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ABSTRACT: OBJECTIVES: To use the Androgen Excess-PCOS Society (AE-PCOS) criteria in adolescents to diagnose polycystic ovary syndrome (PCOS) and identify the prevalence of metabolic risk factors. STUDY DESIGN: Retrospective chart review of adolescents (>2 years postmenarche) presenting at a specialty clinic from 2008 through 2010 with complete evaluation for PCOS and metabolic risk were reviewed. Metabolic risk in adolescents with PCOS was compared with those with ≤1 AE-PCOS criteria. RESULTS: Of the 205 adolescents evaluated, 66% were found to have PCOS based on the AE-PCOS criteria. The most common presenting symptom was menstrual irregularity, followed by acne, hirsutism, and weight gain. Adolescents with PCOS had a significantly higher prevalence of obesity, hypertension, and low level of high-density lipoprotein cholesterol. Subjects with PCOS had ≥1 metabolic risk factor compared with the subjects without PCOS (63.6% vs 33.3%, P = .002). More adolescents with PCOS had ≥2 abnormal metabolic risk factors excluding body mass index compared with those without PCOS (P < .02). The prevalence of metabolic syndrome (≥3 risk factors) was 10.8% in adolescents with PCOS compared with 1.7% in those without PCOS (P < .04). CONCLUSIONS: Adolescents diagnosed with PCOS based on the AE-PCOS criteria are at a significantly increased risk of ≥1 metabolic abnormality. Our data underscore the need to accurately diagnose PCOS in the adolescent population instead of delaying the diagnosis to adulthood. Further, using similar criteria for the diagnosis of PCOS in adolescents (>2 years postmenarche) and adults will be more convenient for the clinician.
The Journal of pediatrics 12/2012; · 4.02 Impact Factor
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ABSTRACT: PRO--PCOS is associated with low-grade systemic inflammation as evidenced by elevation of multiple markers of inflammation such as C-reactive protein, interleukin-18, monocyte chemoattractant protein-1 and white blood cell count as well as endothelial dysfunction and increased oxidative stress. CON--Current studies examining the evidence for low grade inflammation in PCOS are small, heterogeneous for the diagnosis, confounded by degree of adiposity and do not consistently demonstrate a clinically relevant increase in the above mentioned biomarkers.
Fertility and sterility 01/2012; 97(1):7-12. · 3.97 Impact Factor
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ABSTRACT: To perform a systematic review and meta-analysis of studies that compared the prevalence of anxiety symptoms in women with polycystic ovary syndrome (PCOS) and control women.
Meta-analysis and systematic review.
University practice.
Cross-sectional studies comparing PCOS subjects and geographically matched clearly defined non-PCOS control subjects with data on age and body mass index (BMI).
Anxiety screening tool.
The primary analysis contrasted prevalence of anxiety. Cochrane Review Manager 5.0.24 software was used to construct forest plots comparing frequency of anxiety symptoms in case and control subjects.
Of 613 screened articles, nine met our selection criteria for a systematic review and four were included in the meta-analysis. The prevalence of generalized anxiety symptoms was available in four studies and was significantly greater in PCOS subjects (42/206, 20.4%) compared to controls (8/204, 3.9%). The odds for anxiety symptoms were significantly greater in women with PCOS compared with control subjects (odds ratio 6.88, 95% confidence interval 2.5-18.9). The mean anxiety score was significantly increased in three of the remaining five studies. Other anxiety disorders, such as social phobia, panic attacks, and obsessive compulsive disorders, were assessed infrequently.
Our systematic review suggests an increased odds of anxiety symptoms in women with PCOS, underscoring the importance of screening all women with PCOS for anxiety symptoms. Follow-up evaluation and treatment are essential, because generalized anxiety disorder is a chronic condition. Potential contributors for anxiety symptoms, such as hirsutism, obesity, and/or infertility may be specific to women with PCOS but need further investigation.
Fertility and sterility 11/2011; 97(1):225-30.e2. · 3.97 Impact Factor
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ABSTRACT: Polycystic ovary syndrome (PCOS) and depression both have a high prevalence in reproductive-aged women. This study aimed to determine the prevalence of abnormal depression scores in women who meet currently recognized definitions of PCOS compared with women in a well-defined control group.
