Free Testosterone Levels Research Articles

SAT376 Luteinizing Hormone Secretion in Hyperandrogenic Girls Taking Spironolactone or Metformin

Abstract Disclosure: C.M. Burt Solorzano: None. M. Gilrain: None. S.H. Kim: None. C.R. McCartney: None. Peri-pubertal hyperandrogenism (HA) typically relates to excess adrenal and/or ovarian androgen production in response to adrenocorticotropin (ACTH) and/or luteinizing hormone (LH), respectively. Spironolactone and metformin are commonly used medications to treat adolescent androgen excess. We examined how end-organ responsiveness and LH pulse patterns are affected by these medications in adolescents with HA. We studied free testosterone (T) levels (including baseline and peaks after ACTH and recombinant human chorionic gonadotropin [r-hCG] stimulation), oral glucose tolerance testing (OGTT), and 12-hr overnight LH secretion (sampled q 10 min) in post-menarcheal girls with HA before and after 3-months of either spironolactone (100 mg BID) or metformin (500 mg BID). Free T was calculated using total T (LC-MS/MS) and sex hormone binding globulin (SHBG).To date, 3 girls (aged 12-18) have been studied using spironolactone and 4 girls (aged 14-17) using metformin. (1 girl was studied twice, once with each medication.) After spironolactone treatment, free T changed by -19% (-58 to +37) (median [range]) unstimulated, by -53% (-62 to -15) after ACTH, and by -54% (-66 to +12) after r-hCG. Peak insulin level during OGTT changed by +28% (+16 to +98). Overnight LH pulse frequency changed by -64% (-89 to -10) and LH mean by -74% (-89 to -17). Two subjects in the spironolactone group demonstrated luteal LH patterns despite serum progesterone concentrations < 0.7 ng/mL. In the metformin group, free T changed by +35% (-32 to +125) unstimulated, by 36% (-54 to +66) after ACTH, and by 21% (-41 to +105) after r-hCG. Peak insulin level during OGTT changed by -47% (-74 to +102). LH pulse frequency changed by +10% (-29 to +22) and LH mean by +1% (-2 to +74). To summarize findings to date, mean LH and LH pulse frequency decreased in all three subjects taking spironolactone, including marked reductions in two subjects who demonstrated luteal LH patterns. While free T levels decreased in some of these girls, this seems unlikely to account for such marked changes in LH secretion. And despite similar decreases in T and also decreases in peak insulin in some girls taking metformin, LH pulse frequency did not change markedly. LH pulse patterns in two girls taking spironolactone suggest a progesterone-like effect on LH pulsatility. Spironolactone can cause irregular uterine bleeding, and canrenone (the major metabolite of spironolactone) binds to uterine progesterone receptors competitively (Fernandez MD, Br J Clin Pharm 1983). However, to our knowledge, this is the first report of LH pulse changes in HA girls using spironolactone. Further studies are needed to confirm this finding. Presentation Date: Saturday, June 17, 2023

Salivary testosterone levels are associated with Compulsive Sexual Behavior (CSB) in men but not in women in a community sample.

Despite the inclusion of Compulsive Sexual Behavior (CSB) as a diagnostic entity in the ICD-11 and the increasing number of studies addressing psychological factors leading to its onset and maintenance, little is known about the role of hormonal factors when accounting for this clinical condition (especially in women). This study aimed to provide insights into the association between testosterone levels (i.e., the androgen more intimately linked to sexual desire and arousability) and CSB in both men and women. A total of 80 participants (40 men [Mage = 22.31; SD = 2.93] and 40 women [Mage = 21.79; SD = 2.06]) provided a saliva sample for the estimation of the level of free testosterone and completed a battery of measures assessing CSB and other related sexual domains (sexual sensation seeking and online/offline sexual behavior). In men, salivary testosterone had a positive and significant correlation with three scales assessing CSB (r between 0.316 and 0.334). In women, these correlations were small and non-significant (r between 0.011 and 0.079). In both men and women, the level of salivary testosterone had small non-significant correlations with the other domains of sexual behavior assessed. Individuals' level of testosterone may contribute to the etiopathogenesis of CSB, but only in men. In women, alternative psychological -i.e., motivational, behavioral, or cognitive- processes may be playing a more central role in the expression of this condition.

