Bioavailable Testosterone Levels Research Articles

Effects of Testosterone in Mediating the Relationship Between Daytime Napping and Osteoporosis in European Populations: A Mendelian Randomization Study.

We aimed to explore the causal effect of daytime napping on the risk of osteoporosis and the mediation role of testosterone in explaining this relationship. Summary data for Mendelian randomization (MR) analysis were obtained from the IEU OpenGWAS database. Univariable MR(UVMR) analysis and multiple sensitivity analyses were applied to explore the casual relationship between daytime napping and bone mineral density (BMD)/osteoporosis. We also conducted multivariable Mendelian randomization (MVMR) analysis to evaluate the correlation between testosterone-associated single-nucleotide variations and BMD/osteoporosis. Then, mediation analysis was performed to explore whether the association between daytime napping and BMD/osteoporosis was mediated via testosterone. Genetically predicted daytime napping was significantly associated with femoral neck BMD (β [95% CI]: 0.2573 [0.0487, 0.4660];P = 0.0156), lumbar spine BMD (β [95% CI]: 0.2526 [0.0211, 0.4840];P = 0.0324), and osteoporosis (OR [95% CI]: 0.5063 [0.2578, 0.9942];P = 0.0481). β and 95%CIs indicate the standard deviation (SD) unit of BMD increase per category increase in daytime napping. OR and 95%CIs represent the change in the odds ratio of osteoporosis per category increase in daytime napping. We observed a potentially causal effect of more frequent daytime nappingon higher BMD and a lower risk of osteoporosis. Daytime napping was causally associated with a higher level of bioavailable testosterone (β [95% CI]: 0.1397 [0.0619, 0.2175]; P = 0.0004). β and 95%CIs represent the change in the SD of testosterone per category increase in daytime napping. Furthermore, the causal effects of daytime napping on BMD/osteoporosis were partly mediated by bioavailable testosterone. Daytime napping can efficiently increase BMD and reduce the risk of osteoporosis, and testosterone plays a key mediating role in this process.

The impact of obesity and sexual behavior on prostate cancer risk is mediated by testosterone levels: a mendelian randomization study and mediation analysis

BackgroundThe relationship between obesity, sexual behavior, and prostate cancer (PCa) has been widely debated, contributing to a lack of understanding of its potential mechanisms and hindering the development of effective prevention measures. PurposeThe aim of this study was to examine the causal effect of body mass index (BMI), age at first sexual intercourse (AFS), and bioavailable testosterone levels on PCa while also quantifying the potential roles of mediators. MethodWe conducted a Mendelian randomization (MR) study using summary statistics from genome-wide associations of BMI (152,893 European males), AFS (182,791 European males), bioavailable testosterone (184,205 European males), and PCa (79,148 cases, 61,106 controls, European ancestry). Inverse-variance weighted method, weighted median method, MR-Egger regression, Least Absolute Shrinkage and Selection Operator (LASSO), and outlier test were used for MR analyses. Reverse MR and mediation analysis were performed. Data analyses were conducted from December 2022 to July 2023. ResultsThe results showed that genetic liability to BMI was protective of PCa (OR, 0.82; 95% CI: 0.74-0.91; P = 3.29 × 10−4). Genetic liability to later AFS (OR, 1.28; 95% CI: 1.08-1.53; P = 5.64 × 10−3) and higher bioavailable testosterone levels (OR = 1.11, 95% CI: 1.01–1.24, P = 0.04) were associated with an increased risk of PCa. All of these potential causal effects could only be forwarded and were not affected by prostate specific antigen (PSA) screening. After controlling for bioavailable testosterone levels, the causal impact of BMI and AFS on PCa was no longer significant. The mediation analysis suggested that the causal influence of AFS/BMI on PCa relied on bioavailable testosterone levels. ConclusionIn conclusion, the difference between the univariable and multivariable MR results suggested that the causal influence of BMI and AFS on PCa relied on bioavailable testosterone levels. Further work is needed to identify other risk factors and to elucidate the specific mechanisms that underlie this causal pathway.

Association of sleep traits with male fertility: a two-sample Mendelian randomization study.

