Polycystic ovary syndrome (PCOS) affects 5-10 percent of all fertile women and is associated with anovulation/oligoovulation, hyperandrogenism, and polycystic ovaries. Pharmacological treatment is often effective but associated with unwanted side effects. Acupuncture treatments have been shown to improve menstrual bleeding patterns and ovulation as well as hyperandrogenism, without side effects. The purpose of the present study was to describe the experience of acupuncture for women diagnosed with PCOS.
Eight women with PCOS living in western Sweden, were interviewed following repeated acupuncture treatments. Data was analyzed using systematic text condensation as described by Malterud.
The experience of acupuncture for women diagnosed with PCOS can be described in five categories; the experience of hope, getting results, feelings of responsibility, skepticism and proof of effect, and feeling normal.
Since acupuncture is a promising treatment for the symptoms of the common syndrome PCOS, the present study adds to the knowledge base by providing the important experiences of patients receiving the treatment. Acupuncture provides a possibility for patients to gain hope as the treatment shows results. The results show that acupuncture empowers the patients to take responsibility for their future well-being, although they may have been initially skeptical to the treatment. Because the syndrome had affected them for some time, even small changes offered a chance for them to feel that their bodies were capable of normal function.
The trial is registered at Clinical Trials.gov with Identifier number NCT00484705.
Polycystic ovary syndrome (PCOS), or Stein-Leventhal syndrome, is a common endocrine disorder defined by two of the three following features: i) oligoovulation or anovulation, ii) clinical and/or biochemical signs of hyperandrogenism, or iii) polycystic ovaries, once the related endocrinological and gynaecological disorders have been excluded. PCOS does not exclusively involve the reproductive apparatus , it has a complex number of systemic relevancy symptoms. It leads to Metabolic Syndrome, with severe consequences on the cardiovascular apparatus. Many clinical studies have underlined the connection between PCOS and the cardiovascular risk profile of such female patients, due to a lipid/glucose altered metabolism, hypertension, systemic inflammatory condition (assessable by markers such as VES, TNF-alfa, citokines and C-reactive protein (hsPCR) levels), and vascular injuries. Considering the early onset of the disease, PCOS could be considered as a real cardiovascular risk factor which affects the quality of life seriously. The current review aimed to point out the main connections between PCOS and cardiovascular risk factors according to the latest findings coming from literature data analysis, and try to depict the great influences that such a common disease can have on the patients’ health integrity.
PCOS; Cardiovascular Risk; Metabolic Syndrome; Diabetes; Hypertension
Polycystic Ovary Syndrome (PCOS) represents a common endocrinopathy, with anovulation and hyperandrogenism as cardinal symptoms. In recent years it
has been recognized that insulin resistance is an intrinsec feature of the disorder and plays a central role in pathogenesis. PCOS is associated
with important reproductive morbidity as shown by high prevalence of anovulatory infertility, spontaneous abortion, gestational diabetes
and pre–eclampsia. The association of insulin resistance with this reproductive pathology has been well documented. Due to major implication of
insulin resistance in PCOS pathogenesis, insulin reduction strategies were studied as a possible treatment for infertility in PCOS patients. Weight loss,
even modest was proved to be a simple and efficient method to improve reproductive parameters in PCOS patients and should be recommended to all overweight
and obese patients with infertility. Metformin was showed to induce ovulation, at least in a subset of patients with PCOS, but there are not
unequivocal proves concerning its efficacy for pregnancies and live–birth rate, mainly because few trials studied this aspect. Therefore there are
not enough evidences to recommend metformin for infertility treatment in PCOS. Few small studies with newer thiazolidindiones suggest their efficacy
for ovulation induction, but further extensive studies are needed to confirm these results. In conclusion, reduction of insulin resistance was proved
to ameliorate ovulation rate in PCOS patients, but strong evidences to sustain the utility of insulin–sensitizing drugs as a therapeutic option
for infertility are lacking. Future studies are needed to elucidate these aspects and to characterize the particular subtype of patients with
higher probability to respond to this treatment.
Under-carboxylated osteocalcin (ucOC), the precursor substrate of bone biomarker OC is a potent regulator of energy metabolism by promoting insulin production and adiponectin synthesis and decreasing fat stores. The aim of the present study was to point out the potential role of ucOC in the physiopathology of polycystic ovary syndrome (PCOS), a common disorder defined by the constellation of anovulation, insulinresistance, hyperinsulinemia, obesity and androgen excess.
