Free Testosterone Levels Research Articles

Rapid Liquid Chromatography–Tandem Mass Spectrometry Method for Determination of Total and Free Testosterone in Human Serum and Its Application to Monitoring Biomarker Response of Elite Athletes

Total testosterone (TT) and free testosterone (FT) are important biochemical markers for anabolism of the human body, and can also serve as early screening indicators for overtraining syndrome (OTS). Presently, there is no fast and reliable serum TT and FT determination method in the field of sport science that can meet the requirements of sports research. Thus, a rapid and accurate determination method for serum TT and FT to fill the gap is needed urgently in sports training. Herein, a simple and reliable liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of TT and FT in serum was developed and fully validated, followed by the application of professional athletes in training monitoring. Efficient pretreatments based on only one-step liquid–liquid extraction (LLE) for TT and one-step LLE after a 20 min ultrafiltration for FT were adopted in this study, and the isotope internal standard of testosterone-13C3 was used to ensure the reliability of the whole procedure. A linear range of four orders of magnitude with 0.02–100 ng/mL can meet the concentration range requirement between a higher limit for male TT and a lower limit for female FT. The accuracy, precision, stability, and matrix effect were all within the limits of the guidelines. The serum TT and FT levels of 200 professional athletes (98 male athletes and 102 female athletes) were investigated by this method. Serum TT, FT, and FT/TT levels of professional athletes were significantly higher than the general population, and serum TT levels were significantly higher by LC-MS/MS than by a chemiluminescence immunoassay. In conclusion, the LC-MS/MS method for TT and FT measurement developed in this study is time-saving and easy to operate, which can be used as a reliable method for the determination of serum TT and FT in sports training, offering valuable information for monitoring anabolism of athletes and screening OTS in the early stage.

Androgen Deficiency, Associations and Survival of Men With Stage 4 and 5 Chronic Kidney Disease: A Cohort Study.

Anaemia is a key cause of morbidity in chronic kidney disease (CKD). Androgen deficiency (AD) in males can contribute to anaemia of all causes, including in CKD. We sought to examine the prevalence of AD in men with CKD, the extent to which it contributed to anaemia and whether it was independently associated with long-term survival. This cross-sectional observational study was conducted among males aged 18 years and over with CKD stages 4 and 5. The study analysed morning blood samples with regard to their full blood count, urea and electrolytes, albumin, lipids, testosterone (T) and sex hormone binding globulin, with calculation of free testosterone by mass action equation. Mortality data were obtained 15 years later for survival analysis. Among 322 patients with a mean age of 63 years, the overall prevalence of AD was 68.9%. There was a statistically significant negative correlation between erythropoiesis stimulating agent (ESA) dose and testosterone concentrations (Pearson correlation -0.193, p = 0.05). There was a positive correlation between haemoglobin (Hb) and free testosterone level among patients not on ESA therapy (Pearson correlation 0.331, p < 0.001). Kaplan-Meier plots showed p < 0.001 on log-rank analysis, indicating that AD was significantly associated with worse survival. However, in Cox regression analysis, free testosterone was not associated with survival (95% CI for free testosterone 0.997-1.000). AD is highly prevalent among this population, and increases further with older age and more severe CKD warranting haemodialysis. Association of lower Hb and higher ESA dose with lower T concentration might be causative, which has important pharmaco-economic as well as clinical implications. Lower survival in men with low T, more likely reflects overall poor health rather than causation. A properly constituted randomised controlled study evaluating the effect of native T replacement is warranted in men with CKD and AD.

