Polycystic Ovary Syndrome - Stein-Leventhal Syndrome


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Hum Reprod. 2006 Apr;21(4):930-5. Epub 2005 Dec 22.
Do young women with polycystic ovary syndrome show early evidence of preclinical coronary artery disease?
Topcu S, Caliskan M, Ozcimen EE, Tok D, Uckuyu A, Erdogan D, Gullu H, Yildirir A, Zeyneloglu H, Muderrisoglu H.
Cardiology Department and Obstetrics & Gynecology Department, Konya Teaching and Medical Research Center, Baskent University, Konya, Turkey. semratopcu2003@yahoo.com

BACKGROUND: It is thought that women with polycystic ovary syndrome (PCOS) are at increased risk of developing cardiovascular diseases. METHODS: In this study, we used transthoracic echocardiography to measure coronary flow reserve (CFR) in 28 women with PCOS and in 26 healthy women. RESULTS: The PCOS and the control groups were similar in terms of age (27.1 +/- 4.5 versus 28.8 +/- 4.4 years) and BMI (26.6 +/- 5.7 versus 24.7 +/- 4.4 kg/m2). Fasting insulin levels and homeostasis model assessment insulin resistance index were higher in the PCOS group. LH, the LH/FSH ratio, total testosterone, free testosterone and androstenedione were higher in the PCOS group. FSH, estradiol, prolactin, progesterone, cholesterol, triglyceride and high-sensitive C-reactive protein were similar between the two groups, but homocysteine levels were higher in the PCOS group. Baseline diastolic peak f low velocity (DPFV) (25.0 +/- 4.6 versus 23.3 +/- 2.7 cm/s, P > 0.05), hyperaemic DPFV (71.2 +/- 12.8 versus 73.0 +/- 12.9 cm/s, P > 0.05) and CFR (2.8 +/- 0.8 versus 3.2 +/- 0.8 cm/s, P > 0.05) of the left anterior descending coronary artery were similar between the two groups. CONCLUSION: We conclude that in young women with PCOS and without cardiovascular risk factors, CFR is preserved.


Atherosclerosis. 2006 Apr;185(2):227-39. Epub 2005 Nov 28.
Cardiovascular disease in the polycystic ovary syndrome: new insights and perspectives.
Cussons AJ, Stuckey BG, Watts GF.
Keogh Institute for Medical Research, Nedlands, WA, Australia.

The new millennium has brought intense focus of interest on the risk of cardiovascular disease in women. The polycystic ovary syndrome (PCOS) is a common endocrine disorder in women characterised by hyperandrogenism and oligomenorrhoea. Most women with PCOS also exhibit features of the metabolic syndrome, including insulin resistance, obesity and dyslipidaemia. While the association with type 2 diabetes is well established, whether the incidence of cardiovascular disease is increased in women with PCOS remains unclear. Echocardiography, imaging of coronary and carotid arteries, and assessments of both endothelial function and arterial stiffness have recently been employed to address this question. These studies have collectively demonstrated both structural and functional abnormalities of the cardiovascular system in PCOS. These alterations, however, appear to be related to the presence of individual cardiovascular risk factors, particularly insulin resistance, rather than to the presence of PCOS and hyperandrogenaemia per se. However, given the inferential nature of the evidence to date, more rigorous cohort studies of long-term cardiovascular outcomes and clinical trials of risk factor modification are required in women with PCOS.


Hum Reprod. 2006 Apr;21(4):930-5. Epub 2005 Dec 22.
Do young women with polycystic ovary syndrome show early evidence of preclinical coronary artery disease?
Topcu S, Caliskan M, Ozcimen EE, Tok D, Uckuyu A, Erdogan D, Gullu H, Yildirir A, Zeyneloglu H, Muderrisoglu H.
Cardiology Department and Obstetrics & Gynecology Department, Konya Teaching and Medical Research Center, Baskent University, Konya, Turkey. semratopcu2003@yahoo.com

BACKGROUND: It is thought that women with polycystic ovary syndrome (PCOS) are at increased risk of developing cardiovascular diseases. METHODS: In this study, we used transthoracic echocardiography to measure coronary flow reserve (CFR) in 28 women with PCOS and in 26 healthy women. RESULTS: The PCOS and the control groups were similar in terms of age (27.1 +/- 4.5 versus 28.8 +/- 4.4 years) and BMI (26.6 +/- 5.7 versus 24.7 +/- 4.4 kg/m2). Fasting insulin levels and homeostasis model assessment insulin resistance index were higher in the PCOS group. LH, the LH/FSH ratio, total testosterone, free testosterone and androstenedione were higher in the PCOS group. FSH, estradiol, prolactin, progesterone, cholesterol, triglyceride and high-sensitive C-reactive protein were similar between the two groups, but homocysteine levels were higher in the PCOS group. Baseline diastolic peak f low velocity (DPFV) (25.0 +/- 4.6 versus 23.3 +/- 2.7 cm/s, P > 0.05), hyperaemic DPFV (71.2 +/- 12.8 versus 73.0 +/- 12.9 cm/s, P > 0.05) and CFR (2.8 +/- 0.8 versus 3.2 +/- 0.8 cm/s, P > 0.05) of the left anterior descending coronary artery were similar between the two groups. CONCLUSION: We conclude that in young women with PCOS and without cardiovascular risk factors, CFR is preserved.


