Polycystic Ovary Syndrome in Gynecologic Endocrinology

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in premenopausal women, with a wide spectrum of possible phenotypes, symptoms and sequelae according to the current clinical definition. However, there are women who do not fulfill at least two out of the three commonly used “Rotterdam criteria” and their risk of developing type 2 diabetes or obesity later in life is not defined. Therefore, we addressed this important gap by conducting a retrospective analysis based on 750 women with and without PCOS. We compared four different PCOS phenotypes according to the Rotterdam criteria with women who exhibit only one Rotterdam criterion and with healthy controls. Hormone and metabolic differences were assessed by analysis of variance (ANOVA) as well as logistic regression analysis. We found that hyperandrogenic women have per se a higher risk of developing insulin resistance compared to phenotypes without hyperandrogenism and healthy controls. In addition, hyperandrogenemia is associated with developing insulin resistance also in women with no other Rotterdam criterion. Our study encourages further diagnostic and therapeutic approaches for PCOS phenotypes in order to account for varying risks of developing metabolic diseases. Finally, women with hyperandrogenism as the only symptom should also be screened for insulin resistance to avoid later metabolic risks. Full article

Studies suggest that non-pregnant women with polycystic ovary syndrome (PCOS) may be at elevated risk of 25 hydroxyvitamin D (25(OH)D) deficiency. Furthermore, there is evidence suggesting that 25(OH)D may also play an important role during pregnancy. Data regarding 25(OH)D deficiency during pregnancy in PCOS patients and its association with perinatal outcome is scarce. The aim of the study was to investigate whether mothers with and without PCOS have different 25(OH)D levels at term, how maternal 25(OH)D levels are reflected in their offspring, and if 25(OH)D levels are associated with an adverse perinatal outcome. Therefore, we performed a cross-sectional observational study and included 79 women with PCOS according to the ESHRE/ASRM 2003 definition and 354 women without PCOS and an ongoing pregnancy ≥ 37 + 0 weeks of gestation who gave birth in our institution between March 2013 and December 2015. Maternal serum and cord blood 25(OH)D levels were analyzed at the day of delivery. Maternal 25(OH)D levels did not differ significantly in women with PCOS and without PCOS (p = 0.998), nor did the 25(OH)D levels of their respective offspring (p = 0.692). 25(OH)D deficiency (<20 ng/mL) was found in 26.9% and 22.5% of women with and without PCOS (p = 0.430). There was a strong positive correlation between maternal and neonatal 25(OH)D levels in both investigated groups (r ≥ 0.79, p < 0.001). Linear regression estimates of cord blood 25(OH)D levels are about 77% of serum 25(OH)D concentrations of the mother. Compared to healthy controls, the risk for maternal complications was increased in PCOS women (48% vs. 65%; p = 0.009), while there was no significant difference in neonatal complications (22% and 22%; p = 1.0). However, 25(OH)D levels were similar between mothers and infants with and without perinatal complications. Although the share of women and infants with 25(OH)D deficiency was high in women with PCOS and without PCOS, it seems that the incidence of adverse perinatal outcome was not affected. The long-term consequences for mothers and infants with a 25(OH)D deficiency have to be investigated in future studies. Full article

