Higher Androstenedione Levels Research Articles

Plasma Androstenedione Concentration Can Discriminate Frail versus Non-Frail Men with Prostate Cancer under Androgen Deprivation Therapy.

Androgen deprivation therapy (ADT) is a mainstay of prostate cancer in both adjuvant and palliative settings. Since androgens are crucial for functional status and psychological functions, we evaluated whether blood testosterone, androstenedione, or DHEA concentrations were associated with functional status and psychological alterations in patients with localised (PCa) or metastatic prostate cancer (mPCa) receiving ADT with analogues of luteinising hormone-releasing hormone (LHRH). The five Fried criteria were considered to identify frailty syndrome. In addition, complementary evaluations were carried out to measure other variables of interest. Sleep quality was assessed using the Athens Insomnia Scale, cognitive functions were assessed using the Mini-Mental State Examination, and symptoms of depression were measured using the Yesavage Geriatric Depression Scale. Logistic regression analysis was performed to determine if the androgens level could be related to frailty syndrome, sleep impairment, depressive symptoms, and cognitive functions. The results of the multivariate analyses show that high concentrations of androstenedione were significantly associated with frailty syndrome in both groups (p = 0.018; odds ratio = 4.66, 95% confidence interval [1.30-16.6]). There were significant relationships between frailty syndrome and the systemic concentration of androstenedione (p = 0.01), but not the concentration of testosterone (p = 0.60) or DHEA (p = 0.42). In addition, the results of the non-parametric tests show significant results between a decreased gait speed in the two groups (metastatic and localised) and the concentration of androstenedione (p = 0.015). High androstenedione levels were associated with a slow walking speed in the mCaP group (p = 0.016), while high testosterone levels were associated with a better walking speed in the localised CaP group (p = 0.03). For the concentration of androstenedione in plasma, the area under the curve was 0.72, with a 95% CI of 0.55-0.88 with acceptable values, and with a cut-off point of 4.51 pg/mL, a sensitivity of 82.9%, and specificity of 53.8%. No relationships between the concentration of androgens in plasma and sleep quality, cognitive functions, or symptoms of depression suggest that the changes were specific to frailty syndrome. Further research into the role of androstenedione should be evaluated in follow-up studies in order to recommend its use as a suitable biomarker of frailty syndrome in prostate cancer patients.

FRI371 Serum Androstenedione As An Additive Biomarker In Ectopic Cushing’s Syndrome Evaluation

Abstract Disclosure: S. Zhang: None. J.C. Lo: None. M.G. Jaffe: None. H. Arzumanyan: None. Background: Ectopic Cushing’s syndrome (ECS) results from glucocorticoid excess secondary to ectopic ACTH or CRH producing tumors. Although ECS identification can be challenging when presentation lacks classic Cushing’s features, ectopic ACTH secretion can result in a key constellation of findings that facilitate early clinical recognition. We describe a case of ECS from an ACTH-producing carcinoid tumor of the lung presenting with resistant hypertension, severe hypokalemia, and muscle weakness. In addition to significant hypercortisolism, laboratory findings were notable for high androstenedione levels without concomitant increase in DHEAS and testosterone levels. Case: A 59-year-old female athlete with history of well-controlled hypertension developed difficult to control hypertension, requiring escalation to triple antihypertensive therapy within 3 months. During this time, she had multiple emergency department visits for progressive muscle weakness, hypertension, and persistent hypokalemia despite potassium supplementation. She was hospitalized for further evaluation. Physical examination was notable for bruising, muscle wasting, thin extremities, facial fullness, and disproportionate abdominal adiposity. Workup for Cushing’s syndrome demonstrated ACTH-dependent hypercortisolism and markedly elevated androstenedione 398 ng/dL (normal 20-75 ng/dL) despite normal DHEAS 48 mcg/dL (normal <430 mcg/dL) and total testosterone 11 ng/dL (normal <45 ng/dL) levels. A chest CT identified a 3.8 cm right lower lobe lung mass and transbronchial biopsy confirmed atypical carcinoid tumor. She underwent a right middle and lower lobe bilobectomy with complete tumor resection. Cortisol, androstenedione, and potassium levels rapidly normalized postoperatively, and blood pressure returned to baseline, well-controlled on monotherapy. The patient only required 3 days of hydrocortisone therapy for transient steroid withdrawal symptoms. Conclusions: Our case illustrates a difficult to diagnose uncommon disease presenting with resistant hypertension, hypokalemia and marked androstenedione elevation despite normal DHEAS and testosterone levels. This steroidogenic profile has been reported in other ECS cases and attributed to differential effects of ectopic ACTH production on adrenal androgen biosynthesis (1). Although ECS is rare and the primary lesion can be difficult to identify, disproportionate elevation in androstenedione may prompt recognition of ECS and support early detection and management. Reference: (1) Barbetta L, Dall’Asta C, Re T, Colombo P, Travaglini P, Ambrosi B. Androgen secretion in ectopic ACTH syndrome and in Cushing’s disease: modifications before and after surgery. Horm Metab Res Horm Stoffwechselforschung Horm Metab. 2001;33(10):596-601 Presentation: Friday, June 16, 2023