Background: Previous observational studies have investigated the association between sleep-related traits and male fertility; however, conclusive evidence of a causal connection is lacking. This study aimed to explore the causal relationship between sleep and male fertility using Mendelian randomisation. Methods: Eight sleep-related traits (chronotype, sleep duration, insomnia, snoring, dozing, daytime nap, oversleeping, and undersleeping) and three descriptors representing male fertility (male infertility, abnormal sperm, and bioavailable testosterone levels) were selected from published Genome-Wide Association Studies. The causal relationship between sleep-related traits and male fertility was evaluated using multiple methods, including inverse variance weighting (IVW), weighted median, Mendelian randomisation-Egger, weighted model, and simple model through two-sample Mendelian randomisation analysis. Mendelian randomisation-Egger regression was used to assess pleiotropy, Cochrane's Q test was employed to detect heterogeneity, and a leave-one-out sensitivity analysis was conducted. Results: Genetically-predicted chronotype (IVW,OR = 1.07; 95%CL = 1.04-1.12; p = 0.0002) was suggestively associated with bioavailable testosterone levels. However, using the IVW method, we found no evidence of a causal association between other sleep traits and male fertility. Conclusion: This study found that chronotype affects testosterone secretion levels. However, further studies are needed to explain this mechanism.

Association between ethylene oxide exposure and sex steroid hormone levels in male adults in the United States

Sex steroid hormones play important roles in maintaining our health systems, including reproductive function and developmental health. Ethylene oxide (EtO) is a reactive organic compound that is widely used in the gas sterilization of materials such as foods, spices, and medical devices. Previous studies have suggested that EtO exposure is associated with carcinogenic risk, neurotoxicity, and reproductive toxicity. However, no studies focusing on the relationship between EtO exposure and changes in sex steroid hormone levels have been performed in human. The present study investigated the association between blood EtO levels and serum sex steroid hormone levels in 1,635 adult men from the NHANES 2013-2016. Multivariate linear regression analyses, a positive correlation between blood EtO and total testosterone levels, and the testosterone to estradiol ratio. Moderate EtO exposure was associated with a decrease in estradiol levels, but no relationship was found at the highest exposure range. No significant associations were observed between EtO exposure and free testosterone, bioavailable testosterone, or sex hormone-binding globulin levels. These findings suggest EtO exposure could impact human sex steroid hormone production, although analysis in females and further verification through prospective studies should be performed.

Hepcidin Reduction during Testosterone Therapy in Men with Type 2 Diabetes: A Randomized, Double-Blinded, Placebo-Controlled Study.

A randomized, placebo-controlled, double-blinded study at an academic tertiary-care medical center. Interventions were testosterone gel (TRT, n = 20) or placebo gel (n = 19) for 24 weeks. We included 39 men (50-70 years) with type 2 diabetes (T2D) on metformin monotherapy with bioavailable testosterone levels <7.3 nmol/L. Body composition was assessed with DXA- and MRI-scans; the main study outcomes were serum hepcidin-iron, FGF23, phosphate, klotho, and calprotectin. Hepcidin levels decreased during TRT (β = -9.5 ng/mL, p < 0.001), lean body mass (β = 1.9 kg, p = 0.001) increased, and total fat mass (β = -1.3 kg, p = 0.009) decreased compared to placebo. Delta hepcidin was not associated with changes in lean body mass or fat mass. Iron and the pathways of FGF23-phosphate-klotho and calprotectin were unchanged during TRT. During TRT, the reduction in hepcidin was not associated with circulating iron levels, lean body mass, or fat mass; these findings suggested a direct anti-inflammatory effect of TRT and no indirect effect mediated through these factors.

Is testosterone deficiency a predictive factor for recurrence of urethral stricture?

Testosterone plays a vital role in maintaining tissue homeostasis, and testosterone deficiency may potentially influence the likelihood of urethral stricture recurrence. To evaluate the prognostic value of testosterone levels in the recurrence after direct visual internal urethrotomy in primary short segment bulbar urethral strictures and its clinical reflections. A total of 723 patients who underwent direct vision internal urethrotomy between January 2000 and October 2022 were retrospectively analyzed. After implying exclusion criteria, 116 patients with available data were enrolled. Patients were divided into two groups as recurrence and no recurrence. Age, stricture length, etiology, time of recurrence, diagnosis of previous diabetes mellitus, hypertension, smoking, body mass index, and total testosterone levels were recorded. Free testosterone and bioavailable testosterone values were calculated using total testosterone, albumin, and sex hormone binding globulin values. Hypogonadism was considered as a total testosterone level less than 300ng/dL. Demographic characteristics and total testosterone, free testosterone, and bioavailable testosterone levels were compared between the two groups for statistical significance. The recurrence rates of patients with and without hypogonadism were compared. Recurrence was observed in 41.4% of the cases (n=48). There was no statistically significant difference between the groups in terms of age, body mass index values, diabetes mellitus, hypertension, smoking status, presence of hypogonadism, and etiology (p=0.745, 0.863, 0.621, 0.622, 0.168, 0.051, and 0.232). In terms of total testosterone levels and bioavailable testosterone levels, the recurrence group had significantly lower values (p=0.018 and 0.04). There was no significant difference between the two groups in terms of stricture length (p=0.071). Sixteen of 28 patients with hypogonadism had recurrence, whereas 32 of 88 patients without hypogonadism had recurrence (p=0.051). Testosterone levels have potential to predict recurrence in primary short-segment bulbar urethral strictures. This study represents the inaugural analysis of the impact of testosterone deficiency on recurrence within the cohort of patients with primary short-segment bulbar urethral strictures. Testosterone levels and ratios may serve as predictive factors for identifying recurrent cases in primary short-segment bulbar strictures. For patients at a higher risk of recurrence, urethroplasty may be considered as an initial treatment option, even in cases of primary and short-segment strictures.

