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Anovulation in reproductive years [keywords]
- Depressive symptoms and their relationship with endogenous reproductive hormones and sporadic anovulation in premenopausal women. [JOURNAL ARTICLE]
- Ann Epidemiol 2014 Oct 15; 24(12):920-924.
To determine whether depressive symptoms are associated with ovulation or reproductive hormone concentrations in eumenorrheic women without a reported diagnosis of clinical depression.A prospective cohort of 248 regularly menstruating women, aged 18 to 44 years (27.3 ± 8.2) were evaluated for depressive symptoms at baseline using the 20-item Center for Epidemiological Studies Depression (CES-D) scale and categorized dichotomously (<16, no depressive symptoms [92%] vs. ≥16, depressive symptoms [8%]). Serum concentrations of estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured up to eight times per cycle for up to two menstrual cycles. Linear mixed models estimated associations between depressive symptoms and hormone concentrations, whereas generalized linear mixed models assessed their relationship with sporadic anovulation.No significant associations were identified between depressive symptoms and reproductive hormone levels (all P > .05) or the odds of sporadic anovulation (adjusted odds ratio, 1.1; 95% confidence interval, [0.02-5.0]), after adjusting for age, race, body mass index, perceived stress level, and alcohol consumption.Despite reported associations between mental health and menstrual cycle dysfunction, depressive symptoms were not associated with reproductive hormone concentrations or sporadic anovulation in this cohort of regularly menstruating women with no recent (within 1 year) self-reported history of clinical depression.
- Cardiovascular and metabolic profiles amongst different polycystic ovary syndrome phenotypes: who is really at risk? [Journal Article]
- Fertil Steril 2014 Nov; 102(5):1444-1451.e3.
To study the cardiometabolic profile characteristics and compare the prevalence of cardiovascular (CV) risk factors between women with different polycystic ovary syndrome (PCOS) phenotypes.A cross-sectional multicenter study analyzing 2,288 well phenotyped women with PCOS.Specialized reproductive outpatient clinic.Women of reproductive age (18-45 years) diagnosed with PCOS.Women suspected of oligo- or anovulation underwent a standardized screening consisting of a systematic medical and reproductive history taking, anthropometric measurements, and transvaginal ultrasonography followed by an extensive endocrinologic/metabolic evaluation.Differences in cardiometabolic profile characteristics and CV risk factor prevalence between women with different PCOS phenotypes, i.e., obesity/overweight, hypertension, insulin resistance, dyslipidemia, and metabolic syndrome.Women with hyperandrogenic PCOS (n = 1,219; 53.3% of total) presented with a worse cardiometabolic profile and a higher prevalence of CV risk factors, such as obesity and overweight, insulin resistance, and metabolic syndrome, compared with women with nonhyperandrogenic PCOS. In women with nonhyperandrogenic PCOS overweight/obesity (28.5%) and dyslipidemia (low-density lipoprotein cholesterol ≥3.0 mmol/L; 52.2%) were highly prevalent.Women with hyperandrogenic PCOS have a worse cardiometabolic profile and higher prevalence of CV risk factors compared with women with nonhyperandrogenic PCOS. However, all women with PCOS should be screened for the presence of CV risk factors, since the frequently found derangements at a young age imply an elevated risk for the development of CV disease later in life.
- [Doctor Ma Kun's experience of applying tonifying kidney and promoting blood circulation treatment of anovulatory infertility]. [English Abstract, Journal Article, Research Support, Non-U.S. Gov't]
- Zhongguo Zhong Yao Za Zhi 2014 Feb; 39(4):748-50.
With the ascending attack rate of anovulatory infertility year by year, people also began to pay attention to its treat methods. According to Doctor Ma Kun,who are engaged in clinical work about the treatment for anovulatory infertility, kidney deficiency is the basic pathogenesis and blood stasis is an important factor that has been through. Flexible use of tonifying the kidney and promoting blood circulation treatment of anovulatory infertility in clinic, has achieved remarkable curative effect. Director Ma adjusts menstruation by the different periods, and regulates both patients' negative emotions and sleep quality. Through years of clinical experience accumulation, Director Ma gradually formes special treatment of anovulatory infertility by flexibly using of tonifying the kidney and promoting blood circulation individually.