Assessing the androgenic and metabolic heterogeneity in polycystic ovary syndrome using cluster analysis.

Some but not all women with polycystic ovary syndrome (PCOS) develop the metabolic syndrome (MS). The objective of this study was to determine if a subset of women with PCOS had higher androgen levels predisposing them to MSand whether routinely measured hormonal parameters impacted the metabolic syndrome score (siMS). We included data from a discovery (PCOS clinic data) and a replication cohort (Hull PCOS Biobank) and utilized eight routinely measured hormonal parameters in our clinics (free androgen index [FAI], sex hormone-binding globulin, dehydroepiandrosterone sulphate (DHEAS), androstenedione, luteinizing hormone [LH], follicular stimulating hormone, anti-Müllerian hormone and 17 hydroxyprogesterone [17-OHP]) to perform a K-means clustering (an unsupervised machine learning algorithm). We used NbClust Package in R to determine the best number of clusters. We estimated the siMS in each cluster and used regression analysis to evaluate the effect of hormonal parameters on SiMS. The study consisted of 310 women with PCOS (discovery cohort: n = 199, replication cohort: n = 111). The cluster analysis identified two clusters in both the discovery and replication cohorts. The discovery cohort identified a larger cluster (n = 137) and a smaller cluster (n = 62), with 31% of the study participants. Similarly, the replication cohort identified a larger cluster (n = 74) and a smaller cluster (n = 37) with 33% of the study participants. The smaller cluster in the discovery cohort had significantly higher levels of LH (7.26 vs. 16.1 IU/L, p < .001), FAI (5.21 vs. 9.22, p < .001), androstenedione (3.93 vs. 7.56 nmol/L, p < .001) and 17-OHP (1.59 vs.3.12 nmol/L, p < .001). These findings were replicated in the replication cohort. The mean (±SD) siMS score was higher in the smaller cluster, 3.1 (±1.1) versus 2.8 (±0.8); however, this was not statistically significant (p = .20). In the regression analysis, higher FAI (β = .05, p = .003) and androstenedione (β = .03, p = .02) were independently associated with a higher risk of SiMS score, while higher DHEAS levels were associated with a lower siMS score (β = -.07, p = .03) CONCLUSION: We identified a subset of women in our PCOS cohort with significantly higher LH, FAI, and androstenedione levels. We show that higher levels of androstenedione and FAI are associated with a higher siMS, while higher DHEAS levels were associated with lower siMS.

Androstenedione and Follicle-Stimulating Hormone Concentration Predict the Progression of Frailty Syndrome at One Year Follow-Up in Patients with Localized Breast Cancer Treated with Aromatase Inhibitors.

Background: The standard treatment in postmenopausal women with estrogen- and progesterone-positive localized breast cancer consists of aromatase inhibitors (AROi). The ability of AROi to promote or worsen frailty syndrome over time and the relationship with changes in gonadal hormones concentration in blood have not been investigated. Methods: A prospective study to evaluate the relationship between frailty syndrome and gonadal hormones concentrations in blood at baseline (prior to AROi treatment) and after 6 and 12 months under AROi treatment in post-menopausal women with breast cancer. Frailty syndrome was evaluated by the Fried’ criteria. We evaluated whether hormone concentration at baseline could predict frailty syndrome at follow-up. Results: Multinomial regression analysis showed that of the different hormones, those significantly (p < 0.05) associated to the worsening of frailty syndrome were high androstenedione levels and low follicle-stimulating hormone (FSH) levels in blood. Receiver operating characteristic curve analysis showed both androstenedione and FSH significantly (p < 0.05) discriminate patients who developed or presented worsening of frailty syndrome over time, with acceptable sensitivity (approximately 80% in both cases) but low specificity (40%). Conclusion: Hormonal concentrations before AROi treatment constitute possible biomarkers to predict the progression of frailty syndrome.