Associations between genetically predicted sex and growth hormones and facial aging in the UK Biobank: a two-sample Mendelian randomization study.

Aging is an inescapable process, but it can be slowed down, particularly facial aging. Sex and growth hormones have been shown to play an important role in the process of facial aging. We investigated this association further, using a two-sample Mendelian randomization study. We analyzed genome-wide association study (GWAS) data from the UK Biobank database comprising facial aging data from 432,999 samples, using two-sample Mendelian randomization. In addition, single-nucleotide polymorphism (SNP) data on sex hormone-binding globulin (SHBG) and sex steroid hormones were obtained from a GWAS in the UK Biobank [SHBG, N = 189,473; total testosterone (TT), N = 230,454; bioavailable testosterone (BT), N = 188,507; and estradiol (E2), N = 2,607)]. The inverse-variance weighted (IVW) method was the major algorithm used in this study, and random-effects models were used in cases of heterogeneity. To avoid errors caused by a single algorithm, we selected MR-Egger, weighted median, and weighted mode as supplementary algorithms. Horizontal pleiotropy was detected based on the intercept in the MR-Egger regression. The leave-one-out method was used for sensitivity analysis. SHBG plays a promoting role, whereas sex steroid hormones (TT, BT, and E2) play an inhibitory role in facial aging. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels had no significant effect on facial aging, which is inconsistent with previous findings in vitro. Regulating the levels of SHBG, BT, TT, and E2 may be an important means to delay facial aging.

FRI430 A Case Of Elevated Sex Hormone-binding Globulin Secondary To Variegate Porphyria In A Patient With Hypogonadotropic Hypogonadism

Abstract Disclosure: J. Law: None. C. Yip: Research Investigator; Self; Eli Lilly &amp; Company. Background: Acute porphyria is a group of disorders characterized by enzymatic defects in the heme biosynthetic pathway. The liver is the source of both acute intermittent porphyria (AIP) and variegate porphyria. AIP is known to cause an elevation in sex hormone-binding globulin (SHBG) levels, likely secondary to impaired hepatic function and hepatocyte abnormalities1. We describe a case of elevated SHBG secondary to variegate porphyria, in a male with hypogonadotropic hypogonadism. Case Report: A 44-year-old male presented with an elevated SHBG and symptoms of hypogonadism with low libido, weakness, and fatigue. Fasting morning bloodwork revealed an elevated SHBG at 89 nmol/l (13.5- 71.0), a normal total testosterone level at 12.95 nmol/l (8-32), and a low bioavailable testosterone at 0.82 nmol/l (2.5-10), with confirmatory repeat blood work. His history was significant for longstanding variegate porphyria, manifesting as frequent attacks of abdominal pain. He was on opioids for greater then 10 years for his chronic pain, as well as metoclopramide. On assessment of causes for his elevated SHBG, his TSH was normal at 1.49 mIU/L (0.35-4.30). He did not have cirrhosis, hepatitis, hereditary hemochromatosis, and was not on anticonvulsants. No other cause was found, and his elevated SHBG was deemed secondary to his variegate porphyria. His normal total testosterone level was due to his elevated SHBG, but as mentioned, his bioavailable testosterone was low. His LH and FSH were both inappropriately normal, with his LH being 4.67 IU/L (0.6-12.0) and his FSH 4.7 IU/L (1.0-12.0), in keeping with hypogonadotropic hypogonadism. He went through normal pubertal development and had no anosmia. Workup revealed an elevated prolactin level of 73.8 ug/l (3.5-19.4). He had no galactorrhea or gynecomastia and an MRI sella revealed a normal pituitary gland. His elevated prolactin level was determined to be secondary to his opioid medication and/or metoclopramide use. His hypogonadotropic hypogonadism was deemed secondary to his opioid medications and/or hyperprolactinemia. Conclusion: This case demonstrated variegate porphyria as a likely cause of elevated SHBG, similar to AIP. In patients with variegate porphyria and symptoms of hypogonadism, the SHBG should be measured and if it is elevated, the bioavailable or free testosterone levels should be used in assess instead of relying on the total testosterone levels. As has been previously shown, this case also illustrated the use of opioid medications as a cause of hypogonadotropic hypogonadism.