8462 Synergistic Outcomes Of hCG And GLP1-RA Combination Therapy: Improved Body Composition And Carbohydrate Metabolism

Abstract Disclosure: F. Comite: None. K. O'Malley: None. Objective: Precision medicine prevents and reverses diseases of aging by way of systematic analysis of body composition and extensive blood biomarkers. Andropause, the age-related reduction of free testosterone (FT) in males, elicits symptoms primarily of muscle loss, decreased libido, and diminished energy. Exogenous testosterone therapy (TTx) subsequently increases lean body mass (LBM) and improves both libido and energy levels in affected males. More recently, stimulation of endogenous testosterone from the testes, human Chorionic Gonadotropin (hCG) has emerged as a compelling physiologic alternative to TTx. Common comorbidities to andropause are DMII and/or obesity. Recent literature surrounds the use of GLP-1 receptor agonists to improve insulin sensitivity in these disorders of carbohydrate metabolism. A primary benefit secondary to GLP-1 use is reduction of fat mass; however, concerns of this monotherapy surround loss of muscle.[1] Remarkably, when treated adjunctly with GLP-1s, hCG therapy significantly mitigates muscle loss while maintaining optimal carbohydrate biomarkers. The efficacy and benefits of hormonal optimization through hCG therapy simultaneous to GLP-1 intervention were investigated. Methods: In this retrospective analysis, a cohort of 20 males ≥30 years of age were reviewed at baseline timepoints and 18 months post treatment-initiation. Participants underwent biweekly hCG and weekly GLP-1 subcutaneous injections. Exclusion criteria restricted use of alternative GLP-1/GIP combination medication. Paired T-Tests were used to determine a relationship between LBM, FT, percent body fat (PBF), fasting glucose (FG), fasting insulin (FI), and HbA1c at each timepoint. Results: Body composition analysis as shown via bioelectrical impedance proved baseline PBF (mean=24.60) significantly reduced post-treatment (p&amp;lt;0.05, mean=18.08) for all participants. In addition, relevant carbohydrate metabolic biomarkers FG, FI, and HbA1c provided significant reductions (p&amp;lt;0.05). Initial FT (mean=67.76) and LBM (mean=150.36) increased significantly at follow-up (p&amp;lt;0.05) with values of 167.55 and 154.91, respectively. Discussion: Using metrics of precision medicine, our interpretation reveals a promising combination therapy for males experiencing andropause. The novel use of hCG to optimize FT levels enhances muscle, while simultaneously, fat loss and reversal of harmful carbohydrate metabolic markers resultant from GLP-1 therapy are achieved. Muscle loss due to overall weight loss is thus ameliorated. Our findings merit further investigation of the magnitude of downstream improvements, particularly in energy and libido.

5086 Approaching the Enigma: Unveiling a Pituitary Stalk Lesion with Imaging and Hormonal Patterns

Abstract Disclosure: N. Rodriguez-Morales: None. P. Guido: None. Background: Pituitary stalk lesions (PSL) pose a diagnostic dilemma for endocrinologists. Multiple studies have attempted to associate hormonal imbalances and imaging patterns to a specific etiology (1,2). However, the diagnosis remains a mystery on many occasions. We describe a case of secondary hypogonadism and central DI attributed by a PSL. Clinical Case: A 39-year-old male presented with symptoms of hypogonadism and polyuria. Initial workup was consistent with secondary hypogonadism; decreased free and total testosterone levels (1.8 pg/dL and 9 ng/dL, n&amp;gt;35 pg/dL, n&amp;gt;250 ng/dL), LH (0.2 mIU/mL, n&amp;gt;1.5 mIU/mL), and FSH (&amp;lt;0.7 mIU/mL, n&amp;gt;1.6 mIU/mL). The remaining anterior pituitary hormones were within normal limits. The patient was also polyuric (6.5L urine output in 24hr). HgbA1c was normal. Urine Na, urine Osm demonstrated water diuresis (13 mmol/L and 54 mOsm/kg, respectively). A water deprivation test was performed. Initial urine Osm after water restriction was 119 mOsm/kg, which more than tripled to 575 mOsm/kg after administration of desmopressin, diagnostic of central DI. Pituitary MRI showed a well-circumscribed thickening of the pituitary stalk (6x6x5mm), with uniform enhancement. Evaluation for etiology to rule out germ cell tumor, lymphoma, sarcoidosis, opportunistic infection, tuberculosis, Langerhans cell histiocytosis showed a normal serum hCG, HIV, ACE, LDH, AFP. A lumbar puncture demonstrated normal cytology and was negative for AFB. Whole body bone scintigraphy and chest X-ray were normal. Pituitary deficits were treated with hormone replacement (testosterone and desmopressin), and a repeat MRI showed a stable lesion. Conclusion: Noninvasive testing is key to the evaluation of a pituitary stalk lesion. Careful consideration of inflammatory, infectious, and neoplastic etiologies along with attention to pituitary deficits is very important. Our patient most likely has a craniopharyngioma based on data from other case series (1,2). This case serves to bring additional data to the body of literature on this complicated clinical scenario.

