An updated clinico-investigative approach to diagnosis of cutaneous hyperandrogenism in relation to adult female acne, female pattern alopecia & hirsutism a primer for dermatologists.

INTRODUCTION: Hyperandrogenism is a clinical state consequent to excess androgen production by the ovary, adrenals, or increased peripheral conversion of androgens. The varied manifestations of hyperandrogenism include seborrhea, acne, infertility, hirsutism, or overt virilization of which adult female acne, hirsutism, and female pattern hair loss are of clinical relevance to dermatologists. AREAS COVERED: We limited our narrative review to literature published during period from 1 January 1985 to Dec 2022 and searched PubMed/MEDLINE, Web of Science (WOS), Scopus, and Embase databases with main search keywords were 'Hyperandrogenism,' 'Female,' 'Biochemical,' 'Dermatological', and 'Dermatology.' We detail the common etiological causes, nuances in interpretation of biochemical tests and imaging tools, followed by an algorithmic approach which can help avoid extensive tests and diagnose the common causes of hyperandrogenism. EXPERT OPINION: Based on current data, total testosterone, sex hormone binding globulin, DHEAS, prolactin, free androgen index, and peripheral androgenic metabolites like 3-alpha diol and androsterone glucuronide are ideal tests though not all are required in all patients. Abnormalities in these biochemical investigations may require radiological examination for further clarification. Total testosterone levels can help delineate broadly the varied causes of hyperandrogenism. Serum AMH could be used for defining PCOM in adults.

Discriminatory Value of Steroid Hormones on Polycystic Ovary Syndrome and Clustering of Hyperandrogenism and Metabolic Factors.

OBJECTIVE: We determined (1) if 11-oxygenated androgens better identify polycystic ovary syndrome (PCOS) diagnosis in women with obesity compared to total or free testosterone (T) and free androgen index; (2) how biochemical hyperandrogenism and metabolic factors cluster in a cohort of women with infertility and obesity. METHODS: Women with obesity and PCOS comprised the study group (N = 132). Ovulatory women with obesity and idiopathic, tubal or male factor infertility were the control group (N = 83). Steroid hormones were measured by means of liquid chromatography tandem mass spectrometry. Receiver operating characteristic curves and principal component analysis were used. RESULTS: Women with obesity and PCOS had higher 11-ketotestosterone (11 KT) (1.22 nmol/L [0.84; 1.65] vs 1.05 [0.78; 1.35], P = .04) compared to controls, but not 11ß-hydroxyandrostenedione 4.30 [2.87; 5.92] vs 4.06 [3.22; 5.73], P = .44). 11-ketotestosterone (area under the curve: 0.59) did not better discriminate PCOS in women with obesity compared to: total T (0.84), free T (0.91), and free androgen index (0.85). We identified 4 principal components (PCs) in the PCOS group (72.1% explained variance): (1) insulin resistance status; (2) blood pressure; (3) obesity; (4) androgen status and 4 PCs in the control group (68.7% explained variance) with variables representing metabolism being dispersed in component 2, 3, and 4. CONCLUSIONS: Eleven-oxygenated androgens do not aid in the diagnosis of PCOS in women with obesity. Insulin resistance is the strongest PC in the PCOS group. There is no major dominant characteristic that defines obese non-PCOS women.

Combination of metformin with liraglutide in treating HAIR-AN syndrome in children: A case report and literature review. / 二甲双胍联合利拉鲁肽治疗儿童HAIR-AN综合征1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN) syndrome is a special and rare subtype of polycystic ovarian syndrome. It can lead to hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN) accompanied by acne, hirutism, irregular menstruation, and other androgen excess symptoms. A case of pediatric HAIR-AN syndrome with severe AN was admitted to the Department of Endocrinology, China-Japan Friendship Hospital. The patient's clinical manifestations, laboratory data, imaging features, and gene sequencing were analyzed, and the patient was diagnosed with pediatric HAIR-AN syndrome. Obesity, IR, hyperglycemia, menstrual disorder, and AN were significantly improved after treating with metformin and liraglutide. HAIR-AN syndrome occurs in various forms. When the patient appears unexplained acanthosis nigricans and menstrual disorders, the disease should be considered possible. Early diagnosis and symptomatic supportive treatment can improve the quality of life.

