VEGFA165 can rescue excess steroid secretion, inflammatory markers, and follicle arrest in the ovarian cortex of High A4 cows†.

A population of cows with excess androstenedione (A4; High A4) in follicular fluid, with follicular arrest, granulosa cell dysfunction, and a 17% reduction in calving rate was previously identified. We hypothesized that excess A4 in the ovarian microenvironment caused the follicular arrest in High A4 cows and that vascular endothelial growth factor A would rescue the High A4 phenotype. In trial 1, prior to culture, High A4 ovarian cortex (n = 9) had greater numbers of early stage follicles (primordial) and fewer later-stage follicles compared to controls (n = 11). Culture for 7 days did not relieve this follicular arrest; instead, High A4 ovarian cortex had increased indicators of inflammation, anti-Mullerian hormone, and A4 secretion compared to controls. In trial 2, we tested if vascular endothelial growth factor A isoforms could rescue the High A4 phenotype. High A4 (n = 5) and control (n = 5) ovarian cortex was cultured with (1) PBS, (2) VEGFA165 (50 ng/mL), (3) VEGFA165B (50 ng/mL), or (4) VEGFA165 + VEGFA165B (50 ng/mL each) for 7 days. Follicular progression increased with VEGFA165 in High A4 cows with greater early primary, primary, and secondary follicles than controls. Similar to trial 1, High A4 ovarian cortex secreted greater concentrations of A4 and other steroids and had greater indicators of inflammation compared to controls. However, VEGFA165 rescued steroidogenesis, oxidative stress, and fibrosis. The VEGFA165 and VEGFA165b both reduced IL-13, INFα, and INFß secretion in High A4 cows to control levels. Thus, VEGFA165 may be a potential therapeutic to restore the ovarian steroidogenic microenvironment and may promote folliculogenesis.

A herbal treatment approach for the management of clinical, hormonal and ultrasound parameters in reproductive age group women with polycystic ovarian syndrome: A randomized clinical trial.

Around fifteen percent women of reproductive age have been effected by Polycystic Ovarian Syndrome (PCOS); a complicated disorder; and apparently there is no standard therapy available. Considering this lack, we design present work; for the assessment of a herbal medicine (Femitex-SP4) in managing PCOs. During 2016-17; this study was carried out at Abbasi Shaheed hospital, Karachi, Pakistan. A total of 150 patients aged between 18-44 years were included as per Rotterdam criteria. Patients received 500 mg of powdered herbs in capsule form twice daily. The primary outcomes were regular menstruation and ovulation plus change in fasting blood sugar levels. Changes in free testosterone levels and ovarian morphology was secondary outcome measures. Continuous outcomes before and after treatment were compared by Student's t-test (one tailed, independent). P = 0.05 was considered as significant. Women menstrual cycle was considerably improved. Fasting blood sugar levels did not change (p=0.103392). Progesterone levels were same at the starting point and after treatment (P=0.318322). With complete recovery in 6 patients; a notable change was found in ovarian size. Free testosterone levels were also dropped significantly (p<0.00001). Our main success was drastic improvement in normalizing menstrual cycle during therapy. Herbal treatment is proven to be clinically effective in most of the patients; particularly PCOs patients with menstrual irregularities. Hence, Femitex-SP4 can be taken as a better treatment for PCOs.

Low risk of OHSS with follitropin delta use in women with different polycystic ovary syndrome phenotypes: a retrospective case series.

BACKGROUND: To explore the efficacy of follitropin delta in ovarian stimulation of patients with the Rotterdam ESHRE/ASRM 2003 phenotypes of polycystic ovarian syndrome (PCOS) using a retrospective case series with an electronic file search in a reproductive medicine clinic. CASE PRESENTATION: Seventy-four patients with PCOS undergoing ovarian stimulation according to the individualized dosing algorithm of follitropin delta for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI)/oocyte freezing were included. Follitropin delta resulted in a high number of pre-ovulatory follicles at the end of stimulation as expected in patients with PCOS. There was a large number of oocytes retrieved with an acceptable percentage of metaphase II (MII) oocytes. There were no cases of moderate or severe OHSS across all phenotypes. CONCLUSION: Follitropin delta, using the individualized dosing algorithm, appears to be a safe method of ovarian stimulation with a low risk of OHSS in PCOS patients without sacrificing successful stimulation outcomes.