The identification of hyperandrogenism in polycystic ovary syndrome (PCOS) is concerning because of the poor accuracy of the androgen immunoassays (IA) and controversies regarding which androgens should be measured. The aim of our study was to evaluate the impact of the assessment of testosterone (T) and androstenedione (A) by liquid chromatography in tandem with mass spectrometry (LC/MS-MS), in the diagnosis of PCOS. We evaluated 131 patients referred for suspected PCOS. Fourteen patients in total were excluded, some because of other diagnosis (n = 7) or incomplete diagnostic workup (n = 7). We measured T and A both by IA and LC-MS/MS in the 117 subjects included. We calculated free T (fT) by the Vermeulen formula and recorded clinical and metabolic data. 73 healthy females served as controls to derive immunoassays (IA) and LC-MS/MS reference intervals for T, fT and A. PCOS was confirmed in 90 subjects by IA and in 93 (+3.3%) by LC-MS/MS. The prevalence of biochemical hyperandrogenism in PCOS by LC-MS/MS increased from 81.7% to 89.2% if A was also considered. The most frequently elevated androgens were fT (73.1%) and A (64.5%) and they had similar levels of accuracy in differentiating PCOS and controls (0.34 ng/dL, Sn 91% Sp 89%; 1.16 ng/mL, Sn 91% Sp 88%, respectively). Free testosterone correlated with body mass index (BMI), homeostatic model assessment (HOMA)-index, glycated hemoglobin (HbA1c), and sex-binding globulin (SHBG). The results confirm that LC-MS/MS is slightly more sensitive than IA in the diagnosis of PCOS with LC-MS/MS detecting higher levels of fT and A. Moreover, assessment of fT and A by LC-MS/MS had a similar level of accuracy in discriminating between PCOs and control subjects. Lastly, fT by LC-MS/MS correlates with adverse metabolic parameters. Full article

Background: To investigate insulin sensitivity and glucose metabolism in pregnant lean and overweight polycystic ovary syndrome (PCOS) patients vs. lean and overweight controls without PCOS. Methods: Prospective cohort study on 67 pregnant women (31 with PCOS and 36 controls, subdivided into overweight or obese and normal weight). All women underwent a 2h-OGTT including glucose, insulin, and C-peptide in early- and mid-gestation and were followed-up until delivery. Results: Insulin sensitivity and glucometabolic parameters were comparable between PCOS patients and controls, whereas marked differences were observed between overweight/obese and lean mothers. Impaired whole-body insulin sensitivity at early pregnancy is mainly a consequence of higher BMI (body mass index; p < 0.001) compared to PCOS (p = 0.216), whereby no interaction between overweight/obesity and PCOS was observed (p = 0.194). Moreover, overweight was significantly associated with gestational diabetes (p = 0.0003), whereas there were no differences between women with and without PCOS (p = 0.51). Birth weight was inversely related to whole-body insulin sensitivity (rho = −0.33, p = 0.014) and positively associated with higher pregestational BMI (rho = 0.33, p = 0.012), whereas there was no association with PCOS. Conclusions: Impaired insulin action was mainly a consequence of overweight rather than PCOS. Our data suggest that overweight is more relevant than PCOS for the effects on insulin sensitivity and impaired glucose metabolism. Full article

Data concerning metabolic consequences in women with polycystic ovary syndrome (PCOS) are delivered mainly by cross-sectional studies. In this research, we re-examined 31 Caucasian PCOS women after a median period of 120.9 months to evaluate the changes in metabolic syndrome components. Clinical examination, oral glucose tolerance test with estimations of glucose and insulin, lipids, sex hormone-binding globulin (SHBG) and sex hormones assessments were performed on two occasions. Additionally, the euglycaemic hyperinsulinaemic clamp technique was used at the baseline to assess insulin sensitivity (M-clamp value). In the end, the median age of participants was 35. We observed an increase in glucose concentrations, a decrease in insulin concentrations and no changes in insulin resistance markers. Final mean glucose, mean insulin, Matsuda index and body mass index (BMI) were correlated with baseline M-clamp value and SHBG (p < 0.01). During the follow-up, no one in the sample developed diabetes. The annualised incidence rate for conversion from normoglycaemia to prediabetes totalled 4.5%. Baseline BMI, free androgen index, fasting glucose and M-clamp value were identified as prediabetes predictors in young PCOS women (respectively, OR = 1.17, OR = 1.42, OR = 1.2, OR = 0.73, p < 0.05). Prediabetes appeared in 76.47% of the women with a final BMI of ≥ 25 kg/m² and in 7.14% of the normal-weight women (p = 0.0001). In conclusion, we report a high rate of adverse change in glucose metabolism in overweight and obese participants, a deterioration in β-cell function and strong correlations between metabolic parameters assessed in the third and the fourth decade in PCOS women, emphasising the role of early intervention to prevent cardiometabolic diseases. Full article

