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Medicina (Kaunas, Lithuania) Jan 2024Polycystic ovary syndrome (PCOS) manifests a multifactorial pathology characterized by polycystic ovaries, menstrual cycle disorders, varying degrees of... (Review)
Review
Polycystic ovary syndrome (PCOS) manifests a multifactorial pathology characterized by polycystic ovaries, menstrual cycle disorders, varying degrees of hyperandrogenism, and an ad-verse metabolic risk profile. The position of hyperandrogenism in this syndrome has been extensively studied. A multitude of mechanisms place it in the position of cause but also of consequence; therefore, ongoing research efforts are focused on identifying medications that can effectively reduce levels of androgens in women with PCOS. Moreover, lipid abnormalities are common in this population, with up to 70% of patients having dyslipidemia. Statins may have potential therapeutic benefits for women with PCOS, as they have been shown to improve insulin resistance and reduce the risk of cardiovascular disease. In addition, their role in accelerated steroidogenesis by limiting one source of cholesterol, influencing enzymatic activity, and providing several other beneficial mechanisms is widely investigated. This review aimed to provide a comprehensive overview of the pathogenesis of androgen excess and dyslipidemia in PCOS, as well as the therapeutic potential of statins.
Topics: Humans; Female; Polycystic Ovary Syndrome; Hyperandrogenism; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin Resistance; Dyslipidemias
PubMed: 38399531
DOI: 10.3390/medicina60020244 -
Journal of Pediatric and Adolescent... Jun 2024The objective was to establish whether aspects of ovarian morphology correlate with reproductive and metabolic features during the first postmenarcheal year using data...
Ovarian Morphology in Girls Longitudinal Cohort Study: Pilot Evaluation of Ovarian Morphology as a Biomarker of Reproductive and Metabolic Features during the First Gynecological Year.
OBJECTIVE
The objective was to establish whether aspects of ovarian morphology correlate with reproductive and metabolic features during the first postmenarcheal year using data from the Ovarian Morphology in Girls (OMG!) cohort study. The feasibility of transabdominal ultrasonography to assess ovarian features was also determined.
METHODS
Healthy adolescent females enrolled in a prospective cohort study. Study visits occurred at 6-10, 11-13, 17-19, and 23-25 months postmenarche and entailed a physical exam, transabdominal ultrasound, and fasting blood draw. Participants maintained menstrual diaries throughout the study. The present analysis reflects participants who completed the study visit at 6-10 months postmenarche. Associations between ovarian morphology or average cycle length with reproductive and metabolic features were assessed by Spearman correlations and linear regression.
RESULTS
Forty participants enrolled in the OMG!
STUDY
Thirty-one participants initiated study procedures at 6-10 months postmenarche, and data were available for analysis for 29 participants. Image quality was judged as partially visible or excellent in 90% of the left and 78% of the right ovaries assessed, with all images collected having sufficient image quality to provide measurements of at least 1 ovarian marker. The follicle number per ovary and ovarian volume were positively associated with anti-Müllerian hormone levels and negatively associated with fasting insulin. The average cycle length was only associated negatively with triglycerides.
CONCLUSION
Transabdominal ultrasonography in the early postmenarcheal period provides sufficient resolution to enable estimations of antral follicle count and ovarian size. Ovarian features in early gynecological life may correspond with measures of reproductive and metabolic function.
Topics: Humans; Female; Ovary; Ultrasonography; Adolescent; Prospective Studies; Longitudinal Studies; Pilot Projects; Anti-Mullerian Hormone; Biomarkers; Ovarian Follicle; Insulin; Cohort Studies; Child
PubMed: 38395192
DOI: 10.1016/j.jpag.2024.02.004 -
Adult-type granulosa cell tumor associated with elevated luteinizing hormone: Two rare case reports.Medicine Feb 2024Adult-type granulosa cell tumors (AGCTs), which account for 2% to 5% of all malignant ovarian tumors, are rare sex cord-stromal tumors that usually secrete excess...
INTRODUCTION
Adult-type granulosa cell tumors (AGCTs), which account for 2% to 5% of all malignant ovarian tumors, are rare sex cord-stromal tumors that usually secrete excess estrogens, but they can also secrete androgens.
PATIENT CONCERNS
We report 2 patients of childbearing age with AGCT who presented with the complaint of abnormal menstruation and elevated luteinizing hormone (LH), and mildly elevated testosterone.