Association between genetically proxied HMGCR inhibition and male reproductive health: A Mendelian randomization study.

The causal associations between statin use and male sex hormone levels and related disorders have not been fully understood. In this study, we employed Mendelian randomization for the first time to investigate these associations. In two-sample Mendelian randomization framework, genetic proxies for hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition were identified as variants in the HMGCR gene that were associated with both levels of gene expression and low density lipoprotein cholesterol (LDL-C). We assessed the causal relationship between HMGCR inhibitor and 5 sex hormone levels/2 male-related diseases. Additionally, we investigated the association between 4 circulating lipid traits and outcomes. The "inverse variance weighting" method was used as the primary approach, and we assessed for potential heterogeneity and pleiotropy. In a secondary analysis, we revalidated the impact of HMGCR on 7 major outcomes using the summary-data-based Mendelian randomization method. Our study found a significant causal association between genetic proxies for HMGCR inhibitor and decreased levels of total testosterone (TT) (LDL-C per standard deviation = 38.7mg/dL, effect = -0.20, 95% confidence interval [CI] = -0.25 to -0.15) and bioavailable testosterone (BT) (effect = -0.15, 95% CI = -0.21 to -0.10). Obesity-related factors were found to mediate this association. Furthermore, the inhibitor were found to mediate a reduced risk of prostate cancer (odds ratio = 0.81, 95%CI = 0.7-0.93) by lowering bioavailable testosterone levels, without increasing the risk of erectile dysfunction (P = .17). On the other hand, there was a causal association between increased levels of LDL-C, total cholesterol, triglycerides (TG) and decreased levels of TT, sex hormone-binding globulin, and estradiol. The use of HMGCR inhibitor will reduce testosterone levels and the risk of prostate cancer without the side effect of erectile dysfunction. LDL-C, total cholesterol, and TG levels were protective factors for TT, sex hormone-binding globulin, and estradiol.

Assessing the Casual Association between Sex Hormone Levels and Fracture Risk: A Two-Sample Mendelian Randomization Study.

Prior observational studies have reported that levels of sex hormones constitute a risk factor for the fracture. The aim of this study was to ascertain whether there is a causal relationship between the levels of sex hormones and the risk of fracture through Mendelian randomization (MR). Single-nucleotide polymorphisms (SNPs) associated with two indicators of sex hormone levels, circulating sex hormone-binding globulin (SHBG) and bioavailable testosterone levels, as exposures were selected from a large genome-wide association study (GWAS) from UK Biobank. The summary statistics for 11 different types of fracture as outcomes from the FinnGen consortium. This study employed the two-sample MR approach. For the main analysis, the inverse-variance-weighted (IVW) method was utilized. To assess the heterogeneity of MR results, the IVW method and MR-Egger method were utilized. To evaluate potential pleiotropy, MR-Egger regression was conducted. Additionally, a leave-one-SNP-out test was performed to assess the robustness of MR results to the exclusion of any individual SNP. The MR analyses demonstrated a conspicuous impact of SHBG on the risk of pathological fracture with osteoporosis (OP). We found that an increase of one standard deviation (SD) in SHBG correspondingly increased the risk of pathological fracture with OP [odds ratio (OR) 2.42, 95% confidence interval (CI), 1.52-3.85; p = 1.93 × 10-4 ]. The bioavailable testosterone showed the negative casual genetic associations with fractures of foot and forearm. An increase of one SD in the genetically predetermined bioavailable testosterone was associated with a reduction of 37% in the risk of fracture of foot (OR 0.63, 95% Cl 0.49 to 0.81; p = 3.37 × 10-4 ), as well as a 39% decrease in the risk of fracture of forearm (OR 0.61, 95% Cl 0.50 to 0.76; p = 5.40 × 10-6 ). Our study confirms that individuals experiencing elevated SHBG concentrations showed a major causal effect on pathological fracture with OP. High bioavailable testosterone levels play an important role in preventing the fractures of foot and forearm. Although increasing bioavailable testosterone and decreasing SHBG levels had no casual effect on most fractures in the general population, they are likely to have the most clinically relevant effect on certain fracture risk reduction.