Polycystic Ovarian Syndrome: a Risk Factor for Cardiovascular Disease.

PURPOSE OF REVIEW: Characterize the risk of cardiovascular disease (CVD) in individuals with polycystic ovarian syndrome (PCOS). Review the pathophysiological pathways that confers CVD risk in individuals with PCOS and interventions to reduce CVD risk. RECENT FINDINGS: PCOS is a complex syndrome characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries that has metabolic and cardiovascular implications. Intrinsic hormonal dysregulation and chronic low-grade inflammation play an important role in the progression of atherosclerosis in young premenopausal individuals and development of CVD independently of associated traditional risk factors. Management with metformin reduces CVD risk by reducing atherosclerosis progression. PCOS is an important CVD risk factor among individuals of reproductive age. Early detection and interventions are needed to mitigate development of CVD.

Androgen excess: a hallmark of polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a metabolic, reproductive, and psychological disorder affecting 6-20% of reproductive women worldwide. However, there is still no cure for PCOS, and current treatments primarily alleviate its symptoms due to a poor understanding of its etiology. Compelling evidence suggests that hyperandrogenism is not just a primary feature of PCOS. Instead, it may be a causative factor for this condition. Thus, figuring out the mechanisms of androgen synthesis, conversion, and metabolism is relatively important. Traditionally, studies of androgen excess have largely focused on classical androgen, but in recent years, adrenal-derived 11-oxygenated androgen has also garnered interest. Herein, this Review aims to investigate the origins of androgen excess, androgen synthesis, how androgen receptor (AR) signaling mediates adverse PCOS traits, and the role of 11-oxygenated androgen in the pathophysiology of PCOS. In addition, it provides therapeutic strategies targeting hyperandrogenism in PCOS.

The Role of the Primary Care Physician in the Assessment and Management of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous female endocrine disorder with manifestations that span the hormonal, reproductive, metabolic, and psychological. Primary care physicians (PCPs), also known as family physicians or general practitioners, play a key role in the diagnosis, assessment, and management of PCOS. This article outlines the role of the PCP in the timely and accurate diagnosis, provision of information and education, lifestyle and weight management, and management of key features such as hyperandrogenism, irregular cycles, infertility, emotional well-being, and cardiometabolic risk. PCPs play an essential role as the point of first contact for women and adolescents with or at high risk of PCOS, providers of whole-person care and continuity of care, and coordinators of care within a multidisciplinary team. Optimal management of PCOS requires equitable access to primary care. There is a need for systemic approaches to addressing barriers to provision of quality primary care, such as poor remuneration of longer consultations and low awareness of evidence-based guidelines, to women and adolescents with PCOS.

Examination of newborn DNA methylation among women with polycystic ovary syndrome/hirsutism.

Research suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic modifications. Therefore, we assessed the associations of PCOS traits with neonatal DNA methylation (DNAm) using two independent cohorts. DNAm was measured in both cohorts using the Infinium MethylationEPIC array. Multivariable robust linear regression was used to determine associations of maternal PCOS exposure or preconception testosterone with methylation ß-values at each CpG probe and corrected for multiple testing by false-discovery rate (FDR). In the birth cohort, 12% (102/849) had a PCOS diagnosis (8.1% PCOS without hirsutism; 3.9% PCOS with hirsutism). Infants exposed to maternal PCOS with hirsutism compared to no PCOS had differential DNAm at cg02372539 [ß(SE): -0.080 (0.010); FDR p = 0.009], cg08471713 [ß(SE):0.077 (0.014); FDR p = 0.016] and cg17897916 [ß(SE):0.050 (0.009); FDR p = 0.009] with adjustment for maternal characteristics including pre-pregnancy BMI. PCOS with hirsutism was also associated with 8 differentially methylated regions (DMRs). PCOS without hirsutism was not associated with individual CpGs. In an independent preconception cohort, total testosterone concentrations were associated with 3 DMRs but not with individual CpGs, though the top quartile of testosterone compared to the lowest was marginally associated with increased DNAm at cg21472377 near an uncharacterized locus (FDR p = 0.09). Examination of these probes and DMRs indicate they may be under foetal genetic control. Overall, we found several associations among newborns exposed to PCOS, specifically when hirsutism was reported, and among newborns of women with relatively higher testosterone around conception.

