Psychological parameters in the reproductive phenotypes of polycystic ovary syndrome

Clinical and endocrine characteristics of the main polycystic ovary syndrome phenotypes

Polycystic ovary syndrome (PCOS) is the most common endocrine-gynecologic disorder affecting women of childbearing age. It has a wide range of clinical manifestations, including menstrual irregularity, infertility, hirsutism, acne, and obesity. Studies have confirmed that PCOS can significantly reduce a patient's health-related quality of life (HRQoL). The pathophysiology of PCOS is poorly understood, but it is believed to be caused by the interaction of several factors. Moreover, there is a lack of information about HRQoL among PCOS women in Saudi Arabia. This study aims to assess the HRQoL of PCOS patients by using the Arabic Version of the Polycystic Ovarian Syndrome Health-Related Quality of life Questionnaire (AR-PCOSQ) in Riyadh city. A descriptive cross-sectional study was conducted on 281 women in Riyadh city using the translated questionnaire (AR-PCOSQ) to explore PCOS quality of life among Saudi females. The eligibility criteria were Saudi female who had been diagnosed with PCOS, living in Riyadh city, aged 18 and above, and willing to participate. The sample size was estimated using the 10-events-per variable rule for prediction models (REF). Informed consent was taken from all participants and a Google Form was used to create the survey and collect data. The higher score represents poor QOL. However, the analysis revealed that higher scores of the weight-related QOL had the greatest impact on patients' quality of life in older age groups, including women aged 26 to 35 (beta = 0.143, 95% CI, 0.023 to 0.304, p-value = 0.046) and women aged > 35 (beta = 0.229, 95% CI, 0.039 to 0.428, p = 0.011). Other domains of QOL, such as emotions, body hair, infertility, and menstrual problems, were not significantly predicted by any of the women's demographic characteristics. The findings revealed that PCOS-related conditions such as weight problems, menstrual irregularity, and infertility were associated with a reduction in quality of life.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women, affecting 4.8 % to 18.6 % of women of reproductive age. Between 10 and 19 years of age, PCOS occurs in 3.39 % to 8.03 % of adolescents. Confirmation of diagnosis in adolescent age is difficult because manifestations of PCOS are similar to normal puberty signs (e. g., irregular menstrual cycle, acne, etc.). New evidence-based guidelines have been issued in 2018 highlighting the diagnostic criteria for establishing PCOS diagnosis in adolescents. These guidelines also recommend a separate identification of risk group patients – adolescent patients for whom both diagnostic PCOS criteria have not yet been confirmed and who should continue to be monitored. It is important to diagnose this disease as early as possible in order to initiate lifestyle adjustments and possibly also begin treatment in a timely manner.In the long term, PCOS increases the risk of developing infertility and type 2 diabetes, cardiovascular disease, insulin resistance and metabolic syndrome. Increased body weight occurring in 40–70 % of adolescents with PCOS significantly increases the risk of chronic non-communicable diseases at a later stage, and maintains PCOS symptoms. PCOS and associated symptoms reduce health-related quality of life (HRQOL). Binge eating is more common in patients with PCOS. The most effective tactics of therapy are lifestyle changes, so it is particularly important to recognise patients at increased risk of developing PCOS, to diagnose them early and to offer treatment that is most relevant to the needs of the individual and improves their quality of life.The aim of the doctoral thesis is to explore intergenerational, genetic, quality of life and binge eating aspects in teenagers with PCOS.The study contains several sections. To evaluate the intergenerational bond, 57 teenagers with PCOS and their mothers were included in Section I. The section studies the relationship between patients with PCOS and their mothers. In addition to PCOS patients, Section II also includes healthy adolescent patients and patients at risk. The role of the most common variation of protein-coding genes involved in the activity of the Hypothalamic-Pituitary-Ovarian axis (FSHR, ESR2, LHCGR, GNRHR) in PCOS development and in the PCOS clinical presentation was studied by including 63 adolescents with a diagnosis of PCOS, 67 healthy control patients and 22 patients at risk. The role of CYP21A2 gene variations in PCOS development and clinical phenotype was established in 55 PCOS patients, 49 control patients and 23 patients at risk. Additionally, components of HRQOL, binge eating and factors affecting the total HRQOL were analysed in 63 PCOS patients and 66 control patients. The study concluded that it was not possible to predict clinical symptoms associated with PCOS in adolescents based on PCOS symptoms in their mothers. The role of protein-coding gene variations that are involved in the functioning of sex hormones was also not found, in regard to PCOS development. However, it was found that the homozygous minor allele carriers within variations of specific genes (ESR2 rs4986938 and LHCGR rs2293275) had a higher total testosterone level in blood than patients who were not carriers of these alleles. The most important components that affected HRQOL in adolescents with PCOS were the diagnosis of PCOS as such, the degree of binge eating, and the percentile of the body mass index. At the same time, HRQOL was most affected by concerns about body hair and body weight. There was no difference in the frequency of binge eating between PCOS patients and adolescent control group patients.In this study, no link was found between the diagnosis of PCOS or associated symptoms in mothers and the phenotype of adolescents with PCOS. Individual alleles have been associated with the clinical presentation of PCOS. There is a better understanding of the components of HRQOL that affect PCOS the most and require particular attention in clinical practice. Further research with a larger sample-size is needed. Furthermore, longitudinal data on the population studied in this project would provide a more accurate insight into the development of the disease at a later age.

