Research Progress on the Mechanism Between Polycystic Ovary Syndrome and Abnormal Endometrium

As a highly dynamic tissue, the endometrium is periodically shed in response to the secretion of estrogen and progesterone. After menarche, the endometrium of healthy women proliferates and differentiates under the action of steroid hormones (e.g., 17β-estradiol and progesterone) that are secreted by the ovaries to provide appropriate conditions for embryo implantation. Polycystic ovary syndrome (PCOS), a prevalent endocrine and metabolic disorder in reproductive-aged women, is usually associated with multiple cysts within the ovaries and excess levels of androgen and is characterized by hirsutism, acne, menstrual irregularity, infertility, and increased risk of insulin resistance. Multiple factors, such as anovulation, endocrine-metabolic abnormalities, and inflammation, can disrupt the endometrium in PCOS patients and can lead to endometrial hyperplasia, pregnancy complications, or even cancer. Despite many recent studies, the relationship between PCOS and abnormal endometrial function is still not fully understood. In this review, we investigate the correlation of PCOS patient endometrium with anovulation, hyperandrogenemia, insulin resistance, progesterone resistance, and inflammatory cytokines, aiming to provide a theoretical basis for the treatment of disorders caused by endometrial dysfunction in PCOS patients.

Metformin abrogates pathological TNF-α-producing B cells through mTOR-dependent metabolic reprogramming in polycystic ovary syndrome

B cells contribute to the pathogenesis of polycystic ovary syndrome (PCOS). Clinically, metformin is used to treat PCOS, but it is unclear whether metformin exerts its therapeutic effect by regulating B cells. Here, we showed that the expression level of TNF-α in peripheral blood B cells from PCOS patient was increased. Metformin used in vitro and in vivo was able to reduce the production of TNF-α in B cells from PCOS patient. Administration of metformin improved mouse PCOS phenotypes induced by dehydroepiandrosterone (DHEA) and also inhibited TNF-α expression in splenic B cells. Further, metformin induced metabolic reprogramming of B cells in PCOS patients, including the alteration in mitochondrial morphology, the decrease in mitochondrial membrane potential, ROS production and glucose uptake. In DHEA-induced mouse PCOS model, metformin altered metabolic intermediates in splenic B cells. Moreover, the inhibition of TNF-α expression and metabolic reprogramming in B cells of PCOS patients and mouse model by metformin were associated with decreased mTOR phosphorylation. Together, TNF-α-producing B cells are involved in the pathogenesis of PCOS, and metformin inhibits mTOR phosphorylation and affects metabolic reprogramming, thereby inhibiting TNF-α expression in B cells, which may be a new mechanism of metformin in the treatment of PCOS.

CLINICAL, METABOLIC, ENDOCRINE AND SONOGRAPHIC CHARACTERISTICS OF OBESE ADOLESCENT WITH PCOS

Introduction- PCOS is a complex metabolic, endocrinopathy and reproductive disorder that results in the production of androgens and is associated with insulin resistance. Adolescents with PCOS are more obese than normal adolescents and have an increased risk of metabolic syndrome. In obese adolescent increasing abdominal adiposity, worsening insulin sensitivity and Dyslipoproteinemiadyslipoproteinemia give rise to NAFLD in adulthood. This study aimed to investigate the association between PCOS, obesity, NAFLD and Metabolic syndrome in adolescents with PCOS. MATERIALAND METHOD- Retrospective study of 24 obese adolescent PCOS patients. with mean BMI 32.89 kg/m2. Data were taken from 1st January 2015 to 31st December 2020. PCOS patients were diagnosed according to Rotterdam 2003 criteria. Data were collected from the medical records of the patients including clinical history, height, weight, blood pressure, waist circumference and Modied Ferriman-Gallway score for hirsutism. Laboratory values were obtained ultrasound nding of polycystic ovarian disease and fatty liver were obtained from the records. RESULTS:- 2 In our study, the mean age was 15.2 yr The mean body mass index was 32.89 kg/m and the mean age of menarche was 12.3 yr. Hirsutism was present in 75% by modied FG Score system, Family history of PCOS was present in 29.16%, Family history of Cardiovascular disease was present in 12.5%. Afamily history of diabetes mellitus was present in 20.83%. The majority 87.5% of the obese adolescent girl's were presented with menstrual problems. mostly 70.83% with a history of Oligomenorrhea. Waist circumference, >0.80 was present in 87.5%, 50% of patients were hypertensive. 20.83% were prediabetes, 54.16% of patients were found to have dyslipidaemia and 45.83% of patients had Metabolic syndrome. In our mean LH was 10.6 IU/L, mean FSH was 5.8 IU/L, mean Serum testosterone 18.5 ng/ml, mean Serum prolactin was 21.2 ng/mL and mean Serum TSH was 3.3 µIU/mL.75 % of patients had Polycystic appearing ovarian morphology in USG.45.83 % of obese PCOS patient had NAFLD in USG and 33.33% of obese patients had abnormal liver enzymes with NAFLD in USG nding. CONCLUSION:-In our study, we found both metabolic syndrome and NAFLD were frequent in patients with obese adolescent PCOS conrming a relevant clinical association between these three conditions. This study highlights the importance of preventing obesity during the management of adolescent PCOS. The importance of obesity counselling in obese adolescent women is a must to reduce the risks associated with metabolic syndrome. The therapeutic intervention combined with lifestyle modication may provide better treatment for adolescent PCOS.