No evidence of genetic causal association between sex hormone-related traits and systemic lupus erythematosus: A two-sample Mendelian randomization study.

Previous studies have demonstrated an association between sex hormone-related traits and systemic lupus erythematosus (SLE). However, because of the difficulties in determining sequential temporality, the causal association remains elusive. In this study, we used two-sample Mendelian randomization (MR) to explore the genetic causal associations between sex hormone-related traits and SLE. We used a two-sample MR to explore the causal association between sex hormone-related traits and SLE. The summarized data for sex hormone-related traits (including testosterone, estradiol (E2), sex hormone-binding globulin (SHBG), and bioavailable testosterone (BT)) originated from large genome-wide association studies (GWASs) of European descent. Aggregated data for SLE were derived from the FinnGen consortium (835 cases and 300,162 controls). Random-effects inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, weighted mode, and fixed-effects IVW methods were used for the MR analysis. Random-effects IVW was the primary method used to analyze the genetic causal association between sex hormone-related traits and SLE. Heterogeneity of the MR results was detected using the IVW Cochran's Q estimates. The pleiotropy of MR results was detected using MR-Egger regression and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. Finally, leave-one-out analysis was performed to determine whether MR results were affected by a single single-nucleotide polymorphism (SNP). Random-effects IVW as the primary method showed that testosterone (odds ratio (OR), 0.87; 95% confidence interval (CI), 0.41-1.82; P = 0.705), E2 (OR, 0.95; 95% CI, 0.73-1.23; P = 0.693), SHBG (OR, 1.25; 95% CI, 0.74-2.13; P = 0.400), and BT (OR, 0.99; 95% CI, 0.67-1.47; P = 0.959) had no potential causal association with SLE. The MR-Egger, weighted median, simple mode, weighted mode, and fixed-effects IVW methods all indicated consistent results. The results of the MR-Egger regression showed that there was no pleiotropy in our MR analysis (P > 0.05). The IVW Cochran's Q estimates showed that the MR analysis results of E2, SHBG, and BT on SLE had no heterogeneity (P > 0.05), but testosterone and SLE had heterogeneity (P < 0.05). The leave-one-out analysis confirmed that a single SNP did not affect the MR results. Our MR analysis demonstrated that genetically predicted testosterone, E2, SHBG, and BT levels were not associated with SLE risk, but the roles of other non-genetic pathways cannot be ruled out. Key Points • This is the first MR study to explore the causal association of sex hormone-related traits with SLE. • No evidence to support causal associations between sex hormone-related traits and SLE. • Our MR analysis may provide novel insights into the causal association between sex hormone-related traits and SLE risk.

Putative causal inference for the relationship between obesity and sex hormones in males: a bidirectional Mendelian randomization study.

Obesity is a chronic disease with a high prevalence rate and is an established risk factor for human health. Body mass index (BMI) is a common and primary indicator used in assessing obesity. This work aims to investigate the putative causal relationship among BMI, sex hormone-binding globulin (SHBG), bioavailable testosterone (BioT), and estradiol levels. We conducted a bidirectional Mendelian randomization study, using single-nucleotide polymorphisms (SNPs) strongly associated with BMI, SHBG, BioT, and estradiol as instrumental variables. All SNPs were identified from the genome-wide association study (GWAS) summary data of large sample studies recruiting more than 150,000 European adult male individuals. The inverse-variance-weighted (IVW) approach was used as a primary algorithm for putative causal estimation. Genetically predicted elevated BMI was associated with decreased SHBG (IVW, β = -0.103, 95% confidence interval [CI] [-0.113 to -0.092], P = 1.50 × 10-77) and BioT levels (IVW, β = -0.139, 95% CI [-0.165 to -0.113], P = 9.54 × 10-26) and high estradiol levels (IVW, β = 0.014, 95% CI [0.009-0.019], P = 2.19 × 10-7). Increased SHBG levels were causally associated with low BMI (IVW, β = -0.051, 95% CI [-0.098 to -0.005], P = 0.030) and BioT (IVW, β = -0.126, 95% CI [-0.175 to -0.077], P = 5.97 × 10-7) and high estradiol levels (IVW, β = 0.046, 95% CI [0.035-0.056], P = 6.51 × 10-17). Conversely, no evidence of an effect of estradiol imbalance on SHBG levels (IVW, β = 1.035, 95% CI [-0.854 to 2.926], P = 0.283) and BMI (IVW, β = 0.091, 95% CI [-0.094 to 0.276], P = 0.336) was obtained. However, increased BioT levels were causally associated with lower SHBG levels (IVW, β = -0.044, 95% CI [-0.061 to -0.026], P = 8.76 × 10-7), not BMI (IVW, β = -0.006, 95% CI [-0.035 to 0.023], P = 0.679). The findings support a network putative causal relationship among BMI, SHBG, BioT, and estradiol. SHBG, BioT, and estradiol may partly mediate the effect of obesity on male health. Reasonably modulating BioT and estradiol, especially SHBG, facilitated the attenuation of the harmful effects of obesity on male health.