Clinical Implications of Polycystic Ovary Syndrome in Adolescents.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy, affecting as many as 5% to 20% of women of reproductive age, depending on the diagnostic criteria applied. Features of PCOS include physiologic anovulation, hyperandrogenism, elevated luteinizing hormone, and increased gonadotropin-releasing hormone pulse frequency, which often manifest physically as acne and hirsutism. The clinical presentation of PCOS often mimics normal pubertal physiologic development, which may delay diagnosis and treatment of the condition in adolescent girls. A diagnosis of PCOS has life-long implications and is associated with increased risk for infertility, obesity, Type 2 diabetes, endometrial hyperplasia, uterine carcinoma, metabolic disorder, and cardiovascular disease. In this article, we provide an overview of clinical presentation, diagnostic criteria, health consequences, and current evidence-based clinical guidelines for the appropriate diagnosis and management of PCOS in adolescents.

Association of obesity and anovulatory infertility / Associação entre obesidade e infertilidade anovulatória

ABSTRACT Objective To verify the association of obesity and infertility related to anovulatory issues. Methods This case-control study was carried out with 52 women, aged 20 to 38 years, divided into two groups (infertile − cases − and fertile − control), seen at outpatient clinics, in the period from April to December, 2017. Results We found significant evidence that obesity negatively affects women's fertility (p=0.017). The group of infertile women was 7.5-fold more likely to be obese than fertile women. Conclusion Strategies that encourage weight control are indicated for women with chronic anovulation, due to hight metabolic activity of adipose tissue.

RESUMO Objetivo Verificar em mulheres a associação entre obesidade e infertilidade relacionada a questões anovulatórias. Métodos Estudo de caso-controle com 52 mulheres, de 20 a 38 anos, divididas em dois grupos (mulheres inférteis − casos − e férteis − controles), atendidas em ambulatórios, no período de abril a dezembro de 2017. Resultados Verificou-se evidência significativa de que a obesidade afeta negativamente na fertilidade das mulheres (p=0,017). O grupo de mulheres inférteis teve 7,5 vezes mais chances de serem obesas quando comparadas às mulheres férteis. Conclusão Estratégias que estimulem o controle do peso são indicadas para mulheres com anovulação crônica devido à elevada atividade metabólica do tecido adiposo.

Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting ∼10% to 15% of reproductive-aged women worldwide. Diagnosis requires two of the following: hyperandrogenism, oligo-ovulation or anovulation, and polycystic ovaries. In addition to reproductive dysfunction, many women with PCOS display metabolic abnormalities associated with hyperandrogenism. Recent studies have reported that the gut microbiome is altered in women with PCOS and rodent models of the disorder. However, it is unknown whether the gut microbiome plays a causal role in the development and pathology of PCOS. Given its potential role, we hypothesized that exposure to a healthy gut microbiome would protect against development of PCOS. A cohousing study was performed using a letrozole-induced PCOS mouse model that recapitulates many reproductive and metabolic characteristics of PCOS. Because mice are coprophagic, cohousing results in repeated, noninvasive inoculation of gut microbes in cohoused mice via the fecal-oral route. In contrast to letrozole-treated mice housed together, letrozole mice cohoused with placebo mice showed significant improvement in both reproductive and metabolic PCOS phenotypes. Using 16S rRNA gene sequencing, we also observed that the overall composition of the gut microbiome and the relative abundance of Coprobacillus and Lactobacillus differed in letrozole-treated mice cohoused with placebo mice compared with letrozole mice housed together. These results suggest that dysbiosis of the gut microbiome may play a causal role in PCOS and that modulation of the gut microbiome may be a potential treatment option for PCOS.

Menstrual Cycle Changes as Women Approach the Final Menses: What Matters?

Increased variability in menstrual cycle length marks the onset of the menopausal transition, with the likelihood of long cycles increasing as women approach menopause. This article describes the STRAW+10 bleeding criteria for recognizing onset of the early and late menopausal transition, as well as the specific bleeding changes a woman may experience during this life stage, including how women's bleeding experiences differ. The high probability of episodes of excessive and prolonged bleeding as women approach their final menstrual period is documented, as is the continuing probability of ovulation as women reach their final menstrual period.

