Serum Androgen Concentrations Research Articles

Accelerated Early Childhood Growth Is Associated With the Development of Earlier Adrenarche and Puberty.

Small birth size and increased postnatal growth have been associated with earlier timing of adrenarche and puberty, but it is not well known whether these factors alone or together lead to earlier maturation. This work aimed to search for different growth trajectories using a clustering approach to analyze the effects of birth size and postnatal growth on adrenarchal and pubertal development. Altogether 351 children (48% girls) were examined prospectively at ages 6 to 9 and 9 to 11 years. Birth and early-growth data were collected retrospectively. Main outcome measures included clinical signs of adrenarche and puberty, and serum androgen concentrations (dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone). We detected 4 clusters with different birth sizes and postnatal growth trajectories: 1) children with average birth size and increased postnatal growth (AI), 2) children with small birth size and increased postnatal growth (SI), 3) children with average birth size and postnatal growth (AA), and 4) children with small birth size and average postnatal growth (SA). Thelarche at age 9 to 11 was most common and serum androgens at ages 6 to 9 and 9 to 11 years were highest in girls belonging to the AI and SI groups. Similar patterns in the onset of puberty and in androgen levels were not seen in the SA group. Increased early growth and weight gain predict higher serum androgen concentrations and earlier onset of puberty in girls. Adrenarche and puberty do not appear to be shifted earlier in children with small birth size who do not have catch-up growth.

Dietary fat quality and serum androgen concentrations in middle-aged men

Background/ObjectivesAverage testosterone concentrations in men have declined over the last few decades. The reasons for this are not fully known, but changes in dietary fat quality have been suggested to have a role. This study aimed to investigate the associations of different dietary fatty acids with serum androgen concentrations.Subjects/MethodsA total of 2546 men with a mean age of 53 from the Kuopio Ischaemic Heart Disease Risk Factor Study were included in this cross-sectional study. Associations between dietary saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA) and trans (TFA) fatty acids and concentrations of serum total and free testosterone and steroid hormone binding globulin (SHBG) were analyzed with analysis of covariance and linear regression analysis. Associations of isocaloric replacement of nutrients and androgen concentrations were analyzed with multivariate nutrient-density models.ResultsAfter adjustment for age, examination year and energy intake, higher SFA intake was associated with higher serum total and free testosterone and SHBG concentrations, and higher PUFA intake with lower concentrations. However, the associations were attenuated and not statistically significant after further adjustments for potential confounders. MUFA and TFA intakes were not associated with androgen concentrations. In isocaloric substitution models, replacing dietary protein with SFA was associated with higher serum total testosterone and SHBG concentrations. After excluding men with history of CVD or diabetes (n = 1021), no statistically significant associations were found.ConclusionsDietary fat quality was not independently associated with serum androgen concentrations in middle-aged men. However, replacing protein with SFA may be associated with higher serum androgen concentrations.

PCOS during the menopausal transition and after menopause: a systematic review and meta-analysis.

Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited. We performed a systematic review and meta-analysis of data on the pathophysiology, clinical manifestations, diagnosis, prognosis, and treatment of women ≥45 years of age-peri- or postmenopausal-with PCOS. Studies published up to 15 April 2023, identified by Entrez-PubMed, EMBASE, and Scopus online facilities, were considered. We included cross-sectional or prospective studies that reported data from peri- or postmenopausal patients with PCOS and control women with a mean age ≥45 years. Three independent researchers performed data extraction. Meta-analyses of quantitative data used random-effects models because of the heterogeneity derived from differences in study design and criteria used to define PCOS, among other confounding factors. Sensitivity analyses restricted the meta-analyses to population-based studies, to studies including only patients diagnosed using the most widely accepted definitions of PCOS, only menopausal women or only women not submitted to ovarian surgery, and studies in which patients and controls presented with similar indexes of weight excess. Quality of evidence was assessed using the GRADE system. The initial search identified 1400 articles, and another six were included from the reference lists of included articles; 476 duplicates were deleted. We excluded 868 articles for different reasons, leaving 37 valid studies for the qualitative synthesis, of which 28 studies-published in 41 articles-were considered for the quantitative synthesis and meta-analyses. Another nine studies were included only in the qualitative analyses. Compared with controls, peri- and postmenopausal patients with PCOS presented increased circulating total testosterone (standardized mean difference, SMD 0.78 (0.35, 1.22)), free androgen index (SMD 1.29 (0.89, 1.68)), and androstenedione (SMD 0.58 (0.23, 0.94)), whereas their sex hormone-binding globulin was reduced (SMD -0.60 (-0.76, -0.44)). Women with PCOS showed increased BMI (SMD 0.57 (0.32, 0.75)), waist circumference (SMD 0.64 (0.42, 0.86)), and waist-to-hip ratio (SMD 0.38 (0.14, 0.61)) together with increased homeostasis model assessment of insulin resistance (SMD 0.56 (0.27, 0.84)), fasting insulin (SMD 0.61 (0.38, 0.83)), fasting glucose (SMD 0.48 (0.29, 0.68)), and odds ratios (OR, 95% CI) for diabetes (OR 3.01 (1.91, 4.73)) compared to controls. Women with PCOS versus controls showed decreased HDL concentrations (SMD -0.32 (-0.46, -0.19)) and increased triglycerides (SMD 0.31 (0.16, 0.46)), even though total cholesterol and LDL concentrations, as well as the OR for dyslipidaemia, were similar to those of controls. The OR for having hypertension was increased in women with PCOS compared with controls (OR 1.79 (1.36, 2.36)). Albeit myocardial infarction (OR 2.51 (1.08, 5.81)) and stroke (OR 1.75 (1.03, 2.99)) were more prevalent in women with PCOS than controls, the ORs for cardiovascular disease as a whole, coronary artery disease as a whole, breast cancer and age at menopause, were similar in patients and controls. When restricting meta-analysis to studies in which women with PCOS and controls had a similar mean BMI, the only difference that retained statistical significance was a decrease in HDL-cholesterol concentration in the former and, in the two studies in which postmenopausal women with PCOS and controls had similar BMI, patients presented with increased serum androgen concentrations, suggesting that hyperandrogenism persists after menopause, regardless of obesity. Hyperandrogenism appeared to persist during the late-reproductive years and after menopause in women with PCOS. Most cardiometabolic comorbidities were driven by the frequent coexistence of weight excess and PCOS, highlighting the importance of targeting obesity in this population. However, the significant heterogeneity among included studies, and the overall low quality of the evidence gathered here, precludes reaching definite conclusions on the issue. Hence, guidelines derived from adequately powered prospective studies are definitely needed for appropriate management of these women.

P-443 Resumption of ovulation during lifestyle intervention in anovulatory women with PCOS and obesity is associated with reduction of serum AMH and androgens concentrations