The male patient with obesity undergoing metabolic and bariatric surgery: changes in testosterone levels correlate with weight loss after one-anastomosis gastric bypass and Roux-en-Y gastric bypass.

Male obesity secondary hypogonadism (MOSH) is a common disease among men with obesity and can be associated with metabolic syndrome and a variety of metabolic problems ultimately leading to androgen deficiency. Metabolic and bariatric surgery is a well-established treatment option associated with significant weight loss and reduction in metabolic co-morbidities. To evaluate the impact of surgery on plasma levels of sexual hormones and their effect on weight loss comparing 2 surgical methods (one-anastomosis gastric bypass [OAGB] and Roux-en-Y gastric bypass [RYGB]) in male patients with obesity. University hospital, Austria. Patients undergoing OAGB and RYGB between 2012 and 2017 were analyzed retrospectively. Follow-up in this study was up to 24 months. Systemic levels of sexual hormones (luteinizing hormone [LH]), follicle stimulating hormone [FSH], total testosterone [TT], sexual hormone binding globin [SHBG], 17 beta-estradiol [17bE], androstenedione [AS]) were retrieved at each visit. A linear mixed model was used to assess the correlation between changes in testosterone levels and percent excess weight loss (%EWL). In 30.8% of all patients, MOSH was present preoperatively. A significant increase of TT was observed postoperatively that led to a complete resolution of hypogonadism within the period observed. Bioavailable testosterone (bTT) and FSH levels significantly increased each month of follow-up after surgery (all P < .01). Levels of 17bE did not change significantly after surgery. The overall change of TT, comparing preoperative and 1-year postoperative TT levels (ΔTT), significantly correlated with %EWL. Changes in TT levels were not affected by the choice of surgical method. Serum plasma testosterone levels rise significantly after metabolic and bariatric surgery in male patients. The change of testosterone levels seems to play a role in continued weight loss after surgery. This is true irrespective of the surgical method used.

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.

Serum DHEA and Testosterone Levels Associate Inversely With Coronary Artery Calcification in Elderly Men.

Epidemiological and preclinical data support cardiovascular, mainly protective, effects of sex steroids in men, but the mechanisms underlying the cardiovascular actions of sex steroids are poorly understood. Vascular calcification parallels the development of atherosclerosis, but is increasingly recognized as a diversified, highly regulated process, which itself may have pathophysiological importance for clinical cardiovascular events. To investigate the association between serum sex steroids and coronary artery calcification (CAC) in elderly men. We used gas chromatography tandem mass spectrometry to analyze a comprehensive sex steroid profile, including levels of dehydroepiandrosterone (DHEA), androstenedione, estrone, testosterone, estradiol, and dihydrotestosterone, in men from the population-based AGES-Reykjavik study (n = 1287, mean 76 years). Further, sex hormone-binding globulin (SHBG) was assayed and bioavailable hormone levels calculated. CAC score was determined by computed tomography. The main outcome measures were cross-sectional associations between dehydroepiandrosterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and quintiles of CAC. Serum levels of DHEA, androstenedione, testosterone, dihydrotestosterone, and bioavailable testosterone showed significant inverse associations with CAC, while estrone, estradiol, bioavailable estradiol, and SHBG did not. DHEA, testosterone, and bioavailable testosterone remained associated with CAC after adjustment for traditional cardiovascular risk factors. In addition, our results support partially independent associations between adrenal-derived DHEA and testes-derived testosterone and CAC. Serum levels of DHEA and testosterone are inversely associated with CAC in elderly men, partially independently from each other. These results raise the question whether androgens from both the adrenals and the testes may contribute to male cardiovascular health.