In this prospective case–control investigation, 78 young premenopausal women, i.e. 52 PCOS patients and 26 age- and body mass index (BMI)-matched healthy controls, were successively enrolled. Recruitment of PCOS patients was performed according to Androgen Excess-Polycystic Ovary Syndrome (AE-PCOS) Society 2006 criteria. All study participants were subjected to clinical examination, whole-body composition assessment and measurements of serum ucOC, OC (1-49), glucose and lipids, insulin, total testosterone (TT), estradiol, sex-hormone binding globulin (SHBG), high-sensitivity C-reactive protein (Hs-CRP) and β-CrossLaps.
BMI-stratified multivariate analysis revealed significantly higher ucOC levels in PCOS vs. controls in lean (p = 0.001) but not overweight and obese study participants (p = 0.456). Notably, a positive correlation between ucOC and TT (p = 0.018), calculated free testosterone (cFT, p = 0.028) and serum insulin (p = 0.036), respectively, was found to be confined to the lean analysis subgroup. Furthermore, in stepwise multiple regression models, β-CrossLaps and cFT were able to predict 46.71% of serum ucOC variability. (1-43/49)OC failed to be significantly associated to any PCOS trait.
Circulating ucOC concentration is related to key endocrine PCOS characteristics in a weight-dependent manner. Within the bone-pancreas loop, high ucOC may favor insulin release in lean hyperandrogenic women to compensate for impaired insulin sensitivity.
Polycystic ovary syndrome; Osteocalcin; Testosterone; Insulin; Anovulation; Bone turnover; Obesity
Women affected by polycystic ovary syndrome (PCOS) are known to be at higher risk of cardiovascular disease. The aim of this study was to identify the artery that first is affected by early pre-atherosclerotic changes in PCOS.
Twenty-nine women with PCOS aged 17 to 27 years and 26 healthy nonhyperandrogenic volunteers with regular menses (control women) aged 16 to 28 years were enrolled. All PCOS patients were overweight or obese (body mass index [BMI] ≥ 25). Diagnosis of PCOS was performed in line with the 2003 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Accordingly, PCOS was defined when at least two of the following three features were present after exclusion of other etiologies: 1) oligomenorrhea and or anovulation; 2) hyperandrogenism and/or hyperandrogenemia; and 3) polycystic ovaries visible at ultrasound. Androgen excess or related disorders were excluded. The intima-media thickness (IMT) of common carotid arteries and common femoral arteries and the anteroposterior diameter of the infrarenal abdominal aorta were measured by ultrasound. Lutenizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, total testosterone, androstenedione, and sex hormone-binding globulin (SHBG) serum levels were measured between the 3rd and the 6th day of spontaneous or progestin-induced menstrual cycle. Our study was performed in the absence of any medical treatment.
Women with PCOS showed a higher LH to FSH ratio (p < 0.01), increased fasting insulin (p < 0.001), total testosterone (p < 0.001), and androstenedione (p < 0.001) levels, and lower SHBG concentrations (p < 0.001) compared to control women. BMI and waist-to-hip ratio were also higher in women with PCOS (p < 0.000 and p < 0.001, respectively). Women with PCOS also showed increased total cholesterol (p < 0.001), triglyceride (p < 0.001), and apolipoprotein B (p < 0.001) levels. Vascular data showed women with PCOS had a higher anteroposterior diameter than control women (p < 0.005). However, when analysis of covariance was performed and BMI was entered into the model as a covariate, anteroposterior diameter did not maintain a significant association with PCOS.
This study shows that anteroposterior diameter of the infrarenal abdominal aorta, but not IMT of common carotid arteries or common femoral arteries, is higher in women with PCOS than in women without this disease. This represents the earliest atherosclerotic change in women with PCOS. However, this alteration seems to be due to body weight secondary to PCOS and not due to PCOS per se.