Abstract Study question Are there differences in AMH and androgens concentrations between women with PCOS who resume ovulation (RO+) and those remain anovulatory (RO-) during lifestyle intervention? Summary answer RO+ women showed significant decrease in AMH and 11β-hydroxyandrostenedione concentrations at three months, and increase in SHBG concentrations at six months compared to RO- women. What is known already Lifestyle interventions have been shown to reduce clinical and biochemical hyperandrogenism in women with PCOS. Weight loss of 5-10% may reverse anovulatory status, thereby increasing natural conception rates. However, the underlying mechanisms why some women with PCOS remain anovulatory and others resume ovulation after weight loss are unclear. Reproductive characteristics at baseline and a greater degree of change in endocrine and metabolic features with lifestyle intervention may be crucial for ovulatory response. Study design, size, duration We used data and samples originating from an RCT which examined the efficacy of a six-month lifestyle intervention prior infertility treatment compared to prompt infertility treatment on live birth rate in women with obesity. In total of 577 women with obesity were randomized between 2009 and 2012. Anovulatory women with PCOS who were allocated to the intervention arm of the original RCT (n = 97) were included in the current analysis. Participants/materials, setting, methods We defined women as ovulatory during or after intervention based on the following criteria either: (1) spontaneous pregnancy; Or (2) Treatment strategy after lifestyle intervention; expectant management; (3) or IUI treatment in natural cycles. The steroid hormones were measured using LC-MS/MS. Multilevel analysis with the adjustment of baseline measurements was used to examine differences in changes in AMH and androgens concentrations between RO + (n=34) and RO- groups (n = 61) at three and six months after intervention. Main results and the role of chance At baseline, the mean age was 27.5 ± 3.6 in RO+ group and 27.9 ± 4.1 years in RO- group (p = 0.65). The mean weight was 101.2 ± 9.5 and 105.0 ± 14.6 kg, respectively (p = 0.13). AMH concentrations showed significant differences between RO+ women and RO- women (median and IQR 4.7 [3.2; 8.3] in the RO+ group and 7.2 [5.3; 10.8] ng/mL in the RO- group, p = 0.03). Androgen concentrations did not differ between the two groups. During and after lifestyle intervention, RO+ women had significant decrease in AMH (mean difference: –1.6 ng/mL, 95%CI: –3.0 to –0.20, p = 0.03) and 11β-hydroxyandrostenedione (mean difference: –1.7 nmol/L, 95%CI: –3.1 to –0.41, p = 0.01) concentrations than RO- women at three months. SHBG concentrations were significantly increased in RO+ compared to RO- women at six months (mean difference: 11 nmol/L, 95%CI: 1.1 to 22, p = 0.03). Changes in 11-ketotestosterone (three months mean difference: –0.15 nmol/L, 95%CI: –0.49 to 0.20, p = 0.41; six months: –0.39 nmol/L, 95%CI: –1.3 to 0.57, p = 0.43) and testosterone (three months mean difference: 0.13 nmol/L, 95%CI: –0.32 to 0.57, p = 0.58; six months: –0.29 nmol/L, 95%CI: –0.81 to 0.23, p = 0.27) did not differ at three or six months between groups. Limitations, reasons for caution The indirect parameters to confirm ovulatory cycles at the end of lifestyle program and small sample size may limit the robustness of the results. Wider implications of the findings Reduction of serum AMH and androgen concentrations during lifestyle intervention is associated with recovery of ovulatory cycles. When our results are confirmed in other studies, serum AMH and androgens concentrations could be monitored during lifestyle intervention to provide individualized recommendations on resumption of ovulatory cycles in anovulatory women with PCOS. Trial registration number NTR1530

Effects of 2-Year Physical Activity and Dietary Intervention on Adrenarchal and Pubertal Development: The PANIC Study.

Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in general populations. To investigate if a 2-year lifestyle intervention influences circulating androgen concentrations and sexual maturation in a general population of children. We conducted a 2-year physical activity and dietary intervention study in which 421 prepubertal and mostly normal-weight 6- to 9-year-old children were allocated either to a lifestyle intervention group (119 girls, 132 boys) or a control group (84 girls, 86 boys). The main outcome measures were serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone concentrations, and clinical adrenarchal and pubertal signs. The intervention and control groups had no differences in body size and composition, clinical signs of androgen action, and serum androgens at baseline. The intervention attenuated the increase of DHEA (P = .032), DHEAS (P = .001), A4 (P = .003), and testosterone (P = .007) and delayed pubarche (P = .038) in boys but it only attenuated the increase of DHEA (P = .013) and DHEAS (P = .003) in girls. These effects of lifestyle intervention on androgens and the development of pubarche were independent of changes in body size and composition, but the effects of intervention on androgens were partly explained by changes in fasting serum insulin. A combined physical activity and dietary intervention attenuates the increase of serum androgen concentrations and sexual maturation in a general population of prepubertal and mostly normal-weight children, independently of changes in body size and composition.