J Clin Endocrinol Metab. 2004 Aug;89(8):3696-701.
Erratum in: J Clin Endocrinol Metab. 2004 Nov;89(11):5621.
Comment in: J Clin Endocrinol Metab. 2004 Aug;89(8):3694-5.
The cardiovascular risk of young women with polycystic ovary syndrome: an observational, analytical, prospective case-control study.
Orio F, Palomba S, Spinelli L, Cascella T, Tauchmanovà L, Zullo F, Lombardi G, Colao A.
Department of Molecular and Clinical Endocrinology and Oncology, University Federico II, Naples, Italy. francescoorio@virgilio.it

To evaluate the cardiovascular risk of polycystic ovary syndrome (PCOS), we investigated lipid profile, metabolic pattern, and echocardiography in 30 young women with PCOS and 30 healthy age- and body mass index (BMI)-matched women. PCOS women had higher fasting glucose and insulin levels, homeostasis model assessment score of insulin sensitivity, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels, and TC/high density lipoprotein cholesterol (HDL-C) ratio and lower HDL-C levels than controls. Additionally, PCOS women had higher left atrium size (32.0 +/- 4.9 vs. 27.4 +/- 2.1 mm; P < 0.0001) and left ventricular mass index (80.5 +/- 18.1 vs. 56.1 +/- 5.4 g/m(2); P < 0.0001) and lower left ventricular ejection fraction (64.4 +/- 4.1 vs. 67.1 +/- 2.6%; P = 0.003) and early to late mitral flow velocity ratio (1.6 +/- 0.4 vs. 2.1 +/- 0.2; P < 0.0001) than controls. When patients and controls were grouped according to BMI [normal weight (BMI, >18 and <25 kg/m(2)), overweight (BMI, 25.1-30 kg/m(2)), and obese (BMI, >30 kg/m(2))], the differences between PCOS women and controls were maintained in overweight and obese women. In normal weight PCOS women, a significant increase in left ventricular mass index and a decrease in diastolic filling were observed, notwithstanding no change in TC, LDL-C, HDL-C, TC/HDL-C ratio, and TG compared with controls. In conclusion, our data show the detrimental effect of PCOS on the cardiovascular system even in young women asymptomatic for cardiac disease.


Endocr Rev. 2003 Jun;24(3):302-12.
Polycystic ovary syndrome and cardiovascular disease: a premature association?
Legro RS.
Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. rsl1@psu.edu

Women with polycystic ovary syndrome (PCOS) are often assumed, a priori, to be at increased risk for cardiovascular disease (CVD), given the high prevalence of the metabolic syndrome X among them. There is, however, no single definition of PCOS, and for that reason a comparison of studies that have analyzed its association with CVD is compromised from the start. Long-term studies of well characterized women with PCOS are lacking, and the link to primary cardiovascular events such as stroke or myocardial infarction remains more speculative than substantive. Epidemiological studies that have focused on isolated signs and stigmata of PCOS, such as polycystic ovaries, hyperandrogenism, or chronic anovulation, have found mixed results. There are studies that suggest a slight increase in cardiovascular events in women with polycystic ovaries, with perhaps stronger evidence between an increased risk of cardiovascular events in women with menstrual irregularity. However, there is little evidence for an association between hyperandrogenism per se and cardiovascular events. Furthermore, there are less data to substantiate an increased risk of events in women with PCOS identified on the basis of a combination of signs and symptoms, such as hyperandrogenic chronic anovulation. The existing data suggest that PCOS may adversely affect or accelerate the development of an adverse cardiovascular risk profile, and even of subclinical signs of atherosclerosis, but it does not appear to lower the age of clinical presentation to a premenopausal age group. Future studies to identify the risk of cardiovascular events in women with PCOS will benefit from clear and extensive phenotyping of PCOS abnormalities at baseline, from a prospective design, from larger sample sizes, and from longer follow-up.


Jpn Heart J. 2002 Sep;43(5):487-93.
QT dispersion in patients with polycystic ovary syndrome.
Alpaslan M, Onrat E, Yilmazer M, Fenkci V.
Department of Cardiology, Faculty of Medicine, Afyon Kocatepe University, Turkey.