polycystic ovary syndrome; antero-posterior diameter; infrarenal abdominal aorta; intimia-media thickness
It is estimated that as many as 1.4 million Canadian women may be afflicted with polycystic ovary syndrome (PCOS). Although PCOS is heralded as one of the most common endocrine disorders occurring in women, its diagnosis, management, and associated long-term health risks remain controversial. Historically, the combination of androgen excess and anovulation has been considered the hallmark of PCOS. To date, while these symptoms remain the most prevalent among PCOS patients, neither is considered an absolute requisite for the syndrome. Inclusion of ultrasonographic evidence of polycystic ovaries as a diagnostic marker has substantially broadened the phenotypic spectrum of PCOS, yet much debate surrounds the validity of these newly identified milder variants of the syndrome. Difficulty in resolving the spectrum of PCOS stems from the continued use of inconsistent and inaccurate methods of evaluating androgen excess, anovulation, and polycystic ovaries on ultrasound. At present, there is no clear-cut definition of biochemical hyperandrogenemia, particularly since we depend on poor laboratory standards for measuring androgens in women. Clinical signs of hyperandrogenism are ill-defined in women with PCOS, and the diagnosis of both hirsutism and polycystic ovarian morphology remains alarmingly subjective. Lastly, there is an inappropriate tendency to assign ovulatory status solely on the basis of menstrual cycle history or poorly timed endocrine measurements. In this review, we elaborate on these limitations and propose possible resolutions for clinical and research settings. By stimulating awareness of these limitations, we hope to generate a dialogue aimed at solidifying the evaluation of PCOS in Canadian women.
PMID: 18786289 CAMSID: cams574
Polycystic ovary syndrome; hyperandrogenism; hirsutism; menstruation disturbances; ultrasonography
Aim. To compare the basic endocrine profile and outcomes of in vitro fertilization (IVF) in women with polycystic ovary syndrome (PCOS), ovulatory polycystic ovaries (PCO), or normal ovaries (NO). Methods. The basic clinical features and in vitro fertilization and embryo transfer outcome in patients receiving IVF or intracytoplasmic sperm injection (ICSI) were retrospectively analyzed. Results. The body mass index, basal luteinizing hormone, and testosterone levels were significantly lower in patients with ovulatory PCO compared to those in patients with PCOS. The PCOS patients exhibited the shortest duration of ovarian stimulation and lowest dose of gonadotropin, followed by the ovulatory PCO and NO patients. The ovulatory PCO and PCOS patients showed similar levels of E2 on the human chorionic gonadotropin treatment day and numbers of oocytes, which were both significantly higher than those of the NO patients. The fertilization rate of the PCOS patients was significantly lower than the other two groups. Compared to NO patients, the cleavage rate was lower in both PCOS and ovulatory PCO patients, however, the number of available embryos was significantly more in these two groups. The incidence of the moderate to severe ovarian hyperstimulation syndrome (OHSS) was markedly higher in the PCOS and ovulatory PCO patients. Conclusion. Ovulatory PCO patients do not express similar endocrine abnormalities as PCOS patients. Although the fertilization rate and cleavage rate were relatively low in PCOS patients, ultimately, all the three groups showed similar transferred embryo numbers, clinical pregnancy rates, and implantation rates. Since the incidence of OHSS was much higher in the PCOS and ovulatory PCO patients, we should take more care of these patients and try to prevent severe OHSS.
Obesity or overweight affect most of patients with polycystic ovary syndrome (PCOS). Phenotypes are the clinical characteristics produced by the interaction of heredity and environment in a disease or syndrome. Phenotypes of PCOS have been described on the presence of clinical hyperandrogenism, oligoovulation and polycystic ovaries. The insulin resistance is present in the majority of patients with obesity and/or PCOS and it is more frequent and of greater magnitude in obese than in non obese PCOS patients. Levels of sexual hormone binding globulin are decreased, and levels of free androgens are increased in obese PCOS patients. Weight loss treatment is important for overweight or obese PCOS patients, but not necessary for normal weight PCOS patients, who only need to avoid increasing their body weight. Obesity decreases or delays several infertility treatments. The differences in the hormonal and metabolic profile, as well as the different focus and response to treatment between obese and non obese PCOS patients suggest that obesity has to be considered as a characteristic for classification of PCOS phenotypes.
Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting women of reproductive age and characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. There are no published data on this syndrome in Libyan patients.
Aims and objectives
To assess the frequency of clinical and biochemical features of PCOS in our patient population, and to compare this with data collected in other parts of the world.
Subjects and methods
A retrospective analysis of patient records at the endocrine clinic in Benghazi was undertaken. Patient inclusion was according to Rotterdam ESHRE/ASRM criteria. Clinical features, associated diseases, family history, hormone levels, and ultrasonography results were analyzed.
