Examining the Effects of Herbs on Testosterone Concentrations in Men: A Systematic Review.
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ABSTRACT:
SUBMITTER: Smith SJ
PROVIDER: S-EPMC8166567 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n?=?871) and two de novo replication cohorts (n?=?4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p?=?1.2×10(-41) and rs6258, p?=?2.3×10(-22)). Subjects with ? 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p?=?5.6×10(-16)). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.
| S-EPMC3188559 | biostudies-literature
Project description:ObjectiveTo determine the prevalence of subnormal testosterone concentrations in patients with obesity and with type 2 diabetes in a primary care clinic population.Research design and methodsFree testosterone concentrations of 1,849 men (1,451 nondiabetic and 398 diabetic) in the Hypogonadism In Males (HIM) study were analyzed. The HIM study was a U.S.-based cross-sectional study designed to define the prevalence of hypogonadism in men aged >45 years. Free testosterone was measured by equilibrium dialysis.ResultsThe prevalence of subnormal free testosterone concentrations in lean, overweight, and obese nondiabetic men was 26% (n = 275), 29% (n = 687), and 40% (n = 489), respectively (P < 0.001 for trend), and 44% (n = 36), 44% (n = 135), and 50% (n = 227), respectively, in diabetic men (P = 0.46 for trend within group and P < 0.05 compared with nondiabetic men). The mean free testosterone concentration of diabetic men was significantly lower than that of nondiabetic men. Free testosterone concentrations were negatively and significantly (P < 0.001) related to age (r = -0.37), BMI (r = -0.18), and sex hormone-binding globulin (r = -0.11) in multiple regression analysis. The average decline of free testosterone concentrations was 7.8 pg/ml per decade in nondiabetic men and 8.4 pg/ml per decade in diabetic men.ConclusionsForty percent of obese nondiabetic men and 50% of obese diabetic men aged >or=45 years have subnormal free testosterone concentrations. In view of its high prevalence, obesity is probably the condition most frequently associated with subnormal free testosterone concentrations in males. The concomitant presence of diabetes is associated with an additional increase in the prevalence of subnormal free testosterone concentrations.
| S-EPMC2875421 | biostudies-literature
Project description:ContextA novel formulation of oral testosterone (T) undecanoate (TU) was evaluated in a phase 3 clinical trial.ObjectiveDetermine efficacy, short-term safety, and alignment of new oral TU formulation with current US approval standards for T replacement therapy.DesignRandomized, active-controlled, open-label study.Setting and patientsAcademic and private clinical practice sites; enrolled patients were clinically hypogonadal men 18 to 65 years old.MethodsPatients were randomized 3:1 to oral TU, as prescribed (JATENZO®; n = 166) or a topical T product once daily (Axiron®; n = 56) for 3 to 4 months. Dose titration was based on average T levels (Cavg) calculated from serial pharmacokinetic (PK) samples. T was assayed by liquid chromatography-mass spectrometry/mass spectrometry. Patients had 2 dose adjustment opportunities prior to final PK visit. Safety was assessed by standard clinical measures, including ambulatory blood pressure (BP).Results87% of patients in both groups achieved mean T Cavg in the eugonadal range. Sodium fluoride-ethylenediamine tetra-acetate plasma T Cavg (mean ± standard deviation) for the oral TU group was 403 ± 128 ng/dL (~14 ± 4 nmol/L); serum T equivalent, ~489 ± 155 ng/dL (17 ± 5 nmol/L); and topical T, 391 ± 140 ng/dL (~14 ± 5 nmol/L). Modeling/simulation of T PK data demonstrated that dose titration based on a single blood sample 4 to 6 h after oral TU dose yielded efficacy (93%) equivalent to Cavg-based titration (87%). Safety profiles were similar in both groups, but oral TU was associated with a mean increase in systolic BP of 3 to 5 mm Hg.ConclusionA new oral TU formulation effectively restored T to mid-eugonadal levels in hypogonadal patients.
| S-EPMC7282712 | biostudies-literature
Project description:ObjectiveTo assess the relative effects of individual testosterone products among hypogonadal men.DesignSystematic review and network meta-analysis.MethodsWe searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (25 May 2017) for randomised-controlled trials (RCTs) and non-randomised studies (NRS) that involved hypogonadal men given testosterone replacement therapy (TRT) for ≥3 months. Comparators were placebo, another TRT, or the same product at a different dose. Outcomes were quality of life, depression, libido, erectile function, activities of daily living and testosterone levels, as well as cardiovascular death, myocardial infarction, stroke, prostate cancer, heart disease, diabetes, serious adverse events, withdrawals due to adverse events and erythrocytosis. RCT data were pooled via meta-analysis and network meta-analysis. Risk of bias was assessed using Cochrane's risk of bias tool (RCTs) andScottish Intercollegiate Guidelines Network (SIGN)50 (NRS).ResultsEighty-seven RCTs and 51 NRS were included. Most were at high or unclear risk of bias, with short treatment duration and follow-up. When compared as a class against placebo, TRT improved quality of life (standardised mean difference (SMD) -0.26, 95% CI -0.41 to -0.11), libido (SMD 0.33, 95% CI 0.16 to 0.50), depression (SMD -0.23, 95% CI -0.44 to -0.01) and erectile function (SMD 0.25, 95% CI 0.10 to 0.41). Most individual TRTs were significantly better than placebo at improving libido (6/10). Only one TRT was better than placebo at improving quality of life, and no individual TRTs improved depression or erectile function. There was no increased risk of adverse events, with the exception of withdrawals due to adverse events with the use of some TRTs.ConclusionDespite a class effect of improving quality of life, depression, erectile function and libido, major improvements were not observed with the use of any individual product. We observed no statistically significant increase in the risk of adverse events; however, longer-term high-quality trials are needed to fully assess the risk of harm.Prospero registration numberCRD42014009963.