SAT383 Case Study: Impact of Weight Reduction and Oral Contraceptive Pills on Hyperandrogenism

Abstract Disclosure: A. Syeda: None. T.L. Anderson: None. D. Millar: None. P. Madhavan: None. Introduction: Polycystic ovarian syndrome (PCOS) is a commonly encountered cause of hyperandrogenism which could interfere with fertility. Typical therapeutic options for hyperandrogenism including hormonal contraceptives and anti-androgen medication are contraindicated when planning pregnancy. This case highlights the profound impact of weightloss and oral contraception use to treat severe hyperandrogenism in select cases. Case: A 31-year-old female presented for initial evaluation of hyperandrogenism noted during evaluation for infertility. Laboratory investigations revealed a free testosterone level of 172 ng/dL (n:9-55 ng/dl), SHBG of 17 nmol/L (25-122 nmol/L), DHEAS of 306 ug/dL (n:99-340 ug/dL), TSH of 1.79 uIU/mL (n:0.35-4.96 uIU/mL), ACTH of 12.1 (n:7.2-63.3 pg/mL), cortisol of 9.6 ug/dL (7-23 ug/dL), prolactin of 7.85 ng/mL (3.34-26.72 ng/mL). The patient reported hirsutism, increasing body hair, darkening of skin and significant weight gain over the past 4 years. Menstrual cycles have been reported as being irregular since menarche. Vital signs were stable with a blood pressure of 112/84 mm Hg. Physical examination was remarkable for generalized obesity, hirsutism, and acanthosis nigricans, no abnormal abdominal striae were appreciated. Considering significant elevation in testosterone levels despite low SHBG, an MRI of abdomen and pelvis was obtained which demonstrated ovarian cysts with no concern for ovarian malignancy. CT of the abdomen without contrast was negative for adrenal mass. The overall clinical picture was suggestive of a diagnosis of PCOS. As the patient was planning pregnancy, oral contraceptive agents and spironolactone were deferred initially. The patient was encouraged to lose weight with lifestyle modifications and was started on up titrating dose of Metformin as tolerated. The patient complied with the recommendations and over the course of two years her weight decreased from 171 lbs. to 158 lbs. In the interim, she was placed on oral contraceptive pills for 2 months to undergo hysteroscopy. Subsequently, the testosterone levels normalized to 17 ng/dL. Conclusion: Although previous research has demonstrated the significance of weight loss, for reducing symptoms in patients with PCOS, this role has not been well elucidated in cases of severe hyperandrogenism without a neoplastic cause. The mechanism of interaction between weight loss, oral contraceptive pills and decreased androgens is based on the reduction in insulin resistance which causes a decrease in theca cell androgen synthesis and an increased SHBG. Additionally, a decrease in adiposity reduces the conversion of Δ4-androstenedione to testosterone. Notably, in this case there is potentially a causal relationship between the patient's weight loss of 13 pounds (7.6% of her body weight), OCP use and her return to normal testosterone levels. Presentation Date: Saturday, June 17, 2023

Sex Differences and Cytokine Profiles among Patients Hospitalized for COVID-19 and during Their Recovery: The Predominance of Adhesion Molecules in Females and Oxidative Stress in Males.

The severity and mortality of coronavirus disease 2019 (COVID-19) are greater in males than in females, though the infection rate is the same in the two sexes. We investigated sex hormone differences associated with the hyperinflammatory immune response to SARS-CoV-2 on the basis of patients' cytokine profiles and vaccination statuses. Clinical and laboratory data of 117 patients with COVID-19 were collected to examine sex differences associated with oxidative stress markers, neutrophil extracellular traps (NETs), and plasma cytokine levels up to 5 months from hospital admission. The testosterone and free testosterone levels were low in male patients with COVID-19 and returned to normal values after recovery from the disease. The dihydrotestosterone (DHT) levels were transiently reduced, while the sex hormone-binding globulin levels were decreased in post-COVID-19 male patients. The levels of the inflammatory cytokines interleukin-6 (IL-6) and IL-10 appeared generally increased at diagnosis and decreased in post-COVID-19 patients. In females, the concentration of tumor necrosis factor-alpha was increased by four times at diagnosis. The levels of the coagulation markers intercellular adhesion molecule-1 (ICAM-1) and E-selectin were consistently upregulated in post-COVID-19 female patients, in contrast to those of vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and chemokine IL-8. DHT increased the levels of reactive oxygen species in the neutrophils of male patients, while estradiol decreased them in females. Markers for NET, such as circulating DNA and myeloperoxidase, were significantly more abundant in the patients' plasma. Sex hormones have a potential protective role during SARS-CoV-2 infection, which is weakened by impaired testosterone synthesis in men.

Erectile dysfunction in copper and cobalt miners: a cross-sectional study in the former Katanga province, Democratic Republic of the Congo.

