-5.72 to 14.78+/-7.41 microg/ml, P < 0.006). Neither resistin, nor adiponectin correlated with the indices of IR, lipids, or other hormonal parameters of the PCOS. There was, however, a significant negative correlation between serum resistin and adiponectin (P = 0.001). In conclusion, we observed a strong negative correlation between serum adiponectin and resistin, despite the lack of direct correlation with the indices of IR. Given the opposite effects of resistin and adiponectin on the inflammatory process, we speculate that relative proportion of adiponectin-to-resistin might potentially influence cardiometabolic risk in women with the PCOS independently of IR parameters. The observed increase in adiponectin during OGTT requires further study.

Adiponectin↗

PubMed2003

Differential expression of the angiogenic factor genes vascular endothelial growth factor (VEGF) and endocrine gland-derived VEGF in normal and polycystic human ovaries.

Angiogenesis is a key aspect of the dynamic changes occurring during the normal ovarian cycle. Hyperplasia and hypervascularity of the ovarian theca interna and stroma are also prominent features of the polycystic ovary syndrome (PCOS), a leading cause of infertility. Compelling evidence indicated that vascular endothelial growth factor (VEGF) is a key mediator of the cyclical corpus luteum angiogenesis. However, the nature of the factor(s) that mediate angiogenesis in PCOS is less clearly understood. Endocrine gland-derived (EG)-VEGF has been recently identified as an endothelial cell mitogen with selectivity for the endothelium of steroidogenic glands and is expressed in normal human ovaries. In the present study, we compared the expression of EG-VEGF and VEGF mRNA in a series of 13 human PCOS and 13 normal ovary specimens by in situ hybridization. EG-VEGF expression in normal ovaries is dynamic and generally complementary to VEGF expression in both follicles and corpora lutea. A particularly high expression of EG-VEGF was detected in the Leydig-like hilus cells found in the highly vascularized ovarian hilus. In PCOS ovaries, we found strong expression of EG-VEGF mRNA in theca interna and stroma in most of the specimens examined, thus spatially related to the new blood vessels. In contrast, VEGF mRNA expression was most consistently associated with the granulosa cell layer and sometimes the theca, but rarely with the stroma. These findings indicate that both EG-VEGF and VEGF are expressed in PCOS ovaries, but in different cell types at different stages of differentiation, thus suggesting complementary functions for the two factors in angiogenesis and possibly cyst formation.

Adult↗