Background: The use of different definitions and diagnostic approaches of polycystic ovary syndrome (PCOS) and recurrent miscarriage (RM) has led to a wide range of prevalence rates in the literature. Despite the persistent controversy about the factual prevalence of PCOS in RM, a vast number of studies have revealed evidence about their association with each other. The goals of this study were to evaluate the prevalence of polycystic ovarian morphology and PCOS within the RM population, performing meta-analyses with the obtained data from this study, together with previous reports on this topic and evaluating reproductive outcome in women with RM and PCOS. Methods: A retrospective cohort study with 452 women with RM and a meta-analysis were conducted. The main outcome parameter was the prevalence of PCOS in RM patients. Results: In the retrospective study, the prevalence of PCOS in RM was 9.5%. Negative results for the selected risk factors for RM were present in 283 patients (62.6%). From all evaluated possible underlying causes for RM, only the presence of thrombophilic disorders was significantly associated with PCOS (PCOS: 20.9% versus no PCOS: 7.8%, p = 0.010). In the meta-analysis of three studies on PCOS in RM patients, which used the revised Rotterdam criteria for defining PCOS, an estimated pooled prevalence of 14.3% (95% CI: 6.2–24.9) was found. In the retrospective data set, women in the PCOS group revealed significantly higher luteinizing hormone (LH), testosterone, and Anti-Mullerian hormone (AMH) levels than age- and body mass index (BMI)-matched controls with RM negative for the selected risk facotrs (p < 0.05). The rate of further miscarriages was significantly higher in PCOS women than in controls (71.4% versus 53.6%, respectively; p = 0.031). Conclusions: The prevalence of PCOS seems slightly increased in women with RM. Women with PCOS suffering from RM showed a significantly higher risk for further miscarriage and decreased chances of having a life birth of about 18% which did not reach statistical significance. Therefore, we assume that PCOS plays a moderate role in RM. Full article

Both polycystic ovary syndrome (PCOS) and psoriasis are associated with insulin resistance and metabolic syndrome. Nonetheless, the incidence of psoriasis in patients with PCOS is unclear. We used the Longitudinal Health Insurance Research Database (LHID) in Taiwan from 2000 to 2012 to perform a retrospective population-based cohort study to elucidate the occurrence of psoriasis in PCOS patients. Patients with PCOS without psoriasis in the index year (the year of PCOS diagnosis) were recruited as the PCOS group. Those without PCOS nor psoriasis (control group) were selected using propensity score matching at a ratio of 4:1. Hazard ratios (HRs) were obtained using the Cox proportional hazards regression model. In total, 4707 and 18,828 patients were included in the PCOS and control groups, respectively. The incidence rates of psoriasis in the control and PCOS groups were 0.34 and 0.70 per 1000 person-years, respectively. The risk of psoriasis was higher in the PCOS group by an HR of 2.07 (95% confidence interval [CI] = 1.25–3.43) compared with the control group. In conclusion, the incidence of psoriasis in the PCOS group was higher than that in the control group. Further studies should be conducted to investigate the mechanism underlying the association, and to benefit the long-term management of patients with PCOS. Full article