A multicentre cross-sectional clinical study on female sexual dysfunction in postmenopausal Chinese women

ObjectiveThe aim of this study was to investigate the factors affecting the sex lives of postmenopausal Chinese women, especially the influence of body weight, climacteric symptoms and androgens. MethodsA total of 437 postmenopausal women were investigated in the Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University and two allied medical institutions from April 2020 to March 2021. Sociodemographic data were collected. Female sexual dysfunction was evaluated using the Female Sexual Function Index (FSFI). The modified Kupperman index was used to assess climacteric symptoms. Methods based on liquid chromatography-tandem mass spectrometry were employed to measure the serum levels of total testosterone, bioavailable testosterone, free testosterone, androstenedione and dehydroepiandrosterone. Pearson's correlation coefficient and multiple linear regression analyses were performed to determine the correlation between characteristics and FSFI scores. ResultsThe multivariate linear regression analysis revealed that the modified Kupperman index score and the factor unsatisfactory marital relations had the strongest negative correlations with all FSFI domains (P < 0.05); secondary education level was negatively associated with desire, arousal and orgasm (P < 0.05). Total testosterone positively affected the score for pain (P < 0.05). There was no correlation between bioavailable testosterone, free testosterone, androstenedione and dehydroepiandrosterone and all FSFI domains (P > 0.05). ConclusionClimacteric symptoms and sociodemographic factors had a notable effect on sexual function. It is necessary to provide more attention to and intervention for their climacteric symptoms to improve the quality of life of postmenopausal women.

PD11-12 THE EFFECT OF CLOMIPHENE CITRATE ON PATIENT REPORTED OUTCOME MEASURES

You have accessJournal of UrologyCME1 Apr 2023PD11-12 THE EFFECT OF CLOMIPHENE CITRATE ON PATIENT REPORTED OUTCOME MEASURES Jessica Schardein, Kia Fendereski, Zane Randell, Soren Keihani, Joshua Horns, and James Hotaling Jessica SchardeinJessica Schardein More articles by this author , Kia FendereskiKia Fendereski More articles by this author , Zane RandellZane Randell More articles by this author , Soren KeihaniSoren Keihani More articles by this author , Joshua HornsJoshua Horns More articles by this author , and James HotalingJames Hotaling More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003251.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Clomiphene Citrate (CC) is a medication that can be used in hypogonadal men in lieu of testosterone to increase testosterone levels while preserving or improving fertility. Patient reported outcome measures for this medication are limited, especially regarding sexual functioning. Our objective is to assess whether self-reported changes in androgen deficiency symptoms and erectile function are observed along with changes in hormone levels and semen parameters in men taking CC. METHODS: We performed a retrospective review of all patients on CC between 2014 and 2018 for hypogonadism and/or infertility. Patient characteristics including age and body mass index (BMI) along with hormone levels, semen parameters, and self-reported questionnaire scores were obtained. Patients who completed blood work for total testosterone and bioavailable testosterone, a semen analysis, and hypogonadism and erectile function questionnaires including Androgen Deficiency in Aging Male (ADAM) and Sexual Health Inventory for Men (SHIM) before and 3 months after the initiation of CC were included in the analysis. Patients with documented exogenous testosterone, human chorionic gonadotrophin, or anastrozole use were excluded. Changes in baseline and follow-up data were analyzed using paired-sample t-tests. RESULTS: A total of 97 men were identified and included in the analysis. The mean age and body mass index (BMI) were 33.7 ± 6 years and 31.2 ± 7.3 kg/m2, respectively. All patients were followed for at least 3 months. The use of CC significantly increased both mean total and bioavailable testosterone levels by 236.5 ng/dL and 115.6 ng/dL, respectively (p<0.05). Concentration, total progressive motility and morphology all significantly improved as well (p<0.05). Clinical manifestations included a significant improvement in ADAM scores (p=0.025) and no change in SHIM scores (p=0.278). CONCLUSIONS: As more men are placed on CC for hypogonadism and/or infertility, characterizing patient reported outcomes regarding androgen deficiency symptoms and erectile function are important. The medication is able to raise testosterone levels while increasing semen parameters in addition to improving self-reported hypogonadal symptoms and maintaining erectile function scores. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e337 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jessica Schardein More articles by this author Kia Fendereski More articles by this author Zane Randell More articles by this author Soren Keihani More articles by this author Joshua Horns More articles by this author James Hotaling More articles by this author Expand All Advertisement PDF downloadLoading ...

Genetically elevated bioavailable testosterone level was associated with the occurrence of benign prostatic hyperplasia.