Hyperandrogenism.

Hyperandrogenism is a common condition encountered by pediatric and adolescent physicians. Most girls with hyperandrogenism represent physiological pubertal variation; pathology may be present in a substantial minority. Systematic evaluation is essential to avoid unnecessary work-up in physiological causes while not missing pathological causes. Polycystic ovarian syndrome (PCOS), unexplained, persistent hyperandrogenism of ovarian origin, is the most common form in adolescent girls. The high prevalence of physiological peripubertal hirsutism, anovulation, and polycystic ovarian morphology results in mislabeling many girls as having the polycystic ovarian syndrome, a disorder with lifelong implications. The use of strict criteria of age-specific anovulation, hyperandrogenism, and duration is essential to reduce their stigmatization. The exclusion of secondary causes by screening tests (cortisol, thyroid profile, prolactin, and 17OHP) is essential before undertaking treatment for PCOS. Lifestyle measures, estrogen-progesterone preparations, antiandrogens, and metformin are the cornerstone of managing the disorder.

AMH as part of the diagnostic PCOS workup in large epidemiological studies.

OBJECTIVES: Previous studies have shown good correlation between polycystic ovarian morphology (PCOM) and serum anti-Müllerian hormone (AMH) levels. We evaluated the utility of AMH as a surrogate for PCOM as a part of the polycystic ovary syndrome (PCOS) diagnosis by describing how the use of different AMH cut-off values would change the prevalence of PCOS. METHODS: A general population-based birth cohort study. Anti-Müllerian hormone concentrations were measured from serum samples taken at age 31 years (n = 2917) using the electrochemiluminescence immunoassay (Elecsys). Anti-Müllerian hormone data were combined with data on oligo/amenorrhoea and hyperandrogenism to identify women with PCOS. RESULTS: The addition of AMH as a surrogate marker for PCOM increased the number of women fulfilling at least two PCOS features in accordance with the Rotterdam criteria. The prevalence of PCOS was 5.9% when using the AMH cut-off based on the 97.5% quartile (10.35 ng/mL) and 13.6% when using the recently proposed cut-off of 3.2 ng/mL. When using the latter cut-off value, the distribution of PCOS phenotypes A, B, C, and D was 23.9%, 4.7%, 36.6%, and 34.8%, respectively. Compared with the controls, all PCOS groups with different AMH concentration cut-offs showed significantly elevated testosterone (T), free androgen index (FAI), luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH) ratio, body mass index (BMI), waist circumference, and homoeostatic model assessment of insulin resistance (HOMA-IR) values, as well as significantly decreased sex hormone-binding globulin (SHBG) values. CONCLUSIONS: Anti-Müllerian hormone could be useful surrogate for PCOM in large data sets, where transvaginal ultrasound is not feasible, to aid the capturing of women with typical PCOS characteristics. Anti-Müllerian hormone measurement from archived samples enables retrospective PCOS diagnosis when combined with oligo/amenorrhoea or hyperandrogenism.