The mean age of the 318 PCOS patients at presentation was 25.8 years (range 15–44 years), and the majority (67%) were 20–29 years old at presentation. Of all patients, 57% were obese (BMI≥30), 93% had oligo-/amenorrhea, 91% were hirsute, and 74% had ultrasound features of polycystic ovaries. Diabetes mellitus was diagnosed in 9% of all PCOS patients and hypertension in 4%. Total serum testosterone was elevated in 26% of the patients, and serum prolactin was elevated in 31%. Thyroid disease was noted among 5.3% of the patients, and a history of diabetes or hypertension among first-degree relatives was seen in (16%) and (8%) of the patients respectively.
Chronic anovulation and hirsutism are the dominant features of PCOS in our patient population. More than half were obese, and the prevalence of diabetes, hypertension and thyroid disease in our patients seemed to be underestimated in comparison to other parts of the world.
polycystic; ovary; hirsutism; diabetes; obesity
To construct and validate a questionnaire for use in diagnosis of polycystic ovary syndrome (PCOS).
All participants completed a questionnaire, which asked clinical questions designed to assist in the diagnosis of PCOS, before their appointments with an endocrinologist. Following completion of the questionnaire, the endocrinologist (blinded to the answers) made or excluded a diagnosis of PCOS using clinical criteria and biochemical data as indicated. Questions were then evaluated for their power to predict PCOS, and a model was constructed using the most reliable items to establish a system to predict a diagnosis of PCOS.
An outpatient reproductive endocrinology clinic in Calgary, Alta.
Adult women patients who had been referred to the clinic. Fifty patients with PCOS and 50 patients without PCOS were included in the study.
MAIN OUTCOME MEASURES
Demographic information, medical history, related diagnoses, menstrual history, and fertility history.
A history of infrequent menses, hirsutism, obesity, and acne were strongly predictive of a diagnosis of PCOS, whereas a history of failed pregnancy attempts was not useful. A history of nipple discharge outside of pregnancy strongly predicted no diagnosis of PCOS. We constructed a 4-item questionnaire for use in diagnosis of PCOS; the questionnaire yielded a sensitivity of 85% and a specificity of 85% on multivariate logistic regression and a sensitivity of 77% and a specificity of 94% using the 4-item questionnaire. Predictive accuracy was validated using a second sample of 117 patients, in addition to internal validation using bootstrap analysis.
We have constructed a simple clinical tool to help diagnose PCOS. This questionnaire can be easily incorporated into family physicians’ busy practices.
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. It is characterized by chronic anovulation, hyperandrogenism, obesity and a predisposition to type 2 diabetes mellitus (T2DM). Since obesity plays an important role in the etiology of PCOS, we sought to determine if variants in the perilipin gene (PLIN), a gene previously implicated in the development of obesity, were also associated with PCOS. We typed six single nucleotide polymorphisms (haplotype tagging and/or previously associated with obesity or related metabolic traits) in PLIN in 305 unrelated non-Hispanic white women (185 with PCOS and 120 without PCOS). None of the variants was associated with PCOS (P < 0.05). However, the variant rs1052700*A was associated with increased risk for glucose intolerance (impaired glucose tolerance or T2DM) in both non-PCOS (OR = 1.75 [1.02-3.01], P = 0.044) and PCOS subjects (OR = 1.67 [1.08-2.59], P = 0.022). It was also associated with increased LDL (P = 0.007) and total cholesterol levels (P = 0.042). These results suggest that genetic variation in PLIN may affect glucose and lipid metabolism in women both with and without PCOS.
Perilipin; polycystic ovary syndrome (PCOS); type 2 diabetes mellitus; glucose; lipid
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. PCOS is considered to be not only a reproductive endocrinopathy, but also a metabolic disorder. The objective of the present study was to characterize the anthropometric and dietary profile of women with PCOS and to compare it with that of healthy age-matched women.
In this case-control study, 65 women with PCOS served as cases. The control group consisted of 65 age-matched healthy women. For each participant, demographic, anthropometric and dietary intake data were gathered and compared between the two groups.