Recent studies identified several risk factors of benign prostatic hyperplasia (BPH), including dyslipidemia, type 2 diabetes mellitus, hypertension, and obesity. But they were not so reliable and some studies contradicted with one another. Hence, a reliable method is urgently needed to explore exact factors that facilitated BPH development. The study was based on Mendelian randomization (MR) design. All participants were from the most recent genome-wide association studies (GWAS) with large sample size. The causal associations between nine phenotypes (total testosterone level, bioavailable testosterone level, sex hormone-binding globulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, type 2 diabetes mellitus, hyper-tension, and body mass index) and BPH outcome were estimated. Two sample MR, bidirectional MR, and multivariate MR (MVMR) were performed. Increase in bioavailable testosterone level was able to induce BPH based on nearly all combination methods [beta (95% confidence interval (CI)): 0.20 (0.06-0.34) for inverse variance weighted (IVW)]. The other traits seemed to interact with testosterone level and did not cause BPH generally. Higher triglycerides level was likely to raise bioavailable testosterone level [beta (95% CI): 0.04 (0.01-0.06) for IVW]. In MVMR model, bioavailable testosterone level was still associated with BPH occurrence [beta (95% CI) 0.27 (0.03-0.50) for IVW]. We for the first time validated the central role of bioavailable testosterone level in the pathogenesis of BPH. The complex associations between other traits and BPH should be further investigated.

The association between sex hormones and periodontitis among American adults: A cross-sectional study.

After adulthood, as a person grows older, the secretion of sex hormones in the body gradually decreases, and the risk of periodontitis increases. But the relationship between sex hormones and periodontitis is still controversial. We investigated the association between sex hormones and periodontitis among Americans over 30 years old. 4,877 participants containing 3,222 males and 1,655 postmenopausal females who had had periodontal examination and detailed available sex hormone levels, were included in our analysis from the 2009-2014 National Health and Nutrition Examination Surveys cycles. We applied multivariate linear regression models to estimate the connection between sex hormones and periodontitis after converting sex hormones into categorical variables through tertile. Additionally, to ensure the stability of the analysis results, we carried out a trend test, subgroup analysis, and interaction test. After fully adjusting the covariates, estradiol levels were not associated with periodontitis in both males and females with a P for trend = 0.064 and 0.064, respectively. For males, we found that sex hormone-binding globulin was positively associated with periodontitis (tertile3 vs tertile1: OR=1.63, 95% CI=1.17-2.28, p = 0.004, P for trend = 0.005). Congruously, free testosterone (tertile3 vs tertile1: OR=0.60, 95% CI=0.43-0.84, p = 0.003), bioavailable testosterone (tertile3 vs tertile1: OR=0.51, 95% CI=0.36-0.71, p < 0.001), and free androgen index (tertile3 vs tertile1: OR=0.53, 95% CI=0.37-0.75, p < 0.001) was found to be negatively associated with periodontitis. Moreover, subgroup analysis of age found a closer relationship between sex hormones and periodontitis in those younger than 50 years. Our research suggested that males with lower bioavailable testosterone levels affected by sex hormone-binding globulin were at a higher risk of periodontitis. Meanwhile, estradiol levels were not associated with periodontitis in postmenopausal women.

Associations of sex-related steroid hormones and proteins with alcohol dependence: A United Kingdom Biobank study

BackgroundSex-related steroid hormones and proteins may contribute to the sex differences in the characteristics and health consequences of alcohol use disorder. This study aimed to examine the associations between alcohol dependence (AD) and sex-related hormones/proteins using a population-based dataset. MethodsWe retrieved serum total testosterone (TT) and estradiol (TE2), sex hormone binding globulin (SHBG), and albumin levels along with clinical data from the UK Biobank. Hormone/protein levels were compared between AD (lifetime AD and/or related diagnoses; 2218 males; 682 females) and control (no aforementioned diagnoses and AUDIT<8; 198,058 males; 250,830 females) groups with sex-dependent linear regression models adjusting for age and body mass index. Moderation and mediation analyses were performed to test whether SHBG was a moderator and/or mediator between hormones and AD or current drinking. ResultsAD males had higher TT, TE2, and SHBG levels but lower bioavailable testosterone, bioavailable estradiol, and albumin levels than controls (padjusted<0.001). After adjusting for menopause, AD females had higher TT and lower albumin levels than controls (padjusted<0.001). These differences remained after accounting for current drinking frequency (p < 0.001). SHBG moderated TT’s effect on AD in males (pinteraction<0.001). SHBG was a positive mediator between TT and AD in both sexes and between TE2 and AD in males (p < 0.001), but a negative mediator between TT and current drinking in controls (both sexes) and AD males (p < 0.001). ConclusionsTestosterone and estradiol levels are altered in males and females with AD distinctly regardless of current drinking frequency. SHBG may play a critical role in these associations.