Lifestyle treatment in women with polycystic ovary syndrome: predictors of weight loss and dropout.

BackgroundPolycystic ovary syndrome (PCOS) affects 5%–10% of women in their reproductive years. Most women with PCOS struggle with obesity during their entire life. Knowing which determinants contribute to a successful lifestyle change is important to optimize treatment options for women with PCOS.ObjectiveThis analysis of secondary outcome measures aimed to determine factors of ≥5% weight loss and dropout in all arms of the study and separately in the lifestyle intervention (LI) and control (care as usual [CAU]) groups.Study designWomen diagnosed with PCOS (N = 183) and a Body Mass Index (BMI) above 25 kg/m2 were included. Participants were assigned to (1) 20 lifestyle sessions involving cognitive behavioral therapy (CBT), (2) 20 lifestyle sessions involving CBT with additional short message service (SMS), or (3) to control (CAU). A generalized linear regression was performed to identify determinants of ≥5% weight loss. Logistic regression was performed to identify determinants of dropout. All models were corrected by including baseline weight as a covariate.ResultsLI (OR 4.906, p = .001) was associated with ≥5% weight loss, while higher depression scores (OR 0.549, p = .013) had a negative association. Restraint eating was a positive factor for ≥5% weight loss in LI but a negative in CAU. Higher baseline weight (OR 1.033, p = .006), LI with SMS (OR 4.424, p = .002), and higher levels of androstenedione (OR 1.167, p = .026) were associated with dropout.ConclusionsDepression and eating behavior were associated with ≥5% weight loss. Women with PCOS should be screened for depression and eating behavior before a LI.

Exposure of zebrafish larvae to water accommodated fractions of weathered crude oil alters steroid hormone concentrations with minimal effect on cholesterol.

Crude oil has multiple toxic effects in fish, particularly during their early life stages. Recent transcriptomics studies have highlighted a potential effect on cholesterol homeostasis and biosynthesis, but have not investigated effects on steroid hormones, which are biosynthetically downstream metabolites of cholesterol. We exposed zebrafish (Danio rerio) embryos and larvae to 3 concentrations of a high energy water accommodated fraction (HEWAF) of crude oil and measured effects on cholesterol and steroid hormones at 48 and 96h post fertilization (hpf). HEWAF exposure caused a small decrease in cholesterol at 96 hpf but not 48 hpf. HEWAF-exposed larvae had higher levels of androstenedione, testosterone, estradiol, cortisol, corticosterone, and progesterone at 96 hpf compared to controls, while effects at 48 hpf were more modest or not present. 2-Methoxyestradiol was lower following HEWAF exposure at both time points. Dihydrotestosterone was elevated in one HEWAF concentration at 48 hpf only. Our results suggest that hormone imbalance may be an important toxic effect of oil HEWAF exposure despite no major effect on their biosynthetic precursor cholesterol.

O-159 Prediction of weight loss and drop-out in a lifestyle intervention in women with pcos: A randomized controlled trial