There was no significant difference between the mean of the body mass index of the two groups, but the mean of waist circumference was significantly higher in the PCOS group, than the control group (P = 0.016). Compared to the normal weight PCOS patients, a significantly higher percentage of overweight patients had hirsutism (P = 0.009). In dietary analysis, women with PCOS consumed more calories and more fat than healthy women (P = 0.001 and P = 0.019, respectively).
It is concluded that in PCOS patients, android obesity is a common feature and this abdominal adiposity may be related to the syndrome's complications. PCOS symptoms were more severe in overweight patients than the normal weight. Regarding the dietary pattern, it was indicated that patients with PCOS consume more calories and more fat in their diets and this might have been correlated to their disease.
Diet; hirsutism; obesity; polycystic ovary syndrome
Hirsutism represents a primary clinical indicator of androgen excess. The most common endocrine condition causing hirsutism is polycystic ovary syndrome (PCOS). Diagnosing PCOS is not easy as the signs and symptoms are heterogenous. The newest diagnostic guideline made by the Androgen Excess and PCOS Society in 2006, claims the presence of hyperandrogenism, and ovarian dysfunction (oligo / anovulation and / or polycystic ovaries). Obesity associated reproductive and metabolic dysfunctions may aggravate the symptoms of PCOS. PCOS might be underdiagnosed in non obese women because lean PCOS phenotypes might be underestimated for the syndrome. Effective medical treatment of PCOS and associated hirsutism depends on the endocrinological expertise and experience of the therapist in each individual case. An algorithm for the treatment has not been established yet.
Endocrinology; hirsutism; medical treatment; polycystic ovary syndrome
The polycystic ovary syndrome (PCOS), a common endocrine disorder in women of child-bearing age, mainly characterised by chronic anovulation and hyperandrogenism, is often associated with insulin resistance (IR) and obesity. Its etiology and the role of IR and obesity in PCOS are not fully understood. We examined the influence of validated genetic variants conferring susceptibility to obesity and/or type 2 diabetes mellitus (T2DM) on metabolic and PCOS-specific traits in patients with PCOS.
We conducted an association study in 386 patients with PCOS (defined by the Rotterdam-criteria) using single nucleotide polymorphisms (SNPs) in or in proximity to the fat mass and obesity associated gene (FTO), insulin-induced gene-2 (INSIG2), transcription factor 7-like 2 gene (TCF7L2) and melanocortin 4 receptor gene (MC4R). To compare the effect of FTO obesity risk alleles on BMI in patients with PCOS to unselected females of the same age range we genotyped 1,971 females from the population-based KORA-S4 study (Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4).
The FTO risk allele was associated with IR traits and measures of increased body weight. In addition, the TCF7L2 SNP was associated with body weight traits. For the SNPs in the vicinity of INSIG2 and MC4R and for the other examined phenotypes there was no evidence for an association. In PCOS the observed per risk allele effect of FTO intron 1 SNP rs9939609 on BMI was +1.56 kg/m2, whereas it was +0.46 kg/m2 in females of the same age range from the general population as shown previously.
The stronger effect on body weight of the FTO SNP in PCOS might well have implications for the etiology of the disease.
Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by anovulation, hyperandrogenism, and polycystic ovaries. Because of the heterogeneous nature of PCOS, women affected by the condition often require a customized approach for ovulation induction when trying to conceive. Treating symptoms of PCOS in overweight and obese women should always incorporate lifestyle changes with the goal of weight-loss, as many women with PCOS will ovulate after losing 5%–10% of their body weight. On the other hand, other factors must be considered including the woman’s age, age-related decline in fertility, and previous treatments she may have already tried. Fortunately, multiple options for ovulation induction exist for women with PCOS. This paper reviews specific ovulation induction options available for women with PCOS, the benefits and efficacy of these options, and the related side effects and risks women can anticipate with the various options that may affect treatment adherence. The paper also reviews the recommended evidence-based strategies for treating PCOS-related infertility that allow for incorporation of the patient’s preference. Finally, it briefly reviews emerging data and ongoing studies regarding newer agents that have shown great promise as first-line agents for the treatment of infertility in women with PCOS.
