Are women with polycystic ovary syndrome resistant to activated protein C?

OBJECTIVE: This study was performed to test the hypothesis that an increased prevalence of activated protein C (APC) resistance in women with polycystic ovary syndrome (PCOS) puts them at increased risk of miscarriage and thrombosis. DESIGN: Case control study. SETTING: A district general hospital in the United Kingdom. PATIENT(S): Forty-one women with PCOS and 25 controls. INTERVENTION(S): Clinical histories, ultrasound scans, and venepunctures. MAIN OUTCOME MEASURE(S): Diagnosis of PCOS or control, clinical histories, APC resistance according to an activated partial thromboplastin time-based assay. RESULT(S): There was no significant difference in the proportion of women with APC resistance in both groups (three women in the PCOS group [7%] vs. one woman in the control group [4%]). The prevalence of APC resistance in the entire study population was 6.5%. In the PCOS group, 29% (12/41) gave a positive family history of thrombosis compared with 8% (2/25) in the control group. None of the women with a positive family history of thrombosis had abnormal antithrombin 111, protein C, or protein S levels. CONCLUSION(S): This study suggests that women with PCOS may have the same prevalence of APC resistance as the background population and that APC resistance may not put them at a higher risk of thrombosis or miscarriage compared with the case of the general population.

The plasminogen activator system in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the plasminogen activator system in women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: A district general hospital in the United Kingdom. PATIENT(S): Eleven women with PCOS and 12 controls. INTERVENTION(S): Venipunctures for assays of the plasminogen activator system. MAIN OUTCOME MEASURE(S): Euglobulin clot lysis times, plasminogen activator inhibitor 1 (PAI-1) activity, fibrinogen, plasminogen, and alpha-2 antiplasmin concentrations in plasma. RESULT(S): Women with PCOS may had a significantly longer euglobulin clot lysis time (mean +/- SD, 389 +/- 164 minutes vs. 220 +/- 110 minutes), a higher PAI-1 activity (mean +/- SD, 19.7 +/- 12 arbitrary units (AU) per mL vs. 10.9 +/- 7.9 AU/mL), and a higher fibrinogen level (mean +/- SD, 4.02 +/- 0.64 g/L vs. 3.15 +/- 0.6 g/L) compared to controls. CONCLUSION(S): Women with the PCOS may have an imbalance in the plasminogen activator system that is tilted toward a reduced production of the proteolytic enzyme plasmin. Systemically, this may increase their risk of cardiovascular disease, but at cellular level in the ovaries, it may result in impaired follicular rupture and anovulation.

Ultrasound criteria in the diagnosis of polycystic ovary syndrome (PCOS).

Not all women with the polycystic ovary syndrome (PCOS) on ultrasound (US) will have the syndrome, and clinical and biochemical features of PCOS may be present without US features. The sensitivity of US in detecting PCOS was, therefore, prospectively determined in 72 women (32 PCOS and 40 controls). The most sensitive features were the presence of 10 or more follicles (82% and 69% in the left and right ovary) and a peripheral distribution of follicles (81.8% and 71.9% in the left and right ovary). Although ovarian enlargement and stromal brightness were not as sensitive as the previous criteria, stromal brightness was most specific. Combining all the criteria predicted a diagnosis of PCOS or control correctly in 86.4% of cases. This study shows that established US criteria of polycystic ovaries remain of value in the diagnosis of PCOS; however, the discrepancy between the left and right ovaries is an interesting but unexplained finding.

Polycystic ovaries.

Transvaginal ultrasound is currently the gold standard for diagnosing polycystic ovaries. The results of studies using ultrasound suggest a prevalence in young women of at least 20%. Between 5% and 10% of these women with polycystic ovaries shown on ultrasound will have the classical symptoms of polycystic ovary syndrome such as infertility, amenorrhoea or signs of hirsutism and obesity, as originally described by Stein and Leventhal in 1935. However, the significance of polycystic ovaries in asymptomatic women is still under investigation, as is the role of Doppler (pulsed and colour) and three-dimensional ultrasound. Ultrasound has also contributed to our understanding of the local and systemic haemodynamic changes associated with polycystic ovaries, although the relationship of these changes to morbidity and mortality is unknown.

Evaluation of a one-stop clinic for the rapid assessment of post-menopausal bleeding.

In this study, we evaluated the management of postmenopausal bleeding at our one-stop clinic where the first line investigations were a transvaginal ultrasound scan and a pipelle endometrial biopsy. The records of 212 women seen in this clinic in 1994 were reviewed. One hundred and forty-four women (67.9%) were evaluated and reassured in one visit. The mean waiting period following referral to the clinic by the general practitioner was 36 days (range 6-157 days), and only 45 women (21%) required a hysteroscopy. The commonest diagnosis made was endometrial atrophy or no significant endometrial pathology (130 women (61.3%). Endometrial cancer was diagnosed in 12 women (5.6%), and one case of previously unsuspected ovarian cancer was detected. Our findings show that most women with post-menopausal bleeding can be assessed in one visit, and hysteroscopy is not always necessary in the initial assessment of this complaint.

