Insulin Dynamics in Young Women with Polycystic Ovary Syndrome and Normal Glucose Tolerance across Categories of Body Mass Index

Background

Evidence favours insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate insulin metabolism in young women with PCOS but normal glucose tolerance as compared with age, body mass index and insulin resistance-matched controls to answer the question whether women with PCOS hypersecrete insulin in comparison to appropriately insulin resistance-matched controls.

Research Design and Methods

Sixty-nine cases were divided according to their body mass index (BMI) in normal-weight (N = 29), overweight (N = 24) and obese patients (N = 16). Controls were 479 healthy women (age 16–49 y). Whole body Insulin Sensitivity (WBISI), fasting, and total insulin secretion were estimated following an oral glucose tolerance test (C-peptide deconvolution method).

Results

Across classes of BMI, PCOS patients had greater insulin resistance than matched controls (p<0.0001 for all the comparisons), but they showed higher fasting and total insulin secretion than their age, BMI and insulin resistance-matched peers (p<0.0001 for all the comparisons).

Conclusion

Women with PCOS show higher insulin resistance but also larger insulin secretion to maintain normal glucose homeostasis than age-, BMI- and insulin resistance-matched controls.     

Menstrual Cycle Phase Modulates Emotional Conflict Processing in Women with and without Premenstrual Syndrome (PMS) – A Pilot Study

Background

Premenstrual syndrome (PMS) is characterized by a cluster of psychological and somatic symptoms during the late luteal phase of the menstrual cycle that disappear after the onset of menses. Behavioral differences in emotional and cognitive processing have been reported in women with PMS, and it is of particular interest whether PMS affects the parallel execution of emotional and cognitive processing. Related to this is the question of how the performance of women with PMS relates to stress levels compared to women without PMS. Cortisol has been shown to affect emotional processing in general and it has also been shown that women with severe PMS have a particular cortisol profile.

Methods

We measured performance in an emotional conflict task and stress levels in women with PMS (n = 15) and women without PMS (n = 15) throughout their menstrual cycle.

Results

We found a significant increase (p = 0.001) in the mean reaction time for resolving emotional conflict from the follicular to the luteal cycle phase in all subjects. Only women with PMS demonstrated an increase in physiological and subjective stress measures during the luteal menstrual cycle phase.

Conclusions

Our findings suggest that the menstrual cycle modulates the integration of emotional and cognitive processing in all women. Preliminary data are supportive of the secondary hypothesis that stress levels are mediated by the menstrual cycle phase only in women with PMS. The presented evidence for menstrual cycle-specific differences in integrating emotional and cognitive information highlights the importance of controlling for menstrual cycle phase in studies that aim to elucidate the interplay of emotion and cognition.     

Prevalence of ultrasonography proved polycystic ovaries in North Indian women with type 2 diabetes mellitus

Background  

Polycystic ovaries (PCO) and their clinical expression (the polycystic ovary syndrome [PCOS]) as well as type 2 diabetes mellitus (T2DM) are common medical conditions linked through insulin resistance. We studied the prevalence of PCO and PCOS in women with diet and/or oral hypoglycemic treated T2DM and non-diabetic control women.     

The effect of stage of estrous cycle and follicular maturation on ovarian inhibin production in sheep