Evaluation of three hormonal protocols for anovulatory lactating cows under regulations restricting the use of estrogenic compounds.

When European Union regulations restricted the use of estrogenic compounds in food-producing animals, refined hormonal protocols were no longer applicable for anovulatory cows. However, Ovsynch and its adaptations are routinely and uniformly applied to all cows regardless of ovarian function. To evaluate their efficacy on anovulatory cows, 143, 147 and 144 anovulatory cows received Ovsynch, Presynch and G6G protocols, respectively. In comparison, 150 cyclic cows were bred without using a synchronized protocol. Results showed that cows in the Presynch group had luteolysis responding to the last prostaglandin F2α (PGF2α ) injection greater than the Ovsynch group. The serous progesterone levels at the first gonadotropin-releasing hormone of Ovsych and the last PGF2α injection was greater in the G6G group than the other two hormonal treatment groups. Concentrations of Ca2+ and total protein in cervical mucus in all three hormone-treated groups before artificial insemination (AI) were significantly different from the controls. The G6G group obtained a greater pregnancy rate compared with Ovsynch and Presynch, but significantly less than the controls. For open cows in the Ovsynch group, estrus rate within 24 days after the first AI was significantly less than the controls. In conclusion, the G6G treatment resulted to better reproductive performance in anovulatory cows.

Inositol treatment of anovulation in women with polycystic ovary syndrome: a meta-analysis of randomised trials.

Polycystic ovary syndrome is a common cause of anovulation and infertility, and a risk factor for development of metabolic syndrome and endometrial cancer. Systematic review and meta-analysis of randomised controlled trials (RCT) that evaluated the effects of inositol as an ovulation induction agent. We searched MEDLINE, EMBASE, Cochrane and ISI conference proceedings, Register and Meta-register for RCT and WHO trials' search portal. We included studies that compared inositol with placebo or other ovulation induction agents. Quality of studies was assessed for risk of bias. Results were pooled using random effects meta-analysis and findings were reported as relative risk or standardised mean differences. We included ten randomised trials. A total of 362 women were on inositol (257 on myo-inositol; 105 on di-chiro-inositol), 179 were on placebo and 60 were on metformin. Inositol was associated with significantly improved ovulation rate (RR 2.3; 95% CI 1.1-4.7; I2 = 75%) and increased frequency of menstrual cycles (RR 6.8; 95% CI 2.8-16.6; I2 = 0%) compared with placebo. One study reported on clinical pregnancy rate with inositol compared with placebo (RR 3.3; 95% CI 0.4-27.1), and one study compared with metformin (RR 1.5; 95% CI 0.7-3.1). No studies evaluated live birth and miscarriage rates. Inositol appears to regulate menstrual cycles, improve ovulation and induce metabolic changes in polycystic ovary syndrome; however, evidence is lacking for pregnancy, miscarriage or live birth. A further, well-designed multicentre trial to address this issue to provide robust evidence of benefit is warranted. TWEETABLE ABSTRACT: Inositols improve menstrual cycles, ovulation and metabolic changes in polycystic ovary syndrome.

Elevated circulating micro-ribonucleic acid (miRNA)-200b and miRNA-429 levels in anovulatory women.

OBJECTIVE: To study the role of micro-RNA (miRNA)-200b and miRNA-429 in human ovulation and to measure their expression levels in ovulatory and anovulatory patients. DESIGN: Micro-RNA-200b and miRNA-429 expression analysis in human serum and granulosa cells at different phases of the ovulation cycle in normal cycling women and women undergoing assisted reproductive technology cycles. SETTING: University-affiliated hospital and academic research laboratory. PATIENT(S): Forty women (7 normally ovulating, 15 normally ovulating with pure male infertility factor, and 18 with polycystic ovary syndrome) were included in this study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The expression profile of circulating miRNAs and granulosa cells was assessed by means of real-time quantitative reverse transcription-polymerase chain reaction analysis. RESULT(S): We identified miRNA-200b and miRNA-429 in the sera of all women tested. These miRNA expression levels were elevated during the early follicular phase of the cycle compared with serum levels during the early luteal phase. Anovulatory women, diagnosed with polycystic ovary syndrome, expressed significantly higher levels of miRNA-200b and miRNA-429 compared with spontaneously ovulating women. Ovulation induction with exogenous gonadotropins during an IVF cycle reduced these levels to the levels measured in normal ovulating women. CONCLUSION(S): Our findings suggest an involvement of miRNA-200b and miRNA-429 in the pituitary regulation of human ovulation. Although it is unclear whether this altered miRNA expression profile is a cause or a result of anovulation, the levels of these molecules in the serum of anovulatory women may serve as serum biomarkers for the ovulation process.