BACKGROUND Polycystic ovary syndrome (PCOS) is a common condition in women of reproductive age with well established metabolic abnormalities. There are numerous diagnostic criteria generating several reproductive diagnostic phenotypes [National Institute of Health (NIH) hyperandrogenic anovulatory PCOS and non-NIH PCOS including hyperandrogenic ovulatory or non-hyperandrogenic anovulatory PCOS]. There is ongoing debate regarding the optimal diagnostic criteria for PCOS and on the metabolic implications of newer non-NIH PCOS phenotypes. METHODS We reviewed the literature on the presence of risk factors for type 2 diabetes (DM2) and cardiovascular disease (CVD) across the reproductive diagnostic phenotypes of PCOS with the aims of comparing the metabolic features of the NIH and non-NIH groups and identifying potential high metabolic risk phenotypes of PCOS. RESULTS NIH PCOS patients present with greater obesity, abdominal obesity, insulin resistance (IR) and risk factors for DM2 and CVD compared with non-NIH ovulatory and non-hyperandrogenic PCOS patients. Where differences in metabolic features exist between the phenotypes, they are generally related to the degree of total and abdominal obesity. There is emerging evidence suggesting ovulatory and non-hyperandrogenic PCOS have greater metabolic abnormalities than controls primarily linked to abdominal adiposity. There is currently no evidence that non-hyperandrogenic PCOS is associated with a less adverse metabolic profile than ovulatory PCOS. CONCLUSIONS Current metabolic evidence appears to justify the inclusion of both non-NIH PCOS groups (ovulatory and non-hyperandrogenic) as PCOS subgroups. NIH PCOS is associated with a more adverse metabolic profile including greater total and abdominal obesity, IR and risk factors for CVD and DM2 than non-NIH phenotypes.