Cardiac risk factors are observed more frequently in patients with polycystic ovary syndrome (PCOS). On the other hand, increased QT dispersion, which is a risk factor for cardiac arrhythmias and sudden death, has not been investigated in this syndrome. In this study, we evaluated QT dispersion in PCOS patients without overt heart disease. Thirty-six consecutive women with PCOS (mean age 24+/-5 years) and 36 healthy women of similar ages (mean age 24+/-4 years) participated in this study. PCOS was diagnosed if there were polycystic ovaries by ultrasound (enlarged ovaries with > or =8 cysts 2-8 mm in diameter), oligoamenorrhea (intermenstrual interval >35 days), hirsutism (Ferriman-Gallwey score, > or =7) and elevated serum levels of testosterone (> or =2.7 nmol/L). Electrocardiograms were recorded at a paper speed of 50 mm/s. QT intervals were manually measured by a cardiologist. All intervals were corrected for heart rate according to Bazett's formula: QTc interval=QT interval/square root of the RR interval. Mean values of body mass index, heart rate, and blood pressure were not significantly different between the two groups (P>0.05). No significant differences in QT intervals (maximum QT, minimum QT, QT dispersion, minimum corrected QT, maximum corrected QT, and corrected QT dispersion) were observed between the two groups (P>0.05). Our results suggest that the risk of ventricular arrhythmias or sudden cardiac death is not increased in PCOS patients.


Fertil Steril. 2001 Sep;76(3):511-6.
Comment in: Fertil Steril. 2002 Apr;77(4):855-6; author reply 856-7.
Fertil Steril. 2002 Apr;77(4):857-8.
Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular risk in patients with polycystic ovary syndrome.
Yarali H, Yildirir A, Aybar F, Kabakçi G, Bükülmez O, Akgül E, Oto A.
Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. yarali@ada.net.tr

OBJECTIVE: To assess cardiac flow parameters in patients with polycystic ovary syndrome (PCOS). DESIGN: A prospective case-control study. SETTING: University-based hospital. PATIENT(S): Thirty consecutive patients with PCOS were enrolled. Thirty women with regular menstrual cycles served as the controls. INTERVENTION(S): Systolic and diastolic function parameters were assessed by standard two-dimensional and M-mode echocardiography. Insulin sensitivity was evaluated by a standard 75-g oral glucose tolerance test and area-under-curve insulin analysis. Serum hormones, lipid profile, homocysteine, vitamin B(12), folate, fibrinogen, uric acid, and plasminogen activator inhibitor-I concentrations were measured. MAIN OUTCOME MEASURE(S): Systolic and diastolic function parameters, insulin sensitivity and serum homocysteine levels. RESULT(S): The mean serum homocysteine and uric acid concentrations were significantly higher in the PCOS group. Patients with PCOS had significant hyperinsulinemia. All systolic function parameters were comparable between the two groups. However, patients with PCOS had significantly lower peak mitral flow velocity in early diastole and significantly lower ratio between the early and late peak mitral flow velocities and also had significantly longer isovolumic relaxation time, reflecting a trend for nonrestrictive-type diastolic dysfunction. The area-under-curve insulin correlated positively with peak mitral flow velocity in late diastole (r = 0.375). The mean cholesterol/high-density lipoprotein ratio correlated negatively with mean mitral flow velocity in early diastole (E) peak (r = -0.474). The mean fasting insulin level correlated negatively with mean E/A ratio (r = -0.387). CONCLUSION(S): Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular disease risk in patients with PCOS.


Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):2414-21.
Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women.
Talbott EO, Guzick DS, Sutton-Tyrrell K, McHugh-Pemu KP, Zborowski JV, Remsberg KE, Kuller LH.
Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance. An adverse lipid profile has also been observed in PCOS-affected women, suggesting that these individuals may be at increased risk for coronary heart disease at a young age. The objective of the present study was to evaluate subclinical atherosclerosis among women with PCOS and age-matched control subjects. A total of 125 white PCOS cases and 142 controls, aged >/=30 years were recruited. Collection of baseline sociodemographic data, reproductive hormone levels, and cardiovascular risk factors was conducted from 1992 to 1994. During follow-up (1996 to 1999), these women underwent B-mode ultrasonography of the carotid arteries for the evaluation of carotid intima-media wall thickness (IMT) and the prevalence of plaque. A significant difference was observed in the distribution of carotid plaque among PCOS cases compared with controls: 7.2% (9 of 125) of PCOS cases had a plaque index of >/=3 compared with 0.7% (1 of 142) of similarly aged controls (P=0.05). Overall and in the group aged 30 to 44 years, no difference was noted in mean carotid IMT between PCOS cases and controls. Among women aged >/=45 years, PCOS cases had significantly greater mean IMT than did control women (0.78+/-0.03 versus 0.70+/-0.01 mm, P:=0. 005). This difference remained significant after adjustment for age and BMI (P:<0.05). These results suggest that (1) lifelong exposure to an adverse cardiovascular risk profile in women with PCOS may lead to premature atherosclerosis, and (2) the PCOS-IMT association is explained in part by weight and fat distribution and associated risk factors. There may be an independent effect of PCOS unexplained by the above variables that is related to the hormonal dysregulation of this condition.