Comparison of uterine, endometrial and ovarian blood flow by transvaginal color Doppler ultrasound in ovulatory and anovulatory cycles.

OBJECTIVES: Blood flow to uterus and ovaries is demonstrated to be altered during mensturation. Studies has been published stating that blood flow differs also in ovulatory and anovulatory cycles. In this study, using color Doppler ultrasound, we aim to compare uterine, endometrial and ovarian blood flow during ovulatory and anovulatory cycles. MATERIAL AND METHODS: Women volunteers who are aged between 18-40 had no endocrinological problem and not recieving exogenous hormone therapy were included to study. Blood levels of FSH, LH, E2, prolactine, DHEAS, free T4 were collected in early follicular phase. Uterina, subendometrial and intraovarian artery blood flow pulsatility and resistance indexes were analysed using Doppler USG technique. Patients were called out to control on 21st of cycle and progesterone levels were analysed. Patients who has ovulation signs in USG and progesterone level above 5 ng/mL were included to ovulatory cycle group. Patient who has no signs of ovulation in ultrasound and has not enough progesterone level were included to anovulatory cycle group. RESULTS: LH and E2 levels were significantly higher in anovulatory patients. No correlation was found between endometrial blood flow resistance and basal E2, prolactine, testosterone levels. However, DHEAS levels were related to endometrial blood flow resistance in anovulatory cycles. No correlation was found between ovarian blood flow resistance/uterine blood flow resistance and basal E2, prolactine, testosterone, DHEAS levels. CONCLUSIONS: There is statistically significant difference between endometrial, ovarian, uterine artery blood flow resistance in ovulatory and anovulatory cycles. Blood flow resistance was found to be increased in anovulatory patients. Increased E2 levels in anovulatory cycles were related to endometrial linethickness and endometrial volume.

PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Insulin action and lipotoxicity in the development of polycystic ovary syndrome: A review.

Polycystic ovary syndrome (PCOS) is a common condition affecting women of reproductive age. This disorder is characterized by hyperandrogenism and anovulation and is frequently associated with comorbidities such as infertility, metabolic syndrome, type 2 diabetes, and cardiovascular risk factors. Although the causes of PCOS are unknown, this review focuses on the most accepted theory involving insulin action but will also elaborate on a novel concept: the role of lipotoxicity in the development of androgen overproduction, in addition to its known role in insulin resistance. This review will also shed a spotlight on 2 drugs that target lipotoxicity and are, therefore, known or promising for the treatment of PCOS manifestations: peroxisome proliferator-activated receptor γ and angiotensin II type 2 receptor agonists. This paper, therefore, emphasizes the need to further explore the pathophysiology of PCOS and particularly the role of lipotoxicity. Indeed, this new mechanism deserves attention to develop therapeutic approaches that will directly target the root of this condition and not only bandage its associated consequences.

Alcohol intake, reproductive hormones, and menstrual cycle function: a prospective cohort study.