The search was performed in MEDLINE, EMBASE Classic plus EMBASE, PsycINFO, Current Contents-Clinical Medicine and Current Contents-Life Sciences and Web of Science. Cochrane software Review Manager 5.0.24 was used to construct forest plots comparing risk of abnormal depression scores in those in the PCOS and control groups.
Studies with well-defined criteria of women with PCOS and control groups of women without PCOS, with demographic information including age and body mass index (BMI), were included. Of 752 screened articles, 17 met the selection criteria for systematic review and 10 studies were included in the meta-analysis.
Data were abstracted independently by three reviewers. All studies were cross-sectional and most used the Rotterdam criteria for the diagnosis of PCOS (n=10). The odds ratio (OR) for abnormal depression scores was 4.03 (95% confidence interval [CI] 2.96-5.5, P<.01) in women with PCOS (n=522) compared with those in the control groups (n=475). A subanalysis showed that the odds for abnormal depression scores was independent of BMI (OR 4.09, 95% CI 2.62-6.41). Several validated tools were used to screen for depression; the common tool used was the Beck Depression Inventory.
The results of our study suggest the need to screen all women with PCOS for depression using validated screening tools. Women with PCOS are at an increased risk for abnormal depression scores independent of BMI.
Obstetrics and Gynecology 01/2011; 117(1):145-52. · 4.73 Impact Factor
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ABSTRACT: Polycystic ovary syndrome (PCOS) is recognized as the most common endocrinopathy in reproductive-aged women. The symptoms of PCOS vary with age, race, weight, and medications, adding to the challenges of accurate diagnosis. Adolescent patients pose particular diagnostic problems because characteristics of normal puberty often overlap with signs and symptoms of PCOS. This article reviews the diagnosis of PCOS in adolescents.
Reviews in obstetrics and gynecology 01/2011; 4(2):45-51.
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ABSTRACT: Women with polycystic ovary syndrome (PCOS) often have cardiovascular disease (CVD) risk factors. The Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society created a panel to provide evidence-based reviews of studies assessing PCOS-CVD risk relationships and to develop guidelines for preventing CVD.
An expert panel in PCOS and CVD reviewed literature and presented recommendations.
Only studies comparing PCOS with control patients were included. All electronic databases were searched; reviews included individual studies/databases, systematic reviews, abstracts, and expert data. Articles were excluded if other hyperandrogenic disorders were not excluded, PCOS diagnosis was unclear, controls were not described, or methodology precluded evaluation. Inclusion/exclusion criteria were confirmed by at least two reviewers and arbitrated by a third.
Systematic reviews of CVD risk factors were compiled and submitted for approval to the AE-PCOS Society Board.
Women with PCOS with obesity, cigarette smoking, dyslipidemia, hypertension, impaired glucose tolerance, and subclinical vascular disease are at risk, whereas those with metabolic syndrome and/or type 2 diabetes mellitus are at high risk for CVD. Body mass index, waist circumference, serum lipid/glucose, and blood pressure determinations are recommended for all women with PCOS, as is oral glucose tolerance testing in those with obesity, advanced age, personal history of gestational diabetes, or family history of type 2 diabetes mellitus. Mood disorder assessment is suggested in all PCOS patients. Lifestyle management is recommended for primary CVD prevention, targeting low-density and non-high-density lipoprotein cholesterol and adding insulin-sensitizing and other drugs if dyslipidemia or other risk factors persist.
The Journal of clinical endocrinology and metabolism 04/2010; 95(5):2038-49. · 6.50 Impact Factor
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ABSTRACT: Pregnancies with mean yolk sac diameter>or=5 mm on early ultrasound require monitoring and counseling about a threefold increased risk for first-trimester loss independent of maternal risk factors such as age, body mass index, polycystic ovary syndrome, smoking, and diabetes. In addition, our study shows for the first time that enlarged yolk sac diameter may be associated with an increased risk of preterm delivery.