Abstract Study question Which patient related determinants contribute to a ≥ 5% weight loss and drop-out? Summary answer Participating in the lifestyle treatment and a worse body image at baseline were significantly associated with ≥5% weight loss. What is known already In general, three-component interventions including diet, exercise, and cognitive behavioral therapy have shown to be effective at the long-term to achieve weight loss. In a lifestyle program for infertile women, higher external eating behavior scores and not receiving previous support by a dietician were associated with weight loss. In a short term lifestyle program for women with PCOS, weight loss was associated with better quality of life scores and attendance of study appointments. Little has been published about the potential role of PCOS characteristics, psychological and behavioral variables on the ability to achieve weight loss in this group of women. Study design, size, duration The present study is a longitudinal RCT to study the effectiveness of a three component 1-year cognitive-behavioural lifestyle intervention on weight loss in overweight/obese women with PCOS. A total of 183 participants were randomly assigned to three groups: 1) CBT provided by the multidisciplinary team or; 2) CBT provided by the multidisciplinary team and Short Message Service (SMS) or; 3) usual care: women are encouraged to lose weight through publicly available services (control group). Participants/materials, setting, methods Women with menstrual cycle disorders are systematically screened using a standardised protocol. Data of 183 women diagnosed with PCOS according to the Rotterdam criteria, a Body Mass Index above 25 kg/m² were included. All variables were measured at start and at three, six, nine and twelve months. Main results and the role of chance The multivariable mixed-effect logistic regression model showed that participation in the lifestyle treatment (HR 2.3, P = 0.012) and a worse body image (FNAE) (HR 0.95, P = 0.023) at baseline were significantly associated with ≥5% weight loss. Drop-out was predicted by participation in the lifestyle treatment (OR 0.2 P = 0.003), additional short message service (OR 3.7, P = 0.008), smoking (OR 0.3, P = 0.22), drinking alcohol (OR 2.4, P = 0.04), higher levels of androstenedione (OR 1.2, P = 0.047). Also, women who achieved spontaneous pregnancies were more likely to drop-out (OR 0.09, P = 0.002). Limitations, reasons for caution A limitation of our study is the high discontinuation rate we observed especially after 3 months of the intervention. Therefore a statistical method was chosen that included all available data even if participants dropped out during the study period. Wider implications of the findings A three-component lifestyle intervention program for obese women with PCOS is effective for weight loss. The group of women with a more negative body image should receive additional treatment before entering such a lifestyle intervention to achieve better results. Trial registration number Registered at the Netherlands National Trial Register with number NTR2450 on August 2nd, 2010.

Physical Performance Regarding Handgrip Strength in Women with Polycystic Ovary Syndrome.

The present study aimed to investigate the physical performance of handgrip strength (HGS) in women with polycystic ovary syndrome (PCOS). A case-control study that included 70 women with PCOS and 93 age-matched healthy women aged between 18 and 47 years with body mass index (BMI) between 18 Kg/m2-39.9 Kg/m2. The serum levels of total testosterone, androstenedione, insulin, estradiol, thyroid-stimulating hormone (TSH), prolactin, sex hormone-binding globulin (SHBG), and 17-hydroxyprogesterone (17-OHP) were measured. The free androgen index (FAI) and the homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. The body composition regions of interest (ROIs) were assessed by dual-energy X-ray absorptiometry (DXA), and the handgrip strength (HGS) was evaluated for both the dominant and the non-dominant hands with a manual Sammons Preston (Bolingbrook, IL, US) bulb dynamometer. Women with PCOS had high serum levels of total testosterone (p < 0.01), androstenedione (p = 0.03), and insulin (p < 0.01), as well as high FAI (p < 0.01) and HOMA-IR (p = 0.01) scores. Compared with the non-PCOS group, the PCOS group had greater total lean mass in the dominant hand (p < 0.03) and greater HGS in both the dominant and the non-dominant hands (p < 0.01). The HGS was correlated with lean mass (p < 0.01). Women with PCOS have greater HGS. This may be associated with age and BMI, and it may be related to lean mass. In addition, the dominance effect on muscle mass may influence the physical performance regarding HGS in women with PCOS.

High DHEAS Level in Girls Is Associated with Earlier Pubertal Maturation and Mild Increase in Androgens throughout Puberty without Affecting Postmenarche Ovarian Morphology

Objective: To assess whether the presence of high DHEAS (HD) at 7 years determines different timing, sequence, and rate of pubertal events, and whether it is associated with adrenal and/or ovarian hyperandrogenism and changes in ovarian morphology throughout puberty. Methods: In a longitudinal study of 504 girls, clinical evaluation was performed every 6 months after 7 years of age to detect Tanner stages; hormonal and anthropometric measurements were conducted at thelarche (B2), breast Tanner 4 (B4), and 1 year after menarche; ultrasonographic evaluation was also performed after menarche. The girls were classified as HD if their DHEAS level was >42.1 µg/dL (>75th percentile) around 7 years. Results: HD around 7 years is associated with a younger age at thelarche, pubarche, and menarche. Girls with HD had higher androstenedione and total testosterone levels, and a higher free androgen index (FAI), and lower levels of antimüllerian hormone (AMH) at B2, and higher levels of androstenedione and FAI at B4 and after menarche. All these results were significant even after adjusting for body mass index, age at first DHEAS determination, and birth weight. One year after menarche, polycystic ovarian morphology was detected in 7.6 and 7.3% of the HD and the normal DHEAS group, respectively. Ovarian volume was correlated with AMH, testosterone, androstenedione, and LH but not with DHEAS around 7 years. Conclusion: Prepubertal HD in normal girls was associated with earlier thelarche, pubarche, and menarche, and a mild androgen increase throughout puberty. We believe continuous follow-up of this cohort is important to prospectively address the interrelationships between biochemical adrenarche and early growth as determinants of ovarian function.