- Anti-mullerian hormone as a diagnostic and prognostic tool for PCOS patients. [Journal Article, Research Support, Non-U.S. Gov't]
- J Assist Reprod Genet 2014 Oct; 31(10):1311-6.
To determine whether the measurement of serum AMH can be used to diagnose PCOS and as a tool to predict the prognosis of PCOS.This is a case-control study. Women of reproductive age (18-35 years) were recruited consecutively at a tertiary academic hospital during the period of March 2009-October 2011 and were divided into case (PCOS patients defined by the Rotterdam criteria) and control groups (non-PCOS patients). Menstrual history, clinical manifestations of hyperandrogenism, ovarian ultrasound assessments, and the levels of AMH, LH, FSH, and estradiol were collected.Seventy-one cases and 71 controls were recruited. AMH serum levels were significantly higher in PCOS patients than in controls. The Area Under the Curve (AUC) of the serum AMH assay in PCOS patients reached a value of 0.870. With a cut-off value of 4.45 ng/ml, the serum AMH level had a sensitivity of 76.1 % and a specificity of 74.6 %. The most common phenotypes of PCOS in this study were anovulation and polycystic ovary (63.4 %). However, the mean level of AMH was highest in the phenotypes of anovulation, polycystic ovaries and hyperandrogenism (11.1 ng/ml).In Indonesian women, AMH can be used as an alternative diagnostic criteria for PCOS patients with a cut-off value of 4.45 ng/ml. AMH value rise when hyperandrogenism is present therefore serum AMH levels also reflect the phenotype of PCOS. However, these findings must be confirmed with larger clinical studies.
- Recombinant human luteinizing hormone to trigger ovulation: randomized, controlled, dose-finding pilot study in ovulation induction. [Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't]
- J Reprod Med 2014 Jul-Aug; 59(7-8):355-66.
To evaluate recombinant human luteinizing hormone (r-hLH) versus urine-derived human chorionic gonadotropin (u-hCG) to trigger ovulation in women (aged 20-40 years) with WHO Group II anovulatory infertility undergoing ovulation induction (OI) with recombinant human follicle-stimulating hormone (r-hFSH) (150 IU/day starting dose).For this Phase II, open-label, dose-finding pilot study, patients were randomized to doses of 825, 2,750, 5,500, 11,000, or 22,000 IU r-hLH or u-hCG (5,000 IU). Primary endpoints were ovulation and ratio of ruptured follicles/follicle > or = 15 mm (day of r-hLH/ u-hCG administration). Secondary endpoints included monofollicular ovulation and clinical pregnancy rates.All 67 randomized patients completed treatment. All patients in the r-hLH 2,750 (13/13), 5,500 (12/ 12), 11,000 IU (13/13), and u-hCG 5,000 IU (12/ 12) groups ovulated; 3/5 patients in the r-hLH 825 IU and 2/12 in the r-hLH 22,000 IU group failed to ovulate (p = 0.105 between evaluable groups). The mean ratio of ruptured follicles/ follicle > or = 15 mm was 1.1 (p = 0.675 between groups). The monofollicular ovulation rate was 15/60 (25%). Two cases of ovarian hyperstimulation syndrome were reported.This open-label, pilot study (conducted in 1999-2001) suggests that the minimal effective dose of r-hLH to trigger ovulation in women with WHO Group II anovulatory infertility undergoing OI with r-hFSH (150 IU starting dose) was 2,750 IU.
- Diverse impacts of aging on insulin resistance in lean and obese women with polycystic ovary syndrome: evidence from 1345 women with the syndrome. [Journal Article]
- Eur J Endocrinol 2014 Sep; 171(3):301-9.