DIAGNOSIS
The ovarian tumors had hormonal activity.
INTERVENTIONS
The 2 patients underwent laparoscopic left adnexectomy. The second patient underwent 4 cycles of chemotherapy with paclitaxel and carboplatin as adjuvant treatments.
OUTCOMES
Their postoperative pathology confirmed AGCTs. Also, their menstrual cycle returned to normal, with normal serum LH and testosterone levels. There was no sign of recurrence.
CONCLUSION
The cases suggest that elevated serum LH levels may be a sign of unknown tumors in cases of oligomenorrhea or secondary amenorrhea. It is useful to evaluate the serum levels of inhibin B and anti-Müllerian hormone to improve the early recognition of ovarian granulosa cell tumors.
Topics: Adult; Female; Humans; Granulosa Cell Tumor; Luteinizing Hormone; Ovarian Neoplasms; Amenorrhea; Testosterone
PubMed: 38363935
DOI: 10.1097/MD.0000000000037069 -
Annales D'endocrinologie Apr 2024A high prevalence of increased DHEAS (dehydroepiandrosterone sulfate) levels (about a third of cases) has been reported in women with polycystic ovary syndrome (PCOS)....
INTRODUCTION
A high prevalence of increased DHEAS (dehydroepiandrosterone sulfate) levels (about a third of cases) has been reported in women with polycystic ovary syndrome (PCOS). This excess of adrenal androgens remains a mystery in this ovarian pathology. It is well known that DHEAS production correlates negatively with age, and study populations of women with PCOS are generally young. To avoid this bias, a study was carried out on a large population of women with PCOS and control women, using normal DHEAS values for each age group, to better assess prevalence and better understand the link between PCOS and DHEAS.
METHODS
A retrospective cross-sectional study was conducted at the Lille University Hospital. A total of 1223 patients with PCOS according to the Rotterdam criteria and 517 control women were included. DHEAS elevation was diagnosed according to the standards of the Lille University Hospital Institute of Biochemistry and Molecular Biology, based on patient age. The prevalence of increased serum DHEAS levels was calculated in each population and according to PCOS phenotype. Correlations were assessed between serum DHEAS levels and clinical, hormonal, and metabolic markers, with adjustment for age.
RESULTS
Prevalence of increased DHEAS was significantly higher in the PCOS group than in the control group (8.1 vs. 4.3%; OR=1.98 (95%CI: 1.23-3.19), P=0.005, and OR=1.07 (95%CI: 1.05-1.09), P=0.014 without and with adjustment for BMI respectively), and in phenotypes A and C than in controls (OR=2.88 (95%CI: 1.76 to 4.72), P<0.001 and OR=2.81 (95%CI: 1.39 to 5.67), P=0.004 respectively), but not in phenotype D. A correlation was found between DHEAS level and total testosteronemia (r=0.34, P<0.001), androstenedione (r=0.24, P<0.001), 17 hydroxyprogesteronemia (r=0.22, P<0.001) and age (r=0.25, P<0.001). No correlations were found with AMH, LH or FSH, and a very weak positive correlation was found with BMI (r=0.15; P<0.001).
CONCLUSION
Using age-dependent norms, DHEAS elevation was found in only 8.1% of women with PCOS (11% in the case of phenotypes A and C) versus 4.3% in controls and women with phenotype D. DHEAS levels correlated only with other androgens, and not (or only minimally) with other ovarian, pituitary or metabolic markers. DHEAS assay therefore appears to be of no interest for positive diagnosis or understanding of the pathophysiology of PCOS, except in case of very high testosterone levels.
Topics: Female; Humans; Polycystic Ovary Syndrome; Retrospective Studies; Cross-Sectional Studies; Androgens; Testosterone
PubMed: 38360397
DOI: 10.1016/j.ando.2024.01.011 -
European Journal of Obstetrics,... Apr 2024To explore the distribution of Rotterdam-based PCOS phenotypes and their associations with anthropometric parameters predictive of cardiometabolic risks in Ukrainian...
OBJECTIVE
To explore the distribution of Rotterdam-based PCOS phenotypes and their associations with anthropometric parameters predictive of cardiometabolic risks in Ukrainian referral PCOS women.