DEHP Induced Oxidative Stress Suppress Sperm Quality and Serum Androgen Concentration in Wistar Rats

DEHP Induced Oxidative Stress Suppress Sperm Quality and Serum Androgen Concentration in Wistar Rats

Role of C-type natriuretic peptide in polycystic ovary syndrome.

To evaluate serum C-type natriuretic peptide (CNP) and androgen concentrations in women with polycystic ovary syndrome (PCOS), and compare them with the healthy group. The present study was carried out prospectively at the Near East University Hospital, between July 15, 2019 and September 1, 2020. Out of the 90 patients aged between 18 and 40 years old who were enrolled, the final study population consisted of 36 patients with PCOS and 30 healthy women. Body mass index, free androgen index, serum androstenedione, total testosterone, free testosterone, and CNP were significantly higher and serum sex-hormone-binding globulin level was lower in the PCOS group. We revealed that serum CNP levels are high in PCOS patients. The mechanism of the relationship between this increase and hyperandrogenism or anovulation is not known, but these findings provide a direction for new studies. GOV: NCT04006171.

Can analysis of serum androgens aid in the diagnosis of polycystic ovary syndrome (PCOS) in adolescents?

ABSTRACT Introduction Polycystic ovary syndrome (PCOS) is a female metabolic disorder that is characterized by ovulatory dysfunction, elevated serum androgen concentrations, and polycystic ovarian morphology (PCOM). However, diagnosis of PCOS in adolescents is challenging. Areas covered The mechanisms of PCOS pathophysiology are discussed that include: i) dysregulation of the levels of steroidal enzymes ii) abnormalities in the secretion of gonadotropin releasing hormone, luteinizing hormone, and follicle stimulating hormone , and iii) abnormalities in ovarian Thecal and Granulosa cell function. Current clinical diagnosis protocols for PCOS in women are covered. The challenges in diagnosis of PCOS particularly in adolescents are highlightedWe highlighted an important unmet need for an accurate serum test for the early diagnosis of adolescent girls with PCOS. Expert opinion Steroid metabolite profiling that captures hyperandrogenism has shown some early promise to serve as a biomarker for early diagnosis of PCOS in women, something that would be especially useful in adolescents.

Soy Formula Is Not Estrogenic and Does Not Result in Reproductive Toxicity in Male Piglets: Results from a Controlled Feeding Study.

Soy infant formula which is fed to over half a million infants per year contains isoflavones such as genistein, which have been shown to be estrogenic at high concentrations. The developing testis is sensitive to estrogens, raising concern that the use of soy formulas may result in male reproductive toxicity. In the current study, male White-Dutch Landrace piglets received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17-beta-estradiol (2 mg/kg/d) (M + E2) or supplemented with genistein (84 mg/L of diet; (M + G) from postnatal day 2 until day 21. E2 treatment reduced testis weight (p < 0.05) as percentage of body weight, significantly suppressed serum androgen concentrations, increased tubule area, Germ cell and Sertoli cell numbers (p < 0.05) relative to those of Sow or Milk groups. Soy formula had no such effects relative to Sow or Milk groups. mRNAseq revealed 103 differentially expressed genes in the M + E2 group compared to the Milk group related to endocrine/metabolic disorders. However, little overlap was observed between the other treatment groups. These data suggest soy formula is not estrogenic in the male neonatal piglet and that soy formula does not significantly alter male reproductive development.