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in &amp;lt; 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone &amp;lt; 2.6 ng/dL; Total testosterone: &amp;lt; 10ng/dL; and Free androgen index &amp;lt; 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

7874 Management Of “Hyperandrogenism” Confounded By Dermatology Biotin Prescriptions

Abstract Disclosure: S.S. Sundar: None. S. Shankar: None. M.S. Vaishnav: None. L. Lekkala: None. S. Sathyanarayana: None. C. Siddlingappa: None. K. M: None. T.-. Kamala: None. R.B. V: None. V. Nath: None. M.D. Chitra: None. P. Ravikumar: None. Introduction: Immunoassay interferences include: Cross-reactions, heterophile antibodies, biotin and anti-analyte antibodies, with positive or negative bias, leading to difficulties in clinical decision-making (confounding diagnosis, unnecessary investigations or inappropriate treatments). The interfering substance may be exogenous (e.g., drug or substance absorbed by patient) or endogenous (e.g., antibodies produced by patient). Clinical Case 2023 Dec 1 Dermatology management for hyperandrogenism 28-year-old female evaluated for acne 3 years (increased 4 months), hair fall 6 months and hirsutism 3 years (threading) Total Testosterone 443 ng/dL (10-55) CLIA Free Testosterone 8.9 pg/mL (0.1-6.4) ELISA DHEAS 209 µg/dL (35-430) CLIA S Cortisol 8 am 6.9 µg/dL (2.6-10.5) CLIA LH 4.2 mIU/mL (1.9-12.5); FSH 5.3 mIU/mL (3.0-8.0) T3 133 ng/dL (80-200); T4 8.5 ug/dL (4.8-12.7), TSH 3.78 µIU/mL (0.5-5.3) HbA1c 5.0%; Glucose fasting 81 mg/dL; Insulin fasting 39.4 mU/L (3-25); HOMA-IR 5.2; HOMA%B 380; HOMA%S 19.2; T3 133 ng/dL (80-200) 2023 Dec 14 Endocrinology for “scaringly” very high testosterone levels Menstrual history: Menarche 11 years; Cycles regular. Unmarried Family history: Diabetes++; Hirsutism+; Infertility- Physical exam: Height 159 cm; Weight 55 kg; BMI 21.8 kg/m2; Ferriman Gallwey score 11; Pulse 75; BP 79/62; Thyroid: Grade 0. In view of total testosterone levels in “neoplastic androgen excess” range, further endocrinology evaluations (multiple labs and assays) were carried out. However, discordance between the mild clinical versus severe biochemical hyperandrogenism was noted. Review of the dermatology prescription indicated that patient had consumed only one 10 mg tablet of biotin 36 hours before the earlier blood draw obtained by dermatologist. Total Testosterone 22.3 and 33.8 ng/dL (6-82) ECLIA; 19.7 (15-70) LCMS Free Testosterone 0.69 pg/mL (&amp;lt; 2.85) (ELISA) DHEAS 101 µg/dL (45-380) LCMS Androstenedione 104 ng/dL (75-205) LCMS 17OH Progesterone 0.89 ng/mL (0.16-2.05) EIA; 0.40 (0.35-2.9) LCMS S Cortisol 5.92 ug/dl (6-18) ECLIA; 5.45 (5-23) LCMS FSH 2.74; LH 6.07; Prolactin 20.1 ng/mL (4.7-23.3) T3 114 ng/dL; T4 7.2 µg/dL; TSH 1.29 Diagnosis Falsely elevated total testosterone (and free testosterone) levels due to biotin immunoassay interference. Clinical Lessons: Very limited studies exist confirming the exact clinical indications for biotin (eg: improvement of hair quality or quantity, or nail growth). FDA warning highlights biotin’s interference (false elevations or reductions) with immunoassays relying on biotin-streptavidin technology. Physicians must ask patients about supplement usage, and discontinue biotin for 8 hours for patients taking 10 mg/day, 3 days for 100-300 mg/day, 7 days for children taking 2 and 15 mg/kg/daily, and inform laboratory if diagnostic test was performed while taking biotin. Presentation: 6/2/2024

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in &amp;lt; 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone &amp;lt; 2.6 ng/dL; Total testosterone: &amp;lt; 10ng/dL; and Free androgen index &amp;lt; 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