The African Copperbelt is a site of intense artisanal and industrial mining and refining of copper and cobalt. We aimed to investigate factors that are possibly associated with erectile dysfunction (ED) in metal miners in the former Katanga province of the Democratic Republic of the Congo. In a cross-sectional study of 138 miners and 139 controls (bakers), we administered questionnaires to obtain sociodemographic and occupational data and to assess male sexual function (International Index of Erectile Function [IIEF]) and marital relation quality (Revised Dyadic Adjustment Scale). Furthermore, we measured trace metals in blood and urine, as well as testosterone and thyroid hormones in serum. Outcomes included the prevalence of questionnaire-derived ED and the relation of ED with individual characteristics, serum testosterone, and environmental factors. Miners were on average 4years older than bakers (mean ± SD, 37.5 ± 6.9 vs 33.3 ± 5.7 years). Miners had significantly lower scores than bakers on the IIEF (median [IQR], 66 [49-73] vs 73 [66-74]) and the 3 domains of the Revised Dyadic Adjustment Scale (consensus, satisfaction, cohesion). Free testosterone was significantly lower in miners than bakers (ng/dL; 8.11 [6.90-10.10] vs 10.52 [8.83-12.58]; P ˂ .001). In miners, sex hormone-binding globulin correlated positively with blood Pb and urinary Cd. In a multivariable analysis, mild to moderate ED or moderate ED (IIEF-erectile function score ≤18) was significantly associated with having a mining-related job (adjusted odds ratio [aOR], 2.6; 95% CI, 1.3-5.3), work seniority ˃5years (aOR, 2.3; 95% CI, 1.1-4.6), alcohol consumption (aOR, 2.8; 95% CI, 1.2-6.7), and aphrodisiacs use (aOR, 4.2; 95% CI, 2.2-8.0). Mediation analysis showed that marital relationship partially mediated the relation between work seniority >5years in mining and ED. The high prevalence of ED found in artisanal mine workers indicates that work-related factors should be considered as possibly contributing, directly or indirectly, to sexual dysfunction in men. Strengths include being the first epidemiologic study documenting ED with validated questionnaires and its possible determinants, including exposure to toxic metals, among young artisanal miners vs a suitable control group. Limitations are the cross-sectional design with convenience sampling and absence of objective confirmation of ED. As compared with controls, miners reported poorer sexual function and lower quality of their marital relationship, and they had lower free testosterone levels, which may be due to their high exposure to trace metals.

A-048 Accurate Measurement of Free Testosterone in Serum using Equilibrium Dialysis Coupled with ID-UHPLC-MS/MS

Abstract Background Assessment of free testosterone (FT) has been recommended in recent clinical practice guidelines as a biomarker for diagnosis and management of testosterone related disorders such as male testosterone deficiency due to hypogonadism and female androgen excess due to polycystic ovary syndrome (PCOS). FT is currently measured using direct commercial immunoassays, assays using equilibrium dialysis (ED) or other separation techniques. Though the ED approach is recognized as the recommended approach, it is laborious and technically challenging for routine clinical use. The CDC Clinical Standardization Program is developing a high throughput automated method using the ED procedure coupled with isotope dilution ultra-high-performance liquid chromatography tandem mass spectrometry (ID-UHPLC-MS/MS) that is suitable for routine patient care and large-scale epidemiologic studies. Methods Serum samples are dialyzed in a custom-designed multi-well plate against a protein-free HEPES buffer (pH 7.4) at 37 °C until equilibrium. After isolating endogenous FT from protein-bound testosterone by ED, isotope-labeled internal standard (13C3-testosterone) was added to the dialysate for quantification. Certified pure primary reference material (National Measurement Institute-M914) was used to prepare calibrators, enabling traceability and ensuring measurement trueness. FT was further isolated from the dialysate matrix using supported liquid extraction and a chromatographic separation from interfering compounds and quantitation by tandem MS. Results The measurement ranges covered 0.2–1000 ng/dL for testosterone, with the bias within ±5% and precision less than 10% CV. A total of 45 samples with a wide range of total testosterone (TT, 21–912 ng/dL) and SHBG (11–129 nmol/L) were analyzed and showed the suitability of this assay to measure the serum free testosterone levels in normal, hypogonadal males as well as in the majority of normal females and females with androgen excess. The application of 48-well format plate and automated liquid handler system significantly improves the throughput of sample preparation. In addition, comparison of the TT results measured with the presented TT method with calculated TT concentrations, suggest that on average calculation overestimates TT concentration by 34%. Conclusion The described high throughput method for FT allows for sufficiently accurate and precise measurement for routine applications including large epidemiologic studies to help with establishing reference intervals.

Association Between Vitamin D Deficiency and Testosterone Levels in Adult Males: A Systematic Review.