Fertility and sterility 02/2010; 94(4):1535-7. · 3.97 Impact Factor
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ABSTRACT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with multiple comorbidities such as diabetes, dyslipidemia, hypertension, and metabolic syndrome, all of which predispose women with PCOS to early atherosclerosis. Women with PCOS also have a higher prevalence of subclinical atherosclerosis, as reflected in dysregulation of endothelial function, increased carotid intimal-medial thickness, and presence of coronary artery calcification. Preliminary data indicate that serum biomarkers of cardiovascular disease such as high-sensitivity C-reactive protein, homocysteine, and adiponectin are abnormal in women with PCOS. There is limited data on abnormalities in the coagulation and fibrinolytic systems, however. The risk of venous thrombosis is unclear in the PCOS population, and further studies are urgently required to address whether first-line treatment for PCOS with oral contraceptive pills is advisable.
Seminars in Thrombosis and Hemostasis 10/2009; 35(7):613-20. · 4.52 Impact Factor
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ABSTRACT: We sought to study the association between intrauterine device (IUD) use and endometrial cancer.
A comprehensive search of literature published through April 2007 was conducted, studies reviewed, and data abstracted. Data from ten studies were pooled and analyzed using both fixed- and random-effects models to examine the association of ever use of an IUD and endometrial cancer.
Based on the random effects model, a protective crude association between IUD use and endometrial cancer was observed (odds ratio [OR] = 0.39; 95% confidence interval [CI] = 0.29-0.51; heterogeneity p < 0.001) with a pooled adjusted risk of OR = 0.54 (95% CI, 0.47-0.63; heterogeneity p = 0.40). A decreased risk of endometrial cancer also was seen for increased years of IUD use (OR for 5 years of use 0.88; 95% CI = 0.84-0.92; n = 5; heterogeneity p = 0.14), increased years since last IUD use (OR for 5 years of use 0.91; 95% CI, 0.86-0.95; n = 4; heterogeneity p = 0.02), and increased years since first IUD use (OR for 5 years of use 0.89; 95% CI, 0.83-0.95; n = 4; heterogeneity p = 0.04).
Our results suggest that nonhormonal IUD use may be associated with a decreased risk for endometrial cancer; however, the exact mechanism for this association is unclear. Future investigations should address the difference in the proposed association by specific type of IUDs.
Annals of epidemiology 06/2008; 18(6):492-9. · 2.95 Impact Factor
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ABSTRACT: To determine the conversion risk and predictors for depression in women with polycystic ovary syndrome.
Prospective longitudinal study.
University practice.
Subjects with polycystic ovary syndrome who had participated in a previous study.
None.
The Primary Care Evaluation of Mental Disorders Patient Health Questionnaire was used to diagnose major depressive disorder and other depressive syndromes, anxiety syndromes, and binge eating disorder. Subjects completed a questionnaire on knowledge about polycystic ovary syndrome and treatment satisfaction.
A total of 60 of 103 subjects responded to the second survey. Mean time between the two surveys was 22 months (range 12-26 months). The overall prevalence of depression was 40% (24/60). Of these, 10 women screened positive for major depressive disorder or other depressive syndromes and 14 were receiving antidepressant medications. There were 11 new cases identified in the second survey (19% conversion). Total subjects with mood disorders in this study were 34/60 (56.6%), including 11.6% with anxiety syndromes and 23.3% with binge eating disorder. Difficulties with menstrual function, fertility, and body image (weight, hirsutism, acne) were not significantly different in women with and without depression.
There is a significant risk for mood disorders (defined by the Diagnostic and Statistical Manual of Mental Disorders-IV) in women with polycystic ovary syndrome. This finding together with a high conversion risk for depression over a 1- to 2-year period underscores the importance of routine screening and aggressive treatment of mental health disorders in this population.
Fertility and sterility 03/2008; 91(1):207-12. · 3.97 Impact Factor
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Anuja Dokras
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ABSTRACT: Polycystic ovary syndrome (PCOS) is a common endocrinopathy associated with an increasing number of cardiovascular comorbidities. The relationship between insulin resistance and PCOS was described more than 3 decades ago. Women with PCOS also have an increased prevalence of several established cardiovascular risk factors such as diabetes, hypertension, and dyslipidemia. These factors contribute to the increased risk of endothelial dysfunction, increased carotid artery intima media thickness, and coronary artery calcification noted in women with PCOS compared with controls. Although truncal obesity is very prevalent in PCOS, these surrogate markers of atherosclerosis have been shown to be independent of body weight in young, asymptomatic subjects. Metabolic syndrome is a cluster of risk factors that also confer an increased risk of cardiovascular disease. Women with PCOS have also been shown to have a significantly higher prevalence of metabolic syndrome compared with age-matched controls. Currently, there are no longitudinal studies confirming increased cardiovascular morbidity and/or mortality in women with PCOS. However, the early presence of traditional and other cardiovascular risk factors underscores the need to screen and aggressively counsel and treat these women to prevent future symptomatic cardiovascular disease.