7438 DAX1/NR0B1 Related Adrenal Hypoplasia Congenita Without Hypogonadotropic Hypogonadism

Abstract Disclosure: R.L. Figueiredo: None. J.B. Drummond: None. A. Meireles: None. J.L. Machado: None. G. Vidigal: None. B.S. Rocha: None. Background: X-linked congenital adrenal hypoplasia (AHC) is a rare disease caused by genetic mutations in DXA1/NRB01 gene, which encodes a nuclear hormone receptor expressed in the adrenal cortex, gonads, hypothalamus and anterior pituitary gland, occurring in less than 1:12,500 live births (1,2). AHC is characterized by primary adrenal insufficiency (PAI) associated with hypogonadotropic hypogonadism (HH) and impaired spermatogenesis (oligospermia or azoospermia). Although DAX1/NR0B1 mutations can manifest with different phenotypes, HH is mostly present, which makes this present case a diagnostic challenge. Clinical case: A 23-year-old man presented with typical symptoms of adrenal insufficiency at the age of 7 (abdominal pain, dehydration, nausea, vomiting and cutaneous hyperpigmentation). Initial testing was consistent with primary adrenal failure: elevated ACTH levels (1250pg/mL, RR&amp;lt;46pg/mL) and very low serum cortisol (0.8mcg/dL, RR 3-20mcg/dL). Etiological investigation excluded autoimmune etiology (negative anti-adrenal and anti-21-hydroxylase antibodies) as well as adrenoleukodystrophy (normal very long chain fatty acid levels). Physical exam revealed normal virilization, testicular volume and penile length. The patient reported normal libido and sexual function. Hormonal evaluation showed normal total testosterone (424 and 713ng/dL, RR 165 to 753ng/dL) as well as calculated free testosterone (7.2 and 11.4ng/mL, RR&amp;gt;3.8ng/mL) levels. Abdominal CT showed signs of bilateral adrenal hypoplasia. We then proceeded to genetic testing that revealed a pathological variant c.625C&amp;gt;T:p (Gln 209*) in hemizygosity in exon 1 of the DAX 1/NR0B1 gene. This is a nonsense mutation that introduces a premature stop codon. This variant is not present on the global and Brazilian genetic databases (gnomAD and ABraOM) and has not been previously described in the literature. The patient is currently being treated for adrenal insufficiency with the lowest tolerated dose of prednisone (7.5mg/day) and fludrocortisone 0.1mg/day. Conclusion: Etiological investigation of patients with PAI is essential to understand the evolution of the disease, monitoring extra-adrenal manifestations and the possibility of genetic counseling for the family. An intact hypothalamic-pituitary gonadal axis should not preclude genetic evaluation for a DAX/NR0B1 mutation in patients with PAI and suspected AHC. Further studies will clarify if this specific mutation carries a genotype-phenotype correlation in patients with AHC without HH.

Simultaneous determination and association between serum levels of irisin and chemerin in PCOS.

To determine the serum levels of irisin, chemerin and insulin in women with polycystic ovary syndrome, and to compare their levels with respect to bodyweight and body mass index. The case-control study was conducted at the Department of Clinical Chemistry, College of Medicine, Mustansiriyah University, Baghdad, Iraq, from December 2020 to February 2022, and comprised healthy controls in group I who were matched for bodyweight and body mass index with polycystic ovary syndrome women in group II. Subjects and cases were inducted using purposive sampling technique Subgroups were also formed on the basis of normal body mass index, and overweight-obese status. Serum irisin, chemerin, insulin and free testosterone levels, anthropometric measurements, lipid profile as well as hormonal and biochemical parameters were noted. Data was analysed using SPSS 25. Of the 88 subjects, 32(36.4%) were in group I with mean age 25.1±4.7 years, and 56(63.6%) in group II with mean age 25.0±6.3 years (p>0.05). Both the groups were divided into two equal subgroups A and B. Group II had significantly higher mean body mass index (p=0.007) and adult body fat (p=0.018). Group II women had significantly high fasting serum insulin levels (p<0.001) and homeostatic model assessment for insulin resistance values (p<0.001). Serum irisin had significant positive correlation with serum chemerin (p=0.014) in group II. Serum free testosterone, irisin and chemerin were significantly higher (p<0.001) in group II compared to group I except for chemerin which showed no significant differences among women with normal body mass index (p=0.071). Serum levels of irisin and chemerin could serve as biomarkers of polycystic ovary syndrome.