Vitamin D deficiency and its potential impact on testosterone levels have been subjects of scientific interest. This systematic review aims to evaluate the association between vitamin D deficiency and testosterone levels in adult males and examine the effects of vitamin D supplementation on testosterone. A comprehensive literature search was conducted in accordance with the PRISMA guidelines across PubMed, Google Scholar, and ScienceDirect. The inclusion criteria involved studies published in English between 2013 and 2023, which investigated the correlation between vitamin D and testosterone levels in adult males. The process of data extraction and synthesis encompassed various aspects, including study characteristics, participant demographics, measurement methods, and outcomes pertaining to the association. The initial search resulted in a pool of 354,235 articles. Through the application of relevant filters and the review of titles and abstracts, 48 articles were chosen for further assessment. Out of these, eight studies fulfilled the inclusion criteria and were ultimately incorporated into the final review. The included studies consisted of four cross-sectional studies, three randomized controlled trials (RCTs), and one analysis utilizing Mendelian randomization. The results showed heterogeneity among the studies, as some reported a positive correlation between vitamin D levels and testosterone, while others did not find a significant association. The effects of vitamin D supplementation on testosterone levels were inconclusive, with limited evidence of significant changes in total testosterone. However, potential influences on sex hormone-binding globulin and free testosterone levels were observed. To establish more definitive evidence regarding the impact of vitamin D on testosterone levels, there is a need for further well-designed, long-term RCTs that encompass diverse populations.

Testosterone and Peripheral Arterial Disease.

Testosterone levels in men begin declining in the early years of adulthood, with a 1-2% reduction/year. Low testosterone levels in men are associated with obesity, metabolic syndrome, diabetes mellitus, dyslipidaemia, hypertension and increased cardiovascular mortality. However, observational studies of testosterone levels in males and their relationship with peripheral arterial disease (PAD) have yielded mixed results; only some cohorts show a clear association with low free testosterone levels. This discrepancy may, in part, be due to methodological issues with estimating free testosterone but also to different effects of testosterone on the vessel wall and metabolism. While testosterone improves glycaemic control, has anti-obesity effects and induces vasodilation, it also stimulates platelet aggregation and increases the haematocrit. Androgen deprivation treatment for advanced prostate cancer may be associated with elevated cardiovascular risk, as is testosterone abuse for performance enhancement. On the other hand, judicious treatment of male hypogonadism or testosterone treatment of trans-men appears to be safe.

Long-acting glucagon-like peptide 1 receptor agonists boost erectile function in men with type 2 diabetes mellitus complaining of erectile dysfunction: A retrospective cohort study.

The pharmacological management of erectile dysfunction (ED) in type 2 diabetes (T2D) is challenging as ED has a multifactorial etiology. The therapeutic potential of certain antihyperglycemic medications, such as glucagon-like peptide 1 receptor agonists (GLP-1RAs), has yet to be entirely studied in this setting. A retrospective cohort study was conducted on 108 outpatients (median age 60 [56, 65] years) with T2D complaining of ED. Data were extracted from a database referring to patients with a 1-year follow-up on stable treatment with metformin alone (n=45) and GLP-1RAs as an add-on to metformin (n=63). Erectile function was assessed by the 5-item International Index of Erectile Function (IIEF5) at baseline and after 1 year of stable treatment . Values were compared between baseline (T0) and after 12 months of treatment (T12). ED was confirmed in all at baseline, with an IIEF5 score range between 13 and 19 points. After 12 months of treatment, glucose managementwas better in patients treated with GLP-1RAs plus metformin (HbA1c T0: 8.3±0.2 vs. HbA1c T12: 7%±0.3%, p<0.0001) than in those on metformin alone (HbA1c T0: 7±0.5vs. HbA1c T12: 7.3±0.4, p=0.0007). GLP-1RAs plus metformin over metformin alone resulted in a significant weight loss (-5.82±0.69kg, p<0.0001), reduction in waist circumference (-4.99±0.6cm, p<0.0001), improvement inHbA1c (-0.56%±0.13%, p<0.0001), and fasting plasma glucose (-25.54±3.09mg/dL, p<0.0001), increase in total (+41.41±6.11ng/dL, p<0.0001) and free (0.44±0.09 ng/dL, p<0.0001) testosterone levels, and gain in self-reported erectile function (IIEF5 score: +2.26±0.26, p<0.0001). The gain in the IIEF5 score was more relevant in patients with higher baseline IIEF5 score (estimated coefficient: 0.16±0.08, p=0.045), those having carotid stenosis (0.50±0.24, p=0.045), and showing weight loss from baseline (-0.08±0.03, p=0.013). The leading determinant of the final IIEF5 score was a 1-year treatment with GLP-1RAs plus metformin over metformin alone (2.74±0.53, p<0.0001). GLP-1RAs plus metformin over metformin alone improved ED regardless of different background characteristics of patients and partially irrespective of therapeutic targets achieved after 12 months of treatment. GLP-1RAs may have induced positive vasculature effects, resulting in improved erectile function in T2D. Due to the retrospective nature of the study, a potential cause-effect relationship between the use of GLP-1RAs plus metformin over metformin alone in improving ED cannot be verified and confirmed. Randomized clinical trials are needed to provide evidence supporting the use of GLP-1RAs for treating ED in T2D.