Relevance: The clinical picture of polycystic ovary syndrome (PCOS) is extremely polymorphic, especially in adolescence. At the same time, the diagnostic criteria of PCOS in adolescence are still under discussion, and the hormonal parameters, including anti-Mullerian hormone range and hyperandrogenism, are not determined. The aim of the present study was to characterize the pivotal clinical and hormonal features of PCOS in adolescents and to establish the age-specific thresholds of the most essential hormonal parameters. Design: A case-control study. Methods: The study included 130 girls with PCOS according to the complete Rotterdam criteria, aged 15 to 17 years. The control group consisted of 30 healthy girls with a regular menstrual cycle of the same age. A complete clinical and laboratory examination, hormonal assays, and ultrasound of the pelvic organs were performed. The serums anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, prolactin, estradiol, 17α-OH progesterone (17α-OHP), androstenedione, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, and free androgen index (FAI) were analyzed. The diagnostic accuracy of AMH, FAI, LH/FSH, T, and androstenedione levels in predicting PCOS in adolescents was established using a logistic regression model and calculating area under the receiver operator characteristic (ROC) curve (AUC). Results: The serum levels of LH (9.0 (5.4–13.8) vs. 3.7 (2.5–4.7) IU/L; p < 0.0001), LH/FSH (1.6 (1.0–2.3) vs. 0.7 (0.5–1.1); p < 0.0001), 17α–OHP (4.1 (3.2–5.1) vs. 3.4 (2.7–3.8) nmol/L; p = 0.0071), cortisol (464.0 ± 147.6 vs. 284.0 ± 129.7 nmol/L; p < 0.0001), prolactin (266.0 (175.0–405.0) vs. 189.0 (142.0–269.0) mIU/L; p = 0.0141), T (1.9 (1.2–2.5) vs. 0.8 (0.7–1.1) nmol/L; p < 0.0001), androstenedione (15.8 (11.6–23.2) vs. 8.3 (6.5–10.8) ng/mL; p < 0.0001), AMH (9.5 (7.5–14.9) vs. 5.8 (3.8–6.9) ng/mL; p < 0.0001), FAI (5.5 (2.8–7.0) vs. 1.6 (1.1–2.3); p < 0.0001), SHBG (37.0 (24.7–55.5) vs. 52.9 (39.0–67.6) nmol/L; p = 0.0136), DHEAS (6.8 ± 3.2 vs. 5.1 ± 1.5 μmol/L; p = 0.0039), and leptin (38.7 ± 27.1 vs. 23.7 ± 14.0 ng/mL; p = 0.0178) were significantly altered in the PCOS patients compared to the controls. Multivariate analysis of all studied hormonal and instrumental parameters of PCOS in adolescents revealed as the most essential: AMH level > 7.20 ng/mL, FAI > 2.75, androstenedione > 11.45 ng/mL, total T > 1.15 nmol/L, LH/FSH ratio > 1.23, and the volume of each ovary > 10.70 cm³ (for each criterion sensitivity ≥ 75.0–93.0%, specificity ≥ 83.0–93.0%). The diagnostic accuracy of PCOS determination was 90.2–91.6% with the combined use of either four detected indexes, which was significantly higher than the use of each index separately. The accuracy of PCOS diagnostics reached 92% using AMH and leptin concentrations when the value of the logistic regression function [85.73 − (1.73 × AMH) − (0.12 × Leptin)] was less than 70.72. Conclusions: The results of the study estimate the threshold for AMH, FAI, androstenedione, testosterone, LH/FSH, and ovarian volume, which could be suggested for use in the PCOS diagnostics in adolescents with a high sensitivity and specificity. Moreover, the combination of either four determined indexes improved the diagnostic accuracy for the PCOS detection in adolescents. Full article

