Polycystic ovary syndrome (PCOS) is the most prevalent endocrine and metabolic disorder in premenopausal women, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Patients frequently present comorbidities, including obesity, insulin resistance, and impaired glucose and lipid metabolism. The diverse clinical presentation may mimic various endocrine disorders, making the diagnosis challenging in some clinical circumstances. Prolactin (PRL) is a recommended biomarker in the initial diagnostic workup to rule out hyperprolactinemia (HPRL). The traditional role of PRL is linked to lactation and the reproductive system. Recent research highlights PRL’s emerging role in metabolic homeostasis. PRL influences metabolism directly by interacting with the pancreas, liver, hypothalamus, and adipose tissue. Its influence on an individual’s metabolism is intricately tied to its serum concentration. While deficient and very high levels of PRL can negatively affect metabolism, intermediate–normal to moderately high levels may promote metabolic health. In women with PCOS, PRL levels may be altered. Research results on different aspects of the relationship between PCOS and the impact of various levels of PRL on metabolic homeostasis are limited and inconsistent. In this narrative literature review, we comprehensively examined data on serum PRL levels in PCOS patients. We investigated the correlation between a favorable metabolic profile and serum PRL levels in this population. Furthermore, we explored the concept of beneficial PRL effects on metabolism and discussed the potential therapeutic application of dopamine agonists in PCOS treatment. Lastly, we emphasized several promising avenues for future research in this field.

Prolactin in Polycystic Ovary Syndrome: Metabolic Effects and Therapeutic Prospects

Background: The literature provides limited evidence of cord blood leptin levels in gestational diabetes mellitus (GDM), with contradictory and inconsistent results with respect to their possible implications for maternal, perinatal, and future complications. Methods: MEDLINE/PubMed, Embase, Scopus, and Web of Science databases were searched in order to investigate the state of evidence on the association of leptin profile in cord blood during perinatal complications in GDM. We critically assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analyses were performed, and heterogeneity and publication bias were analyzed. Results: sixteen primary-level studies were included, recruiting 573 GDM and 1118 control pregnant women. Cord blood leptin levels were significantly higher in GDM participants compared to controls (standardized mean difference [SMD] = 0.59, 95% confidence intervals (CI) = 0.37 to 0.80, p < 0.001). All subgroups also maintained significant differences stratified by continents (Asia: SMD = 0.91, 95% CI = 0.45 to 1.37, p < 0.001; Europe: SMD = 0.38, 95% CI = 0.20 to 0.56, p < 0.001), analysis technique (ELISA: SMD = 0.70, 95% CI = 0.44 to 0.97, p < 0.001; RIA: SMD = 0.30, 95% CI = 0.11 to 0.49, p = 0.002), and sample source (plasma: SMD = 0.71, 95% CI = 0.33 to 1.09, p < 0.001; serum: SMD = 0.55, 95% CI = 0.34 to 0.77, p < 0.001). Conclusion: Cord blood leptin levels were significantly higher in GDM compared to controls. Further research is needed to clarify its role as a predictive biomarker of subsequent metabolic diseases in mothers with GDM and offspring.

Significance of Umbilical Cord Leptin Profile during Pregnancy in Gestational Diabetes Mellitus—A Systematic Review and Meta-Analysis