Association between lower urinary tract symptoms and polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to analyze the association between lower urinary tract symptoms and polycystic ovary syndrome. METHODS: A total of 180 women were enrolled in this prospective study. Demographic data, body mass index, waist circumference, modified Ferriman-Gallwey scores, biochemical parameters, ultrasonographic findings, and maximum urinary flow rate (Q max) were analyzed. In addition, the Beck Depression Inventory, Beck Anxiety Inventory, and Bristol Female Lower Urinary Tract Symptom Scored Form questionnaires were evaluated for each subject. RESULTS: The mean age of patients was calculated as 23.78±3.04 years, which was similar for both groups (p=0.340). Body mass index, waist circumference, Beck Depression Inventory, Beck Anxiety Inventory, Bristol Female Lower Urinary Tract Symptom Scored Form, and modified Ferriman-Gallwey scores were significantly higher in group 2 (p<<0.001). Hyperandrogenism, lipid profile, and glucose metabolism disorders were more frequent in group 2 (p<<0.05). Bladder capacity (Q max), bladder wall thickness, and post-void residual volume values were similar in both groups (p>>0.05). CONCLUSION: In our study, a close relationship was observed between polycystic ovary syndrome and lower urinary tract symptoms. In this context, we think that a detailed urinary system evaluation of women with polycystic ovary syndrome is extremely important.

A Model Combining Testosterone, Androstenedione and Free Testosterone Index Improved the Diagnostic Efficiency of Polycystic Ovary Syndrome.

OBJECTIVE: Hyperandrogenism is frequently observed in patients with polycystic ovary (PCO). The purpose of this study was to develop an easy-to-use tool for predicting polycystic ovary syndrome (PCOS) and to evaluate and compare the value of androstenedione (Andro) and other hormone indicators in the diagnosis of patients with hyperandrogenic PCOS. METHODS: This study included 139 women diagnosed with hyperandrogenic PCOS according to the Rotterdam criteria and 74 healthy control women from Shanghai Tenth People's Hospital. The serum hormone levels of the patients and controls were measured using a chemiluminescence immunoassay and incorporated for further analysis. RESULTS: Total testosterone (TT), Andro, dehydroepiandrosterone sulfate (DHEAS), and free androgen index (FAI) were significantly higher in the PCOS group than the control group. Further, Andro, follicle-stimulating hormone (FSH), luteinizing hormone (LH), TT, FAI, and LH/FSH in the hyperandrostenedione group were higher than the normal Andro group. The Youden index was the highest for Andro (0.65), with 81.82% sensitivity and 83.16% specificity. Correlation analysis showed that FSH, LH, TT, FAI, insulin sensitivity index, and LH/FSH were positively correlated with Andro, while fasting blood glucose and 2-hour postprandial blood glucose were negatively correlated with Andro. CONCLUSIONS: The model using Andro, TT, and FAI may help to identifying women with undiagnosed PCOS. Serum Andro is a meaningful biomarker for hyperandrogenism in PCOS patients and may further aid disease diagnosis.

Practical considerations for diagnosis and treatment of polycystic ovary syndrome in adolescence - distilling guidelines into clinical practice.

PURPOSE OF REVIEW: The diagnostic criteria for polycystic ovary syndrome (PCOS) in adults may overdiagnose PCOS in adolescents. Since 2015, three guidelines have developed adolescent-specific diagnostic criteria and treatment recommendations. In this review, we compare and contrast the recommendations to assist in the practical application to clinical practice. RECENT FINDINGS: The guidelines agree that hyperandrogenism with menstrual irregularity be diagnostic criteria for PCOS in adolescents yet have slight differences in how to diagnose hyperandrogenism and in the definition of menstrual irregularity. The diagnostic option of 'at risk for PCOS' is recommended for those girls presenting with criteria within 3 years of menarche or with hyperandrogenism without menstrual irregularity, with re-assessment later in adolescence. Lifestyle changes is first line treatment. Treatment with combined oral contraceptives or metformin is suggested, using patient characteristics and preferences to guide decision-making. SUMMARY: PCOS is associated with long term reproductive and metabolic complications and will present during adolescence. Yet, diagnostic features may overlap with normal adolescent physiology. The recent guidelines strove to develop criteria to accurately identify girls with PCOS allowing early surveillance and treatment yet avoid overdiagnosis of normal adolescents.

Oxytocin receptor (OXTR) is a risk gene for polycystic ovarian syndrome.