Investigation of body mass index, insulin resistance and diabetes in patients with hirsutism.

IntroductionObese woman with hirsutism have increased risk for developing insulin resistance and diabetes mellitus.AimTo evaluate patients with hirsutism, report the hormone levels, body mass index (BMI), insulin resistance and diabetes in our study population and compare our results with those of similar research conducted in other countries.Material and methodsHormones were measured with radioimmunoassay/immunoradiometric assay methods. Oral glucose tolerance test was done only in a selected group of women (with positive anamnesis for diabetes, women with polycystic ovary syndrome (PCOS) and overweight/obese women). The level of blood glucose was measured after drinking the liquid containing 75 g glucose. Blood was taken to measure glucose, insulin and C-peptide levels after 30 min, 60 min and 3 h.ResultsWomen with PCOS (27.4%) had higher BMI than women with other causes of hirsutism. Among 135 of the women with hirsutism, 9.6% were underweight, 60% were with normal weight, 20.7% were overweight and 9.6% were obese. Obesity was more frequent in PCOS and hyperandrogenism groups. Women with hirsutism had higher levels of androstenedione, dehydroepiandrosterone sulfate (DHEAS), total testosterone, free testosterone, lower levels of sex hormone-binding globulin (SHBG). Insulin resistance was present in 20 (14.8%) women and diabetes in 2 (1.4%) women.ConclusionsObesity was associated with increased hirsutism. In our study we found that insulin resistance should be assessed in hirsute women with PCOS regardless of their BMI as insulin resistance was found in hirsute women irrespective of whether they were overweight, obese, of normal weight or underweight. Groups at risk (hirsute, obese, diabetes) should be identified and treated.

Case-control study of endogenous sex steroid hormones and risk of endometrial cancer.

Epidemiologic evidence regarding the role of endogenous sex hormones in endometrial cancer etiology remains inconsistent. The objective of this study was to investigate if circulating levels of endogenous estrone, estradiol, sex hormone binding globulin (SHBG), testosterone, and androstenedione are associated with endometrial cancer risk. We conducted a population-based case-control study of 522 incident endometrial cancer cases and 976 population controls, in Alberta, Canada from 2002 to 2006. Study participants completed in-person interviews and provided fasting blood samples. Sex hormone levels were determined by enzyme-linked immunosorbent assays. Higher levels of androstenedione were associated with increased endometrial cancer risk (OR 1.44, 95% CI 1.04-2.02). Endometrial cancer risk in pre- and peri-menopausal women was reduced for the highest versus lowest quartiles of estrone (OR 0.44, 95% CI 0.22-0.88) and estradiol (OR 0.30, 95% CI 0.14-0.65), but in post-menopausal women, the endometrial cancer risk was increased for the highest versus lowest quartile of androstenedione (OR 1.82, 95% CI 1.25-2.65). In addition, endometrial cancer risk in normal/underweight women was decreased for the highest versus lowest quartile of serum SHBG (OR 0.39, 95% CI 0.19-0.84). Overall, positive associations were found for androstenedione concentrations, while sub-group analyses revealed = inverse associations with estrogens and SHBG. Results of this study provide empirical evidence for the role of circulating sex hormones in endometrial cancer etiology and highlight the importance of modifiable factors that contribute to changes in sex hormone concentration levels.

Advanced Glycation End Products (AGEs) May Be a Striking Link Between Modern Diet and Health.