Background: Polycystic ovarian syndrome (PCOS) is a hyperandrogenic condition characterized by polycystic ovarian morphology and chronic oligo-anovulation.  When it is combines with hypothyroidism and hyperprolactinemia, this condition can have severe consequences, may even lead to infertility. 
Case Presentation: This case study illustrates the complexity of PCOS and the significance of a multidisciplinary approach to its diagnosis and therapy. The patient is a 24-year-old non diabetic nonsmoker female with PCOS who has been attempting to conceive for seven years. The patient presented to the hospital with irregular menstrual cycles and a desire to become pregnant. The patient had previously been unsuccessfully treated with Clomid and letrozole. The patient's BMI was determined to be 23. 3 and a pelvic scan indicated PCO ovaries. Laboratory results revealed hyperprolactinemia (53 ng/ml) and subclinical hypothyroidism (TSH 12.6 uIU/ml, T4 0.54 ng/dL- TPO antibodies:187 IU/mL, Anti thyroglobulin antibodies 235 IU/mL), but a pituitary gland MRI was normal. Thyroid US features going with Hashimoto thyroiditis. The patient's PCOS symptoms were initially managed with metformin and Duphaston, and then Cabergoline was introduced to address hyperprolactinemia. The patient became pregnant shortly following hyperprolactinemia medication. Prenatal screenings revealed elevated fasting glucose levels and gestational diabetes. The patient's blood sugar was initially controlled by Metformin, but she later required multiple insulin doses to maintain control.  The patient was scheduled for induction of labor at 38 weeks, but a lower segment emergency cesarean surgery was performed due to fetal distress. 
Conclusion: Regular monitoring and management of both PCOS and related conditions such as hypothyroidism and hyperprolactinemia are crucial to ensure the best outcome for the patient. Additionally, we suggest Metformin, Duphaston, Cabergoline to treat PCOS patient having subclinical hypothyroidism and hyperprolactinemia. 
Keywords: Polycystic ovarian syndrome, subclinical hypothyroidism, hyperprolactinemia, gestational diabetes.

/pdf/correlation-of-hyperprolactinemia-subclinical-hypothyroidism-3j6ziw8n.pdf

Correlation of hyperprolactinemia, Subclinical hypothyroidism with Polycystic Ovary Syndrome and infertility

Polycystic ovarian syndrome (PCOS) is a common heterogeneous condition with probably multifactorial genesis. Animal studies have proven the essential role of the sympathetic nervous system in the syndrome development, while human studies are still contradictory. The present study aims to investigate the possible influence of plasma-free metanephrine (MN), and normetanephrine (NMN), nerve growth factor (NGF), and renalase (RNL) on the hormonal and metabolic parameters in women with PCOS and healthy controls.Fifty patients with PCOS and 30 healthy women participated in the study. The plasma-free MN and NMN, NGF, RNL, anti-Mullerian hormone (AMH), gonadotropin, androgen levels, and metabolic parameters were investigated.Plasma-free NMN and NGF concentrations were increased in PCOS individuals, while RNL levels were decreased compared to healthy volunteers. Increased plasma-free NMN (OR = 1.0213 [95%CI 1.0064-1.0364], p = 0.005) and NGF (OR = 1.0078 [95%CI 1.0001-1.0155], p = 0.046) but not MN or RNL levels were associated with a higher risk of PCOS after adjustment for age. Plasma-free NMN levels were positively associated with the LH (r = +0.253; p = 0.039). androstenedione (r = +0.265; p = 0.029), 17-OH progesterone (r = +0.285; p = 0.024), NGF (r = +0.320; p = 0.008), and AMH (r = +0.417; p < 0.001) concentrations of the investigated women. RNL levels were inversely related to the BMI (r = -0.245; p = 0.029), HOMA-IR (r = -0.250; p = 0.030), free testosterone (r = -0.303; p = 0.006) levels. systolic (r = -0.294; p = 0.008) and diastolic (r = -0.342; p = 0.002) blood pressure.Increased sympathetic noradrenergic activity and NGF synthesis might be related to the increased AMH and delta-4 androgen levels in a subgroup of PCOS patients. RNL levels might influence the metabolic status of PCOS patients. Further studies are needed to explore the significance of adrenal medullar and autonomic dysfunction for developing different PCOS phenotypes and their subsequent cardiovascular complications. 