Seminars in Reproductive Medicine 02/2008; 26(1):39-44. · 3.80 Impact Factor
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ABSTRACT: Data suggest that dyssynchrony between day 6 blastocysts and endometrium may impair pregnancy rates in fresh transfer cycles.
Fertility and sterility 02/2008; 89(1):31-2. · 3.97 Impact Factor
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ABSTRACT: To determine the risk of metabolic complications, primarily metabolic syndrome, in all polycystic ovary syndrome (PCOS) phenotypes compared with control subjects.
Retrospective chart review.
University practice.
Women with PCOS (Rotterdam definition; n = 258) and women without PCOS seen during the same time period for an annual exam used as controls (n = 110).
None.
Metabolic syndrome.
Three PCOS phenotypes had a significantly higher prevalence of metabolic syndrome compared with the control subjects: oligomenorrhea/oligo-ovulation (O) + hyperandrogenism (H) + polycystic ovaries (P), age-adjusted odds ratio [OR] 6.3 (95% confidence interval 2.1-18.9); O+H, OR 7.8 (2.2-27.5); and H+P, OR 8.2 (2.3-29.3). There was no significant difference in the prevalence of metabolic syndrome between women with O+P and control subjects, even in obese women. The prevalence of insulin resistance and glucose intolerance was not significantly different between POCS phenotypes
The risk of metabolic syndrome may vary among the four phenotypes of PCOS based on the Rotterdam criteria. This new information may be of relevance in counseling women with PCOS although larger studies may be needed to validate our findings.
Fertility and sterility 12/2007; 88(5):1389-95. · 3.97 Impact Factor
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ABSTRACT: Polycystic ovary syndrome (PCOS) is associated with comorbidities that may contribute to increased risk of cardiovascular disease. PCOS is associated with increased risk of metabolic syndrome, dyslipidemia, and diabetes, but it remains unclear whether traditional cardiovascular (CV) risk factors can help predict coronary artery disease in this population.
The objectives of the study were to detect early-onset subclinical coronary atherosclerosis (using coronary artery calcium as a marker) in young women with PCOS, compared with age- and body mass index-matched controls, and to compare traditional CV risk factors and inflammatory markers in the two groups.
This was a prospective case-control study.
The study was conducted at a university hospital.
Twenty-four obese (body mass index >or= 30 kg/m2) PCOS subjects and 24 obese controls participated.
Coronary artery calcium, inflammatory markers (high-sensitivity C-reactive protein, IL-6, TNFalpha, adiponectin, leptin), fasting blood tests (glucose, lipids, insulin), and dual-energy x-ray absorptiometry scan for body fat distribution were measured.
Coronary artery calcium was detected in eight of 24 PCOS subjects (33%) and two of 24 controls (8%) (odds ratio 5.5, 95% confidence interval 1.03, 29.45, P < 0.03). Traditional CV risk factors did not differ significantly between the two groups, nor did markers of inflammation or adiposity, body fat distribution, or metabolic parameters with the exception of significantly lower quantitative insulin sensitivity check index (marker for insulin resistance) in the PCOS group (P < 0.05).
Young, obese women with PCOS have a high prevalence of early asymptomatic coronary atherosclerosis, compared with obese controls. This increased risk is independent of traditional CV risk factors and novel markers of inflammation. These findings underscore the need to screen and aggressively counsel and treat these women to prevent symptomatic CV disease.
Journal of Clinical Endocrinology & Metabolism 12/2007; 92(12):4609-14. · 6.50 Impact Factor
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ABSTRACT: To reduce the twin rate in our IVF program.
A prospective educational study of infertile couples; a retrospective review of IVF outcomes before vs. after mandatory single embryo transfer (mSBT) policy change.
University-based infertility center.