Intraovarian platelet-rich plasma (PRP) infusion was recently introduced in the context of addressing ovarian insufficiency. Reporting on its effectiveness prior to adopting in clinical routine practice is imperative. This study aims to provide pilot data regarding PRP application for ovarian rejuvenation. Four pilot studies were conducted on poor ovarian response (POR), premature ovarian insufficiency (POI), perimenopause, and menopause, respectively. Each pilot study reports on thirty patients, 120 participants were recruited in total. All participants provided written informed consent prior to treatment. Primary outcome measures for the POR pilot study were levels of anti-müllerian hormone (AMH), antral follicle count (AFC) and oocyte yield. For the POI, perimenopausal and menopausal pilot studies primary outcome measures were restoration of menstrual cycle, and Follicle Stimulating Hormone (FSH) levels. A significant improvement on the hormonal profile and the ovarian reserve status was noted, along with improved intracytoplasmic sperm injection (ICSI) cycle performance concerning POR participants. Menstruation recovery was observed in 18 out of 30 POI patients, along with a statistically significant improvement on levels of AMH, FSH, and AFC. Similarly, 13 out of 30 menopausal women positively responded to PRP treatment. Finally, menstruation regularity, improved hormonal levels and AFC were reported for 24 out of 30 perimenopausal women. To conclude, PRP infusion appears to convey promising results in addressing ovarian insufficiency. Full article

Relevance: Mitochondrial dysfunction and systemic inflammation are believed to play pivotal role in the pathogenesis of polycystic ovary syndrome (PCOS) and related complications of metabolic disorders in adult patients. Though such researches are limited or almost absent in adolescents. The aim of the study is to evaluate the impact of mitochondrial dysfunction and systemic inflammation on PCOS pathogenesis during adolescence with regard to body mass index and insulin resistance. Design: a case-control study. Methods: The study included 95 adolescent girls (15 to 17 years old inclusive) diagnosed with PCOS based on the Rotterdam criteria. The control group consisted of 30 healthy girls of the same age with a regular menstrual cycle. All participants were subjected to a full clinical and instrumental examination, as well as an assessment of the levels of leptin, C-reactive protein (CRP), and malondialdehyde (MDA) as oxidative stress marker. Serum levels of IL-6, IL-10, IL-18, TNF-α, and plasma concentrations of macrophage migration inhibitory factor (MIF), sFas, and sFasL were determined. Patients with PCOS were divided into groups according to the presence of metabolic disorders (MD) (impaired glucose tolerance and/or over insulin resistance) and normal weight or excessive weight (NW or OW). Results: Patients with PCOS of NW in the absence of metabolic disorders (MD−/NW) had a lower concentration of MDA and a higher level of IL-10 compared to healthy girls (p < 0.05). The group (MD−/NW) was characterized with lower levels of CRP, leptin, MDA, and higher levels of sFasL, when compared to OW patients with PCOS in the absence of metabolic disorders (MD−/OW) (p < 0.05). Overweight adolescent girls with PCOS and metabolic disorders (MD+/OW) showed higher CRP, leptin, and a two-fold increase in IL-6 and IL-18 concentrations compared to the control group of healthy girls (p < 0.05 for all parameters). The group (MD+/OW) was also characterized with higher levels of CRP, leptin, MDA, IL-18, MIF (p < 0.05), when compared to overweight patients with PCOS in the absence of metabolic disorders (MD−/NW). In comparison with the MD−/OW group, the obese insulin resistant girls with PCOS (MD+/OW) had a highera level of IL-18 (p < 0.05). Moreover, the MD+/OW girls demonstrated a significant increase in CRP, MDA and IL-18 levels when compared to the MD+/NW group (p < 0.05). OW girls with PCOS without MD (MD−/OW) had lower concentrations of sFasL compared to healthy girls (p < 0.05), and higher levels of MDA compared to MD+/NW (p < 0.05). Adolescent girls of NW with PCOS and with MD (MD+/NW) had lower levels of MDA compared to the control group of healthy girls (p < 0.05). These data are confirmed by a correlation analysis and two-factor ANOVA test. Conclusions: Lean girls with PCOS demonstrate the protective mechanism of decrease in oxidative stress mediated by the activation of antioxidant defense, reduction of lipid peroxidation and systemic inflammation. Excessive weight and metabolic disorders in adolescents with PCOS are the most significant factors in reducing the capacity of antioxidant systems, activation of oxidative stress, mitochondrial dysfunction, and systemic inflammation. Full article