STUDY DESIGN
It was a cross-sectional study conducted by the Ukrainian Society of Gynecological Endocrinology between September 2021 and January 2022 involving 42 clinics in 10 regional centres representing the major geographical parts of Ukraine. Two hundred obstetrician-gynecologists whose practice facilities corresponded to study criteria were committed to entering records of their PCOS patients aged 20-45 years into the uniform data collection forms. The recorded parameters were: PCOS phenotype with the mandatory assessment of biochemical hyperandrogenism, age, BMI, waist circumference, and hyperandrogenism symptoms.
RESULTS
5254 patients' records were completed. Phenotype A was the most prevalent - 47.7 %, phenotypes B, C, and D were almost equally distributed in the studied population: 17.6 %, 17.4 %, and 17.3 % respectively. The total prevalence of androgenic phenotypes based on the presence of biochemical hyperandrogenism was 82.7 %. The incidence of obesity and hyperandrogenism symptoms, and mean BMI values were higher in phenotypes A and B compared to C and D. At the same time, the presence of 34.1 % and 46.2 % of normal-weight subjects in phenotypes A and B respectively, supports the fact that the excessive BMI is not a universal characteristic of androgenic phenotypes. In younger age groups, phenotypes C and D demonstrated the predominance of normal weight, but in older subgroups, the situation changed: in the age group of 36-45 y.o. compared to 18-25 y.o., the percentage of overweight and obese subjects for the non-classic phenotypes increased more than for the classic ones: C (OR = 3.91, 95 % CI: 2.41-6.38), D (OR = 4.14, 95 % CI: 2.64-6.52), A (OR = 2.30, 95 % CI:1.72-2.08), and B (OR = 2.56, 95 % CI:1.69-3.89).
CONCLUSIONS
In thoroughly assessed Ukrainian referral PCOS population the classic phenotypes prevailed as in other clinical cohorts. The classic phenotypes were characterized by the higher rate of adiposity and severity of clinical hyperandrogenism. At the same time, obese, overweight, and normal-weight subjects were present in all phenotypes, and the risk of obesity in non-classic phenotypes was higher in older age groups.
Topics: Humans; Female; Aged; Adult; Middle Aged; Polycystic Ovary Syndrome; Hyperandrogenism; Cross-Sectional Studies; Overweight; Ukraine; Androgens; Phenotype; Obesity
PubMed: 38354601
DOI: 10.1016/j.ejogrb.2024.02.011 -
Journal of Endocrinological... Feb 2024Postmenopausal hyperandrogenism is a rare condition that requires identifying those women bearing a life-threatening tumor. We aimed to study diagnostic work-up and...
PURPOSE
Postmenopausal hyperandrogenism is a rare condition that requires identifying those women bearing a life-threatening tumor. We aimed to study diagnostic work-up and management of postmenopausal androgen excess, proposing an algorithm for clinical decision supporting.
METHODS
We conducted an observational cross-sectional study and longitudinal follow-up including 51 consecutive menopausal patients reported for hyperandrogenism between 2003 and 2023 to our clinics. We assessed diagnostic testing accuracy and performance by receiver operating characteristic curves, their respective areas under the curve (AUC), and 95% confidence intervals (95%CI), for distinguishing between benign and malignant conditions, and androgen excess source.
RESULTS
Most commonly, postmenopausal hyperandrogenism derived from benign conditions such as ovarian hyperthecosis (n = 9). However, four (8%) patients had borderline/malignant tumors arising at the ovaries (n = 3) or adrenals (n = 1). These latter were more likely to develop virilization than those with benign disorders [specificity(95%CI)]: 0.87 (0.69; 0.92)]. Circulating total testosterone [AUC(95%CI): 0.899 (0.795; 1.000)] and estradiol [AUC(95%CI): 0.912 (0.812; 1.000)] concentrations showed good performances for discriminating between both conditions. Transvaginal-ultrasonography found two out of three potentially malignant ovarian neoplasms, and another was apparent on a pelvic computed tomography scan. An adrenal computed tomography scan also located an androgen-secreting carcinoma.
CONCLUSIONS
Clinical or biochemical features of an aggressive androgen-secreting tumor should lead to urgently obtaining a targeted imaging. At first, an abdominal-pelvic CT scan represents the best choice to perceive adrenal malignancy, and may identify aggressive ovarian tumors. When warning signs are lacking, a calm and orderly work-up allows properly addressing the diagnostic challenge of postmenopausal hyperandrogenism.
PubMed: 38349517
DOI: 10.1007/s40618-023-02297-9 -
Journal of Neuroendocrinology Mar 2024Excess levels of circulating androgens during prenatal or peripubertal development are an important cause of polycystic ovary syndrome (PCOS), with the brain being a key...