Obesity is associated with hyperandrogenemia in a nationally-representative sample of U.S. girls aged 6–18 years

Abstract Context Studies have associated obesity with peri-pubertal hyperandrogenemia. However, these studies were performed in academic centers and could have been influenced by selection bias. Objective To investigate if free testosterone levels are elevated in peri-pubertal girls with obesity. Design/Setting We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2013–2016 databases. Participants 1,299 girls aged 6–18 years residing in U.S. Main Outcome Measures Mean free testosterone concentration (calculated from total testosterone and sex hormone-binding globulin). Results Among girls aged 6–9 years, mean (95% CI) free testosterone was 0.33 pg/ml (0.28–0.38) in healthy weight girls vs. 0.86 pg/ml (0.67–1.05) in girls with obesity. Among girls aged 10–14 years, free testosterone was 2.29 pg/ml (2.05–2.53) in healthy weight girls vs. 4.10 pg/ml (3.60–4.60) in girls with obesity. Among girls aged 15–18 years, free testosterone was 3.33 pg/ml (2.96–3.70) in healthy weight girls and 5.64 pg/ml (4.93–6.36) in girls with obesity. Girls with obesity in all age groups had higher free testosterone levels compared to healthy weight girls. In each age group, the 95% CIs for free testosterone did not overlap between healthy weight vs. obesity subgroups. A multiple regression model accounted for 42% of the variance in free testosterone (R2=0.42), and both weight and age categories were independent predictors of free testosterone (p&amp;lt;0.0001 for each). Conclusion In a nationally-representative sample of U.S. girls, obesity is associated with elevated free testosterone, suggesting an important relationship between obesity and peri-pubertal hyperandrogenemia.

Association of Adiposity Phenotypes with 27-Hydroxycholesterol and Sex Hormones: The Multiethnic Cohort Study.

The distribution of body fat has been linked to circulating levels of lipids and sex-steroid hormones. The cholesterol metabolite and endogenous selective estrogen receptor modulator, 27-hydroxychlolesterol (27HC), may be influenced by adiposity phenotypes, particularly among females. No study has examined the relationships of 27HC and steroid hormones with adiposity phenotypes. To investigate the associations of 27HC and steroid hormones with detailed adiposity phenotypes among a multiethnic population of postmenopausal females. A cross-sectional study was conducted among 912 postmenopausal females from the Multiethnic Cohort- Adiposity Phenotype study. Multivariable linear regression examined the associations of circulating levels of 27HC, steroid hormones, and sex hormone-binding globulin (SHBG) with detailed adiposity phenotypes, adjusting for demographics, lifestyle factors, diabetes status, and use of lipid lowering drugs. Subgroup analyses were conducted across race and ethnicity. Total fat mass (P-trend=0.003), subcutaneous adipose tissue (SAT) (P-trend=0.006), and superficial subcutaneous adipose tissue (sSAT) (P-trend=4.41x10-4) were inversely associated with circulating 27HC levels. In contrast, visceral adipose tissue (VAT) (P-trend=0.003) and liver fat (P-trend=0.005) were positively associated with 27HC levels. All adiposity phenotypes were associated with higher levels of free estradiol, testosterone and lower levels of SHBG. Generally, similar patterns of associations were observed across race and ethnicity. Adiposity phenotypes, such as SAT, VAT, and liver fat, were differentially associated with circulating 27HC, while consistent directions of associations were seen for circulating hormones among postmenopausal females. Future studies are warranted to further understand the biology and relationships of 27HC and adiposity-related diseases.

Sexual function in patients with testicular neoplasm before specialized treatment methods. Clinical trial

Introduction. Testicular neoplasms (TN) are one of the most common oncological diseases among young men. Currently the sexual function of such patients remains understudied. The aim of the study was to assess the state of sexual function in men with testicular neoplasms before treatment.Material and methods. The cross-sectional continuous single-center study included 35 men with TN. The average age of patients was 34.2–8.2 years (95% CI: 31.4-37.1). The comparison group included 28 healthy volunteers, average age 30.5–4.9 years (95% CI: 28.6-32.4). Some social characteristics of the patient (marriage and children), the state of sexual function (using the IIEF-15 and ICF questionnaires), the level of anxiety and depression (according to the HADS scale), the levels of total and free testosterone, globulin-binding sex hormone (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin were evaluated.Results. Patients in the main group showed a decrease in erection in 10 (28.6%), satisfaction with sexual intercourse in 12 (34.3%), impaired orgasmic function in 2 (5.7%), decreased libido and overall satisfaction in 9 (25.7%). Nonparametric analysis revealed a statistically significant decrease in libido (p &lt; 0.05), satisfaction with sexual intercourse (p &lt; 0.05) and overall satisfaction (p = 0.007) in patients of the main group compared with the control group. Patients with testicular neoplasms had disorders of the mental component – in 12 (34.3%), erection – in 20 (57.1%), neurohumoral – in 25 (71.4%), ejaculatory – in 10 (28.6%) patients. Subclinical depression was observed in 13 (37.1%) and clinically pronounced depression in 11 (31.4%) patients of the main group. Anxiety and depression were statistically significantly more common in the main group (p = 0.0013). The level of anxiety and depression was more pronounced in unmarried (p = 0.013) children-free patients (p = 0.025). Low levels of total testosterone were detected in 13 (39.4%), free testosterone in 12 (38.7%), LH in 11 (33.3%), FSH in 6 (18.7%) patients from the main group. Elevated levels of LH were recorded in 4 (12.1%), FSH in 4 (12.5%), prolactin in 2 (6.9%) and SHBG in 1 (5%).Conclusion. Patients with TN have a deterioration in sexual function compared to a healthy population of the same age group. The further studies are needed to access the influence of tumor histology and treatment of sexual function.