Insulin resistance and hyperandrogenemia observed in polycystic ovary syndrome (PCOS) are associated with metabolic disturbances and could be connected with body composition pattern. To date, several studies defining the parameters of body composition using dual energy X-ray absorptiometry (DXA) method in the group of PCOS patients have been published, however, without the analysis in different phenotypes. The aim of the present study was to investigate the relationships between serum androgens concentration, insulin resistance and distribution of fat mass using DXA method in various PCOS phenotypes according to the Rotterdam criteria. We examined 146 women: 34 (38%) had PCOS phenotype A, 20 (23%) phenotype B, 20 (23%) phenotype C and 15 (16%) phenotype D (with mean age of each phenotype 25 years), and 57 control subjects (mean age of 25.5 years). Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Serum concentrations of testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEA-S) were assessed and free androgen index (FAI) was calculated. In phenotypes A, B and C, we observed higher FAI in comparison to the control group (all p < 0.01). Serum concentrations of androstenedione and DHEA-S were higher in phenotypes A and C in comparison to the control group (all p < 0.01). However, only in phenotype A we found higher visceral adipose tissue (VAT) mass and android/gynoid ratio (A/G ratio) in comparison to the control group (all p < 0.01). In phenotype A, we observed connection of VAT with FAI (r = 0.58, p < 0.01). Accordingly, A/G ratio was related with FAI in all phenotypes (all p < 0.05). Additionally, in phenotype C, A/G ratio was related to serum concentrations of DHEA-S and androstenedione (r = 0.46, p = 0.03; r = 0.53, p = 0.01, respectively). We also found connections of HOMA-IR with VAT and A/G ratio in all phenotypes (all p < 0.05). Women with phenotype A had higher amount of VAT and A/G ratio in comparison to the control group. Serum concentration of androgens and insulin resistance are connected with VAT and A/G ratio in normoandrogenic and hyperandrogenic PCOS phenotypes. Full article

Objectives: The aetiology of polycystic ovary syndrome (PCOS) is not particularly mapped; however, a complex interaction of various factors, such as genetic, environmental and intrauterine factors, can be assumed. Experimental animal studies and clinical observations support the hypothesis that developmental programming by excess intrauterine steroid is relevant. The aim of the study was to investigate whether mothers with and without PCOS exhibit different androgen and anti-Mullerian hormone (AMH) levels at the end of pregnancy and how maternal hormone levels are reflected in their offspring. Methods: Between March 2013 and December 2015, we performed a prospective cross-sectional study at the Medical University of Graz. We included 79 women with PCOS according to the ESHRE/ASRM 2003 definition and 354 women without PCOS, both with an ongoing pregnancy ≥37 + 0 weeks of gestation, who gave birth in our institution. Primary outcome parameters were the levels of maternal and neonatal androgens (testosterone, free testosterone, androstenedione) and AMH at delivery. Results: Androgen levels in female offspring of PCOS and non-PCOS women at birth did not differ, while maternal hormone levels differed significantly. Androgen levels in PCOS boys were significantly higher when compared to levels in PCOS girls. Discussion: Our findings do not support the hypothesis that maternal androgen excess contributes to elevated androgen concentrations in the female offspring. Nevertheless, the effects of the increased androgen concentrations in mothers on their offspring have to be investigated in future studies. Full article