Twenty-four Scottish Blackface ewes (mean weight 50.0 +/- 0.1 kg with ovulation rate 1.3 +/- 0.1) were randomly divided into 4 groups of 6 animals. Under general anesthesia, following the collection of a timed sample of ovarian venous blood, the ovaries of these animals were collected either on Day 10 of the luteal phase or 12, 24, and 48 h after a luteolytic dose of a prostaglandin (PG) F2 alpha analogue (cloprostenol 100 micrograms i.m.) administered on Day 10. All follicles greater than 3 mm were dissected from the ovaries and incubated in Medium 199 (M199) at 37 degrees C for 2 h, following which the granulosa cells were harvested and incubated in triplicate for 24 h in M199 with or without ovine FSH or ovine LH. Plasma and culture media samples were assayed for inhibin, estradiol (E2), androstenedione (A4), and testosterone (T) by specific RIA. After correcting for hematocrit, ovarian secretion rates were calculated from the product of the plasma concentration and flow rate. The rate of ovarian inhibin secretion during the luteal phase was similar from ovaries categorized on the basis of presence of luteal tissue (1.0 +/- 0.3 and 0.9 +/- 0.5 ng/min for CL present and absent, respectively), confirming that the ovine CL does not secrete appreciable amounts of inhibin. Inhibin secretion was higher (p less than 0.05) at 12 h after PG-induced luteolysis but not at 24 or 48 h compared to values for luteal phase control ewes. Although ovaries containing large estrogenic follicles (greater than or equal to 4 mm in diameter and classified as estrogenic from in vitro criteria) secreted the most inhibin (55%; p less than 0.05), both ovaries containing large nonestrogenic follicles (33%) and small (11%; less than 4 mm in diameter) follicles secreted appreciable amounts of inhibin. This contrasted strongly with E2 where greater than 80% of the steroid was secreted by large estrogenic follicles. The rate of ovarian inhibin secretion was positively correlated (p less than 0.05) with the rate of E2, A4, and T secretion. Overall, there was no significant effect of stage of cycle on follicular inhibin content after 2 h incubation in vitro, release of inhibin by follicles incubated in vitro, or synthesis of inhibin by granulosa cells cultured in vitro. FSH and LH had no effect on the production of either inhibin or estradiol by cultured granulosa cells. Follicular diameter was positively correlated (p less than 0.001) with follicular inhibin and steroid release. Follicular inhibin content after 2 h incubation in vitro was more highly correlated with inhibin release by incubated follicles (r = 0.7; p less than 0.001) than with inhibin synthesis by granulosa cells in vitro (0.4; p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)     

Cloning of a novel inhibin alpha cDNA from rhesus monkey testis

Background  

Inhibins are dimeric gonadal protein hormones that negatively regulate pituitary FSH synthesis and secretion. Inhibin B is produced by testicular Sertoli cells and is the primary circulating form of inhibin in most adult male mammals. Inhibin B is comprised of the inhibin alpha subunit disulfide-linked to the inhibin/activin betaB subunit. Here we describe the cloning of the cDNAs encoding these subunits from adult rhesus monkey testis RNA.     

Association of TRB3 Q84R polymorphism with polycystic ovary syndrome in Chinese women

Background  

Tribbles 3 (TRB3) affects insulin signalling by inhibiting insulin-stimulated Akt phosphorylation and subsequent activation. A single nucleotide polymorphism located in the second extron of the human TRB3 gene is thought to be associated with insulin resistance. The latter is a core abnormality in PCOS independent of obesity. The present study was designed to clarify the relationships of TRB3 Q84R polymorphism with PCOS in a Chinese women group.     

The relationship between polycystic ovary syndrome,glucose tolerance status and serum preptin level

Background  

Polycystic ovary syndrome (PCOS) is linked to obesity, impaired glucose tolerance and diabetes. Recently, studies have found that preptin enhances insulin secretion in rats and might play a role in the pathogenesis of diabetes and PCOS in humans. The aim of this study was to evaluate the relationship between PCOS, glucose tolerance status, and serum preptin level.     

Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients

Background  

Various endometrial abnormalities have been associated with luteal phase deficiency: a significant dyssynchrony in the maturation of the glandular epithelium and the stroma and a prevalence of out-of-phase endometrial biopsy specimens. Out-of phase endometrium is a controversial disorder related to failed implantation, infertility and early pregnancy loss. Given that the regulation of the apoptotic process in endometrium of luteal phase deficiency is still unknown, the aim of this study was to evaluate cell proliferation, apoptosis and the levels of the main effector caspase, caspase-3 in the luteal in-phase and out-of-phase endometrium.     

Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis

Background  

The effects of gonadotrophin-releasing hormone agonist (GnRH-a) administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes.     

The effect of the presence and pattern of luteinizing hormone stimulation on ovulatory follicle development in sheep

The aim of this study was to examine the role of LH on the growth of the large preovulatory follicle and its secretion of hormones in sheep. Ewes with ovarian autotransplants were treated with GnRH-antagonist at the time of luteal regression and different LH regimes applied for 60-66 h before administration of an ovulatory stimulus (hCG). In Experiment 1 (N = 24; n = 8), ewes received either no LH or constant or pulsatile infusion of LH at the same dose (1.25 microg/h). In Experiment 2 (N = 12, n = 6), LH was constantly infused at a rate of 1.25 microg or 2.5 microg oLH/h. In Experiment 1, animals receiving either pulsatile or constant LH exhibited increases in estradiol and inhibin A secretion (P < 0.001) and a depression in FSH (P < 0.001) that resembled the normal follicular phase. Similarly in Experiment 2, doubling the dose of LH resulted in a two-fold increase in ovarian estradiol secretion (P < 0.05) but no other changes. All animals receiving LH, regardless of the pattern of stimulation, ovulated and established a normal luteal phase. In contrast, no LH treatment resulted in constant immuno-active LH without pulses, unchanged FSH and inhibin A concentrations (P < 0.05), and basal estradiol secretion (P < 0.001). Morphologically normal large antral follicles were observed in this group and although corpora lutea formed in response to hCG, progesterone profiles were abnormal. In conclusion, these results suggest that LH is an essential requirement for normal ovulatory follicle development and subsequent luteal function and show that a pulsatile mode of LH stimulation is not required by ovulatory follicles.     