polycystic ovary syndrome; anovulation; clomiphene citrate; letrozole; metformin; obesity
Polycystic ovary syndrome (PCOS), the most common endocrine disorder of pre-menopausal women, is characterized by chronic hyperandrogenism, oligoanovulation, obesity and insulin resistance. Importantly, PCOS women are at increased risk for glucose intolerance, type 2 diabetes and cardiovascular disorders. Recent reports indicate an unexpectedly high prevalence of obstructive sleep apnea (OSA) in PCOS. Alterations in sex steroids (i.e. high androgen and low estrogen levels) and increased visceral adiposity in PCOS could potentially contribute to the increased prevalence of OSA in this disorder. There is some evidence to suggest that there may be strong associations between the presence and severity of OSA and the metabolic disturbances that characterize PCOS. Causal mechanisms in the link between PCOS and OSA remain to be elucidated. Clinicians who manage PCOS patients should be aware of the high prevalence of OSA in these patients and systematically evaluate these women for sleep disturbances.
PCOS; visceral adiposity; obesity; insulin resistance; OSA
Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disorder associated with obesity and insulin resistance that often precedes the development of type-2 diabetes. Rats continuously exposed to dihydrotestosterone from prepuberty display typical reproductive and metabolic PCOS characteristics including anovulation, polycystic ovaries, insulin resistance, and obesity.
Our aim was to investigate if resveratrol improves reproductive and metabolic functions in PCOS rats. The effect was compared to exercise.
Control and PCOS rats were treated with vehicle or resveratrol (400 mg · kg−1 · day−1) for 5-6 weeks. Another group of PCOS rats received vehicle treatment and exercised for 5-6 weeks. Insulin sensitivity was determined by euglycemic-hyperinsulinemic clamp.
The glucose infusion rate was lower in the PCOS-vehicle group compared to control-vehicle rats (P < 0.05). Exercise increased insulin sensitivity compared with PCOS-vehicle rats (P < 0.05), but resveratrol did not. Resveratrol treatment and exercise resulted in smaller adipocytes, upregulated estrogen-related receptor α gene expression in subcutaneous fat, and improved estrus cyclicity in the previously acyclic PCOS rats.
Although resveratrol had positive effects on adiposity and cyclicity in a similar manner to exercise, resveratrol does not seem to be a good candidate for treating insulin resistance associated with PCOS because no improvement in insulin sensitivity was observed in PCOS rats on normal chow.
Lipocalin-2 is a novel adipokine that appears to play a role in the development of insulin resistance. Serum lipocalin-2 levels are elevated in obese patients. Obesity and insulin resistance are cardinal characteristics of the polycystic ovary syndrome (PCOS). However, there are limited data on serum lipocalin-2 levels in patients with PCOS. The aim of the present study was to assess serum lipocalin-2 levels in PCOS.
We studied 200 patients with PCOS and 50 healthy female volunteers.
Serum lipocalin-2 levels were slightly higher in women with PCOS compared with controls (65.4 +/- 34.3 vs. 60.3 +/- 26.0 ng/ml, respectively) but this difference did not reach statistical significance. In contrast, lipocalin-2 levels were higher in overweight/obese women with PCOS than in normal weight women with the syndrome (76.2 +/- 37.3 vs. 54.5 +/- 27.2 ng/ml, respectively; p < 0.001). Serum lipocalin-2 levels were also higher in overweight/obese controls compared with normal weight controls (70.1 +/- 24.9 vs. 50.5 +/- 23.7 ng/ml, respectively; p = 0.004). In the total study population (patients with PCOS and controls), lipocalin-2 levels were independently correlated with the body mass index (p < 0.001). In women with PCOS, lipocalin-2 levels were independently correlated with the waist (p < 0.001).
Obesity is associated with elevated serum lipocalin-2 levels. In contrast, PCOS does not appear to affect lipocalin-2 levels.
Polycystic ovaries and impaired fertility are the result of abnormal folliculogenesis. Our objective was to determine the role of four candidate folliculogenesis genes in the development of polycystic ovary syndrome (PCOS). Women with and without PCOS (335 cases, 198 controls) were genotyped for single nucleotide polymorphisms in GDF9, BMP15, AMH, and AMHR2. Variants in these genes were not associated with PCOS. Certain GDF9 variants were associated with hirsutism scores and parity in PCOS patients. GDF9 may thus serve as a modifier gene. These results suggest that inherited defects in folliculogenesis are not major factors in the genetic susceptibility to PCOS.
folliculogenesis; polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among premenopausal women, who often develop insulin resistance. We tested the hypothesis that insulin resistance in skeletal muscle of patients with polycystic ovary syndrome (PCOS) is an intrinsic defect, by investigating the metabolic characteristics and gene expression of in vitro differentiated myotubes established from well characterized PCOS subjects.