Polycystic ovary syndrome, diabetes and cardiovascular disease: risks and risk factors.

Polycystic ovary syndrome is one of the most common endocrine disorders in the human, affecting approximately 10% of women of reproductive age. Although originally considered a gynaecological disorder, the syndrome is associated with a wide range of endocrine and metabolic abnormalities, including insulin resistance. Affected women are at an increased risk of developing gestational and non-insulin dependent diabetes and there is an association with cardiovascular risk factors including obesity, hypertension, dyslipidaemia, hyperhomocysteinaemia, increased intima media thickness and impaired vascular elasticity. The effect on cardiovascular mortality is currently unclear. However, in view of the proven links with diabetes and the cardiovascular risk markers, this condition should be considered within the province of physicians as well as gynaecologists.

Raised plasminogen activator inhibitor-1 (PAI-1) is not an independent risk factor in the polycystic ovary syndrome (PCOS).

BACKGROUND: It has been postulated that an insulin-driven increase in plasminogen activator inhibitor-1 (PAI-1) levels may link insulin resistance to anovulatory infertility in women with PCOS and that it may place them at increased risk of thromboembolic disease. However, previous studies have been conflicting because many have failed to control for body mass index (BMI) which may affect PAI-1. The aim of this study was to investigate PAI-1 activity in women with PCOS and to compare it with unaffected controls of a similar BMI. DESIGN AND PATIENTS: 41 women with PCOS and 25 weight-matched controls participated in this cross-sectional study. Patients were evaluated clinically and by pelvic ultrasound and fasting blood samples were taken for haematological and biochemical tests. MEASUREMENTS: PAI-1 activity, insulin, glucose, triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, FSH, LH, PRL, testosterone, SHBG, 17-hydroxyprogesterone, plasminogen, fibrinogen (alpha2 antiplasmin, blood pressure and insulin sensitivity with a homeostasis model assessment (HOMA) computer programme. RESULTS: There was no significant difference in BMI or in (log) PAI-1 activity in women with PCOS compared with controls (BMI 29.5 +/- 5.6 vs. 28.4 +/- 6.3 kg/m2, P = 0.25 and PAI-1 2.56 (SD 0.85) vs. 2.14 (SD 0.98) au/ml, P = 0.07). The median fasting insulin level was significantly higher (17 (4.6-134.5) vs. 9.6 (3.7-41.5) mU/l, P < 0.01), and insulin sensitivity significantly lower in the PCOS group, ( 43.17% (5. 48-160) vs. 82.8% (21.8-193), P < 0.01). Women with PCOS also had a significantly higher free androgen index, LH/FSH ratio and a lower HDL/total cholesterol ratio. However blood pressure and all other lipid and haematological measurements were not significantly different between both groups. There were significant positive correlations between (log) PAI-1 activity and BMI (rho = 0.61), triglycerides (rho = 0.49) and fasting insulin (rho = 0.60) and a negative correlation with HDL cholesterol (rho = - 0.46). Triglyceride concentrations showed the most significant relationship with (log) PAI-1 activity on multiple regression. 29% of PCO women (12/41) gave a positive family history of thrombosis compared to 8% (2/25) in the control group. CONCLUSION: Plasminogen activator inhibitor-1 activity is not raised in women with PCOS independent of obesity and these results do not support the hypothesis that it may contribute to their anovulatory infertility, or increase their risk of thrombosis. The only significant metabolic features of the PCOS independent of obesity are insulin resistance, hyperinsulinaemia and lower HDL/total cholesterol ratio. The higher frequency of a positive family history of thrombosis in these women nevertheless requires further explanation.

Immunohistochemical detection of plasminogen activator inhibitor-1 in polycystic ovaries.

Anovulation in women with polycystic ovary syndrome (PCOS) is incompletely understood. The concentration of the glycoprotein plasminogen activator inhibitor-1 (PAI-1) is raised in insulin resistance. This has been described in the granulosa and theca cell layers of the animal but not the human ovary. This study was performed to investigate the location of PAI-1 in the human ovary and investigate whether it may contribute to anovulation in PCOS. PAI-1 was localized immunohistochemically and quantitated using computer image analysis in 17 ovarian follicles from five women with a diagnosis of PCOS and compared with 15 follicles from six normal ovaries. PAI-1 was predominantly found in the granulosa and theca cells in both polycystic and normal ovaries. Image analysis did not reveal a difference in the PAI-1 signal from polycystic compared with normal ovaries. This study shows that PAI-1 plays a role in human ovulation, but its role in PCOS requires further research.