/pdf/plasma-free-metanephrines-nerve-growth-factor-and-renalase-3sqqfc7p.pdf

Plasma-free metanephrines, nerve growth factor, and renalase significance in patients with PCOS

Abstract Context To investigate how short sleep duration (SSD) during pregnancy is related to neurodevelopmental delays in offspring, we aimed to inform pregnancy sleep guidelines and promote maternal health and child development. Objective To identify the associations between SSD during pregnancy and offspring neurodevelopmental delay and to determine whether fetal glucose metabolism plays a role in SSD and neurodevelopmental delays. Methods This cohort study followed 7059 mother–child pairs from the Maternal &amp; Infants Health in Hefei cohort, and collected sleep data during pregnancy via the Pittsburgh Sleep Quality Index at weeks 24 to 28 and 32 to 36. Neurodevelopmental outcomes from 6 to 36 months postpartum were assessed via the Denver Developmental Screening Test-II and the Gesell Development Diagnosis Scale. Cox proportional hazard regression was used to analyze the link between maternal SSD and neurodevelopmental delay risk. Mediation analysis was used to evaluate the role of cord blood serum C-peptide levels. Three hospitals and children's health centers in Hefei were involved. Results The stratified analysis revealed a significant association between mothers with SSD during midpregnancy and neurodevelopmental delay in boys (adjusted HR 2.05, 95% CI 1.29, 3.25). Cord blood marker analysis revealed a positive relationship between cord blood serum C-peptide levels and neurodevelopmental delay in offspring (RR 0.04, 95% CI 0.00, 0.08). The proportion of the association between SSD and neurodevelopmental delay mediated by cord blood C-peptide was 11.05%. Conclusion Maternal SSD during pregnancy was continuously associated with an increased incidence of neurodevelopmental delay with sex differences among offspring. This association may be mediated in part by increased higher levels of cord C-peptide. 

Association of Maternal Short Sleep Duration With Neurodevelopmental Delay in Offspring: A Prospective Cohort Study

Women with polycystic ovary syndrome (PCOS) are reported to have different levels of prolactin (PRL) compared to women without PCOS. This study aimed to evaluate the PRL levels in women with PCOS, compared to the control group, before and after adjustment for potential confounders. Using a logical combination of keywords, a comprehensive search was carried out in PubMed and Web of Science, from inception to 30 August 2022. Weighted mean differences (WMDs) with corresponding 95% CIs in PRL levels were employed with a random-effects model. I2 was applied to evaluate heterogeneity among studies. A meta-regression analysis and subgroup analysis were conducted to explore heterogeneity sources. Publication bias was assessed by the Egger test. Thirty-two studies, measuring PRL levels in 8551 PCOS patients according to the Rotterdam criteria and 13,737 controls, were included in the meta-analysis. Pooled effect size suggested that the overall weighted mean difference (WMD) of PRL level was significantly higher in women with PCOS, compared to controls (WMD = 1.01, 95% CI: 0.04–1.98, p = 0.040). The result of meta-regression adjusted for age, BMI, and the continent of origin, revealed no confounding effect on results. Sub-group analysis of PRL levels according to the continent of origin showed significantly higher PRL levels among Eurasian PCOS patients compared to the control; this difference was not statistically significant in the subgroups of women from Asia, Europe, and South America. In conclusion, PRL levels in patients who were diagnosed according to the Rotterdam criteria were significantly higher than non-PCOS participants. Slightly higher levels of PRL could be presented as a diagnostic feature of PCOS.

/pdf/a-meta-analysis-of-observational-studies-on-prolactin-levels-1ohldo31.pdf

A Meta-Analysis of Observational Studies on Prolactin Levels in Women with Polycystic Ovary Syndrome

