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Anovulation in reproductive years [keywords]
- Lifecycle of polycystic ovary syndrome (PCOS): from in utero to menopause. [Journal Article, Research Support, N.I.H., Extramural]
- J Clin Endocrinol Metab 2013 Dec; 98(12):4629-38.
Polycystic ovary syndrome (PCOS) is diagnosed during the reproductive years when women present with 2 of 3 of the following criteria: 1) irregular menstrual cycles or anovulation, 2) hyperandrogenism, and 3) PCO morphology. However, there is evidence that PCOS can be identified from early infancy to puberty based on predisposing environmental influences. There is also increasing information about the PCOS phenotype after menopause. The goal of this review is to summarize current knowledge about the appearance of PCOS at different life stages and the influence of reproductive maturation and senescence on the PCOS phenotype.PubMed, the bibliography from the Evidence-Based PCOS Workshop, and the reference lists from identified manuscripts were reviewed.The current data suggest that daughters of women with PCOS have a greater follicle complement and mild metabolic abnormalities from infancy. PCOS is often diagnosed in puberty with the onset of hyperandrogenism and may be preceded by premature pubarche. During the reproductive years, there is a gradual decrease in the severity of the cardinal features of PCOS. Menopausal data suggest that the majority of women who had PCOS during their reproductive years continue to manifest cardiovascular risk factors. However, the majority do not present an increased risk for cardiovascular morbidity and mortality, perhaps because women with no history of PCOS may catch up after menopause.The current data provide a comprehensive starting point to understand the phenotype of PCOS across the lifespan. However, limitations such as a bias of ascertainment in childhood, age-based changes during reproductive life, and the small numbers studied during menopause point to the need for additional longitudinal studies to expand the current knowledge.
- Renaming PCOS--a two-state solution. [Journal Article, Research Support, N.I.H., Extramural]
- J Clin Endocrinol Metab 2013 Nov; 98(11):4325-8.
It has become evident over the past 30 years that polycystic ovary syndrome (PCOS) is more than a reproductive disorder. It has metabolic sequelae that can affect women across the lifespan. Diagnostic criteria based on the endocrine features of the syndrome, hyperandrogenism and chronic anovulation, such as the National Institutes of Health (NIH) criteria, identify women at high metabolic risk. The additional phenotypes defined by the Rotterdam diagnostic criteria identify women with primarily reproductive rather than metabolic dysfunction.The aim is to discuss the rationale for a separate name for the syndrome that is associated with high metabolic risk while maintaining the current name for the phenotypes with primarily reproductive morbidity.The NIH Office for Disease Prevention-Sponsored Evidence-Based Methodology Workshop on Polycystic Ovary Syndrome recommended that a new name is needed for PCOS. POSITIONS: The authors propose that PCOS be retained for the reproductive phenotypes and that a new name be created for the phenotypes at high metabolic risk.There should be two names for the PCOS phenotypes: those with primarily reproductive consequences should continue to be called PCOS, and those with important metabolic consequences should have a new name.
- Usual dietary isoflavone intake and reproductive function across the menstrual cycle. [Controlled Clinical Trial, Journal Article, Research Support, N.I.H., Intramural]
- Fertil Steril 2013 Dec; 100(6):1727-34.
To assess the association of total isoflavone intake with ovulatory function, including sporadic anovulation in healthy premenopausal women.Prospective cohort study.University.Participants included 259 healthy regularly menstruating women aged 18-44 years.None.Serum concentrations of E2, free E2, P, LH, FSH, and SHBG and sporadic anovulation in healthy premenopausal women.Isoflavone intake was not associated with E2, free E2, P, LH, and FSH concentrations. Consumption in the highest quartile (Q4: 1.6-78.8 mg/d) was significantly associated with greater SHBG concentrations (β = 0.09; 95% confidence interval [CI] 0.02-0.16), compared with the first quartile (Q1: 0.0-0.3 mg/d).Isoflavone intake was not associated with sporadic anovulation (Q4 vs. Q1: odds ratio 0.87, 95% CI 0.32-1.66). Dietary isoflavone intake among young premenopausal women was not related to sex hormone concentrations or anovulation, but was associated with minimally increased SHBG concentrations. These results suggest potential endocrine effects with no subsequent effects on ovulation, easing concerns regarding their impacts on fertility.