The Maillard reaction is a simple but ubiquitous reaction that occurs both in vivo and ex vivo during the cooking or processing of foods under high-temperature conditions, such as baking, frying, or grilling. Glycation of proteins is a post-translational modification that forms temporary adducts, which, on further crosslinking and rearrangement, form permanent residues known as advanced glycation end products (AGEs). Cooking at high temperature results in various food products having high levels of AGEs. This review underlines the basis of AGE formation and their corresponding deleterious effects on the body. Glycated Maillard products have a direct association with the pathophysiology of some metabolic diseases, such as diabetes mellitus type 2 (DM2), acute renal failure (ARF), Alzheimer’s disease, dental health, allergies, and polycystic ovary syndrome (PCOS). The most glycated and structurally abundant protein is collagen, which acts as a marker for diabetes and aging, where decreased levels indicate reduced skin elasticity. In diabetes, high levels of AGEs are associated with carotid thickening, ischemic heart disease, uremic cardiomyopathy, and kidney failure. AGEs also mimic hormones or regulate/modify their receptor mechanisms at the DNA level. In women, a high AGE diet directly correlates with high levels of androgens, anti-Müllerian hormone, insulin, and androstenedione, promoting ovarian dysfunction and/or infertility. Vitamin D3 is well-associated with the pathogenesis of PCOS and modulates steroidogenesis. It also exhibits a protective mechanism against the harmful effects of AGEs. This review elucidates and summarizes the processing of infant formula milk and the associated health hazards. Formulated according to the nutritional requirements of the newborn as a substitute for mother’s milk, formula milk is a rich source of primary adducts, such as carboxy-methyl lysine, which render an infant prone to inflammation, dementia, food allergies, and other diseases. We therefore recommend that understanding this post-translational modification is the key to unlocking the mechanisms and physiology of various metabolic syndromes.

IS TESTOSTERONE PROGNOSTIC IN PROSTATE CANCER TREATMENT? THE UROLOGICAL STANDPOINT.

SUMMARYProstate cancer (PC) is known as an androgen-dependent tumor with testosterone as its natural growth factor, its action is mediated by the androgen receptor (AR) important for the biology and progression of PC. During aging a progressive decline in testosterone levels begins, caused by disability of aged Leydig cells to produce testosterone in response to luteinizing hormone. Surgical treatment of PC can influence the hypothalamic-pituitary-gonadal axis with less impact on it compared to patients treated with radiation. Patients with pre-operative low baseline testosterone level had mean Gleason score higher and AR expression was higher; significantly lower testosterone levels were recorded in patients with lymph node metastases. But some data are conflicting, and some results are opposite to those mentioned before. These data show that there is no significant association between all sex hormone in men and lethal PC or total mortality. In patients with metastatic PC, results showed that elevation of baseline androstenedione levels was predictive of prostate-specific antigen (PSA) response; higher baseline androstenedione levels were associated with an improved overall survival. In these patients, the relationship between serum testosterone and PC prognosis varies in different clinical settings and according to androgen deprivation therapy administration.

Altered umbilical sex steroids in preterm infants born small for gestational age

Background: Boys born small for gestational age (SGA) are at increased risk of testicular dysgenesis syndrome, and girls born SGA face the risk of polycystic ovary syndrome later in life. Our aim was to study whether neonates born SGA have an altered profile of steroid hormones at birth.Materials and methods: A total of 168 singletons (99 boys, 69 girls) born at 32.0–36.9 gestational weeks were recruited to a population-based, university hospital, single-center study. Of these, 31 infants (17 boys, 14 girls) were born SGA. The concentrations of dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, cortisone, and cortisol were analyzed in umbilical cord serum with mass spectrometry.Results: Girls born SGA had higher levels of androstenedione than girls born appropriate for gestational age (AGA) (4.0 versus 2.6 nmol/L, p = .002). Boys born SGA had lower levels of estrone than boys born AGA (33 822 versus 62 471 pmol/L, p = .038). Infants born SGA had lower levels of cortisone than infants born AGA, both in girls (340 versus 579 nmol/L, p = .010) and in boys (308 versus 521 nmol/L, p = .045). Furthermore, boys born SGA had a higher cortisol/cortisone ratio than boys born AGA (0.41 versus 0.25, p = .028). Gestational age correlated with DHEAS (boys r = 0.48, p = .000, girls r = 0.35, p = .013), and cortisol (boys r = 0.48, p = .000, girls r = 0.29, p = .039).Conclusions: In moderate-to-late preterm infants born SGA, we observed a different steroid hormone profile in cord serum. Girls born SGA show increased levels of androstenedione and boys born SGA show decreased levels of estrone in cord serum, which could be related to placental aromatase deficiency in intrauterine growth restriction.