BACKGROUND: Although habitual low-to-moderate alcohol intake has been linked with reduced all-cause mortality and morbidity, the effect of recent alcohol intake on female reproductive function has not been clearly established. OBJECTIVE: We assessed the relation between acute alcohol consumption, reproductive hormones, and markers of menstrual cycle dysfunction including sporadic anovulation, irregular cycle length, luteal phase deficiency, long menses, and heavy blood loss. DESIGN: A total of 259 healthy, premenopausal women from Western New York were followed for ≤2 menstrual cycles (2005-2007) and provided fasting blood specimens during ≤8 visits/cycle and four 24-h dietary recalls/cycle. Linear mixed models were used to estimate associations between previous day's alcohol intake and hormone concentrations, whereas Poisson regression was used to assess RR of cycle-average alcohol intake and menstrual cycle function. RESULTS: For every alcoholic drink consumed, the geometric mean total and free estradiol, total and free testosterone, and luteinizing hormone were higher by 5.26% (95% CI: 1.27%, 9.41%), 5.82% (95% CI: 1.81%, 9.99%), 1.56% (95% CI: 0.23%, 2.90%), 1.42% (95% CI: 0.02%, 2.84%), and 6.18% (95% CI: 2.02%, 10.52%), respectively, after adjustment for age, race, percentage of body fat, perceived stress, pain-medication use, sexual activity, caffeine, and sleep. Binge compared with nonbinge drinking (defined as reporting ≥4 compared with <4 drinks/d, respectively) was associated with 64.35% (95% CI: 18.09%, 128.71%) and 63.53% (95% CI: 17.41%, 127.73%) higher total and free estradiol. No statistically significant associations were shown between cycle-average alcohol intake and menstrual cycle function. CONCLUSION: Although recent moderate alcohol intake does not appear to have adverse short-term effects on menstrual cycle function, including sporadic anovulation, potential protective and deleterious long-term effects of alterations in reproductive hormones on other chronic diseases warrant additional investigation.

The Polycystic Ovary Morphology-Polycystic Ovary Syndrome Spectrum.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of chronic hyperandrogenic anovulation. Two-thirds of PCOS patients have functionally typical PCOS, with typical functional ovarian hyperandrogenism manifest as 17-hydroxyprogesterone hyper-responsiveness to gonadotropin stimulation. Most, but not all, of the remainder have atypical functional ovarian hyperandrogenism. Many asymptomatic volunteers with polycystic ovary morphology (PCOM) have similar abnormalities. OBJECTIVE: The objective of this paper is to review the relationship of biochemical ovarian function to the clinical spectrum observed in PCOS and in normal volunteers with PCOM. FINDINGS: Adolescents and adults with PCOS are similar clinically and biochemically. Ninety-five percent of functionally typical PCOS have classic PCOS, ie, hyperandrogenic anovulation with PCOM. In addition to having more severe hyperandrogenism and a greater prevalence of PCOM than other PCOS, they have a significantly greater prevalence of glucose intolerance although insulin resistance is similarly reduced. Half of normal-variant PCOM have PCOS-related steroidogenic dysfunction, which suggests a PCOS carrier state. CONCLUSIONS: There is a spectrum of ovarian androgenic dysfunction that ranges from subclinical hyperandrogenemia in some normal-variant PCOM to severe ovarian hyperandrogenism in most classic PCOS. A minority of mild PCOS cases do not fall on this spectrum of ovarian androgenic dysfunction, but rather seem to have obesity as the basis of their hyperandrogenism, or, less often, isolated adrenal androgenic dysfunction. Half of normal-variant PCOM also do not fall on the PCOS spectrum, and some of these seem to have excessive folliculogenesis as a variant that may confer mild prolongation of the reproductive lifespan. Improved understanding of PCOM in young women is needed.

Prevalence of conditions causing chronic anovulation and the proposed algorithm for anovulation evaluation.

AIM: This study investigated the prevalence of disease-causing chronic anovulation and proposes a logical investigation flowchart to facilitate diagnosis in women presenting with chronic anovulation. MATERIAL AND METHODS: The cross-sectional retrospective study was performed using 293 reproductive-aged women who were diagnosed with chronic anovulation at the Gynecologic Endocrinology Unit, Faculty of Medicine, Chiang Mai University between January 2008 and December 2012. The demographic data, laboratory investigations and diagnoses were collected. RESULTS: Among 293 patients recruited into the study, the common causes of anovulation were polycystic ovary syndrome (PCOS) (73.4%), prolactin disorder (13.3%) and unexplained chronic anovulation (7.5%). The less common causes were thyroid disorders, congenital adrenal hyperplasia, adrenal tumors and Cushing's disease. There was a strong positive association between the levels of 17-hydroxyprogesterone and/or dehydroepiandrosterone sulfate with the levels of testosterone and androstenedione. The sensitivity and specificity of serum luteinizing hormone to accurately diagnose PCOS were 29.38% and 55.56% (P = 0.03). The luteinizing hormone/follicle-stimulating hormone ratio ≥ 3 had a sensitivity and specificity at 18.56% and 92.86% (P = 0.03) for PCOS diagnosis. CONCLUSION: Serum androstenedione, testosterone, thyroid-stimulating hormone, prolactin levels and pelvic ultrasonography should be included in the initial investigations for anovulation. The 17-hydroxyprogesterone and dehydroepiandrosterone sulfate levels can be used for secondary anovulation evaluations.