MANAGEMENT OF INFERTILITY DUE TO PCOS BY AYURVEDIC REGIME: A CASE REPORT

Polycystic ovarian Syndrome (PCOS) otherwise known as Stein Leventhal Syndrome is known to be the most common endocrine disorder in a woman of reproductive age and leading cause of infertility nowadays. World Health Organization (WHO) has estimated that there are one out of forty newly reported cases of PCOS worldwide. Here is case study of a 27 years old female patient residing in Jaipur who consulted in OPD of National Institute of Ayurveda (NIA) Jaipur on 10.05.2019 with the chief complaints of unable to conceive since 2 years, delayed and scanty menstruation since 11/2 year. The patient was having history of depression and had antidepressants for 1 year. Her Ultrasonography findings were suggestive of PCOS. Patient was treated with Brahmi Ghrita orally with milk for 3 cycles. Go Ghrita Matra Basti for 2 cycles with proper counselling before and during the treatment as patient was a K/C/O depression. Patient missed her periods on 20.09.2019 and did her UPT which was found to be positive. Adequate antenatal care with all necessary examinations and advises was given to her and she delivered a full-term female baby on 18.06.2020. From this case study it is concluded that Brahmi ghrita and Go Ghrita Matra Basti are effective in treating Infertility due to POCS.

Anti-Mullerian Hormone as A Diagnostic Tool for PCOS Patient : Study in a Tertiary Level Hospital

Polycystic ovary syndrome (PCOS) is a frequently encountered problem affecting 6-11% women of reproductive age.1 Purpose of the study was to determine whether serum AMH level can be used to diagnose PCOS. Methods: It was a cross sectional study conducted among 55 sub-fertile women of reproductive age (18-35 year) in a tertiary level hospital during the period of January 2018 to December 2018. The study subjects were divided into group I (PCOS patient with subfertility by Rotterdam Criteria 2003) and group II (non PCOS subfertile patients of reproductive age). Menstrual history, obstetrical history, physical examination, clinical assessment of androgenesis, ovarian ultrasound assessment and level of AMH, FSH, LH were collected. Result: Twenty five PCOS & 30 non PCOS sub-fertile patients were recruited. Mean age in PCOS & non PCOS were 25.24±4.03 years and 27.8±5.01 years respectively. The mean serum AMH in PCOS was 11.03±3.78 ng/ml and in non PCOS was 3.93±1.92 ng/ml, their difference was statistically significant. Conclusion: AMH can be used as a diagnostic aid for PCOS. J Shaheed Suhrawardy Med Coll, December 2019, Vol.11(2); 142-146

Difference of Cyclooxygenase-2 (COX2) Expression in Endometrium Between Patients with Polycystic Ovary Syndrome (PCOS) and Fertile Women

Objective: The study was conducted to determine whether there were differences in COX-2 expression in endometrial women with PCOS compared to fertile women. Methods: This study is a case-control study investigating the relationship between exposure (research factors) and disease, by comparing case group and control group based on their exposure status. The samples of this study were infertile polycystic ovary syndrome patients who were treated at the Sekar Fertility Clinic in Dr. Moewardi Hospital Surakarta, and fertile women seeking treatment at Dr. Moewardi Hospital Surakarta. The number of samples were 60 subjects consisting of 30 PCOS patients and 30 fertile women. The expression of COX-2 in endometrial biopsy LH + 5 until LH + 10 which meet the inclusion with Rotterdam criteria and exclusion criteria was checked by immunohistochemistry. The data was analyzed using the Mann-Whitney test. Results: The mean COX-2 expression in PCOS (10.83 ± 5.35) in fertile women (37.00 ± 7.76), p = 0.005. Regression test of COX-2 by adjusting external variables (occupation, age, education, menstrual disorders, familial history, menstrual cycle, menarche, obesity, contraception history) shows also higher expression in PCOS patient with OR = -7.063; CI = 0.462–108.066; p = 0.160. Conclusion: COX-2 expression in endometrium of women with PCOS is lower than it is in fertile women.