Excess levels of circulating androgens during prenatal or peripubertal development are an important cause of polycystic ovary syndrome (PCOS), with the brain being a key target. Approximately half of the women diagnosed with PCOS also experience metabolic syndrome; common features including obesity, insulin resistance and hyperinsulinemia. Although a large amount of clinical and preclinical evidence has confirmed this relationship between androgens and the reproductive and metabolic features of PCOS, the mechanisms by which androgens cause this dysregulation are unknown. Neuron-specific androgen receptor knockout alleviates some PCOS-like features in a peripubertal dihydrotestosterone (DHT) mouse model, but the specific neuronal populations mediating these effects are undefined. A candidate population is the agouti-related peptide (AgRP)-expressing neurons, which are important for both reproductive and metabolic function. We used a well-characterised peripubertal androgenized mouse model and Cre-loxP transgenics to investigate whether deleting androgen receptors specifically from AgRP neurons can alleviate the induced reproductive and metabolic dysregulation. Androgen receptors were co-expressed in 66% of AgRP neurons in control mice, but only in <2% of AgRP neurons in knockout mice. The number of AgRP neurons was not altered by the treatments. Only 20% of androgen receptor knockout mice showed rescue of DHT-induced androgen-induced anovulation and acyclicity. Furthermore, androgen receptor knockout did not rescue metabolic dysfunction (body weight, adiposity or glucose and insulin tolerance). While we cannot rule out developmental compensation in our model, these results suggest peripubertal androgen excess does not markedly influence Agrp expression and does not dysregulate reproductive and metabolic function through direct actions of androgens onto AgRP neurons.
Topics: Animals; Female; Humans; Mice; Pregnancy; Agouti-Related Protein; Androgens; Dihydrotestosterone; Mice, Knockout; Neurons; Obesity; Peptides; Polycystic Ovary Syndrome; Receptors, Androgen; Virilism
PubMed: 38344844
DOI: 10.1111/jne.13370 -
Leader vs follower in the tango of polycystic ovary syndrome: Insulin resistance vs androgen excess.Acta Obstetricia Et Gynecologica... Feb 2024
PubMed: 38339869
DOI: 10.1111/aogs.14802 -
Molecules (Basel, Switzerland) Jan 2024Floating wheat is a classical herbal with potential efficacy in the treatment of hyperhidrosis. Aiming at revealing the main components and potential mechanisms of...
Floating wheat is a classical herbal with potential efficacy in the treatment of hyperhidrosis. Aiming at revealing the main components and potential mechanisms of floating wheat, a comprehensive and unique phytopharmacology profile study was carried out. First, common wheat was used as a control to look for chemical markers of floating wheat. In the screening analysis, a total of 180 shared compounds were characterized in common wheat and floating wheat, respectively. The results showed that floating wheat and common wheat contain similar types of compounds. In addition, in non-targeted metabolomic analysis, when taking the contents of the constituents into account, it was found that there indeed existed quite a difference between floating wheat and common wheat and 17 potential biomarkers for floating wheat. Meanwhile, a total of seven components targeted for hyperhidrosis were screened out based on network pharmacology. Seven key differential components were screened, among which kaempferol, asiatic acid, sclareol, enoxolone, and secoisolariciresinol had higher degree values than the others. The analysis of interacting genes revealed three key genes, namely, MAP2K1, ESR1, and ESR2. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses showed that various signaling pathways were involved. Prolactin signaling, thyroid cancer, endocrine resistance, gonadotropin secretion, and estrogen signaling pathways were the main pathways of the intervention of floating wheat in excessive sweating, which was associated with the estrogenic response, hormone receptor binding, androgen metabolism, apoptosis, cancer, and many other biological processes. Molecular docking showed that the screened key components could form good bindings with the target proteins through intermolecular forces. This study reveals the active ingredients and potential molecular mechanism of floating wheat in the treatment of hyperhidrosis and provides a reference for subsequent basic research.
Topics: Triticum; Network Pharmacology; Antiperspirants; Molecular Docking Simulation; Hyperhidrosis; Drugs, Chinese Herbal; Medicine, Chinese Traditional
PubMed: 38338298
DOI: 10.3390/molecules29030553 -
JCEM Case Reports Feb 2024
PubMed: 38322546
DOI: 10.1210/jcemcr/luae012