Improvement in Testosterone Production by Acorus gramineus for the Alleviation of Andropause Symptoms.

Acorus gramineus has a number of beneficial effects, including protective effects against age-related disorders. In this study, the effects of A. gramineus on testosterone production and andropause symptoms were evaluated. We first treated TM3 mouse Leydig cells, responsible for testosterone production, with A. gramineus aqueous extract at different concentrations. In TM3 cells, the testosterone concentration increased in a concentration-dependent manner compared with those in the control. In addition, at 400 μg/mL extract, the mRNA expression level of the steroidogenic enzyme CYP11A1 was increased. Subsequently, 23-week-old Sprague-Dawley (SD) rats exhibiting an age-related reduction in serum testosterone (approximately 80% lower than that in 7-week-old SD rats) were administered A. gramineus aqueous extract for 8 weeks. Serum total testosterone and free testosterone levels were higher and serum estradiol, prostate-specific antigen levels, and total cholesterol levels were lower in the AG50 group (A. gramineus aqueous extract 50 mg/kg of body weight/day) than in the OLD (control group). The AG50 group also showed significant elevations in sperm count, grip strength, and mRNA expression of StAR, CYP11A1, 17β-HSD, and CYP17A1 compared with those in the OLD group. In conclusion, A. gramineus aqueous extract facilitated steroidogenesis in Leydig cells, elevated testosterone levels, lowered serum estradiol and total cholesterol levels, and increased muscle strength and sperm count, thus alleviating the symptoms of andropause. These findings suggest that A. gramineus aqueous extract is a potentially effective therapeutic agent against various symptoms associated with andropause.

Is There a Relationship of Cortisol and Sex Steroid Hormones With Mental Health in Middle-Aged Adults? The FIT-AGEING Study

ObjectiveMental health has emerged as a worldwide concern given the increasing incidence of anxiety and depression disorders in the last years. Cortisol and sex steroid hormones have been demonstrated to be important regulators of mental health processes in older adults. However, the evidence considering these integrated variables in apparently healthy middle-aged individuals has not been thoroughly addressed. The present study aimed to investigate the association of the plasma cortisol, testosterone, free testosterone, sex hormone–binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) levels with mental health in middle-aged adults. MethodsThis cross-sectional study included a cohort of 73 middle-aged adults aged 45 to 65 years (women, 53%). Plasma cortisol, testosterone, SHBG, and DHEAS were assessed using a competitive chemiluminescence immunoassay. Free testosterone was calculated from the total testosterone and SHBG. Self-reported depression severity, generic health-related quality of life, hope, satisfaction with life, and optimism-pessimism were evaluated using the Beck Depression Inventory-II (BDI-II), 36-Item Short-Form Health Survey, Adult Hope Scale, Satisfaction with Life Scale, and Life Orientation Test-Revised, respectively—with higher total scores of these scales indicating greater levels of these variables. ResultsThe testosterone and free testosterone levels were inversely associated with the BDI-II values in men (all P ≤ .042). The cortisol levels were positively related with the Satisfaction with Life Scale scores, whereas the testosterone, free testosterone, SHBG, and DHEAS levels were negatively correlated with the BDI-II values in women (all P ≤ .045). ConclusionIn summary, these results suggest that the increased levels of steroid hormones—within the normal values—are associated with better mental health in middle-aged adults.

SHBG, Free Testosterone, and Type 2 Diabetes Risk in Middle-aged African Men: A Longitudinal Study.