- The prevalence of phenotypic subgroups in Greek women with polycystic ovarian syndrome. [Journal Article]
- Clin Exp Obstet Gynecol 2013; 40(2):253-6.
Since 2003, when the American Society for Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE) sponsored consensus established criteria for polycystic ovarian syndrome (PCOS) diagnosis, the phenotypic spectrum of the syndrome has been significantly broadened.This survey makes an effort to distinguish PCOS according to phenotypic expression and to estimate its prevalence in a Greek population.Greek women from 18 to 35 years of age, who visited the outpatient department, claiming either irregular menstruation (oligo- or anovulation, OA) or clinical manifestations of hyperandrogenemia (HA) were recruited. They gave full disease history and underwent clinical examination, including transvaginal ultrasound (TVUS) scan to identify PCO morphology. Blood samples were collected to perform hormonal and metabolic analyses. Acute or chronic disorders were excluded. Finally, 266 PCOS women constituted the study population.The full-blown phenotype (HA+OA+PCO) is the predominant phenotype in this Greek population.
- [Polycystic ovary syndrome: physiopathology review]. [English Abstract, Journal Article, Review]
- Rev Fac Cien Med Univ Nac Cordoba 2013; 70(1):27-30.
Polycystic ovary syndrome (PCOS), the most common gynecological endocrinopathy in women of reproductive age, is characterized by hyperandrogenism, chronic anovulation and /or polycystic ovaries. Although the cause of PCOS is still unknown, there are several hypotheses attempting to explain the primary defect; the most commonly accepted is insulin resistance. Due to its high prevalence, the patients have increased risk of developing metabolic and cardiovascular alterations. The compensatory hyperinsulinemia contributes to hyperandrogenism in different ways: by stimulating ovarian androgen synthesis and inhibiting hepatic production of sex hormone binding globulin. From the study of the intrauterine environment in recent years it has been suggested that PCOS may have an origin in utero associated with prenatal exposure to androgens. The aim of this paper is to review the main mechanisms proposed to cause the syndrome.
- Prevalence of polycystic ovary syndrome in women in China: a large community-based study. [Journal Article, Research Support, Non-U.S. Gov't]
- Hum Reprod 2013 Sep; 28(9):2562-9.
What is the prevalence of polycystic ovary syndrome (PCOS) in Han Chinese women from different communities?The prevalence of PCOS in Chinese women aged 19-45 years is 5.6%.The prevalence of PCOS is reported to range from 5 to 10% but to the best of our knowledge the Han Chinese population has not been studied.A large-scale epidemiological study was carried out between October 2007 and September 2011 in 15 924 Han Chinese women of reproductive age (19-45 years) from the 10 provinces and municipalities in China.A total of 16 886 women from 152 cities and 112 villages were involved in the study. All study participants received a questionnaire and underwent a physical and transvaginal ultrasound examination. Blood samples were collected from a subsample of women (n = 3565) for analysis of metabolic markers and hormones. Based on the Rotterdam PCOS criteria, we assessed hyperandrogenism (H), chronic anovulation (O) and polycystic ovaries (P). Following diagnosis, women with PCOS were assigned to one of four different phenotypes. Finally, the prevalence and related risks of PCOS among Chinese women were estimated based on all the data sources.A total of 16 886 women were initially involved in the study and 15 924 eligible participants then completed the study; the overall response rate was 94.3% (15 924/16 886). The prevalence of PCOS in the Chinese community population was 5.6% (894/15 924). Blood samples were analyzed from 833 of these women who were assigned to the four PCOS phenotypes as follows: 19% H + O, 37% H + P, 15% O + P and 29% H + O + P. Comparing the 833 women with PCOS to 2732 women without PCOS indicated that PCOS occurs in younger women (P < 0.05) and these women were prone not only to menstrual problems, hyperandrogenism, PCO and infertility but also metabolic syndrome (MS) and insulin resistance (IR). However, there was no significant difference in the rate of hypertension or hyperlipemia between the two groups. Obese patients with PCOS had a higher rate of MS (16 versus 48%), IR (7 versus 28%), hypertension (8 versus 30%) and hyperlipemia (48 versus 73%) compared with non-obese patients (all P < 0.05), respectively. The rates of metabolic complications in patients with PCOS increased with age.Age and ethnic origin contribute to the differing manifestations of PCOS; therefore, sampling is one of the most important issues in epidemiological research into PCOS. Owing to the mobility of the Chinese population, the survey among resident populations caused a certain deviation in the age distribution.The prevention and treatment of PCOS, particularly in those who are obese, are essential in Chinese women of reproductive age.This study was supported by National Science Fund for Distinguished Young Scholars, Capital Medical Development Scientific Research Fund and National Key Technology R&D Program. Ten participant university hospitals and the National Center for Chronic and Noncomunicable Disease Control and Prevention participated. All authors have nothing to disclose.