To evaluate the incidence of endometriosis in polycystic ovary syndrome (PCOS) patients who did not present with any endometriosis symptoms and underwent laparoscopic ovarian drilling (LOD) for clomiphene citrate (CC) resistance, 225 and 630 women with CC-resistant PCOS without classic endometriosis symptoms were included in a retrospective study and a meta-analysis, respectively. All women underwent LOD. The main outcome parameter was the prevalence of incidental endometriosis. Laparoscopy revealed endometriosis in 38/225 (16.9%) women (revised American Fertility Society (rAFS) stage I: 33/38, 86.8%; rAFS stage II: 5/38, 13.2%). When women with CC-resistant PCOS without endometriosis were compared, lower body mass index (BMI) and lower 25-hydroxy-vitamin D levels were associated with the presence of endometriosis at laparoscopy (odds ratios (OR): 0.872, 95% confidence intervals (95%CI): 0.792–0.960; p = 0.005 and OR: 0.980, 95%CI: 0.962–0.999; p = 0.036; respectively). The inclusion criteria for the meta-analysis were fulfilled by 4/230 reports about LOD. After correction for study heterogeneity, the pooled prevalence of incidental endometriosis was 7.7% in women with CC-resistant PCOS. In conclusion, the rate of incidental endometriosis in women with CC-resistant PCOS might reflect the prevalence of asymptomatic endometriosis. All cases were affected by minimal or mild disease. Since the literature lacks reports on associated clinical outcomes, the relevance of this entity in such patients should be the subject of further studies. Full article

Polycystic ovary syndrome (PCOS) has reproductive and metabolic properties that may be linked to periodontitis (PD). This study aimed to update and render a robust critical assessment on all evidence linking PCOS and PD, and appraising a hypothetical bidirectional association. Five databases (PubMed, Scholar, EMBASE, Web of Science and CENTRAL) were searched up to May 2020. Case-control and cohort studies on the association of PCOS and PD were included. The risk of bias of observational studies was assessed through the Newcastle-Ottawa Scale (NOS). Random effects meta-analyses of standardized mean difference (SMD) and risk ratio (RR) were performed. We followed Strength of Recommendation Taxonomy (SORT) to appraise the strength and quality of the evidence. Twelve case-controls fulfilled the inclusion criteria (876 with PCOS and 48170 healthy controls), all scored as having a low risk of bias. Meta-analysis revealed that PCOS females have 28% more risk towards PD, and PD females have 46% more risk to have PCOS. PCOS females with PD had higher gum bleeding, periodontal pocket depth and clinical attachment loss than non-PCOS females with PD. Populations with undefined periodontal status contribute to underestimated results. On the basis of the available evidence, it is possible to assume a bidirectional link between PCOS and PD. That is, PCOS increases by 28% the risk of having PD and in the same fashion, PD increases by 46% the risk of having PCOS. Furthermore, women with PCOS were associated with worsening clinical characteristics and inflammation of PD. These findings suggest that PCOS and PD may be linked. Hence, further prospective and clinical trial studies with nonsurgical periodontal therapy are necessary to clarify the existence of an increased risk of PCOS in women with PD and vice-versa. Full article

Polycystic ovary syndrome (PCOS) is a complex disorder associated with ovarian dysfunction, infertility, menstrual irregularity, and hormonal impairments. Over the last decade, several studies have shown that some PCOS women have insulin resistance (InsR) and hyperinsulinemia, apart from being overweight or obese. Therefore, a crucial clinical aspect is that PCOS patients might develop glucose intolerance and type 2 diabetes. Insulin-sensitizing drugs have been used as first-line treatment to improve hyperinsulinemia in women with PCOS. Although reducing PCOS symptoms and signs, several used insulin-sensitizer drugs may induce side effects, which reduces compliance. D-chiro-inositol (DCI), which is a naturally occurring stereoisomer of inositol, has been classified as an insulin-sensitizer and seems to mitigate multiple InsR-related metabolic alterations in PCOS with a safe profile. However, according to a multi-targeted design, the supplementation with DCI can be synergistically integrated by combining other potential insulin-sensitizing drugs and/or nutraceuticals. The literature provides the initial support for using several unexplored nutraceutical interventions that may target relevant metabolic abnormalities associated with InsR in PCOS. With a need to promote interest in clinical research, this review aims to discuss the efficacy of DCI and the role of emerging nutraceuticals for managing InsR in PCOS. Full article