Assessment of anovulation in eumenorrheic women: comparison of ovulation detection algorithms.

OBJECTIVE: To compare previously used algorithms to identify anovulatory menstrual cycles in women self-reporting regular menses. DESIGN: Prospective cohort study. SETTING: Western New York. PATIENT(S): Two hundred fifty-nine healthy, regularly menstruating women followed for one (n=9) or two (n=250) menstrual cycles (2005-2007). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prevalence of sporadic anovulatory cycles identified using 11 previously defined algorithms that use E2, P, and LH concentrations. RESULT(S): Algorithms based on serum LH, E2, and P levels detected a prevalence of anovulation across the study period of 5.5%-12.8% (concordant classification for 91.7%-97.4% of cycles). The prevalence of anovulatory cycles varied from 3.4% to 18.6% using algorithms based on urinary LH alone or with the primary E2 metabolite, estrone-3-glucuronide, levels. CONCLUSION(S): The prevalence of anovulatory cycles among healthy women varied by algorithm. Mid-cycle LH surge urine-based algorithms used in over-the-counter fertility monitors tended to classify a higher proportion of anovulatory cycles compared with luteal-phase P serum-based algorithms. Our study demonstrates that algorithms based on the LH surge, or in conjunction with estrone-3-glucuronide, potentially estimate a higher percentage of anovulatory episodes. Addition of measurements of postovulatory serum P or urine pregnanediol may aid in detecting ovulation.

Influence of oral contraceptives on anthropomorphometric, endocrine, and metabolic profiles of anovulatory polycystic ovary syndrome patients.

OBJECTIVE: To evaluate the influence of oral contraceptive pills (OCPs) on anthromorphometric, endocrine, and metabolic parameters in women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective cross-sectional cohort study for the period 1993-2011. SETTING: Tertiary university hospital. PATIENT(S): PCOS patients, who never, ever, or at time of screening were using OCPs were included. A total of 1,297 patients, of whom 827 were white, were included. All PCOS patients diagnosed according to the Rotterdam 2003 consensus criteria were divided into three groups: current users, (n = 76; 6% of total), ever users (n = 1,018; 78%), and never users (n = 203; 16%). Ever users were subdivided based on the OCP-free interval. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Anthromorphometric (blood pressure, cycle duration) and ultrasound (follicle count, mean ovarian volume) parameters, endocrine (SHBG, testosterone, free androgen index, antimüllerian hormone [AMH]) and lipid profiles. RESULT(S): Current users and ever users were compared with never users. In current users, SHBG was increased and androgen levels decreased. Patients with an OCP-free interval of <1 year had a higher mean follicle count, higher AMH level, and increased serum androgen level compared with never users. SHBG levels remained increased until 5-10 years after cessation of OCP use. CONCLUSION(S): OCP use causes a milder phenotypic presentation of PCOS regarding hyperandrogenism. However, it does not alter parameters associated with increased health risks.

Visceral adiposity index (VAI) is related to the severity of anovulation and other clinical features in women with polycystic ovary syndrome.