A preliminary study on the induction of dioestrous ovulation in the mare – a possible method for inducing prolonged luteal phase

Background  

Strong oestrous symptoms in the mare can cause problems with racing, training and handling. Since long-acting progesterone treatment is not permitted in mares at competition (e.g. according to FEI rules), there is a need for methods to suppress unwanted cyclicity. Spontaneous dioestrous ovulations in the late luteal phase may cause a prolongation of the luteal phase in mares.     

Association between the prevalence of hyperuricemia and reproductive hormones in polycystic ovary syndrome

Background

The prevalecne of hyperuricemia in polycystic ovary syndrome (PCOS) is still uncertain. We aimed to investigate the prevalence of hyperuricemia in PCOS and to determine the influence of reproductive hormones on uric acid concentration.

Methods

This retrospective cross-sectional study was performed at a large reproductive medicine center. Between March 2007 and October 2016, a total of 1,183 women with PCOS and 10,772 women without PCOS were included. PCOS was diagnosed according to the Rotterdam criteria. Anthropometric parameters, blood pressure, uric acid, reproductive hormones, glucose and lipids were measured in all subjects.

Results

The serum uric acid (SUA) level was higher in women with PCOS than in women without PCOS. The prevalence of hyperuricemia in women with PCOS (25.48%) was significantly higher than that in women without PCOS (8.74%). Analysis stratified for age and body mass index (BMI) showed that both the SUA level and the prevalence of hyperuricemia were higher in women with PCOS of different age and BMI groups than in women without PCOS. After adjusting for age, BMI and estimated glomerular filtration rate (eGFR), logistic regression analysis revealed that the luteinizing/follicle-stimulating hormone (LH/FSH) ratio (odds ratio (OR)?=?1.20, 95% CI?=?1.01–1.43) and testosterone level (OR?=?1.56, 95% CI?=?1.27–1.90) were positively associated with the prevalence of hyperuricemia in females with PCOS.

Conclusions

The serum uric acid (SUA) level and the prevalence of hyperuricemia markedly increased in women with PCOS. The testosterone level was positively associated with the SUA level and the prevalence of hyperuricemia in females with PCOS.

     

Pregnancy outcome in women with polycystic ovary syndrome comparing the effects of laparoscopic ovarian drilling and clomiphene citrate stimulation in women pre-treated with metformin: a retrospective study

Background  

Ovarian stimulation in women with polycystic ovary syndrome (PCOS) increases the risk for perinatal complications. Ovulation induction by laparoscopic ovarian drilling (LOD) might improve the overall pregnancy outcomes. The aim of our study was to assess the adverse events or effects on pregnancy of LOD and clomiphene citrate (CC) stimulation in patients who received metformin.     

Digit ratios by computer-assisted analysis confirm lack of anatomical evidence of prenatal androgen exposure in clinical phenotypes of polycystic ovary syndrome

Background  

We recently showed that women with four clinical phenotypes of polycystic ovary syndrome (PCOS) do not demonstrate anatomical evidence of elevated prenatal androgen exposure as judged by a lower ratio of the index (2D) to ring (4D) finger. However, those findings conflicted with a previous study where women with PCOS had lower right hand 2D:4D compared to healthy female controls. Both these studies used Vernier calipers to measure finger lengths - a method recently shown to be less reliable at obtaining finger length measurements than computer-assisted analysis.     