To investigate longitudinal changes in SHBG and free testosterone (free T) levels among Black middle-aged African men, with and without coexistent HIV, and explore associations with incident dysglycaemia and measures of glucose metabolism. This longitudinal study enrolled 407 Black South African middle-aged men, comprising primarily 322 men living without HIV (MLWOH) and 85 men living with HIV (MLWH), with normal fasting glucose at enrollment. Follow-up assessments were conducted after 3.1 ± 1.5 years. At baseline and follow-up, SHBG, albumin, and total testosterone were measured and free T was calculated. An oral glucose tolerance test at follow-up determined dysglycaemia (impaired fasting glucose, impaired glucose tolerance, type 2 diabetes) and glucose metabolism parameters including insulin sensitivity (Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and beta(β)-cell function (disposition index). The primary analysis focussed on MLWOH, with a subanalysis on MLWH to explore whether associations in MLWOH differed from MLWH. The prevalence of dysglycaemia at follow-up was 17% (n = 55) in MLWOH. Higher baseline SHBG was associated with a lower risk of incident dysglycaemia (odds ratio 0.966; 95% confidence interval 0.945-0.987) and positively associated with insulin sensitivity (β = 0.124, P < .001) and β-cell function (β = 0.194, P = .001) at follow-up. Free T did not predict dysglycaemia. In MLWH, dysglycaemia prevalence at follow-up was 12% (n = 10). Neither baseline SHBG nor free T were associated with incident dysglycaemia and glucose metabolism parameters in MLWH. SHBG levels predict the development of dysglycaemia in middle-aged African men but do not exhibit the same predictive value in MLWH.

Anabolic/Catabolic Hormone Imbalance but Still Jumping Further? Negative Association of Free Testosterone With Jumping Performance in Elite Handball Players Following a Preparatory Period

ABSTRACT Purpose: The present study investigated the effects of a 10-week preparatory training period on biomarkers and jumping performance and associations of changes in biomarkers, load, and jumping performance from the beginning (PRE) to the end of the preparatory period (POST) in elite handball players. Methods: Seventeen elite handball players competing in the first Slovenian men’s League were recruited. Training, competition and academic loads were reported weekly, while biomarkers and jumping performance were assessed at PRE and POST. Results: At POST, decreased levels of free testosterone (large effect size [ES] = -1.69, p < .001) and free testosterone to cortisol ratio [FTCR] (large ES = −.95, p = .004) were observed; whereas, better performance on the single leg lateral hop test [SLLH] (large ES = .85, p = .007) and single leg triple hop test [SLTH] (large ES = 1.05, p = .002) were observed compared to PRE. Furthermore, changes in FTCR correlated with changes in cortisol (high r = -.751, p = .001), SLLH (moderate r = -.603, p = .022), and SLTH (moderate r = -.643, p = .013), while changes in free testosterone correlated with SLTH (moderate r = -.645, p = .013). Conclusions: High intensity trainings with a saturated competition schedule can result in disturbed anabolic/catabolic hormone ratio observed through FTCR decrease, which could indicate either an optimal state or early exhaustiveness. It seems that SLLH and SLTH are more sensitive to changes in biomarkers than a single leg hop test. Sport professionals may use the results for individualized monitoring of an athlete’s health and performance, specifically, as an aid for adjusting training loads accordingly to prevent performance declines and potential injury/illness events.

Association Between Andropause and Demographic Factors with Depression Among Police Officers In Bali

Background : Andropause is a health problem in men caused by a decrease in free testosterone levels. Depression is a mental disorder that happens with a person that is related to mood.Objective : This research aims to determine the relationship between Andropause and Depression in police officers in Polda Bali in 2023. Methods : This research is a descriptive-analytical study with a cross-sectional study design. Andropause was assessed using the ADAM questionnaire, and depression was assessed using the PHQ- 9 questionnaire. The sample was selected using a purposive sampling technique. Results : There were 60 respondents in this study. A total of 31 people (51.7%) respondents were positive for Andropause, and 29 people (48.3%) were negative for Andropause. Meanwhile, 12 people (20.0%) of respondents experienced mild depression, and 48 people (80.0%) did not experience depression. Ten (10) respondents experienced Andropause with Depression. There is a significant relationship between Andropause and Depression (p=0.003). The odds ratio (OR 95% CI) obtained was 6.429 (1.270-32.541). Also there is a significant relationship between Stress and Depression with p&lt;0,001 (0,000), with OR 21 (4,4-100,1) Conclusion : The majority of police officers in Polda Bali were found to experience Andropause and Depression, as many as 10 people (32.3%). As age increases, the incidence of Andropause increases, and in the respondent population, most of whom are in the mid-life crisis period, it increases the possibility of depression. Police officers in Polda Bali with Andropause have a 6.429 times greater risk of experiencing depression

Физиологическая роль и клиническое значение глобулина, связывающего половые гормоны, у мужчин.