Non-alcoholic fatty liver disease is associated with hyperandrogenism in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a highly complex reproductive metabolic disorder and women with PCOS have high prevalence of non-alcoholic fatty liver disease (NAFLD). Despite both hyperandrogenism and insulin resistance are common pathophysiologies in NAFLD and PCOS, this association is still controversial. Therefore, the aim of this study is to evaluate the relationship between hyperandrogenism and NAFLD in females diagnosed with PCOS. We recruited 667 women diagnosed with PCOS and 289 women with regular menstrual cycles as control. The PCOS diagnosis was made using National Institute of Child Health and Human Disease criteria. Total and free testosterone levels (TT and TF, respectively), and free androgen index (FAI) were used as measures of hyperandrogenism. Fatty liver index and liver fat score (FLI and LFS, respectively), and hepatic steatosis index (HSI) were used to assess NAFLD. The prevalence of NAFLD in PCOS women evaluated by LFS, FLI, and HIS were 19.9, 10.3, and 32.2%, respectively. In the control group, the incidence was 2.1, 0.7, and 4.2%, respectively. Both FT and FAI levels showed significant association with increased NAFLD-related indices, after adjusting for insulin resistance and other factors (LFS (OR 3.18 (95% CI 1.53–6.63) in FT; 1.12 (1.04–1.22) in FAI), FLI (OR 2.68 (95% CI 1.43–5.03) in FT; 1.13 (1.06–1.20) in FAI), and HSI (OR 3.29 (95% CI 2.08–5.21) in FT; 1.5 (1.09–1.21) in FAI). TT did not exhibit association with any NAFLD index. In women with PCOS, significantly higher rate of NAFLD was observed compared to the control women. The FT and FAI were independently associated with NAFLD in women with PCOS. The findings suggest the possibility of hyperandrogenism contributing to the progression and/or development of NAFLD in PCOS.

Prevalence of Polycystic Ovarian Syndrome in Girls with a History of Idiopathic Central Precocious Puberty

Introduction: The prevalence of polycystic ovarian syndrome (PCOS) in adolescent girls is between 1 and 4.3%. It remains controversial whether women with a history of idiopathic central precocious puberty (ICPP) are at increased risk for PCOS. Our objective was to assess the prevalence of PCOS in adolescents with a history of ICPP compared with healthy adolescents and the prevalence of PCOS among ICPP girls who have received or not gonadotropin-releasing hormone analogue (GnRHa) treatment. Methods: We assessed post-menarcheal girls with a history of ICPP. Girls were evaluated at gynecological age ≥2.5 years. Data collected were age at menarche, menstrual cycle characteristics, BMI, clinical hyperandrogenism (HA), total and free testosterone levels. PCOS diagnosis was defined by criteria for adolescents. Subjects were also analyzed regarding whether or not they had received GnRHa treatment. Results: Ninety-four subjects were assessed, and 63 had been treated with GnRHa. Menstrual disorders were found in 29%, clinical HA in 36%, and biochemical HA in 23%. Twelve percent met the diagnostic criteria for PCOS. There was no difference in BMI or in the incidence of menstrual dysfunction or hyperandrogenemia between treated and untreated patients. A higher proportion of clinical HA was found in untreated patients when compared to treated girls. The relative risk (RR) of developing PCOS in ICPP girls was 2.5 compared to a population of healthy adolescents. This RR was not higher in patients who received treatment with GnRHa than in those who did not. Conclusion: Adolescent girls with a history of ICPP have an increased risk of PCOS. This risk seems not to be related to GnRHa treatment.

Cyhexatin causes developmental toxic effects by disrupting endocrine system and inducing behavioral inhibition, apoptosis and DNA hypomethylation in zebrafish (Danio rerio) larvae