Periodontal disease in polycystic ovary syndrome

Risk of metabolic complications in the new PCOS phenotypes based on the Rotterdam criteria

Context: The role of endogenous vitamin D and vitamin D receptor (VDR) gene polymorphism in polycystic ovary syndrome (PCOS) is still controversial.Objective: The objective of this study was to investigate for the first time in women with “classic” PCOS phenotype and healthy controls the role of the serum endogenous vitamin D level and VDR gene polymorphisms in PCOS etiology.Design: Ninety-two women with “classic” PCOS phenotype and 85 controls from lower Silesia with comparable body mass index (BMI) were studied. In all women the waist circumference, android/gynoid fat deposit, parameters of lipid and glucose metabolism, testosterone, free androgen index, sex hormone binding globulin (SHBG) and vitamin D were evaluated. Also, VDR gene polymorphisms rs731236, rs7975232, rs1544410 and rs10735810 were assessed.Results: Serum vitamin D levels in both groups were comparable. Also high, comparable frequencies of hypovitaminosis and vitamin D deficiency in both groups were observed. Women with “classic” PCOS phenotype had statistically significantly higher values of all measured parameters, except serum SHBG and high-density lipoprotein (HDL)-cholesterol, which were lower. The frequency of VDR genotype polymorphism was also comparable in both groups.Conclusions: For the first time, we show that endogenous vitamin D deficiency and VDR polymorphisms are not associated with homogeneous “classic” PCOS phenotype.

The Polymorphisms of PPARγ Pro12Ala and PGC-1 Gly482Ser in Chinese Women With Polycystic Ovary Syndrome

To compare pregnancy and neonatal outcomes in women with hyperandrogenic polycystic ovarian syndrome (PCOS) phenotypes compared with nonhyperandrogenic PCOS phenotypes. We conducted a retrospective cohort study of participants in the PPCOS (Pregnancy in Polycystic Ovary Syndrome) I and II randomized controlled trials; all of the participants met the National Institutes of Health diagnostic criteria for PCOS and were then sorted into three of the four Rotterdam criteria categories based on medical interview, demographics, physical examination, and laboratory data. The two hyperandrogenic (A and B) Rotterdam categories were compared with the nonhyperandrogenic phenotype of PCOS (phenotype D). Our outcomes of interest were clinical pregnancy, pregnancy loss, live birth, obstetric complications (including preterm labor, preeclampsia, gestational diabetes, intrauterine growth restriction, and premature rupture of membranes), and neonatal outcomes (including jaundice, respiratory distress syndrome, neonatal hospitalization, and neonatal infection). Of the 1,376 participants included in the study, 1,249 (90.8%) had hyperandrogenic PCOS phenotypes compared with 127 (9.2%) nonhyperandrogenic PCOS (nonhyperandrogenic PCOS). Compared with participants with nonhyperandrogenic PCOS, those with hyperandrogenic PCOS had higher body mass index (BMI) (35.5±8.9 vs 31.9±9.3 kg/m 2 , P <.001), fasting insulin (21.6±27.7 vs 14.7±15.0 micro-international units/mL, P <.001), and homeostatic model assessment for insulin resistance score (5.01±9.1 vs 3.4±4.1, P =.0002). Age and race were similar between groups. Months attempting pregnancy were greater in participants with hyperandrogenic PCOS compared with nonhyperandrogenic PCOS (41.8±37.3 vs 33.9±32.0). The proportion of participants who achieved pregnancy (29.9% vs 40.2%, P =.02) and live birth rates (20.1% vs 33.1%, P =.001) were lower among those with hyperandrogenic PCOS compared with nonhyperandrogenic PCOS, although pregnancy loss rates did not differ significantly (23.9% vs 32.3%, P =.06). The hyperandrogenic PCOS group had lower odds of live birth compared with the nonhyperandrogenic PCOS group (odds ratio [OR] 0.51, CI, 0.34-0.76), even after adjusting for BMI (adjusted odds ratio [aOR] 0.59, CI, 0.40-0.89). The hyperandrogenic PCOS group also had lower odds of achieving pregnancy compared with the nonhyperandrogenic PCOS group (OR 0.63, CI, 0.44-0.92); however, this association was no longer significant after adjusting for BMI (aOR 0.74, CI, 0.50-1.10). The overall low prevalence of prenatal complications and neonatal outcomes precluded a meaningful comparison between the two groups. Participants with hyperandrogenic PCOS achieved lower rates of pregnancy and live birth compared with those with nonhyperandrogenic PCOS. Evaluating distinct PCOS phenotypes may allow for individualized guidance regarding the probability of pregnancy and live birth. ClinicalTrials.gov , NCT00068861 and NCT00718186.