OBJECTIVE: The clinical phenotype of polycystic ovary syndrome (PCOS) includes reproductive and hormonal aberrations. Visceral adiposity index (VAI) is an indicator which could connect hyperandrogenism and anovulation. The objective was to evaluate the relationship between VAI, menstrual disorders and hormonal, biochemical and ultrasound parameters in women with PCOS. PATIENTS: One hundred and ninety-three women with PCOS diagnosed with Rotterdam criteria. MEASUREMENTS: We correlated VAI with metabolic and clinical features of the syndrome and with indices of inflammation and insulin sensitivity. In addition, we classified the patients into four groups according to the severity of menstrual disorders: Group A (n = 42), with severe menstrual disorders, Group B (n = 83), with mild menstrual disorders, Group C (n = 58), without menstrual disorders and Group D (n = 10) with women with sychnominorroia. RESULTS: In women with PCOS studied, VAI significantly positively correlated with body weight, fasting glucose, insulin, homeostasis model assessment (HOMA) score, white blood cells, platelets, uric acid, free testosterone, oestradiol, total cholesterol, γ-GT, SGPT. Furthermore, a significant inverse correlation between VAI and SHBG, Matsuda index and menstrual cycles per year was documented. From the comparison of the four groups, PCOS women with menstrual disorders had significantly higher VAI and HOMA indices when compared to PCOS without menstrual disorders. CONCLUSIONS: Visceral adiposity index is increased in patients with PCOS in concordance with the severity of anovulation, insulin resistance and inflammation. This index could be a very easy and helpful clinical tool in daily practice to predict insulin resistance in women with PCOS.

Food restriction during lactation suppresses Kiss1 mRNA expression and kisspeptin-stimulated LH release in rats.

Among the numerous physiological changes that accompany lactation is the suppression of the reproductive axis. The aim of this study was to investigate a possible role for the kisspeptin system in the restoration of the hypothalamic-pituitary-gonadal axis during late lactation in rats using a food restriction model that allows manipulation of the duration of lactational anovulation. Kiss1 mRNA expression and kisspeptin-immunoreactive cell counts were examined in both food-restricted dams and ad libitum (AL)-fed dams across late lactation when LH concentrations begin to increase. In the arcuate nucleus, Kiss1 mRNA expression and kisspeptin-positive cell counts were suppressed during late lactation. In the anteroventral periventricular (AVPV), day 15 food-restricted dams had significantly lower AVPV Kiss1 mRNA expression and a decreased LH response to exogenous kisspeptin compared with the AL-fed dams. Following 5 days of ad libitum food intake, these values were restored to levels similar to those in dams that had been fed ad libitum throughout lactation. In conclusion, this study shows that delayed restoration of the reproductive axis due to food restriction is associated with a decrease in kisspeptin sensitivity and low AVPV Kiss1 mRNA in late lactation.

Negative spinal bone mineral density changes and subclinical ovulatory disturbances--prospective data in healthy premenopausal women with regular menstrual cycles.

Subclinical ovulatory disturbances (anovulation or short luteal phases within normal-length menstrual cycles) indicate lower progesterone-to-estrogen levels. Given that progesterone plays a bone formation role, subclinical ovulatory disturbances may be associated with bone loss or less than expected bone gain. Our purpose was to perform a meta-analysis of prospective studies in healthy premenopausal women to determine the overall relationship of subclinical ovulatory disturbances to change in bone mineral density. Two reviewers independently identified from serial literature searches 6 studies meeting inclusion criteria: a 2-year study in 114 young adult women, 2006-2009, Vancouver, Canada; a 2-year study in 189 premenopausal women, 2000-2005, Toronto, Canada; a single-cycle study in 14 young women, 1996-1997, Melbourne, Australia; an 18-month study in 53 women, 1990-1995, Santa Clara, California; a 4-year study in 27 women, 1988-1995, Vancouver, Canada; and a 1-year study in 66 women, 1985-1988, Vancouver, Canada. This meta-analysis included a combined sample size of 473 observations in 436 premenopausal women studied over 1-4 years and aged 14-47 years. The percentage of women with ovulatory disturbances varied significantly from 13% to 82%. Women with more frequent ovulatory disturbances had more negative percentage changes in spine bone mineral density (weighted mean difference = -0.86; P = 0.040) for random-effects analysis. There was significant heterogeneity among these 6 studies (I(2) = 80%). In summary, these data show that regularly menstruating women with more frequent ovulatory disturbances experience more negative changes in bone (approximately -0.9% per year). These cycles with silent estrogen/progesterone imbalance may be clinically important.