Using radiotracer techniques, RT-PCR and enzyme kinetic analysis we examined myotubes established from PCOS subjects with or without pioglitazone treatment, versus healthy control subjects who had been extensively metabolically characterized in vivo. Results Myotubes established from PCOS and matched control subjects comprehensively expressed all insulin-sensitive biomarkers; glucose uptake and oxidation, glycogen synthesis and lipid uptake. There were no significant differences between groups either at baseline or during acute insulin stimulation, although in vivo skeletal muscle was insulin resistant. In particular, we found no evidence for defects in insulin-stimulated glycogen synthase activity between groups. Myotubes established from PCOS patients with or without pioglitazone treatment also showed no significant differences between groups, neither at baseline nor during acute insulin stimulation, although in vivo pioglitazone treatment significantly improved insulin sensitivity. Consistently, the myotube cultures failed to show differences in mRNA levels of genes previously demonstrated to differ in PCOS patients with or without pioglitazone treatment (PLEK, SLC22A16, and TTBK).
These results suggest that the mechanisms governing insulin resistance in skeletal muscle of PCOS patients in vivo are not primary, but rather adaptive.
Polycystic ovary syndrome (PCOS), the most common endocrine disease among premenopausal women, is caused by both genes and environment. We and others previously reported association between single nucleotide polymorphisms (SNPs) in the DENND1A gene and PCOS. We therefore sequenced the DENND1A gene in white patients with PCOS to identify possible alterations that may be implicated in the PCOS pathogenesis. Patients were referred with PCOS and/or hirsutism between 1998 and 2011 (n = 261). PCOS was diagnosed according to the Rotterdam criteria (n = 165). Sequence analysis was performed in 10 patients with PCOS. Additional patients (n = 251) and healthy female controls (n = 248) were included for SNP genotyping. Patients underwent clinical examination including Ferriman-Gallwey score (FG-score), biochemical analyses and transvaginal ultrasound. Mutation analysis was carried out by bidirectional sequencing. SNP genotyping was tested by allelic discrimination in real-time PCR in the additional patients and controls. Sequencing of the DENND1A gene identified eight SNPs; seven were not known to be associated with any diseases. One missense SNP was detected (rs189947178, A/C), potentially altering the structural conformation of the DENND1A protein. SNP genotyping of rs189947178 showed significantly more carriers among patients with PCOS and moderate hirsutism compared to controls. However, due to small sample size and lack of multiple regression analysis supporting an association between rs189947178 and FG-score or PCOS diagnosis, this could be a false positive finding. In conclusion, sequence analysis of the DENND1A gene of patients with PCOS did not identify alterations that alone could be responsible for the PCOS pathogenesis, but a missense SNP (rs189947178) was identified in one patient and significantly more carriers of rs189947178 were found among patients with PCOS and moderate hirsutism vs. controls. Additional studies with independent cohort are needed to confirm this due to the small sample size of this study.
Polycystic ovary syndrome (PCOS) is a complex, heterogeneous disorder of uncertain etiology. Recent studies suggested that insulin resistance (IR) plays an important role in the development of PCOS. In the current study, we aimed to investigate the molecular mechanism of IR in PCOS. We employed genome-wide methylated DNA immunoprecipitation (MeDIP) analysis to characterize genes that are differentially methylated in PCOS patients vs. healthy controls. Besides, we also identified the differentially methylated genes between patients with PCOS-non-insulin resistance (PCOS-NIR) and PCOS-insulin resistance (PCOS-IR). A total of 79 genes were differentially methylated between PCOS-NIR vs. PCOS-IR patients, and 40 genes were differentially methylated in PCOS patients vs. healthy controls. We analyzed these differentially methylated genes by constructing regulatory networks and protein-protein interaction (PPI) networks. Further, Gene Ontology (GO) and pathway enrichment analysis were also performed to investigate the biological functions of networks. We identified multiple categories of genes that were differentially methylated between PCOS-NIR and PCOS-IR patients, or between PCOS patients and healthy controls. Significantly, GO categories of immune response were differentially methylated in PCOS-IR vs. PCOS-NIR. Further, genes in cancer pathways were also differentially methylated in PCOS-NIR vs. PCOS-IR patients or in PCOS patients vs. healthy controls. The results of this current study will help to further understand the mechanism of PCOS.