The role of vitamin D in polycystic ovary syndrome

Are non-esterified fatty acid (NEFA) kinetics altered in women with polycystic ovary syndrome (PCOS)? Women with PCOS, particularly obese subjects, have dysregulated plasma NEFA kinetics in response to changes in plasma insulin and glucose levels, which are associated with insulin resistance (IR) independently of the fasting plasma NEFA levels. Elevated plasma NEFA levels are associated with IR in many disorders, although the homeostasis of NEFA kinetics and its relationship to IR in women with PCOS is unknown. We prospectively compared insulin sensitivity and NEFA kinetics in 29 PCOS and 29 healthy controls women matched for BMI. This study was conducted in a tertiary institution. Plasma NEFA, glucose and insulin levels were assessed during a modified frequently sampled intravenous glucose tolerance test (mFSIVGTT). Minimal models were used to assess insulin sensitivity (Si) and NEFA kinetics (i.e. model-derived initial plasma NEFA level [NEFA0], phi constant [Φ], reflecting glucose-mediated inhibition of lipolysis and measures of maximum rate of lipolysis [SFFA] and NEFA uptake from plasma [KFFA]). The study provides new evidence that women with PCOS have defective NEFA kinetics characterized by: (i) lower basal plasma NEFA levels, measured directly and modeled (NEFA0), and (ii) a greater glucose-mediated inhibition of lipolysis in the remote or interstitial space (reflected by a lower affinity constant [Φ]). There were no differences, however, in the maximal rates of adipose tissue lipolysis (SFFA) and the rate at which NEFA leaves the plasma pool (KFFA). The differences observed in NEFA kinetics were exacerbated, and almost exclusively observed, in the obese PCOS subjects. Our study did not study NEFA subtypes. It was also cross-sectional and based on women affected by PCOS as defined by the 1990 National Institutes of Health (NIH) criteria (i.e. Phenotypes A and B) and identified in the clinical setting. Consequently, extrapolation of the present data to other phenotypes of PCOS should be made with caution. Furthermore, our data is exploratory and therefore requires validation with a larger sample size. Dysfunction in NEFA kinetics may be a marker of metabolic dysfunction in nondiabetic obese women with PCOS and may be more important than simply assessing circulating NEFA levels at a single point in time for understanding the mechanism(s) underlying the IR of PCOS. This work was supported by NIH grants R01-DK073632 and R01-HD29364 to R.A.; a Career Development Award from MD Medical Group, Moscow, RF, to D.L. and Augusta University funds to Y.-H.C. RA serves as consultant to Ansh Labs, Medtronics, Spruce Biosciences and Latitude Capital. U.E., Z.A., D.L., R.M., Y.-H.C., R.C.B. and Y.D.I.C. have no competing interests to declare. Not applicable.

Polycystic ovary syndrome (PCOS) is an endocrine disorder that can result in reduced health-related quality of life (HRQOL). Metabolic changes, particularly insulin resistance and obesity, play a significant role in PCOS pathogenesis. This study examined associations between metabolic factors and HRQOL in PCOS patients. A cross-sectional study of 77 patients was conducted at University Medical Center Mainz. At the time of inclusion in the study, patients had to be over 18 and not undergoing active PCOS therapy. A desire to conceive or fertility therapy led to exclusion. Participants were over 18, not undergoing PCOS therapy, and not seeking pregnancy. HRQOL and psychological distress were measured using the Modified-PCOS-Questionnaire (MPCOSQ) and Hospital Anxiety and Depression Scale (HADS). Linear regression analyses assessed associations between metabolic markers and HRQOL, with significant variables included in a multivariate model. Worsening metabolic markers were linked to lower HRQOL, especially in body hair and menstrual symptom domains. Markers such as HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) levels (P=0.040), elevated VAI (Visceral Adiposity Index) (P=0.035), and increased FLI (Fatty Liver Index) (P=0.023) were associated with diminished HRQOL. In the multivariate regression analysis, only a BMI ≥25kg/m2 (P=0.001) emerged as a statistically significant value. This study showed a significant correlation between metabolic markers, including BMI, FLI, VAI, HOMA-IR, and HRQOL in PCOS patients. BMI was the most meaningful predictor for HRQOL. BMI, despite being controversial and prone to errors, may be more indicative of HRQOL than specific metabolic markers.