Letrozole or Clomiphene Citrate for Induction of Ovulation in Patients with Polycystic Ovarian Syndrome: A Prospective Randomized Trial

Polycystic Ovarian Syndrome (PCOS) is the most common endocrine disorder responsible for subfertility in young women. The aim of the study was to compare the efficacy of Letrozole over Clomiphene citrate (CC) for ovulation induction in patients with PCOS. It was a prospective randomized trial in a private practice setting. The study period was 3 years, which includes 240 sub fertile patients with PCOS. Patients were divided into two groups. Group-A: 120 patients got Letrozole (2.5 mg) tab, 2 tabs once daily from D2-D6 for 3 cycles. Group-B: 120 patients took tab. Clomiphene citrate (50mg), 2 tabs once daily from D2-D6 for 3 cycles. Trans-vaginal ultrasound was done on D12-D13 to document number of follicles, measurement of dominant follicle and endometrial thickness. Ovulation and pregnancy rate was measured. Results showed that Letrozole have significantly better effect on endometrial thickness (Let 9.2 mm vs CC 8.1mm) and pregnancy rate (Let 44% vs CC 24%). In CC, multiple follicles were found (CC 44% vs Let 30%). Ovulation occurred in 65% with Letrozole group and 64% in CC group without a significant statistical difference. The study concluded that Letrozole have better effect for induction of ovulation in PCOS patient in comparison to CC. Faridpur Med. Coll. J. Jul 2018;13(2): 78-81

Triglycerides, independent of Ferriman Gallwey Score, is a main determinant of free testosterone index in PCOS

Background: Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, affecting 5-20% of women worldwide. Hyperandrogenism, as the primary characteristic of PCOS, is not always present in every patient. The hyperandrogenic phenotype of PCOS patients is influenced by both hormonal and metabolic dysfunctions. Therefore, this study aims to determine the correlation between hormone profile, lipid profile, and clinical profile with free testosterone index in subjects with PCOS. Methods: This prospective cross-sectional study was conducted in the Dr. Cipto Mangunkusumo General Hospital between July 2014 and December 2016. The study involved 76 women with PCOS, who were classified into 2 subgroups: 39 subjects in the hyperandrogenism group and 37 subjects in the non-hyperandrogenism group. Each subject underwent physical examination, blood sample collection, and USG examination. Bivariate analysis was done using independent t-tests and Mann Whitney U-tests, while multivariate analysis was done using logistic regression. Results: Triglyceride and testosterone level showed weak (r = 0.232, p = 0.044) and moderate (r = 0.460, p ¡ 0.001) positive correlation with FTI, while SHBG level showed moderate negative correlation (r = -0.483, p ¡ 0.001). Triglyceride was also found to be determinant of hyperandrogenism condition in PCOS patient (OR 0.02, 95% CI 0.00–0.04, p = 0.013). However, there was no significant difference observed between FGS and hyperandrogenism (p = 0.43). Conclusions: Triglycerides, testosterone, and SHBG were associated with hyperandrogenism in PCOS patients, while FGS showed no such association.

PCOS and Hyperprolactinemia: what do we know in 2019?

Polycystic ovary syndrome (PCOS) and hyperprolactinemia (HPRL) are the two most common etiologies of anovulation in women. Since the 1950s, some authors think that there is a pathophysiological link between PCOS and HPRL. Since then, many authors have speculated about the link between these two endocrine entities, but no hypothesis proposed so far could ever be confirmed. Furthermore, PCOS and HPRL are frequent endocrine diseases and a fortuitous association cannot be excluded. The evolution of knowledge about PCOS and HPRL shows that studies conducted before the 2000s are obsolete given current knowledge. Indeed, most of the studies were conducted before consensual diagnosis criteria of PCOS and included small numbers of patients. In addition, the investigation of HPRL in these studies relied on obsolete methods and did not look for the presence of macroprolactinemia. It is therefore possible that HPRL that has been attributed to PCOS corresponded in fact to macroprolactinemia or to pituitary microadenomas of small sizes that could not be detected with the imaging methods of the time. Recent studies that have conducted a rigorous etiological investigation show that HPRL found in PCOS correspond either to non-permanent increase of prolactin levels, to macroprolactinemia or to other etiologies. None of this recent study found HPRL related to PCOS in these patients. Thus, the link between PCOS and HPRL seems to be more of a myth than a well-established medical reality and we believe that the discovery of an HPRL in a PCOS patient needs a standard etiological investigation of HPRL.