To test the hypothesis that the risk of persistent glucose impairment after gestational diabetes mellitus (GDM) is increased in patients with polycystic ovary syndrome (PCOS).
RESEARCH DESIGN AND METHODS
The prospective case-control study included 42 pregnant patients with PCOS and GDM and 84 pregnant control patients with GDM but without clinical and biochemical hyperandrogenism, polycystic ovaries, and oligo-anovulation. The case and control subjects were matched one to two for age and BMI. The glycemic profiles were studied in all subjects 6 weeks, 12 weeks, and 18 months after delivery. The incidence and the relative risk (RR) were calculated for overall persistence of an abnormal glycemic pattern and for each specific alteration, i.e., impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and diabetes mellitus (DM).
At 18 months after delivery, the incidences of IFG, IGT, and IFG-IGT were significantly (P < 0.05) higher in the cases than in the controls. At the 18-month follow-up, the RR for the composite outcome of glucose metabolism impairment in PCOS women was 3.45 (95% CI 1.82–6.58).
Patients with PCOS are at increased risk for a persistent impaired glucose metabolism after GDM.
The polycystic ovary syndrome (PCOS), one of the most common causes of infertility due to anovulation, affects 4–7% of women). Etiology of PCOS remains largely unknown, familial aggregation of cases suggests genetic susceptibility to the disorder. Though genes involved remain unknown, recent evidence points to a gene of the insulin receptor. Genes implicated in ovarian follicular development may also play a role. A fundamental aspect of the syndrome seems to be a defect in insulin metabolism. There is consistent evidence that increase of body weight may favour a more severe hyperandrogenism.
Treatment of PCOS has been mostly symptomatic. Only recently has the use of insulinomimetic or insulin sensitizing agents provided an option to treat the presumed underlying cause of this disorder, which is insulin resistance. Metformin appears to improve risk factors for cardiovascular disease in diabetic and non-diabetic patients, indicating that its use could be associated with a reduction in coronary heart disease in patients with PCOS. The use of metformin in hyperinsulinemic women with PCOS improved the lipid profile, including decreases in total cholesterol, low density lipoprotein cholesterol, and triglyceride concentration.
Polycystic ovary syndrome (PCOS) is defined as chronic anovulation with evidence of hyperandrogenism, after the exclusion of secondary causes. It is commonly linked to obesity and the presence of the metabolic syndrome.
To review the clinical features and medical assessment of adolescents referred for PCOS to gynecology or endocrinology services at The Hospital for Sick Children (Toronto, Ontario).
A chart review was conducted of all adolescents with PCOS referred during a one-year period. Measures included clinical findings, investigations and management.
Forty-one adolescent girls, with a mean age ± SD of 14.7±1.5 years, were reviewed. Common presenting complaints were menstrual irregularities in 35 of 41 girls (85%) and hirsutism in 28 of 41 girls (68%), with 32 of 41 adolescents (78%) having more than one complaint. The majority (31 of 38 [82%]) were overweight or obese. Features associated with the metabolic syndrome (hypertension, dyslipidemia, insulin resistance and obesity) were identified in some adolescents, but were not consistently assessed. Blood pressure was assessed in 38 adolescents, fasting plasma glucose in 27, triglycerides in 22 and cholesterol in 21. Only four of 28 adolescents (15%) who underwent pelvic ultrasound demonstrated ovarian cysts. Investigations and management differed somewhat between endocrinologists and gynecologists. Most adolescents (34 of 41 [83%]) received pharmacological treatment: oral contraceptive pill (21 of 34 [62%]); intermittent medroxyprogesterone acetate to induce withdrawal bleeding (nine of 34 [26%]); metformin (two of 34 [6%]); or oral contraceptive pill and antiandrogen (two of 34 [6%]).
Adolescents with PCOS are at risk of developing metabolic abnormalities. Polycystic ovaries were not a consistent finding. The most commonly prescribed treatment was the oral contraceptive pill. Greater attention should be placed on screening adolescents with PCOS for diabetes, hypertension and dyslipidemia, allowing for earlier identification and management of potentially modifiable cardiovascular risk factors.
Adolescents; Metabolic syndrome; Polycystic ovary syndrome