The main physiological functions of globulin that binds sex hormones (SHBG) in the male body are the transport of sex steroids in hydrophilic blood and the creation of a buffer system that smooths out fluctuations in the concentration of free testosterone. In addition, sex hormone binding globulin can limit the biological activity of sex steroids by reducing the concentration of the free fraction of the hormone, but only when the hypothalamicpituitary-testicular axis is non-functioning or inadequately functioning. If the negative feedback mechanism works correctly, the concentration of SHBG will determine the level of total testosterone, but will not affect the free fraction and, accordingly, the biological activity of sex steroids. It is likely that SHBG has other functions, as indicated by the presence of SHBG receptors in some tissues and the mechanism of SHBG transport into the cell through endocytosis, but the physiological role of these processes is currently unclear and requires further study. From a practical point of view, determining the level of SHBG is necessary primarily to calculate the level of free testosterone, since accurate methods for directly measuring free testosterone are not available in clinical practice. Diagnosing hypogonadism based solely on total testosterone levels is associated with the risk of overdiagnosis, since the concentration of SHBG in the blood can have a significant effect on total testosterone levels without changing free testosterone levels. The use of SHBG as a biomarker for a number of diseases and pathological conditions seems promising. Lower SHBG concentrations are associated with an increased risk of diabetes mellitus, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD), and higher SHBG concentrations are associated with an increased risk of osteoporosis and fractures in older men. At the same time, the question remains open whether SHBG is just a biomarker or is involved in the pathogenesis of the development of these diseases?

Effect of treatment of chronic hepatitis c virus patients with direct-acting anti-retroviral drugs on semen and hormonal parameters

Objective: Hepatitis C virus (HCV) infection is known to influence the seminal and hormonal parameters of infected men. This study was performed to assess the effects of HCV clearance using direct-acting antiviral (DAA) agents on semen and hormonal parameters. Methods: A total of 50 patients with chronic HCV were enrolled, and conventional semen analysis was performed according to World Health Organization guidelines. Basal levels of total testosterone, free testosterone (FT), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin, and sex hormone-binding globulin (SHBG) were assessed before and 3 months after treatment with DAAs.Results: Following DAA treatment, statistically significant increases were observed in sperm motility and the proportion of grade A sperm. Additionally, the percentage of abnormal forms was significantly decreased after treatment (p=0.000). However, no significant differences were observed in semen volume, concentration, or total sperm count. Sex hormone analysis of patients after DAA treatment revealed significant increases in FT, LH, and FSH levels, along with significant decreases in SHBG, prolactin, and E2 levels.Conclusion: Following HCV clearance, we noted an improvement in sperm motility and an increase in the percentage of sperm with normal morphology. Treatment with DAAs was also associated with increased levels of FT and LH, along with decreased levels of SHBG, prolactin, and E2.

Guilingji capsules enhances erectile function by promoting testosterone-dependent angiogenesis in the corpus cavernosum

Background and aimGuilingji capsules (GLJC) have the effect of treating erectile dysfunction (ED). This study aims to explore the potential mechanisms of GLJC in treating ED. Experimental procedureWe conducted network pharmacology analysis of ED-related targets with GLJC components reported in the TCMSP database and GLJC components reported in the literature, respectively. Molecular docking was employed to validate the binding affinity of these molecular targets. Animal experiments were conducted to validate the aforementioned results. The mechanism of GLJC in treating ED was studied using d-galactose-induced aging rats, and orchiectomized rats were used to investigate further whether the mechanism of GLJC in treating ED is related to androgen. Results and conclusionsTwo network pharmacology analyses indicated that Androgen receptor (AR) and fibroblast growth factor 2 (FGF2) are the candidate targets, suggesting that the mechanism of ED treatment by GLJC may be related to androgens and angiogenesis. Molecular docking further validated the effective binding of GLJC components to these two targets. In animal experiments, GLJC significantly increased the frequency of erections and elevated serum free testosterone levels and penile tissue AR expression in aged rats. GLJC also promoted angiogenesis and inhibited penile tissue fibrosis in aged rats by regulating the expression of FGF2, RICTOR/P-AKT/P-FOXO1. However, such regulation was not observed in orchiectomized rats. Therefore, GLJC increased testosterone utilization in d-galactose-induced aging rats and regulated FGF2, RICTOR/P-AKT/P-FOXO1 signaling pathway in a T-dependent manner, promoting corpus cavernosum survival and angiogenesis. This mechanism led to the inhibition of penile fibrosis.