- Androgen profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in healthy normal-weight ovulatory and anovulatory late adolescent and young women. [Journal Article, Research Support, Non-U.S. Gov't]
- J Clin Endocrinol Metab 2013 Jul; 98(7):3058-67.
Physiological transient imbalance typical of adolescence needs to be distinguished from hyperandrogenism-related dysfunction. The accurate determination of circulating androgens is the best indicator of hyperandrogenism. However, reliable reference intervals for adolescent and young women are not available.The aim of the study was to define androgen reference intervals in young women and to analyze the impact of the menstrual phase and ovulation efficiency over the androgen profile as assessed by reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique.Female high school students aged 16-19 years were included in the study.The study was performed on reference subjects properly selected among an unbiased population. Normal-weight, drug and disease free, eumenorrheic females with no signs of hyperandrogenism were included. The steroid hormone profile was determined by a validated in-house LC-MS/MS method. A statistical estimation of overall and menstrual phase-specific reference intervals was performed. A subgroup of anovulatory females was identified based on progesterone circulating levels. The impact of ovulation efficiency over hormonal profile was analyzed.A total of 159 females satisfied healthy criteria. Androgen levels did not vary according to menstrual phase, but a significantly higher upper reference limit was found for T in the luteal phase compared to the follicular phase. Higher T and androstenedione levels were observed in anovulatory compared to ovulatory females, paralleled by higher LH and FSH and lower 17-hydroxyprogesterone and 17β-estradiol levels.This is the first study providing LC-MS/MS-based, menstrual phase-specific reference intervals for the circulating androgen profile in young females. We identified a subgroup of anovulatory healthy females characterized by androgen imbalance.
- The influence of sporadic anovulation on hormone levels in ovulatory cycles. [Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural]
- Hum Reprod 2013 Jun; 28(6):1687-94.
Do ovulatory hormone profiles among healthy premenopausal women differ between women with and without sporadic anovulation?Women with one anovulatory cycle tended to have lower estradiol, progesterone and LH peak levels during their ovulatory cycle.Anovulation occurs sporadically in healthy premenopausal women, but the influence of hormones in a preceding cycle and the impact on a subsequent cycle's hormone levels is unknown.The BioCycle Study was a prospective cohort including 250 healthy regularly menstruating women, 18-44 years of age, from Western New York with no history of menstrual or ovulation disorders. The women were followed with up to eight study visits per cycle for two cycles, most of which were consecutive.All study visits were timed to menstrual cycle phase using fertility monitors and located at the University at Buffalo women's health research center from 2005 to 2007. The main outcomes measured were estradiol, progesterone, LH and follicle-stimulating hormone levels in serum at up to 16 visits over two cycles. Anovulation was defined as peak serum progesterone concentrations ≤5 ng/ml and no serum LH peak detected during the mid- or late-luteal phase visit.Reproductive hormone concentrations were lower during anovulatory cycles, but significant reductions were also observed in estradiol (-25%, P = 0.003) and progesterone (-22%, P = 0.001) during the ovulatory cycles of women with one anovulatory cycle compared with women with two ovulatory cycles. LH peak concentrations were decreased in the ovulatory cycle of women with an anovulatory cycle (significant amplitude effect, P = 0.004; geometric mean levels 38% lower, P < 0.05).Follow-up was limited to two menstrual cycles, and no ultrasound assessment of ovulation was available. Data were missing for a total of 168 of a possible 4072 cycle visits (4.1%), though all women had at least five visits per cycle (94% had seven or more per cycle).These results suggest a possible underlying cause of anovulation, such as a longer-term subclinical follicular, ovarian or hypothalamic/pituitary dysfunction, even among healthy, regularly menstruating women.
- Serum uric acid in relation to endogenous reproductive hormones during the menstrual cycle: findings from the BioCycle study. [Journal Article, Research Support, N.I.H., Intramural]
- Hum Reprod 2013 Jul; 28(7):1853-62.