One hundred ten of 120 consecutive new infertile couples completed the educational study. Outcomes of all embryo transfers (n = 693) performed 17 months before and 17 months after mSBT were evaluated.
A 1-page educational summary of comparative risks of twins vs. singletons to maternal and child health.
Knowledge of twin risks and desired number of embryos transferred before and after education. Pregnancy rates, number of embryos transferred, and multiple-gestation rates before and after mSBT policy.
After education, knowledge of twin risks improved and a significant number of subjects changed their desired outcome to a lower gestational number. There was no change in ongoing pregnancy rates with blastocyst transfer before and after mSBT (63% vs. 58%; NS). Program-wide number of embryos transferred (2.1 +/- 0.6 vs. 1.9 +/- 0.7) and multiple-gestation rates (35% vs. 19%) decreased significantly while pregnancy rates were maintained.
Simple educational materials can improve knowledge of twin pregnancy risks and affect decision making. In high-risk patients, mSBT results in pregnancy rates similar to two-blastocyst transfer, with decreased twin rates.
Fertility and sterility 09/2007; 88(2):354-60. · 3.97 Impact Factor
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ABSTRACT: Polycystic ovary syndrome (PCOS) is associated with several metabolic complications. A few small studies have also suggested an increased risk of depression in women with PCOS. The goals of this study were to estimate the prevalence of depressive disorders in women with PCOS compared with controls and to evaluate the correlation between depression, hyperandrogenism, and other metabolic markers.
Cohort study.
University Hospital.
Women with PCOS (Rotterdam criteria; n = 103). Women without PCOS seen during the same time period for an annual exam were used as control subjects (n = 103).
Primary Care Evaluation of Mental Disorders Patient Health Questionnaire (PRIME-MD PHQ) and the Beck Depression Inventory.
Depressive disorders.
Women with PCOS were at an increased risk for depressive disorders (new cases) compared with controls (21% vs. 3%; odds ratio 5.11 [95% confidence interval (CI) 1.26-20.69]; P<.03). The overall risk of depressive disorders in women with PCOS was 4.23 (95% CI 1.49-11.98; P<.01) independent of obesity and infertility. Compared with the nondepressed PCOS subjects, the depressed PCOS subjects had a higher body mass index (BMI) and evidence of insulin resistance (P<.02).
We report a significantly increased risk of depressive disorders (as defined by the Diagnostic and Statistical Manual IV) in women with PCOS and recommend routine screening in this population.
Fertility and sterility 06/2007; 87(6):1369-76. · 3.97 Impact Factor
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ABSTRACT: Preeclampsia is a prevalent and potentially devastating disorder of pregnancy. Characterized by a sudden spike in blood pressure and urinary protein levels, it is associated with significant obstetric complications. BPH/5 is an inbred mouse model of preeclampsia with borderline hypertension before pregnancy. BPH/5 mice develop hypertension, proteinuria, and endothelial dysfunction during late gestation (after E14.5). We hypothesized that BPH/5 mice might exhibit early feto-placental abnormalities before the onset of maternal disease. All placental cell lineages were present in BPH/5 mice. However, the fetal and placental weights were reduced, with abnormalities in all the placental zones observed starting early in gestation (E9.5-E12.5). The fractional area occupied by the junctional zone was significantly reduced at all gestational timepoints. Markedly fewer CDKN1C-stained trophoblasts were seen invading the proximal decidual zone, and this was accompanied by reductions in Cdkn1c gene expression. Trophoblast giant cell morphology and cytokeratin staining were not altered, although the mRNA levels of several giant cell-specific markers were significantly downregulated. The labyrinth layer displayed decreased branching morphogenesis of endothelial cells, with electron microscopy evidence of attenuated trophoblast layers. The maternal decidual arteries showed increased wall-to-lumen ratios with persistence of actin-positive smooth muscle cells. These changes translated into dramatically increased vascular resistance in the uterine arteries, as measured by pulse-wave Doppler. Collectively, these results support the hypothesis that defects at the maternal-fetal interface are primary causal events in preeclampsia, and further suggest the BPH/5 model is important for investigations of the underlying pathogenic mechanisms in preeclampsia.