C-peptide offers potential as a marker to indicate childhood metabolic outcomes. Measuring C-peptide concentration might have better future utility in the risk stratification of neonates born to overweight or diabetic mothers. Prior research has tried to bring this matter into the light; however, the clinical significance of these associations is still far from reach. Here we sought to investigate the associations between fetomaternal metabolic variables and umbilical cord blood C-peptide concentration.For the present study, 858 pregnant women were randomly selected from among a sub-group of 35,430 Iranian pregnant women who participated in a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. Their umbilical cord (UC) blood C-peptide concentrations were measured, and the pregnancy variables of macrosomia/large for gestational age (LGA) and primary cesarean section (CS) delivery were assessed. The variation of C-peptide concentrations among GDM and macrosomia status was plotted. Due to the skewed distribution of C-peptide concentration in the sample, median regression analysis was used to identify potential factors related to UC C-peptide concentration.In the univariate model, positive GDM status was associated with a 0.3 (95% CI: 0.06 - 0.54, p = 0.01) increase in the median coefficient of UC blood C-peptide concentration. Moreover, one unit (kg) increase in the birth weight was associated with a 0.25 (95% CI: 0.03 - 0.47, p = 0.03) increase in the median coefficient of UC blood C-peptide concentration. In the multivariate model, after adjusting for maternal age, maternal BMI, and macrosomia status, the positive status of GDM and macrosomia were significantly associated with an increase in the median coefficient of UC blood C-peptide concentration (Coef.= 0.27, 95% CI: 0.13 - 0.42, p < 0.001; and Coef.= 0.34, 95% CI: 0.06 - 0.63, p = 0.02, respectively).UC blood concentration of C-peptide is significantly associated with the incidence of maternal GDM and neonatal macrosomia. Using stratification for maternal BMI and gestational weight gain (GWG) and investigating molecular markers like Leptin and IGF-1 in the future might lay the ground to better understand the link between metabolic disturbances of pregnancy and UC blood C-peptide concentration. 

/pdf/umbilical-cord-blood-concentration-of-connecting-peptide-c-1us2r4om.pdf

Umbilical cord blood concentration of connecting peptide (C-peptide) and pregnancy outcomes

Abstract Background Data is inconsistent and, for the most part, not sufficient to demonstrate the association between serum Prolactin (PRL) concentration within the physiologic range and the incidence rate of type 2 Diabetes Mellitus (DM) among men. Moreover, since both PRL and type 2 DM are associated with reproductive hormones, investigating these hormones might improve our understanding of how PRL might impose its effect on the incidence rate of type 2 DM. Methods For the present study, 652 eligible men aged 29–70 with a normal baseline PRL concentration were selected from the Tehran Lipid and Glucose Study (TLGS). Participants were sub-classified into three groups (tertiles) according to the serum concentration of PRL and were followed for 15.8 years. The incidence of type 2 DM and PRL, LH, FSH, testosterone, and AMH concentrations were measured. The effect of hormonal variables on the incidence of type 2 DM was estimated using the log-binomial model, adjusted for major confounding factors. The correlations between PRL and the indicators of glucose and lipid metabolism and other hormonal variables were also explored. Results In the unadjusted model, PRL was not significantly associated with the incidence rate of type 2 DM (RR = 0.98, 95% CI: 0.94 − 1.03). After adjusting for potential confounders, the inverse effect of AMH on the incidence rate of type 2 DM was the only significant association. The analyses also indicated a significant positive association between PRL and LH/FSH ratio ( r = 0.1, P = 0.01). Conclusion No significant association was found between serum PRL concentrations within the physiologic range and the incidence rate of type 2 diabetes mellitus among middle-aged men. Men with higher concentrations of PRL within the physiologic range tended to show higher levels of LH and LH/FSH. AMH was the only variable significantly linked to the incidence rate of type 2 DM in men. 

/pdf/the-effects-of-different-physiologic-concentrations-of-24o70mw5.pdf

The effects of different physiologic concentrations of prolactin in association with reproductive hormones on the incidence of type 2 diabetes mellitus in men: Tehran Lipid and Glucose Study

Comparison of the Effectiveness of Cognitive-behavioral Model Implementation by Peers and Nurses on Anxiety in Patients with Type 2 Diabetes

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A Meta-Analysis of Observational Studies on Prolactin Levels in Women with Polycystic Ovary Syndrome

Umbilical cord blood concentration of connecting peptide (C-peptide) and pregnancy outcomes

The effects of different physiologic concentrations of prolactin in association with reproductive hormones on the incidence of type 2 diabetes mellitus in men: Tehran Lipid and Glucose Study

Comparison of the Effectiveness of Cognitive-behavioral Model Implementation by Peers and Nurses on Anxiety in Patients with Type 2 Diabetes