Do uric acid levels across the menstrual cycle show associations with endogenous estradiol (E2) and reproductive hormone concentrations in regularly menstruating women?Mean uric acid concentrations were highest during the follicular phase, and were inversely associated with E2 and progesterone, and positively associated with FSH.E2 may decrease serum levels of uric acid in post-menopausal women; however, the interplay between endogenous reproductive hormones and uric acid levels among regularly menstruating women has not been elucidated.The BioCycle study was a prospective cohort study conducted at the University at Buffalo research centre from 2005 to 2007, which followed healthy women for one (n = 9) or 2 (n = 250) menstrual cycle(s).Participants were healthy women aged 18-44 years. Hormones and uric acid were measured in serum eight times each cycle for up to two cycles. Marginal structural models with inverse probability of exposure weights were used to evaluate the associations between endogenous hormones and uric acid concentrations.Uric acid levels were observed to vary across the menstrual cycle, with the lowest levels observed during the luteal phase. Every log-unit increase in E2 was associated with a decrease in uric acid of 1.1% (β = -0.011; 95% confidence interval (CI): -0.019, -0.004; persistent-effects model), and for every log-unit increase in progesterone, uric acid decreased by ≈ 0.8% (β = -0.008; 95% CI: -0.012, -0.004; persistent-effects model). FSH was positively associated with uric acid concentrations, such that each log-unit increase was associated with a 1.6% increase in uric acid (β = 0.016; 95% CI: 0.005, 0.026; persistent-effects model). Progesterone and FSH were also associated with uric acid levels in acute-effects models. Of 509 cycles, 42 were anovulatory (8.3%). Higher uric acid levels were associated with increased odds of anovulation (odds ratio 2.39, 95% CI: 1.25, 4.56).The change in uric acid levels among this cohort of healthy women was modest, and analysis was limited to two menstrual cycles. The women in this study were healthy and regularly menstruating, and as such there were few women with high uric acid levels and anovulatory cycles.These findings demonstrate the importance of taking menstrual cycle phase into account when measuring uric acid in premenopausal women, and confirm the hypothesized beneficial lowering effects of endogenous E2 on uric acid levels. These findings suggest that there could be an underlying association affecting both sporadic anovulation and high uric acid levels among young, regularly menstruating women. Further studies are needed to confirm these findings and elucidate the connection between uric acid and reproductive and later cardiovascular health.
- Clinical and biochemical characteristics of polycystic ovary syndrome in Croatian population. [Journal Article]
- Coll Antropol 2012 Dec; 36(4):1413-8.
Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting women of reproductive age. There are many typical signs and symptoms that allow for the diagnosis of PCOS depending on the criteria used. Interestingly, ethnicity influences the extent of these signs and symptoms; therefore, the frequency of symptoms varies between different countries and ethnic groups. The prevalence of this syndrome in Croatia is unknown, and it's clinical and biochemical characteristics have not yet been reported. During this study, we used the Rotterdam criteria to evaluate 365 Croatian women with PCOS, and compared them to 304 age matched controls to assess the clinical and biochemical abnormalities that occur in PCOS patients. The mean age of PCOS patients at presentation was 26.1 +/- 5.9 years and of controls were 28.0 +/- 4.2 years. Women with PCOS has significantly higher body mass index (BMI) than the control group, although in both groups most patients had normal weight (76.2% vs. 87.8%). Abdominal distribution of fat tissue was similar in both groups. Menstrual cycle abnormalities were observed in 90.7% of PCOS patients, and ultrasonographic appearance of polycystic ovaries was reported in 97.3% of PCOS cases. Nearly 75% of patients with PCOS had hirsutism and 49.6% had acne. We recorded significantly higher serum levels of luteinizing hormone (LH), total testosterone (TT), free testosterone (fT) and insulin, while the serum levels of sex hormone binding globuline (SHBG) and follicular stimulating hormone (FSH) were significantly lower than in the control group. Serum glucose values were not significantly different between the groups. In conclusion, chronic anovulation, hirsutism and ultrasound appearance of polycystic ovaries are the dominant features of PCOS in Croatian population. The majority of patients with PCOS had normal body weight. The incidence of insulin resistance in this group of patients is less than the previously described frequency in other populations of patients with PCOS and normal weight.