Dynamics of circulating concentrations of gonadotropins and ovarian hormones throughout the menstrual cycle in the bonnet monkey: role of inhibin A in the regulation of follicle‐stimulating hormone secretion

In higher primates, increased circulating follicle‐stimulating hormone (FSH) levels seen during late menstrual cycle and during menstruation has been suggested to be necessary for initiation of follicular growth, recruitment of follicles and eventually culminating in ovulation of a single follicle. With a view to establish the dynamics of circulating FSH secretion with that of inhibin A (INH A) and progesterone (P₄) secretions during the menstrual cycle, blood was collected daily from bonnet monkeys beginning day 1 of the menstrual cycle up to 35 days. Serum INH A levels were low during early follicular phase, increased significantly coinciding with the mid cycle luteinizing hormone (LH) surge to reach maximal levels during the mid luteal phase before declining at the late luteal phase, essentially paralleling the pattern of P₄ secretion seen throughout the luteal phase. Circulating FSH levels were low during early and mid luteal phases, but progressively increased during the late luteal phase and remained high for few days after the onset of menses. In another experiment, lutectomy performed during the mid luteal phase resulted in significant decrease in INH A concentration within 2 hr (58.3±2 vs. 27.3±3 pg/mL), and a 2‐ to 3‐fold rise in circulating FSH levels by 24 hr (0.20±0.02 vs. 0.53±0.14 ng/mL) that remained high until 48 hr postlutectomy. Systemic administration of Cetrorelix (150 µg/kg body weight), a gonadotropin releasing hormone receptor antagonist, at mid luteal phase in monkeys led to suppression of serum INH A and P₄ concentrations 24 hr post treatment, but circulating FSH levels did not change. Administration of exogenous LH, but not FSH, significantly increased INH A concentration. The results taken together suggest a tight coupling between LH and INH A secretion and that INH A is largely responsible for maintenance of low FSH concentration seen during the luteal phase. Am. J. Primatol. 71:817–824, 2009. © 2009 Wiley‐Liss, Inc.     

Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

Background  

There is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet.     

Risk of Psychiatric Disorders following Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study

Background

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. A higher prevalence of psychiatric comorbidities, including depressive disorder, anxiety disorder, and bipolar disorder has been proved in patients with PCOS. However, a clear temporal causal relationship between PCOS and psychiatric disorders has not been well established.

Objective

We explored the relationship between PCOS and the subsequent development of psychiatric disorders including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder.

Methods

We identified patients who were diagnosed with PCOS by an obstetrician-gynecologist in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without PCOS who were matched according to age and sex. The occurrence of subsequent new-onset psychiatric disorders was evaluated in both cohorts based on diagnoses made by psychiatrists.

Results

The PCOS cohort consisted of 5431 patients, and the comparison cohort consisted of 21,724 matched control patients without PCOS. The incidence of depressive disorder (hazard ratio [HR] 1.296, 95% confidence interval [CI] 1.084–.550), anxiety disorder (HR 1.392, 95% CI 1.121–1.729), and sleep disorder (HR 1.495, 95% CI 1.176–1.899) were higher among the PCOS patients than among the patients in the comparison cohort. In addition, a higher incidence of newly diagnosed depressive disorder, anxiety disorder, and sleep disorder remained significantly increased in all of the stratified follow-up durations (0–1, 1–5, ≥5 y).

Conclusions

PCOS might increase the risk of subsequent newly diagnosed depressive disorder, anxiety disorder, and sleep disorder. The risk of newly diagnosed bipolar disorder, which has often been reported in the literature to be comorbid with PCOS, was not significantly elevated.     

Risks,benefits size and clinical implications of combined oral contraceptive use in women with polycystic ovary syndrome

Background

Polycystic ovary syndrome (PCOS) is a complex condition with high risk for dyslipidemia, dysglycemia, venous thromboembolism, cardiovascular disease and metabolic syndrome. Because the combined oral contraceptive (COC) use has also been associated with impaired fasting glucose, insulin resistance and increased risk of thromboembolism disease, it is rationale to think that the combination of oral contraceptive and PCOS could make it worse or increase the risks.

Objective

To examine the current data regarding potential additional risks and benefits of contraceptive use, highlights the major gap in knowledge for designing future studies and, when possible, suggests an adequate COC formulation for a determined PCOS phenotype.

Methods

English-language publications reporting on the influence of COCS in the development of venous thromboembolism in PCOS patients published until 2017 were searched using PubMed, Cochrane database, and hand search of references found in consulted articles. Ranges of collected data are given; the pooled data are presented as median and first and third quartiles. Wilcoxon signed-ranks test for paired samples was used to compare before-after original data. P value was set at 0.05.

Results

Most of COCs preparations significantly decrease androgens, and increase sex-hormone binding globulin. Therefore, the benefits of COCs are clear in patients with proved hyperandrogenemia. Regarding the impact of COCs on carbohydrate metabolism of PCOS subjects, the data were inconsistent but they tended to show no additional risk. Regarding lipids, most COCs consistently increased high-density lipoprotein cholesterol, triglycerides and total cholesterol concentrations but the clinical implications of these changes need additional studies.