Ambient ozone exposure combined with residential greenness in relation to serum sex hormone levels in Chinese rural adults

BackgroundLong-term exposure to ambient ozone (O3) and residential greenness independently relate to altered hormones levels in urban settings and developed countries. However, independent and their joint associations with progestogen and androgen were sparsely studied in rural regions. Materials and methodsA total of 6211 individuals were recruited in this study. Random forest model was applied to predict the daily average concentrations of O3 using the satellites data. Residential greenness was reflected by the normalized difference vegetation index (NDVI). Liquid chromatography-tandem mass spectrometry was used to measure serum progestogen and androgen concentrations. Gender and menopausal status modified associations of long-term exposure to O3 and residential greenness with hormones levels were analyzed by generalized linear models. ResultsLong-term exposure to O3 was negatively related to 17-hydroxyprogesterone, testosterone, and androstenedione in both men and women (premenopausal and postmenopausal); the estimated β and 95% CI of ln-progesterone in response to per 10 μg/m3 increment in O3 concentration was −0.560 (−0.965, −0.155) in postmenopausal women. Association of long-term exposure to O3 with serum androgen levels in premenopausal and postmenopausal women were alleviated by residing in places with higher greenness. Additionally, a prominent effect of long-term exposure to O3 related to decreased serum progestogen and androgen levels was found in participants with middle- or high-level of physical activity or lower education level. ConclusionsThe results suggested that long-term exposure to high levels of O3 related to decreased serum androgen levels was attenuated by living in high greenness places in women regardless of menopause status. Future studies are needed to confirm the positive health effects of residential greenness on the potential detrimental effects due to exposure to O3.

The influence of ethnicity on outcomes of ovulation induction with clomifene citrate in women with PCOS

Research questionWhat is the influence of ethnicity on the outcome of ovulation induction with clomifene citrate in women with polycystic ovary syndrome (PCOS)? DesignThis was a retrospective cohort study. In total, 420 women diagnosed with PCOS who were of Northern European, Mediterranean, African, South-East Asian or South American descent, and who started ovulation induction treatment with clomifene citrate, were included. All women were treated with clomifene citrate according to a standardized treatment regimen. The minimal effective dose of clomifene citrate and prevalence of clomifene resistance (CRA) were assessed, and the chance of becoming ovulatory was predicted. ResultsDifferences were observed in body mass index (P = 0.008), waist circumference (P = 0.036) and serum LH, insulin and androgen concentrations (all P < 0.001) in women of different ethnicities with PCOS. Compared with women of Northern European descent, the minimal effective dose of clomifene citrate in women of other ethnic groups was not significantly different. The prevalence of CRA (P = 0.574) was similar in all ethnic groups A similar chance of ovulation (P = 0.504) was predicted for the different ethnic groups. ConclusionsThis is the first study aiming to link ethnicity to ovulation induction outcome in PCOS. Although women of different ethnicities who have PCOS exhibit a variation in phenotypic expression, there do not appear to be differences in the prevalence of clomifene-resistant anovulation or the minimal effective dose of clomifene citrate. Furthermore, a prediction model revealed no significant differences in the predicted chance of ovulation. A larger cohort is needed to validate these findings.

Association of Macronutrients Composition, Physical Activity and Serum Androgen Concentration in Young Women with Polycystic Ovary Syndrome.

The roles of dietary macronutrients and physical activity (PA) in patients with PCOS have not been sufficiently reported, especially in adolescent girls. To address this knowledge gap, we evaluated the associations between serum concentrations of total testosterone (tT), free testosterone (fT), androstenedione (A), dehydroepiandrosterone-sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and dietary macronutrients intake as well as different types and levels of PA. The study population consisted of 96 girls of Caucasian ancestry, aged 14–18 years: 61 participants with polycystic ovary syndrome (PCOS) and 35 healthy controls. Serum tT, fT, A, DHEA-S, and SHBG were determined in fasting blood. Macronutrient intake and PA levels were assessed by using the three-day food record method and the Beliefs and Eating Habits Questionnaire (KomPAN), respectively. We found several positive correlations between dietary macronutrients such as total fat, saturated fatty acids (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), and hormonal parameters across the entire cohort and in healthy girls. A positive correlation between SHBG and total protein consumption as well as an inverse correlation between SHBG and carbohydrate intake could be determined. No correlation between androgens and macronutrients was found in the PCOS group. In contrast, we observed an inverse correlation between androgen concentrations (except of DHEA-S) and “work/school” and/or “leisure time” PA only in PCOS patients. Moreover, the hormone levels differed according to PA intensity. In conclusion, the impact of diet and PA was strikingly different in adolescents with and without PCOS. These findings indicate that disturbed hormonal homeostasis in PCOS, at least in the youngest patients, likely “overtrump” dietary influences, and otherwise, PA offers a therapeutic potential that requires further evaluation of the long-term effects in randomized studies. (ClinicalTrial.gov Identifier: NCT04738409.)