Cyhexatin (CYT), an organotin acaricide, is extensively utilized in developing countries to mitigate plant diseases caused by mites and minimize agricultural crop losses. However, the comprehensive mechanisms underlying the developmental stage of non-target organisms remain largely unexplored. In this study, zebrafish embryos were firstly exposed to CYT (0.06, 0.12, and 0.20 ng/mL, referred to as CYTL, CYTM, and CYTH, respectively) from 2 hpf (hours post fertilization) to 30 dpf (days post fertilization). No developmental toxicity was observed in the CYTL and CYTM groups, except for induced deformed phenotypes in the CYTM group at 120 hpf. However, exposure to CYTH resulted in significant reductions in spontaneous movement (24 hpf), heart rate (48 hpf), hatching rate (48 and 72 hpf), body weight (30 dpf), whole body length (30 dpf), and locomotion (30 dpf). Additionally, CYTH exposure induced morphological malformations, including spinal curvature, pericardial edema, and tail curvature in zebrafish larvae. Moreover, CYTH treatment induced apoptosis, increased reactive oxygen species (ROS) production, and resulted in significant reductions in free T3, cholesterol, estradiol, and testosterone levels in zebrafish larvae, while free T4 levels were increased. RNA-Seq analysis indicated that CYTH exposure led to significant alterations in the genome-wide gene expression profiles of zebrafish, particularly in the thyroid hormone and steroid biosynthesis signaling pathways, indicating endocrine disruption. Furthermore, CYTH exposure induced global DNA hypomethylation, reduced S-adenosylmethionine (SAM) levels and the SAM/S-adenosylhomocysteine (SAH) ratio, elevated SAH levels, and suppressed the mRNA expression of DNA methyltransferases (DNMTs) while also downregulating DNMT1 at both the gene and protein levels in zebrafish larvae. Overall, this study partially elucidated the developmental toxicity and endocrine disruption caused by CYT in zebrafish, providing evidence of the environmental hazards associated with this acaricide.

Early Postnatal Experience Modifies Activation of the Pituitary Testicular Complex in Male House Mice (Mus Musculus) Exposed to the Odor of Receptive Con- and Heterospecific Females

For the first time, it was shown that activation of the pituitary–testicular complex in male house mice exposed to the odor of receptive females of their own and closely related species was modified under the influence of early postnatal experience and the maternal environment. We have confirmed associated formation of behavioral and physiological mechanisms of precopulatory isolation in early ontogenesis. The serum levels of free testosterone in males of closely related species M. spicilegus and M. m. wagneri differ, it is significantly lower in mound-building mice. In males fostered by a conspecific female, the level of free testosterone was significantly lower when exposed to a heterospecific female odor in comparison with a conspecific odor. The rearing of M. m. wagneri males by females of a closely related species led to a decrease in the testosterone response caused by exposure to female chemosignals (both con- and heterospecific) and to the absence of differences in the serum level of free testosterone when exposed to the odor of a female of their own or closely related species. These results indicate that the rearing conditions had a significant influence on the formation of hormonal mechanisms of reproductive isolation.

Relation between athletic club affiliation from school age and future serum free testosterone levels in Japan: A cross-sectional study.

Testosterone deficiency is often related to geriatric syndrome including erectile dysfunction, osteo-porosis, depression, cognitive impairment, cardiovascular diseases and frailty. Despite the existence of many studies on short-term exercise and serum testosterone levels, few research have focused on exercise habits from young age and testosterone values in middle-aged male. In this study, we investigated whether belonging to an athletic club from school age could predict serum-free testosterone (FT) levels. The subjects were 1609 middle-aged male outpatients aged 40 years or older (median: 61 years, interquartile range: 54-69) who visited our hospital. Participants had their FT values measured in the morning hours during the period from December 2007 to June 2009. A questionnaire survey on exercise habits was conducted at the same time as the measurements. The exercise habit questionnaire was created based on whether the patients belonged to an athletic club in (a) elementary school, (b) junior high school, (c) high school, (d) college, (e) adult life, and (f) at the time of the test. There was only one positive response to the questionnaire among 456 patients (28% of total), followed by zero for 358 patients (22% of total). The number of patients with low-testosterone levels (FT < 8.5 pg/mL) according to the Japanese diagnostic criteria for late-onset of hypogonadism was 839 (52.1%). In multivariate analysis, it was shown that with low-testosterone levels (FT < 8.5 pg/mL), age (odds ratio [OR]: 1.065, 95% confidence interval [CI]: 1.052-1.079; p < 0.001), hypertension (OR: 3.489, 95% CI: 2.728-4.462; p < 0.001), type-2 diabetes (OR: 3.035, 95% CI: 2.296-4.01; p < 0.001), and dyslipidemia (OR: 2.039, 95% CI: 1.558-2.668; p < 0.001) were risk factors, and more than two positive responses to the questionnaire (OR: 0.886, 95% CI: 0.802-0.980; p = 0.018) were also a significant independent factor. A sports club membership during school years may affect future testosterone levels.