Neonatal Hormone Concentrations and Risk of Testicular Germ Cell Tumors (TGCT).

Background: Testicular germ cell tumor (TGCT) incidence has increased over the last 40 years in the United States. In contrast to TGCT among infants, it is hypothesized that TGCT in adolescents and young men is the result of sex steroid hormone imbalance during early fetal development. However, little is known about the neonatal period when abrupt hormonal changes occur, and direct supporting evidence is scarce due to the difficulties in obtaining prediagnostic specimens.Methods: We conducted a population-based case-control study examining hormone levels at birth among 91 infants (0-4 years) and 276 adolescents (15-19 years) diagnosed with TGCT, and 344 matched controls. Estrogen and androgen levels were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from archived newborn dried blood spots. Logistic regression models were used to estimate the association between each hormone level and TGCT risk.Results: Higher levels of androstenedione were associated with increased TGCT risk among adolescents [odds ratio (OR): 2.33, 95% confidence interval (CI): 1.37-3.97 for highest vs. lowest quartile; P trend = 0.003] but not among infants (OR: 0.70, 95% CI: 0.28-1.77). A similar pattern was observed for testosterone (OR: 1.73, 95% CI: 1.00-3.00,) although the trend was not significant (P trend = 0.12). Associations were stronger among non-Hispanic white subjects, relative to Hispanics. There was no difference by tumor histologic subtype. Estriol (the only detectable estrogen) was not associated with TGCT risk in either age group.Conclusions: Higher levels of neonatal androgens were associated with increased risk of TGCT among adolescents, suggesting that early life hormone levels are related to the later development of TGCT.Impact: This is the first study with direct measures of sex steroid hormones to examine the relationship between estrogens and androgens at birth and risk of adolescent TGCT. Cancer Epidemiol Biomarkers Prev; 27(4); 488-95. ©2018 AACR.

Current smoking is associated with a larger waist circumference and a more androgenic profile in young healthy women from high-risk breast cancer families

The purpose was to elucidate the interplay between current smoking, anthropometric measurements, and endogenous hormone levels in women ≤ 40 years. Questionnaires on lifestyle and reproductive factors were completed by 269 healthy women from high-risk breast cancer families between 1996 and 2006 in Sweden. Blood samples for analyses of plasma testosterone, estradiol, androstenedione, sex hormone-binding globulin, and body measurements were obtained 5–10 days before predicted onset of the next menstrual period. Women without smoking status, who were currently breastfeeding, or using hormonal contraception other than combined oral contraceptives (OCs) were excluded (n = 27). Current smokers (n = 57) had larger waist circumference (adjp = 0.004) and waist-to-hip ratio (WHR) (adjp = 0.007) than non-smokers (n = 185). In non-OC users, adjusted mean androstenedione levels were higher in current smokers compared with non-smokers (10.3 vs. 8.6 nmol/L; adjp = 0.0002). While in current OC users estradiol levels were higher in smokers compared with non-smokers (22.5 vs. 17.4 pg/mL; adjp = 0.012). In multivariable models, WHR was associated with both current smoking (adjp ≤ 0.016) and higher levels of androstenedione (adjp = 0.05) or bioavailable testosterone (adjp = 0.001). Among non-OC users, a more androgenic profile was observed in current smokers compared with non-smokers, but not in current OC users. Irrespective of OC use, current smoking was associated with increased waist circumference.