Polycystic Ovary Syndrome: Pathophysiology, Presentation and Treatment a Mini-Review Article

Abstract Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder which is known as syndrome. The term ‘syndrome’ refers to a collection of clinical features or a phenotype. The specific features of the PCOS phenotype include clinical signs of androgen excess, elevated serum androgen concentrations, irregular menses, and infertility. It is common heterogenous disorder which affects women with different clinical presentations. In the basis of this disease is hormonal imbalance, such as insulin resistance and hyperinsulinemia. This review was based on searching all the available literature in the next databases: Pubmed, ClinicalTrials, Embase, Medline Complete, Web of Science, Cochrane Library, the Chinese Science and Technology Periodical Database (VIP), WanFang Database (Chinese Ministry of Science &amp; Technology). The search terms included hormonal and metabolic aspects, therapy of PCOS, polycystic ovary syndrome, PCOS.We included only randomized clinical intervention trials in young women published in last five years and included 12 articles in our review analysis. More research is needed to clarify the complex pathophysiology of PCOS. No single test is currently available for its diagnosis. Additionally, once diagnosis is established, the options for treatment are of limited number and effectiveness because they target only the symptoms of PCOS. Finally, patients with PCOS have higher rates of metabolic complications, such as cardiovascular disease, but their impact on mortality is not clear. Therefore, more prospective epidemiologic studies on the topic are necessary.

Low serum levels of dehydroepiandrosterone sulfate and testosterone in Albanian female patients with allergic disease

Evidence from several unrelated animal models and some studies conducted in humans, points to the immunomodulatory effects of androgens on various components of the immune system, especially on allergic disorders. This study evaluated the serum concentrations of sex hormones in women with allergy. For this purpose, blood samples were obtained from 78 participants in order to detect serum IgE concentrations, total testosterone, estradiol, progesterone, and DHEA-S. The majority of the subjects (54) in the study were consecutive patients with doctor-diagnosed allergic pathologies: 32 with allergic rhinitis, 10 with asthma and rhinitis, and 12 with skin allergies. In addition, 24 healthy volunteers were included in the research as the control group. The average age of the subjects was 32.54 years (SD ± 11.08 years, range between 4–59 years). All participants stated that they had not used any medical treatment to alleviate any of their symptoms prior to taking part in the research. They all underwent skin-prick tests for common aero-allergens, which was used as criterion for subject selection. Hence, the subjects were selected if they reacted positively to at least one aero-allergen. Their height and weight were measured in order to calculate the BMI. As a result, statistically significant differences between controls and allergic women in serum concentrations of androgens (testosterone, p = 0.0017; DHEA-S, p = 0.04) were found, which lead to the conclusion that the concentration of total serum testosterone and DHEA-S was lower in female patients with allergic diseases compared to controls.

Dynamics of androgens in healthy and hospitalized newborn foals.