Polycystic ovary syndrome (PCOS) represents a moving spectrum of hormonal to metabolic abnormalities, as women with the syndrome are aging. Hormonal abnormalities, anovulation, and hyperandrogenic signs were predominant during the early years of PCOS and fade away with the years. Metabolic abnormalities and insulin resistance (IR) remain throughout the PCOS life cycle; however, it is unclear as to how they change, as women with the syndrome are aging.To evaluate the changes in IR and its associations with clinical, biochemical, hormonal, and ultrasound findings in a large cohort of women with PCOS and controls, as they are aging.A cross-sectional study was carried out to evaluate the diverse impacts of aging on IR.An outpatient clinic was chosen for the study.A total of 1345 women with PCOS (Rotterdam criteria) and 302 controls of Caucasian origin and Greek ethnicity comprised the study group.The impact of age on IR, as calculated using homeostasis model assessment of IR (HOMA-IR) index, and several PCOS characteristics were evaluated.In PCOS, age (-0.045±0.008) was negatively, and BMI positively (0.18±0.007) associated with HOMA-IR (R(2)=0.36). When data were stratified with regard to the BMI status, a negative association of age with HOMA-IR was found in lean, normal, and overweight patients (r: -0.266, -0.233, -0.192, P<0.001), which was neutralized in obese patients (r: -0.009, P: NS). Free androgen index and BMI were positively associated with HOMA-IR in all age quartiles. When mean HOMA-IR values were plotted according to BMI subgroups at different age quartiles, a significant gradual decrease in HOMA-IR was observed in normal (P<0.001) and overweight (P: 0.004), but not obese, women (P: 0.202) across age quartiles.Aging increases IR in obese but not in lean and overweight women with PCOS. As BMI and androgens are positively associated with HOMA-IR and androgens decline through time, it appears that if women with PCOS do not become obese they may exhibit a better metabolic profile during their reproductive years.
- Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. [Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural]
- N Engl J Med 2014 Jul 10; 371(2):119-29.
Clomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome, but aromatase inhibitors, including letrozole, might result in better pregnancy outcomes.In this double-blind, multicenter trial, we randomly assigned 750 women, in a 1:1 ratio, to receive letrozole or clomiphene for up to five treatment cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The polycystic ovary syndrome was defined according to modified Rotterdam criteria (anovulation with either hyperandrogenism or polycystic ovaries). Participants were 18 to 40 years of age, had at least one patent fallopian tube and a normal uterine cavity, and had a male partner with a sperm concentration of at least 14 million per milliliter; the women and their partners agreed to have regular intercourse with the intent of conception during the study. The primary outcome was live birth during the treatment period.Women who received letrozole had more cumulative live births than those who received clomiphene (103 of 374 [27.5%] vs. 72 of 376 [19.1%], P=0.007; rate ratio for live birth, 1.44; 95% confidence interval, 1.10 to 1.87) without significant differences in overall congenital anomalies, though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group (P=0.65). The cumulative ovulation rate was higher with letrozole than with clomiphene (834 of 1352 treatment cycles [61.7%] vs. 688 of 1425 treatment cycles [48.3%], P<0.001). There were no significant between-group differences in pregnancy loss (49 of 154 pregnancies in the letrozole group [31.8%] and 30 of 103 pregnancies in the clomiphene group [29.1%]) or twin pregnancy (3.4% and 7.4%, respectively). Clomiphene was associated with a higher incidence of hot flushes, and letrozole was associated with higher incidences of fatigue and dizziness. Rates of other adverse events were similar in the two treatment groups.As compared with clomiphene, letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00719186.).
- Hemostatic and fibrinolytic abnormalities in polycystic ovary syndrome. [Journal Article]
- Semin Thromb Hemost 2014 Jul; 40(5):600-18.
Polycystic ovary syndrome (PCOS) is the most common form of anovulatory infertility, affecting up to 10% of women of reproductive age. This syndrome was first described in 1935 when American gynecologists Stein and Leventhal associated the presence of ovarian cysts with anovulation, obesity, and hirsutism. For many years, the effects of PCOS on coagulation and fibrinolysis have remained largely unexplored. This review summarizes current knowledge of the effects of PCOS on coagulation and fibrinolysis, and the putative mechanisms by which PCOS may contribute to the development of coagulation and fibrinolytic disorders. To date, there is relatively strong evidence suggesting that PCOS is associated with increased platelet aggregation and decreased plasma fibrinolytic activity. However, whether these hemostatic disorders are linked to the abnormal hormonal system in PCOS remains to be elucidated. Moreover, it should be emphasized that PCOS is a heterogeneous endocrine condition, and that the number of published studies is limited, the sample size of most of these studies is relatively small, and the selection of control subjects has not been always appropriate. Furthermore, well-designed studies on larger cohorts of carefully characterized PCOS patients are needed to provide more comprehensive information on this issue.