Conclusion

The review showed consistent beneficial effect of COCs, particularly for hyperandrogenemic PCOS patients. The benefit size of COC’s use by normoandrogenemic PCOS patients is uncertain and need more investigation. The effects of COC use on carbohydrate metabolism of women with PCOS are still unresolved since most studies are observational but the current results demonstrated that COCs do not make their levels worse and may improve insulin sensitivity. The impact of COCs on lipids of PCOS patients seems to be clearer and most preparations increase total cholesterol, high-density lipoprotein cholesterol and triglycerides. In summary, it is important to balance the potential benefits and risks of the COCs individually before prescribing them for PCOS women.

     

Interleukin-6 Levels in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Background

The change of serum interleukin-6(IL-6) levels in women with polycystic ovary syndrome (PCOS), as well as the relations between IL-6 levels and body mass index (BMI), insulin resistance(IR) and androgen status of PCOS patients, are not fully understood.

Methods

A literature search was performed in October 2015 using PubMed, Embase and the Cochrane Library databases to identify studies. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs).

Results

Twenty articles with 25 case-control studies included 1618 women (922 PCOS patients and 696 controls) were included in this study. IL-6 levels in controls were significantly lower than that of PCOS patients (SMD = 0.78, 95%CI = 0.41–1.16, P<0.001), with significant heterogeneity across studies (I² = 91% and P<0.001). Meta-regression analysis model indicated IR status was the main source of heterogeneity (P = 0.005). Results from group analysis suggested that high IL-6 levels in PCOS were significantly associated with Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR) ratio and total testosterone ratio (T ratio), and was found in both lean and obese women with PCOS. Cumulative meta-analysis results indicated the total effect size (SMD) had tend to be stable since 2012(0.79 to 0.92).

Conclusions

A high IL-6 level is not an intrinsic characteristic of PCOS, but may be a useful monitoring biomarker for the treatment of PCOS.     

Effect of steroid- and inhibin-free ovine follicular fluid on ovarian follicles and ovarian hormone secretion

Treatment of ewes with steroid-free ovine follicular fluid (oFF) during the follicular phase of the oestrous cycle results in the immediate inhibition of the ovarian secretion of oestradiol, inhibin and androgens. An experiment was conducted to determine whether this effect of oFF was due to inhibin, or to direct inhibition of ovarian function by other factors in oFF. Eight ewes in which the left ovary and vascular pedicle had been autotransplanted to a site in the neck were studied during the breeding season. Luteal regression was induced in all animals by injection of cloprostenol (100 micrograms i.m.; PG) on Day 10 of the luteal phase. The animals were divided into two groups (n = 4) and treated with either steroid-free oFF (oFF; 3 ml s.c.; 3.2 microgram p1-26 alpha inhibin/ml) or steroid-free oFF in which the inhibin content had been reduced by greater than 90% (IFoFF; 3 ml s.c.; 0.3 microgram p1-26 alpha inhibin/ml) by affinity chromatography, 24 and 36 h after PG. Samples of ovarian and jugular venous blood were collected at (i) intervals of 4 h from 16 h before until 120 h after PG and (ii) intervals of 10 min from 48 to 52 h after injection of PG to investigate the pattern of pulsatile secretion of ovarian hormones. All ewes had previously been monitored during a normal PG-induced follicular phase. Injection of oFF resulted in an increase (P less than 0.05) in the concentration of inhibin in jugular venous plasma and a profound (P less than 0.001) and prolonged decrease in the peripheral concentration of follicle-stimulating hormone (FSH). Injection of IFoFF had no significant effect on peripheral concentrations of inhibin or FSH in the first 24 h after treatment; thereafter inhibin concentrations fell (P less than 0.01) progressively until 40 h and then increased (P less than 0.01) until 72 h after treatment. In both treatment groups, however, within 24-36 h of treatment the concentration of FSH increased 5-10-fold (P less than 0.001) to a peak that occurred within 48-60 h and then declined to basal concentrations within 72-84 h of treatment. The concentration of luteinizing hormone (LH) in jugular venous plasma increased in both groups after treatment (P less than 0.01), although the rise after injection of oFF only started after 24 h. Thereafter, there was a progressive increase in the concentration of LH, peaks occurring 48-60 h after treatment.(ABSTRACT TRUNCATED AT 400 WORDS)