BackgroundInformation on steroids derived from the adrenal glands, gonads, or fetoplacental unit is minimal in newborn foals.ObjectiveTo measure androgen concentrations in serum and determine their association with disease severity and outcome in hospitalized foals.AnimalsHospitalized (n = 145) and healthy (n = 80) foals.MethodsProspective, multicenter, cross‐sectional study. Foals of ≤3 days of age from 3 hospitals and horse farms were classified as healthy and hospitalized (septic, sick nonseptic, neonatal maladjustment syndrome [NMS]) based on physical exam, medical history, and laboratory findings. Serum androgen and plasma ACTH concentrations were measured with immunoassays. Data were analyzed by nonparametric methods and univariate analysis.ResultsSerum dehydroepiandrosterone (DHEA), androstenedione, testosterone, and dihydrotestosterone (DHT) concentrations were higher upon admission in hospitalized foals (P < .05), were associated with nonsurvival, decreased to 4.9‐10.8%, 5.7‐31%, and 30.8‐62.8% admission values in healthy, SNS, and septic foals, respectively (P < .05), but remained unchanged or increased in nonsurviving foals. ACTH:androgen ratios were higher in septic and NMS foals (P < .05). Foals with decreased androgen clearance were more likely to die (odds ratio > 3; P < .05).Conclusions and Clinical ImportanceSimilar to glucocorticoids, mineralocorticoids, and progestagens, increased serum concentrations of androgens are associated with disease severity and adverse outcome in hospitalized newborn foals. In healthy foals, androgens decrease over time, however, remain elevated longer in septic and nonsurviving foals. Androgens could play a role in or reflect a response to disorders such as sepsis or NMS in newborn foals.

Sex steroids and autoimmune rheumatic diseases: state of the art.

In autoimmune rheumatic diseases, oestrogens can stimulate certain immune responses (including effects on B cells and innate immunity), but can also have dose-related anti-inflammatory effects on T cells, macrophages and other immune cells. By contrast, androgens and progesterone have predominantly immunosuppressive and anti-inflammatory effects. Hormone replacement therapies and oral contraception (and also pregnancy) enhance or decrease the severity of autoimmune rheumatic diseases at a genetic or epigenetic level. Serum androgen concentrations are often low in men and in women with autoimmune rheumatic diseases, suggesting that androgen-like compounds might be a promising therapeutic approach. However, androgen-to-oestrogen conversion (known as intracrinology) is enhanced in inflamed tissues, such as those present in patients with autoimmune rheumatic diseases. In addition, it is becoming evident that the gut microbiota differs between the sexes (known as the microgenderome) and leads to sex-dependent genetic and epigenetic changes in gastrointestinal inflammation, systemic immunity and, potentially, susceptibility to autoimmune or inflammatory rheumatic diseases. Future clinical research needs to focus on the therapeutic use of androgens and progestins or their downstream signalling cascades and on new oestrogenic compounds such as tissue-selective oestrogen complex to modulate altered immune responses.

Evaluation of different antiandrogenic progestins on clinical and biochemical variables in polycystic ovary syndrome

Objectives: The aim of the study was to update the results of a previous study published 10 years ago and compare the effect on hyperandrogenism of a newer progestin, dienogest (DNG), in a combined oral contraceptive (COC) formulation with ethinylestradiol (EE), with that of COCs containing the same dose of EE in combination with drospirenone (DRSP) and chlormadinone acetate (CMA).Methods: Sixty women with polycystic ovary syndrome (PCOS) aged between 16 and 35 and requiring antiandrogenic contraceptive treatment were randomised to one of three treatment groups: EE 30 µg/DRSP 3 mg, EE 30 µg/CMA 2 mg, EE 30 µg/DNG 2 mg. We evaluated the effects of the three COCs on sex hormone-binding globulin (SHBG) and biochemical markers of hyperandrogenism.Results: After 3 months of treatment, serum androgen concentrations were significantly improved in all treatment groups. Serum concentrations of SHBG were significantly increased with all COC treatments (p < 0.0001). Interestingly, DRSP had a greater effect (+218%; p < 0.0001) on serum SHBG concentrations compared with DNG and CMA (p < 0.04 and p < 0.002, respectively). Serum concentrations of total testosterone significantly decreased in all groups (p < 0.0001). DRSP had a significantly greater effect on total testosterone concentrations compared with DNG (p = 0.002) and CMA (p < 0.0001).Conclusion: Our study showed that DNG exerted an important stimulatory effect on SHBG concentrations, which was less than that of DRSP but greater than that of CMA. Similar results were also obtained for dehydroepiandrosterone sulphate and total testosterone.