- Prevalence of metabolic syndrome in the family members of women with polycystic ovary syndrome from North India. [Journal Article]
- Indian J Endocrinol Metab 2014 May; 18(3):364-9.
Polycystic ovary syndrome (PCOS) is the most complex and common endocrine disorder of women in reproductive years. In addition to irregular menstrual cycles, chronic anovulation and hyperandrogenism, it has many metabolic manifestations such as obesity, hyperlipidemia, hyperinsulinemia, insulin resistance, dysglycemia, increased risk of cardiovascular disease or possibly endometrial cancer. Familial clustering of PCOS in consistence with the genetic susceptibility has been described.The present study assessed the clinical, biochemical and hormonal parameters including prevalence of metabolic syndrome by two different criteria in the first- degree relatives of patients with PCOS.The average age of 37 index patients was 23 ± 3.6 years, with the mean age of menarche as 13.3 ± 1.2 years. The mean age and age of menarche in mothers (n = 22) was 48.8 ± 5.1 and 13 ± 1.3 years, respectively, whereas as it was 23.5 ± 4.7 and 13.3 ± 1.2 years in sisters (n = 22), respectively. Metabolic syndrome (MS) defined by International Diabetes Federation (IDF) criteria was present in 10 index patients, 1 brother, 4 sisters, 17 mothers and 15 fathers while as by Adult Treatment Panel III (ATP III) it was in 8 index patients, 5 sisters, 16 mothers and 11 fathers.The presence of MS or related metabolic derangements is high in the family members of women with PCOS.
- Biological variability in serum anti-Müllerian hormone throughout the menstrual cycle in ovulatory and sporadic anovulatory cycles in eumenorrheic women. [Journal Article, Research Support, N.I.H., Intramural]
- Hum Reprod 2014 Aug; 29(8):1764-72.
Does serum anti-Müllerian hormone (AMH) vary significantly throughout both ovulatory and sporadic anovulatory menstrual cycles in healthy premenopausal women?Serum AMH levels vary statistically significantly across the menstrual cycle in both ovulatory and sporadic anovulatory cycles of healthy eumenorrheic women.Studies to date evaluating serum AMH levels throughout the menstrual cycle have conflicting results regarding intra-woman cyclicity. No previous studies have evaluated an association between AMH and sporadic anovulation.We conducted a prospective cohort study of 259 regularly menstruating women recruited between 2005 and 2007.Women aged 18-44 years were followed for one (n = 9) or two (n = 250) menstrual cycles. Anovulatory cycles were defined as any cycle with peak progesterone concentration ≤5 ng/ml and no serum LH peak on the mid or late luteal visits. Serum AMH was measured at up to eight-time points throughout each cycle.Geometric mean AMH levels were observed to vary across the menstrual cycle (P < 0.01) with the highest levels observed during the mid-follicular phase at 2.06 ng/ml, decreasing around the time of ovulation to 1.79 ng/ml and increasing thereafter to 1.93 (mid-follicular versus ovulation, P < 0.01; ovulation versus late luteal, P = 0.01; mid-follicular versus late luteal, P = 0.05). Patterns were similar across all age groups and during ovulatory and anovulatory cycles, with higher levels of AMH observed among women with one or more anovulatory cycles (P = 0.03).Ovulatory status was not verified by direct visualization. AMH was analyzed using the original Generation II enzymatically amplified two-site immunoassay, which has been shown to be susceptible to assay interference. Thus, absolute levels should be interpreted with caution, however, patterns and associations remain consistent and any potential bias would be non-differential.This study demonstrates a significant variation in serum AMH levels across the menstrual cycle regardless of ovulatory status. This variability, although statistically significant, is not large enough to warrant a change in current clinical practice to time AMH measurements to cycle day/phase.This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD (Contracts # HHSN275200403394C, HHSN275201100002I Task 1 HHSN27500001). The authors have no conflicts of interest to declare.