| S-EPMC5701987 | biostudies-literature
Project description:BACKGROUND:Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established. METHODS:We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials--the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants. RESULTS:Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P<0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P=0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups. CONCLUSIONS:In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance. The number of participants was too few to draw conclusions about the risks of testosterone treatment. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00799617.).
| S-EPMC5209754 | biostudies-literature
Project description:Transgender individuals experience incongruence between their gender identity and birth-assigned sex. The resulting gender dysphoria (GD), which some gender-incongruent individuals experience, is theorized to be a consequence of atypical cerebral sexual differentiation, but support for this assertion is inconsistent. We recently found that GD is associated with disconnected networks involved in self-referential thinking and own body perception. Here, we investigate how these networks in trans men (assigned female at birth with male gender identity) are affected by testosterone. In 22 trans men, we obtained T1-weighted, diffusion-weighted, and resting-state functional magnetic resonance imaging scans before and after testosterone treatment, measuring cortical thickness (Cth), subcortical volumes, fractional anisotropy (FA), and functional connectivity. Nineteen cisgender controls (male and female) were also scanned twice. The medial prefrontal cortex (mPFC) was thicker in trans men than controls pretreatment, and remained unchanged posttreatment. Testosterone treatment resulted in increased Cth in the insular cortex, changes in cortico-cortical thickness covariation between mPFC and occipital cortex, increased FA in the fronto-occipital tract connecting these regions, and increased functional connectivity between mPFC and temporo-parietal junction, compared with controls. Concluding, in trans men testosterone treatment resulted in functional and structural changes in self-referential and own body perception areas.
| S-EPMC6248653 | biostudies-literature
Project description:Testosterone has been linked to alterations in the activity of emotion neurocircuitry including amygdala, orbitofrontal cortex (OFC) and insula and diminished functional amygdala/prefrontal coupling. Such associations have only ever been studied using acute measures of testosterone, thus little is known about respective relationships with long-term testosterone secretion. Here, we examine associations between hair testosterone concentration (HTC), an index of long-term cumulative testosterone levels and neural reactivity during an emotional passive viewing task using functional magnetic resonance imaging (fMRI). Forty-six men viewed negative, positive and neutral pictures in the MRI. HTCs were assessed from 2 cm hair segments. The emotional paradigm elicited neural activation in the amygdala, insula and OFC. HTCs were associated with increased reactivity to negative pictures in the insula and increased reactivity to positive pictures in the OFC. We show an association of long-term testosterone levels with increased emotional reactivity in the brain. These results suggest a heightened emotional vigilance in individuals with high trait testosterone levels.
| S-EPMC6917022 | biostudies-literature
Project description:BACKGROUND:Testosterone deficiency (TD) may induce a series of clinical symptoms. Studies have shown that testosterone supplementation may prevent these unfavourable symptoms and improve patients' quality of life. Given the conflicting findings across studies, this systematic review aims to evaluate the effects and risks associated with testosterone supplementation in middle-aged or aging males with TD. METHODS:Electronic databases (MEDLINE, EMBASE, PubMed, and Cochrane. Library were searched to December 2019. The risk of bias of individual included studies and the quality of the aggregate evidence were assessed using the GRADE approach. Our primary outcome was bone mineral density (BMD). Meta-analyses were performed. This systematic review was reported according to the PRISMA statement. RESULTS:A total of 52 randomized controlled trials (RCTs) were included. When compared with placebo, testosterone supplementation did not increase total BMD (short-term: 1081 participants, MD -?0.01?g/cm2, 95% CI -?0.02?g/cm2 to 0.01?g/cm2; long-term: 156 participants, MD 0.04?g/cm2, 95% CI -?0.07?g/cm2 to 0.14?g/cm2), lumbar spine, hip, or femur neck BMD. Furthermore, testosterone supplementation did not decrease the risk of falling or fracture. Lastly, it was found that testosterone supplementation did not increase the risk of cardiovascular events (1374 participants, RR 1.28, 95% CI 0.62 to 2.64), all-cause mortality (729 participants, RR 0.55, 95% CI 0.29 to 1.04), or prostatic events. However, testosterone supplementation may improve sexual function and quality of life (1328 participants, MD -1.32, 95% CI -?2.11 to -?0.52). CONCLUSIONS:The effect of testosterone supplementation on BMD and the risk of falls or fracture remains inconclusive. However, supplementation may benefit patients in the areas of sexual function and quality of life without increasing the risk of cardiovascular events, all-cause mortality, or prostatic events. RCTs with a longer follow-up period are still required. TRIAL REGISTRATION:We registered our protocol in PROSPERO (CRD42018109738).