OBJECTIVE: Oxytocin (OXT) controls appetite, promotes diet-induced energy expenditure, and may protect against obesity. Furthermore, the oxytocin system controls ovarian follicle luteinization and steroidogenesis as well as adrenal steroidogenesis, which if impaired might lead to anovulation and hyperandrogenism, signs found in women with polycystic ovarian syndrome (PCOS). PCOS is a common complex endocrine disorder of reproductive-age women, and it often presents with impaired glucose metabolism, insulin resistance (IR), and type 2 diabetes (T2D). The oxytocin receptor gene (OXTR) may confer a risk for PCOS, conceivably through dysregulation of metabolism, ovarian follicle maturation, and ovarian and adrenal steroidogenesis. Therefore, we aimed to investigate whether OXTR variants confer risk for PCOS. SUBJECTS AND METHODS: In 212 Italian subjects with T2D and PCOS, we have analyzed 22 single nucleotide polymorphisms (SNPs) within the OXTR gene for linkage to and/or linkage disequilibrium (LD, i.e., association) with PCOS. We tested whether the significant risk variants were independent or part of an LD block. RESULTS: We found 5 independent variants significantly linked to/in LD with PCOS within the peninsular families. CONCLUSIONS: This is the first study to report OXTR as a novel risk gene in PCOS. Functional and replication studies are needed to confirm these results.

[Exploration of the clinical pathway for etiological diagnostics of androgen excess in female].

Androgen excess is a common endocrine and metabolic problem in clinical practice, which affects the health of women throughout their life cycle. Usually, its diagnosis and treatment need multidisciplinary cooperation. The etiological diagnosis of female hyperandrogenism should be based on the etiological characteristics at different ages and should be comprehensively evaluated from medical history, physical examination, determination of androgen and other endocrine hormones, functional tests, imaging, and genetic testing, etc. The general principle of androgen excess cause diagnosis is first to determine whether the patient has clinical and/or biochemical androgen excess, then determine whether she conforms to the diagnostic criteria of polycystic ovary syndrome (PCOS), and then determine whether it is a specific disease or not. Finally, mass spectrometry should be adopted for verifying the androgen levels in those without clear causes found to exclude pseudo-elevation, thus it can be diagnosed as idiopathic androgen excess. Exploring the clinical pathway for the etiological diagnosis of female hyperandrogenism has important reference significance for guiding the standardized and accurate diagnosis and treatment of female hyperandrogenism.

The interplay between androgens and the immune response in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a metabolic-reproductive-endocrine disorder that, while having a genetic component, is known to have a complex multifactorial etiology. As PCOS is a diagnosis of exclusion, standardized criteria have been developed for its diagnosis. The general consensus is that hyperandrogenism is the primary feature of PCOS and is associated with an array of physiological dysfunctions; excess androgens, for example, have been correlated with cytokine hypersecretion, adipocyte proliferation, and signaling pathway dysregulation. Another key feature of PCOS is insulin resistance, resulting in aberrant glucose and fatty acid metabolism. Additionally, the immune system plays a key role in PCOS. Hyperandrogenism stimulates some immune cells while it inhibits others, thereby disrupting the normal balance of immune cells and creating a state of chronic inflammation. This low-grade inflammation could contribute to infertility since it induces ovarian dysfunction. This dysregulated immune response in PCOS exhibits autoimmunity characteristics that require further investigation. This review paper examines the relationship between androgens and the immune response and how their malfunction contributes to PCOS.

Polycystic Ovary Syndrome: Common Questions and Answers.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of childbearing age. Its complex pathophysiology includes genetic and environmental factors that contribute to insulin resistance in patients with this disease. The diagnosis of PCOS is primarily clinical, based on the presence of at least two of the three Rotterdam criteria: oligoanovulation, hyperandrogenism, and polycystic ovaries on ultrasonography. PCOS is often associated with hirsutism, acne, anovulatory menstruation, dysglycemia, dyslipidemia, obesity, and increased risk of cardiovascular disease and hormone-sensitive malignancies (e.g., at least a twofold increased risk of endometrial cancer). Lifestyle modification, including caloric restriction and increased physical activity, is the foundation of therapy. Subsequent management decisions depend on the patient's desire for pregnancy. In patients who do not want to become pregnant, oral contraceptives are first-line therapy for menstrual irregularities and dermatologic complications such as hirsutism and acne. Antiandrogens such as spironolactone are often added to oral contraceptives as second-line agents. In patients who want to become pregnant, first-line therapy is letrozole for ovulation induction. Metformin added to lifestyle management is first-line therapy for patients with metabolic complications such as insulin resistance. Patients with PCOS are at increased risk of depression and obstructive sleep apnea, and screening is recommended.

Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is a complex, familial, polygenetic metabolic condition. The Rotterdam criteria are commonly used to diagnose PCOS. Lifestyle changes are the first-line treatment of PCOS. Treatment options for menstrual irregularities and hirsutism are based on the clinical goals and preferences of the patient. Along with treating the symptoms of PCOS, it is essential to screen and treat the comorbid conditions commonly associated with PCOS, including type 2 diabetes mellitus, obesity, nonalcoholic fatty liver disease, hyperlipidemia, obstructive sleep apnea, anxiety, depression, infertility, and vitamin D deficiency.

Prevalence of polycystic ovary syndrome under NIH criteria among the tenth-grade Chinese schoolgirls in Guangzhou area: a cross-sectional epidemiological survey.

BACKGROUND: Polycystic ovary syndrome (PCOS) is currently considered to have a peri-adolescence onset and continuously influence the reproductive and metabolic health of the patients, while the diagnostic criteria among adolescent population haven't been universally unified till now. This survey seeks to preliminarily evaluate the prevalence of PCOS in the tenth grade schoolgirls in Guangzhou area under NIH criteria and analyze the clinical features of adolescents with PCOS. METHODS: The cross-sectional epidemiological survey was carried out among the tenth grade schoolgirls in Guangzhou area by the method of cluster sampling. The contents of this survey included the questionnaire, physical exams and serum measurements. Until now, totally 1294 girls underwent this survey and 1095 serum samples were restored. 235 non-hirsute (mFG < 6), postmenarcheally 2-year girls were randomly selected as the control group, among which the cut-off value of biochemical hyperandrogenemia was set accordingly. The prevalence of PCOS among this population was preliminarily evaluated according to the NIH criteria. RESULTS: Along with the increase of gynecological age, the menstruations of girls was becoming more regular and the incidence of oligomenorrhea or amenorrhea was declining. Even among those who were less than 2 years after menarche, those whose menstrual cycle were longer than 90 days accounted for lower than 5%. The 95th percentile of mFG score was 6 among the girls who were < 2 years after menarche, and 5 among the girls who were > 2 years after menarche. Among the 235 healthy girls, the 95th percentile values of Testosterone (T), Free androgen index (FAI) and Androstenedione (A2) were 2.28 nmol/mL, 4.37, and 5.20 nmol/mL respectively. Based on the NIH criteria, the prevalence of PCOS in this survey was 3.86%. The prevalence of adolescent PCOS tend to slightly increase with age and gynecological age, but the difference was not statistically significant. The prevalence of PCOS among obese girls was markedly higher than that in lean girls. CONCLUSION: Based on the NIH criteria, the prevalence of PCOS among the tenth grade schoolgirls in Guangzhou area was 3.86%. The diagnosis of hyperandrogenism among adolescents should also be based on both clinical and biochemical parameters.

[PCOS - desire for children and pregnancy]. / PCOS ­ Kinderwunsch und Schwangerschaft.

Polycystic ovary syndrome (PCOS) is diagnosed according to the Rotterdam criteria, where two of the following three criteria must be met: Anovulation, hyperandrogenism, and characteristic morphology by sonography. Women diagnosed with PCOS are at higher risk for diabetes and impaired glucose tolerance. Therefore, these women should be carefully counselled about lifestyle measures and improvements in fertility and pregnancy outcomes. Some women benefit from metformin, which needs to be clarified by off-label use. For fertility, mild stimulation is possible in women with unovulatory cycles, whereas women with PCOS need to be monitored more closely for the development of gestational diabetes, preeclampsia or hypertension during pregnancy.