ACUPUNCTURE TREATMENT FOR INFERTILITY DUE TO LOW ANTIMÜLLERIAN HORMONE LEVELS

Antimullerian hormone (AMH) is produced in the ovarian follicles. The levels of the hormone on a blood test show woman’s ovarian reserves which determine the capacity of the egg cells in the ovaries needed for conception. We report a case of a 33-year-old female diagnosed with the primary infertility for 3 years due to unsuccessful natural conceiving. The patient had regular menstrual cycle with duration of only 1 day. The patient’s blood test indicated an insufficiently grown follicles needed for conception, low AMH levels (0.94 ng/mL), and high androstenedione (458 ng/mL) levels. The patient underwent 32 treatment cycles, one treatment every week, over a period of 1 year. After the treatment with acupuncture and infrared lamp, her menstrual cycle was lengthened to 4 days, and the blood analysis showed normally grown ovarian follicles up to 20 mm with good quality and normal hormone levels. According to the theories of the traditional Chinese medicine, this state of the health arises from obstructed energy Qi flow in the liver meridian. This obstruction is created due to some lifestyle changes, which in turn, interrupts the blood flow in the uterus and ovaries and contributes to an imbalance of the hormones. During this treatment, acupuncture points located on the Spleen, Bladder, Heart, Liver, Large Intestine, Gall Bladder, and Du Mai meridians were used. Key words: Acupuncture, Infertility, Treatment, Traditional Chinese medicine

Cross‐sectional association of endogenous steroid hormone, sex hormone‐binding globulin, and precursor steroid levels with hemostatic factor levels in postmenopausal women

Background Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), a normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg). Methods This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated the level of free T. Results One picogram per milliliter higher E1 levels were associated with 0.24% lower PSAg levels (95% Confidence Interval [CI]: -0.35, -0.12) and 1 μg mL-1 higher DHEAS levels were associated with 40.8 nm lower TG peak values (95% CI: -59.5, -22.2) and 140.7 nm×min lower TG endogenous thrombin potential (ETP) (95% CI: -212.1, -69.4). After multiple comparisons correction, there was no evidence for other associations. Conclusions As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin.

The sexuological impact of hormonal contraceptives based on their route of administration

Evidence on the effects of hormonal contraceptives on female sexuality is conflicting. We enrolled 556 women, divided into six groups: two composed of subjects using a combined hormonal contraceptive (COC) containing 0.020 (“COC20”) and 0.030 (“COC30”) mg of ethynyl estradiol (EE), “natural”, using COC containing 1.5 mg of estradiol (E2), “ring”, using a vaginal ring releasing each day 0.015 mg of EE + 0.120 of etonogestrel, “subcutaneous”, using a progestin only subcutaneous contraceptive implant releasing etonogestrel and “controls”, using no hormonal contraceptive methods. The subjects were required to answer to the McCoy female sexuality questionnaire and were subjected to a blood test for hormonal evaluation. An ultrasound evaluation of the dorsal clitoral artery was also performed. The higher McCoy sexological value were recorded in the subdermal group; significant differences were recorded among the groups in terms of hormone distribution, with the higher levels of androstenedione in subdermal and control groups. The ultrasound evaluation of dorsal clitoral artery shows a significative correlation between pulsatility and resistance indices and orgasm parameters of McCoy questionnaire. The recorded difference in the sexual and hormonal parameters among the studied hormonal contraceptives may guide toward the personalization of contraceptive choice.

Steroid hormones in multiple tissues of East Greenland polar bears (Ursus maritimus)

The polar bear (Ursus maritimus) is threatened by climate changes and also from persistent organic pollutants affecting polar bear endocrinology governing growth and reproduction. To provide further insight into basic polar bear endocrinology, we determined the levels of steroids in multiple tissues and plasma from East Greenland polar bears. Tissue samples from 10 polar bears, 5 males (2 adults, 3 juveniles) and 5 females (all juveniles) were obtained from the Inuit hunt in Scoresby Sound during springtime. Eleven steroids: pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, estrone, 17α-estradiol and 17β-estradiol were determined in brain, adrenal cortex, testis, testicular vein, plasma, and ovary using GC–MS/MS. In brain tissue, the neuroactive progestagen pregnenolone (11.9 ± 4.4 ng/g ww) and dehydroepiandrosterone (2.26 ± 0.43 ng/g ww) were found in high concentrations. Very high levels of testosterone and androstenedione were observed in testes (>100 ng/g ww) and plasma from testicular vein (testosterone: 108 ± 41 ng/ml; androstenedione: 35.2 ± 11.1 ng/ml). Additionally, a strong correlation was found between the levels of steroids in testes and testicular vein plasma. Progestagens were found in very high levels in ovaries from juvenile females (>100 ng/g ww). Finally, our study indicates that polar bears synthesize androstenedione via the ∆-4 pathway. The present study adds new insight to our knowledge on polar bear endocrinology, which may be used in future studies on polar bear ecology and studies on some of the threats from pollution and climate changes that these animals are facing.