Biology of Reproduction 01/2007; 75(6):899-907. · 4.01 Impact Factor
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ABSTRACT: Polycystic ovary syndrome (PCOS) is associated with biochemical evidence of early atherosclerosis; however, data regarding vascular function are controversial. We hypothesized that resistance vessel function (mediated by the endothelium or smooth muscle) would be impaired in women with PCOS and aimed to determine the contribution of hyperandrogenism, obesity, or insulin resistance to vascular dysfunction.
Prospective study.
University practice.
Women with PCOS (n = 24) and age/weight-matched controls (n = 22).
Vascular function was assessed by measuring forearm vasodilatation in response to both endothelium-dependent (acetylcholine/bradykinin) and endothelium-independent dilators (nitroprusside/verapamil).
Resistance vessel function.
Forearm vasodilatation to all four drugs was reduced (>50%) in obese PCOS compared to lean PCOS subjects. There was no significant difference in vascular function between obese or lean women with PCOS compared to corresponding controls. Androgen levels did not correlate with vascular function. Stepwise regression analysis showed that body mass index (BMI) contributed maximally to vascular dysfunction (R(2) = 0.47).
This comprehensive study demonstrates for the first time that obese women with PCOS have markedly reduced vascular smooth muscle function compared to lean subjects with PCOS. In our study obesity and insulin resistance, but not hyperandrogenism, appeared to be significant modulators of vascular function.
Fertility and sterility 01/2007; 86(6):1702-9. · 3.97 Impact Factor
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ABSTRACT: Maspin, a tumour suppressor gene, is differentially expressed in the human placenta. Decreased expression of maspin in the first trimester corresponds with the period of maximum trophoblast invasion, suggesting a role in cell invasion and motility. Although methylation of CpG islands regulates maspin expression in cancer cells, the mechanism of maspin regulation in the human placenta is unknown. Our objectives were to determine the role of epigenetic alterations in the regulation of maspin expression in the placenta. Placental samples obtained from 7 to 40 weeks' gestation were used for bisulphite sequencing and chromatin immunoprecipitation (ChIP) PCR. There was no significant change in the methylation indices in the promoter region of maspin throughout gestation. The levels of histone modifications associated with transcriptionally active chromatin were significantly different in placental tissues from second and third trimester relative to those from first trimester. Addition of trichostatin A (TSA) to placental explants increased the maspin mRNA expression (8- to 20-fold), whereas addition of 5-aza-cytidine (5-AzaC) had no effect on maspin expression. Our data suggest that maspin expression in the human placenta is regulated by changes in histone tail modifications. This is the first report of selective histone modifications associated with differential placental gene expression in human gestation.
Molecular Human Reproduction 11/2006; 12(10):611-7. · 3.85 Impact Factor
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ABSTRACT: In addition to numerous health detriments caused by obesity, fertility and pregnancy success may also be compromised. The aims of this study were to compare the effects of obesity and morbid obesity on in vitro fertilization (IVF) outcomes. We also investigated the effects of obesity on obstetric outcomes after IVF treatment.
Retrospective study of women less than 38 years of age during their first fresh IVF cycle (January 1995 to April 2005).
A total of 1,293 women were included in the study, with 236 obese women (body mass index [BMI] = 30-39.9) and 79 morbidly obese women (BMI > or = 40). The morbidly obese group had a 25.3% IVF cycle cancellation rate compared with 10.9% in normal-weight women (odds ratio 2.73, 95% confidence interval 1.49-5.0), P < .001). Morbidly obese women without polycystic ovarian syndrome had an even higher cancellation rate (33%). Women with higher BMI required significantly more days of gonadotropin stimulation but had lower peak estradiol levels (P < .001). There were no significant differences in clinical pregnancy or delivery rates between the four BMI groups. Of the women who delivered, there was a significant linear trend for risk of preeclampsia, gestational diabetes, and cesarean delivery with increasing BMI (P < .03).
We report a significantly higher risk for IVF cycle cancellation in morbidly obese patients with no effect of BMI on clinical pregnancy or delivery rate. However, obese and morbidly obese subjects had a significantly higher risk for obstetric complications. This target population should be aggressively counseled regarding their increased obstetric risk and offered treatment options for weight reduction before the initiation of fertility therapy.
II-2.
Obstetrics and Gynecology 08/2006; 108(1):61-9. · 4.73 Impact Factor