Testosterone and depression in men with heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background Low testosterone levels are frequently seen in men with chronic heart failure. Testosterone interacts with neurotransmitters like dopamine, serotonin, and noradrenaline and its levels affect neurobehavioral characteristics such as irritability, emotional tone, and cognitive function. Depression and anxiety are very frequent in patients with heart failure Purpose To evaluate the relationship between testosterone levels and depression severity in a cohort of males with dilated cardiomyopathy and heart failure. Methods In this cross-sectional single-center study we included 78 Caucasian male patients with dilated cardiomyopathy and chronic heart failure (mean age 58.5 years, range 29 – 80 years old; mean left ventricular ejection fraction 24.54%). All patients were subjected to clinical, biological, and echocardiographic examinations. Depressive symptoms were assessed using the PHQ-9 Depression Test Questionnaire which is a simple 97% sensitivity test used for guiding the diagnosis of depression in high-risk populations including patients with heart failure. Serum total T levels and sex hormone-binding globulin were measured by chemiluminescence assays and free testosterone (FT) levels were calculated. Based on the results from these assays, patients were divided into five groups according to the 5 stages of the PHQ-9 scale (minimal, mild, moderate, moderately severe, and severe). Results Patients with high levels of FT (82.83±55.73 pg/mL) didn’t show any features consistent with depression, however patients with lower levels of FT had a proportional increase in the number of signs and symptoms suggestive of depression (67.97±37.12 pg/mL– mild depression, 45.24±28.52 pg/mL - moderate depression, 29.79±20.32 pg/mL – moderately severe depression, 18.56±14.28 pg/mL- severe depression). Patients with depression also had higher levels of higher C-reactive protein, urea, and creatinine (p&amp;lt;0.001). Conclusion Lower levels of free testosterone are associated with a proportional increase in depressive symptoms in patients with dilated cardiomyopathy and heart failure.

Higher free testosterone in the third trimester was associated withlower abdominal circumference at birth in boys: Odense childcohort.

To investigate associations between maternal testosterone status and offspring birth anthropometrics. Population-based prospective cohort study. University Hospital. 1486 mother-child dyads from Odense Child Cohort. Maternal blood samples were collected at gestational weeks 27-30 and free testosterone (FT) levels were calculated using the Vermeulen equation from total testosterone (TT) analysed by mass spectrometry and sex hormone binding globulin. Associations between FT or TT levels and birth anthropometrics were analysed with multiple linear regression models according to offspring sex with adjustment for maternal age, parity, smoking and educational level. Analyses were repeated with polycystic ovary syndrome as exposure for offspring birth anthropometrics. Offspring birth weight (BW), birth length, abdominal and head circumferences. Maternal mean (SD) age was 30.2 (4.5) years and pre-pregnancy body mass index was 23.5 (5.3) kg/m2 . In boys (n = 787), higher FT was associated with lower birth weight (adjusted doubling constant = -65.53, P = 0.010), shorter birth length (adjusted doubling constant = -0.43, P < 0.001), and lower abdominal circumference (adjusted doubling constant = -0.39, P < 0.001); Higher TT was associated with lower abdominal circumference (adjusted doubling constant = -0.25, P = 0.028). In girls, no associations were found between maternal FT or TT and offspring anthropometrics. Higher maternal free testosterone exposure was linked to reduced birth weight, length and abdominal circumference in boys, whereas girls were not susceptible to maternal testosterone exposure.

Association of free testosterone, glucose level and obesity among women with polycystic ovary syndrome in Soran city, Kurdistan-Iraq

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting approximately 5–10% of women of reproductive age and it is also a major cause of anovulatory infertility. PCOS is associated with obesity and conditions like hirsutism, acne, diabetes, and irregular periods. AimThe present study aimed to evaluate the serum-free testosterone (FT) levels of women afflicted with hirsutism, one of the main physical manifestations of PCOS versus healthy women and determine whether their serum testosterone levels correlate with polycystic ovaries, glucose levels, menstrual abnormalities, and obesity. MethodsThis study assessed 180 women; this included 140 females who suffered from excessive and unwanted hair growth on the chin and 40 healthy women as a control group. Free testosterone levels and fasting blood glucose levels were taken. Prior to the study, ultrasonographic (US) tests were performed for all patients to diagnose polycystic ovaries. ResultsPatients with hirsutism exhibited a significant elevation in free testosterone (FT) compared to the control group. Approximately half of these women were confirmed to have a polycystic ovary, and 42.8% of them were overweight and obese. Additionally, women between 18 and 20 years old (G1) present with the highest level of FT. ConclusionSerum FT levels were significantly increased in hirsute women, and this positively correlated with BMI and glucose levels in women with PCOS. Glucose levels may serve as a potentially effective biomarker in evaluating the severity of hirsutism in women suspected of having PCOS.