Body Composition, Serum Concentrations of Androgens and Insulin Resistance in Different Polycystic Ovary Syndrome Phenotypes.

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.

Serum Androgens Are Independent Predictors of Insulin Clearance but Not of Insulin Secretion in Women With PCOS.

In insulin-resistant individuals, hyperinsulinemia is a key compensatory mechanism, aimed at maintaining glucose homeostasis. Increased secretion and reduced clearance of insulin may both potentially contribute to this phenomenon. Insulin resistance and hyperinsulinemia are common findings in women with polycystic ovary syndrome (PCOS). While there is some information on insulin secretion, very few studies have investigated metabolic clearance rate of insulin (MCRI) in these women. Moreover, there is paucity of data on the relationships between MCRI and the pathophysiological characteristics of PCOS. The aim of the study was to explore these issues. One hundred ninety women with PCOS, diagnosed according to the Rotterdam criteria, with normal glucose tolerance. Assessment of MCRI and clinical, hormonal, and metabolic characteristics of subjects. MCRI and insulin sensitivity were measured by the hyperinsulinemic euglycemic clamp. Serum androgens were assessed by liquid chromatography-mass spectrometry and equilibrium dialysis. A historical sample of healthy women was used to define the corresponding reference intervals. MCRI was impaired in about two-thirds of women with PCOS. Subjects with low MCRI differed from those with normal MCRI for a number of anthropometric, metabolic, and endocrine features. In multivariate analysis, the degree of adiposity, estimates of insulin secretion, and serum androgen concentrations were independent predictors of MCRI. Conversely, age, adiposity, MCRI, and insulin sensitivity, but not serum androgens, were independent predictors of insulin secretion. In women with PCOS, metabolic clearance of insulin is reduced, contributing to generating hyperinsulinemia. Serum androgens are independent predictors of this phenomenon.

Distribution of Body Hair in Young Australian Women and Associations With Serum Androgen Concentrations.

An important element of the diagnosis of polycystic ovary syndrome is hyperandrogenism. To determine the distribution of modified Ferriman-Gallwey (mF-G) scores, as a measure of facial and body hair growth, and associations between the mF-G scores and serum androgen concentrations, including 11-oxygenated androgens. Cross-sectional study of non-health-care-seeking women, aged 18 to 39 years, recruited from the eastern states of Australia from November 2016 to July 2017. Participants provided an mF-G self-assessment that corresponded to their appearance when not using treatment for excess hair. Androgens were measured in 710 women by liquid chromatography and tandem mass spectrometry. The distribution of the mF-G scores was right-skewed. The median (range) mF-G score of all participants (73.1% Caucasian) was 5 (0-36). The mF-G scores were negatively associated with age (rs = 0.124; P < 0.0001) and positively associated with body mass index (BMI) (rs = 0.073; P < 0.0001). Only androstenedione remained significantly associated with mF-G scores when controlling for age and BMI. Cluster analysis identified 2 groups with mF-G score of < 10 and ≥ 10. Repeating the cluster analysis using the combined vector of mF-G score and androstenedione returned a similar cluster structure, and again separated the 2 groups at a mF-G score < 10 versus ≥ 10. A self-assessed mF-G score ≥ 10 is indicative of excess body hair. Androstenedione, as well as testosterone, should be measured when hyperandrogenism is being evaluated. The lack of association between mF-G scores and the 11-oxygenated androgens highlights the need for a better understanding of these steroids.