| S-EPMC7060639 | biostudies-literature
Project description:Testosterone (T) replacement is being increasingly offered to older men with age-related decline in testosterone levels. The effects of long-term testosterone replacement and aromatase inhibition (AI) on glucose homeostasis and cardiometabolic markers were determine in older non-diabetic men with low testosterone levels. Men ?65 years, mean age 71 ± 3 years with serum total T < 350 ng/dL were randomized in a double-blind, placebo-controlled, parallel-group, proof-of-concept trial evaluating the effects of 5 g transdermal testosterone gel (TT) (n = 10), 1 mg anastrozole (n = 10) or placebo (n = 9) daily for 12 months. Homeostatic Model Assessment of insulin resistance (HOMAIR ) was the primary outcome. Secondary outcomes included OGIS in response to OGTT, fasting lipids, C-reactive protein (CRP), adipokines, and abdominal and mid-thigh fat by computed tomography. All outcomes were assessed at baseline and 12 months. After 12 months, absolute changes in HOMAIR in both treatment arms (TT group: -0.05 ± 0.21); (AI group: 0.15 ± 0.10) were similar to placebo (-0.11 ± 0.26), as were CRP and fasting lipid levels. Adiponectin levels significantly decreased in the TT group (-1.8 ± 0.9 mg/L, p = 0.02) and abdominal subcutaneous fat (-60.34 ± 3.19 cm2 , p = 0.003) and leptin levels (-1.5 ± 1.2 ng/mL, p = 0.04) were significantly lower with AI. Mid-thigh subcutaneous fat was reduced in both treatment arms (TT group: -4.88 ± 1.24 cm2 , p = 0.008); (AI group: -6.05 ± 0.87 cm2 , p = 0.0002). In summary, in this proof-of-concept trial, changes in HOMAIR AI were similar in all three groups while the effects of intervention on subcutaneous fat distribution and adipokines were variable. Larger efficacy and safety trials are needed before AI pharmacotherapy can be considered as a treatment option for low T levels in older men.
| S-EPMC5794008 | biostudies-literature
Project description:ImportanceCountering depressive disorders is a public health priority. Currently, antidepressants are the first-line treatment, although they show modest effects. In men, testosterone treatment is a controversial alternative or adjunct treatment option.ObjectivesTo examine the association of testosterone treatment with alleviation of depressive symptoms in men and to clarify moderating effects of testosterone status, depression status, age, treatment duration, and dosage.Data sourcesEnglish-language studies published in peer-reviewed journals identified from PubMed/Medline, Embase, Scopus, PsychINFO, and the Cochrane Controlled Trials Register from database inception to March 5, 2018, using the search terms testosterone, mood, administration, dosage, adverse effects, deficiency, standards, therapeutic use, therapy, treatment, and supplementation.Study selectionRandomized placebo-controlled clinical trials (RCTs) of testosterone treatment that together cover a broad age range and hypogonadal or eugonadal men reporting depressive symptoms on psychometrically validated depression scales.Data extraction and synthesisOf 7690 identified records, 469 were evaluated against full study inclusion criteria after removing duplicates, reviews, and studies that did not examine male patients or testosterone. Quality assessment and data extraction from the remaining 27 RCTs were performed.Main outcomes and measuresPrimary outcomes were testosterone treatment effectiveness (standardized score difference after treatment), efficacy (proportion of patients who responded to testosterone treatment with a score reduction of 50% or greater), and acceptability (proportion of patients who withdrew for any reason).ResultsRandom-effects meta-analysis of 27 RCTs including 1890 men suggested that testosterone treatment is associated with a significant reduction in depressive symptoms compared with placebo (Hedges g, 0.21; 95% CI, 0.10-0.32), showing an efficacy of odds ratio (OR), 2.30 (95% CI, 1.30-4.06). There was no significant difference between acceptability of testosterone treatment and placebo (OR, 0.79; 95% CI, 0.61-1.01). Meta-regression models suggested significant interactions for testosterone treatment with dosage and symptom variability at baseline. In the most conservative bias scenario, testosterone treatment remained significant whenever dosages greater than 0.5 g/wk were administered and symptom variability was kept low.Conclusions and relevanceTestosterone treatment appears to be effective and efficacious in reducing depressive symptoms in men, particularly when higher-dosage regimens were applied in carefully selected samples. However, given the heterogeneity of the included RCTs, more preregistered trials are needed that explicitly examine depression as the primary end point and consider relevant moderators.
| S-EPMC6583468 | biostudies-literature