EARLY POSTNATAL EXPERIENCE MODIFIES ACTIVATION OF THE PITUITARY-TESTICULAR COMPLEX IN MALE HOUSE MICE (&lt;i&gt;MUS MUSCULUS)&lt;/i&gt; EXPOSED TO THE ODOR OF RECEPTIVE CON- AND HETEROSPECIFIC FEMALES

For the first time, data were obtained proving the modification of the activation of the pituitary-testicular complex of male house mice under the influence of early postnatal experience and the maternal environment when exposed to the odor of receptive females of their own and closely related species. We have confirmed the conjugacy of the formation of behavioral and physiological mechanisms of precopulatory isolation in early ontogenesis. The serum level of free testosterone in males of closely related species M. spicilegus and M. m. wagneri differ, it is significantly lower in mound-building mice. The level of free testosterone of males fostered by a conspecific female was significantly lower when they exposed a heterospecific in comparison with a conspecific female odor. The rearing of M. m. wagneri males by females of a closely related species caused a decrease in the testosterone response of males to the exposure of chemosignals from a female (both con-and heterospecific) and led to the absence of differences in the serum level of free testosterone when they exposed to the odor of a female of their own or closely related species. The data obtained indicate a significant influence of the rearing conditions on the formation of hormonal mechanisms of reproductive isolation.

Meta-analysis and construction of simple-to-use nomograms for approximating testosterone levels gained from weight loss in obese men.

Obesity-induced hypogonadism, which manifests as erectile dysfunction and a lack of libido, is a less visible and under-recognized obesity-related disorder in men. We examined the impact of weight loss on total (TT) and free testosterone (FT) levels, and constructed nomograms to provide an easy-to-use visual aid for clinicians. Meta-analysis was conducted using RevMan (v5.3) and expressed in standardized mean differences (SMD) for testosterone. Parallel-scale nomograms were constructed from baseline and target body mass index values to estimate the gain in testosterone. In total, 44 studies were included, comprising 1,774 participants and 2,159 datasets, as some studies included several datasets at different time points. Weight loss was controlled by low calorie diet (LCD) in 19 studies (735 participants, 988 datasets), by bariatric surgery (BS) in 26 studies (1,039 participants, 1,171 datasets), and by both in one study. The median follow-up was 26weeks (interquartile range=12-52). The range of baseline mean age was 21-68yr, BMI: 26.2-71.2kg/m2 , TT: 7-20.2nmol/L and FT: 140-583pmol/L. TT levels increased after weight loss by LCD: SMD (95%CI)=2.5nmol/L (1.9-3.1) and by BS: SMD=7.2nmol/L (6.0-8.4); the combined TT gain was 4.8nmol/L (3.9-5.6). FT levels increased after weight reduction by LCD: SMD=19.9pmol/L (7.3-32.5) and by BS: SMD=58.0pmol/L (44.3-71.7); the combined gain was 42.2pmol/L (31.4-52.9). Greater amounts of total and free testosterone could be gained by weight loss in men with higher baseline BMI, or lower levels of SHBG, TT and FT, while gain in TT was relatively greater in older and FT in younger age. Age-stratified nomograms revealed that compared to older men (>40yr), younger men (≤40yr) gained less TT but more FT for a given weight loss. Both TT and FT levels increased after weight loss, relatively greater with higher baseline BMI, or lower levels of SHBG, TT and FT. Nomograms constructed from a large number of participants with a wide range of BMI and testosterone values provide an evidence-based and simple-to-use tool in clinical practice.

Frequency and Clinical Significance of Low or High Sex Hormone Binding Globulin Levels in Patients Suspected of Harboring Abnormal Testosterone Levels

Purpose: We aim to examine the frequency of low or high sex hormone binding globulin (SHBG) levels and to investigate whether they are associated with comorbidities and hormonal derangements in patients suspected of harboring abnormal testosterone levels. Methods: This was a retrospective study of adult patients who underwent SHBG testing as part of a panel for testosterone at UCLA Health between May and July 2019. Results: A total of 1102 male and 689 female patients underwent SHBG testing; the most common indications of the tests were suspected hypogonadism in male and hyperandrogenism in female patients. Eight male (0.7%, 9.4±1.0 nmol/L) and 66 female patients (9.6%, 21.7±5.2 nmol/L) exhibited low SHBG levels, and 113 male (10.3%, 106.6±29.6 nmol/L) and 118 female (17.1%, 187.1±59.6 nmol/L) patients exhibited high SHBG levels. Patients with low SHBG levels were younger, had higher body mass index, and less commonly receive sex hormone treatments than those with high SHBG levels but they were not different in other assessed clinical parameters. Bioavailable and free testosterone levels were not different in males with low or high SHBG levels but were significantly higher in females with low SHBG levels than in those with high SHBG levels.