Hum Reprod. 1999 Aug;14(8):1949-52.
Alterations in cardiac flow parameters in patients with polycystic ovarian syndrome.
Tiras MB, Yalcin R, Noyan V, Maral I, Yildirim M, Dortlemez O, Daya S.
Department of Obstetrics and Gynecology, Gazi University School of Medicine, Besevler, Ankara, Turkey.

The aim of this study was to examine the echocardiographic profiles of patients with polycystic ovarian syndrome (PCOS). Serum concentrations of follicle stimulating hormone, luteinizing hormone, androstenedione, free testosterone, prolactin, DHEA-SO(4) and 17-OH-progesterone, lipid profile (high and low density lipoproteins, triglyceride and total cholesterol) and basal and total insulin after a glucose tolerance test were measured in 35 patients with PCOS and 35 healthy controls matched for body mass index. Doppler, two dimensional M mode echocardiography was performed for the following indices: isovolumetric relaxation time (IVRT), E wave duration time (EVT), A wave duration time (AVT), E wave deceleration time (DT), peak early diastolic flow velocity (PEV), peak late diastolic flow velocity (PAV), E wave velocity time integral (FVI-E), A wave velocity time integral (FVI-A), atrial filling fraction (AFF), ejection fraction (EF), pre-ejection time (PEP), ejection time (ET) and aortic flow velocity time integral (FVI). Androstenedione, free testosterone, low density lipoproteins and cholesterol concentrations were significantly higher in patients with PCOS. There was no difference in basal and total insulin concentrations. IVRT, AVT, FVI-A, AFF, and PEP were higher in patients with PCOS, while PEV, FVI-E, EF, ET, EVT and EVT/AVT were higher in the control group. There was a positive correlation between basal insulin values and IVRT, and between total insulin values and EF. These changes are consistent with a non-restrictive type of diastolic dysfunction and left ventricular stiffness. PCOS may lead to diastolic dysfunction via hyperinsulinaemia and male type dyslipidaemia.


Clin Endocrinol (Oxf). 1995 Dec;43(6):677-81.
Cardiac flow velocity in women with the polycystic ovary syndrome.
Prelevic GM, Beljic T, Balint-Peric L, Ginsburg J.
Department of Medicine, UCL Medical School, Royal Free Hospital, London, UK.

OBJECTIVE: Women with the polycystic ovary syndrome (PCOS) often have several of the known risk factors for cardiovascular disease, including hyperinsulinaemia. We have therefore investigated variables of cardiac flow in young women with PCOS and related them to blood levels of reproductive hormones (LH, FSH, oestradiol and testosterone) and also of insulin. DESIGN: A prospective study. PATIENTS: Twenty-six young women with PCOS (mean age 22.8 +/- 0.9 years; mean BMI 23.0 +/- 0.8) and 11 healthy age matched women with regular ovulatory cycles (mean age 26.3 +/- 1.7 years; mean BMI 22.9 +/- 0.9). MEASUREMENTS: Cardiac flow was measured by pulsed wave Doppler echocardiography in the follicular phase of the cycle in controls and oligomenorrhoeic women; there was no special timing for amenorrhoeic women. The indicators assessed were: ejection fraction (EF), pre-ejection time (PEP), ejection time (ET), peak systolic flow velocity (PFV), acceleration time (AT), flow velocity integral (FVI), mean acceleration (MA), diastolic time (DT), early diastolic filling time (Ei), atrial filling time interval (Ai), peak velocity of the early diastolic filling (PE) and peak velocity of the atrial filling (PA). Serum LH, FSH, oestradiol, testosterone, SHBG and insulin concentrations were analysed by standard RIA. RESULTS: Significantly lower PFV (1.055 +/- 0.025 vs 1.242 +/- 0.054, P = 0.0006) and MA (17.06 +/- 0.57 vs 23.00 +/- 1.49, P = 0.0001) and longer AT (0.063 +/- 0.001 vs 0.056 +/- 0.004, P = 0.026) were found in women with PCOS as compared to age matched controls. Significant negative correlation between serum fasting insulin concentration and EF (r = -0.725, P = 0.002), PFV (r = -0.719, P = 0.0025), FVI (r = -0.654, P = 0.008) and MA (r = -0.757, P = 0.001) was observed in the 15 women with PCOS in whom insulin was measured. CONCLUSION: An inverse relation between serum fasting insulin level and left ventricular systolic outflow parameters suggests that insulin is associated with the decreased systolic flow velocity observed in women with PCOS.


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