Polymorphism in HSD17B6 is associated with key features of polycystic ovary syndrome

Polycystic Ovary Syndrome (PCOS) is a complex heterogeneous disorder and the most common endocrinopathy amongst women of reproductive age. It is characterized by androgen excess, chronic anovulation and an altered cardiometabolic profile. PCOS is linked to impaired adipose tissue (AT) physiology and women with this disorder present with greater risk for insulin resistance (IR), hyperinsulinemia, central adiposity, nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) than matched for age and body mass index (BMI) women without PCOS. Hyperandrogenaemia appears to be driving adipocyte hypertrophy observed in PCOS under the influence of a hyperinsulinaemic state. Changes in the function of adipocytes have an impact on the secretion of adipokines, adipose tissue-derived proinflammatory factors promoting susceptibility to low grade inflammation. In this article, we review the existing knowledge on the interplay between hyperandrogenaemia, insulin resistance, impaired adipocyte biology, adipokines and chronic low-grade inflammation in PCOS. In PCOS, more than one mechanisms have been suggested in the development of a chronic low-grade inflammation state with the most prevalent being that of a direct effect of the immune system on adipose tissue functions as previously reported in obese women without PCOS. Despite the lack of conclusive evidence regarding a direct mechanism linking hyperandrogenaemia to pro-inflammation in PCOS, there have been recent findings indicating that hyperandrogenaemia might be involved in chronic inflammation by exerting an effect on adipocytes morphology and attributes. Increasing evidence suggests that there is an important connection and interaction between proinflammatory pathways, hyperinsulinemia, androgen excess and adipose tissue hypertrophy and, dysfunction in PCOS. While lifestyle changes and individualized prescription of insulin-sensitizing drugs are common in managing PCOS, further studies are warranted to eventually identify an adipokine that could serve as an indirect marker of adipocyte dysfunction in PCOS, used as a reliable and pathognomic sign of metabolic alteration in this syndrome.

The polycystic ovarian syndrome (PCOS) is the most common endocrine disorder affecting female fertility. In this study, we examined the symptomatology of PCOS and the health-related quality of life among infertility patients suffering from PCOS with different socio-cultural and ethnic background. Symptomatology of PCOS, body composition characteristics as well as socio-economic factors were examined in 49 PCOS infertility patients of the University Clinic for Gynecology and Obstetrics, in Vienna, who originated from two socio-cultural subgroups, Austrian women and Moslem immigrant women. Additionally, the Cronins health-related quality of life questionnaire of women with PCOS was used in order to examine the impact of PCOS symptoms on the individual quality of life of the affected women. In terms of the appearance of the symptoms, the typical heterogeneity of PCOS could be found in both subgroups with no differences. However, differences in the health-related quality of life were impressive. Health-related quality of life of women from an Islamic background was affected to a greater degree than that of Austrian women, although no differences in symptomatology were found. This was true of all five domains investigated (infertility, overweight, hirsutism, menstrual irregularities and emotional problems). First of all, infertility was a dramatic problem for immigrant women. Islamic women had very high reproductive pressure. The Moslem immigrant PCOS women suffer more from infertility than do Austrian women. Health professionals should be sensitive to the ethnicity, religious and cultural background of their patients to provide the best possible medical support.