Androgen Replacement

[Michael Scally MD]

[OA] Testosterone and Its Metabolites: Differential Associations with Cardiovascular and Cerebrovascular Events

As men grow older, circulating testosterone declines while the incidence of cardiovascular disease increases. Thus, the role of sex hormones as biomarkers, and possibly contributing factors to clinical manifestations of cardiovascular disease in the increasing demographic of aging men, has attracted considerable interest.

This review focuses on observational studies of endogenous androgens, namely circulating testosterone and dihydrotestosterone, which have examined their associations with cardiovascular events such as myocardial infarction and stroke. Studies which have examined the associations of endogenous estrogens, namely circulating estradiol, with these outcomes are also discussed.

In large prospective cohort studies of predominantly middle-aged and older men, lower circulating testosterone consistently predicts higher incidence of cardiovascular events. Of note, both lower circulating testosterone and lower dihydrotestosterone are associated with higher incidence of stroke. These associations are less apparent when myocardial infarction is considered as the outcome. Results for estradiol are inconsistent.

Lower circulating testosterone has been shown to predict higher cardiovascular disease-related mortality, as has lower circulating dihydrotestosterone. It is possible that the relationship of circulating androgens to cardiovascular events or mortality outcomes may be U-shaped rather than linear, with an optimal range defining men at lowest risk. Epidemiological studies are observational in nature and do not prove causality.

Associations observed in studies of endogenous androgens need not necessarily translate into similar effects of exogenous androgens. Rigorous randomized controlled trials are needed to clarify the effects of testosterone treatment on cardiovascular risk in men.

Yeap BB. Testosterone and its metabolites: differential associations with cardiovascular and cerebrovascular events in men. Asian J Androl 2017. http://www.ajandrology.com/preprintarticle.asp?id=219729

 

[Michael Scally MD]

The Effect of Testosterone on Cardiovascular Biomarkers

Context - Studies of the possible cardiovascular risk of testosterone treatment are inconclusive.

Objective - To determine the effect of testosterone treatment on cardiovascular (CV) biomarkers in older men with low testosterone.

Design - Double-blind, placebo-controlled trial.

Setting - Twelve academic medical centers in the United States.

Participants - 788 men ≥65 years old with an average of two serum testosterone levels <275 ng/dL who were enrolled in The Testosterone Trials.

Intervention - Testosterone gel, the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months.

Main Outcome Measures - Serum markers of cardiovascular risk, including lipids and markers of glucose metabolism, fibrinolysis, inflammation, and myocardial damage.

Results - Testosterone treatment, compared to placebo, significantly decreased total cholesterol (adjusted mean difference -6.1 mg/dL, p<0.001), high density lipoprotein (HDL) cholesterol (adjusted mean difference -2.0 mg/dL, p<0.001) cholesterol and low density lipoprotein (LDL) cholesterol (adjusted mean difference -2.3 mg/dL, p=0.051) from baseline to month 12.

Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference -1.7 µIU/mL, p=0.02) and HOMA-IR (adjusted mean difference -0.6, p=0.03). Testosterone did not change triglycerides, D-dimer, C-reactive protein, interleukin-6, troponin, glucose or HgbA1c more than placebo.

Conclusions and Relevance - Testosterone treatment for one year of older men with low testosterone was associated with small reductions in cholesterol and insulin but not with other glucose markers or markers of inflammation or fibrinolysis or with troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes.

Mohler IIIER, Ellenberg SS, Lewis CE, et al. The Effect of Testosterone on Cardiovascular Biomarkers in the Testosterone Trials. The Journal of Clinical Endocrinology & Metabolism 2017. http://dx.doi.org/10.1210/jc.2017-02243

 

[Michael Scally MD]

[OA] Testosterone and Cardiovascular Health

Article Highlights

· Normal physiologic levels of testosterone are beneficial to the male cardiovascular (CV) system, and testosterone deficiency is associated with an unfavorable metabolic profile and increased CV disease events.
· The Food and Drug Administration, the American Association of Clinical Endocrinologists/American College of Endocrinology, and an international consensus panel all state that testosterone therapy is safe and reasonable in patients with symptomatic testosterone deficiency.
· Testosterone treatment should be considered for symptomatic men with clinically confirmed hypogonadism; there is no compelling evidence that testosterone therapy either increases or decreases CV disease risk, and testosterone therapy for men with hypogonadism is effective, rational, and evidence based.
· A major research initiative is needed to explore the possible cardioprotective effects of testosterone therapy.


There is an ongoing debate in the medical community regarding the effects of testosterone on cardiovascular (CV) health. For decades, there has been conflicting evidence regarding the association of endogenous testosterone levels and CV disease (CVD) events that has resulted in much debate and confusion among health care providers and patients alike.

Testosterone therapy has become increasingly widespread, and after the emergence of studies that reported increased CVD events in patients receiving testosterone therapy, the US Food and Drug Administration (FDA) released a warning statement about testosterone and its potential risk regarding CV health.

Some of these studies were later found to be critically flawed, and some experts, including the American Association of Clinical Endocrinologists and an expert panel regarding testosterone deficiency and its treatment, reported that some of the FDA statements regarding testosterone therapy were lacking scientific evidence. This article summarizes the current evidence regarding the relationship between testosterone (endogenous and supplemental) and CV health.

A literature review was conducted via search using PubMed and specific journal databases, including the New England Journal of Medicine and the Journal of the American College of Cardiology. Key search terms included testosterone and cardiovascular health, coronary artery disease, heart failure, androgen deprivation therapy, intima-media thickness, and adrenal androgens.

Initial study selection was limited to publications within the past 10 years (January 1, 2007, through December 31, 2016); however, key publications outside of this time frame were selected if they provided important quantitative data or historical perspectives for the review of this topic. The search was further supplemented by reviewing references in selected articles.

Elagizi A, Köhler TS, Lavie CJ. Testosterone and Cardiovascular Health. Mayo Clinic Proceedings. http://dx.doi.org/10.1016/j.mayocp.2017.11.006

 

[Michael Scally MD]

[2018] Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline

Objective - To update the “Testosterone Therapy in Men With Androgen Deficiency Syndromes” guideline published in 2010.

Participants - The participants include an Endocrine Society–appointed task force of 10 medical content experts and a clinical practice guideline methodologist.

Evidence - This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.

Consensus Process - One group meeting, several conference calls, and e-mail communications facilitated consensus development. Endocrine Society committees and members and the cosponsoring organization were invited to review and comment on preliminary drafts of the guideline.

Conclusions - We recommend making a diagnosis of hypogonadism only in men with symptoms and signs consistent with testosterone (T) deficiency and unequivocally and consistently low serum T concentrations.

We recommend measuring fasting morning total T concentrations using an accurate and reliable assay as the initial diagnostic test.

We recommend confirming the diagnosis by repeating the measurement of morning fasting total T concentrations. In men whose total T is near the lower limit of normal or who have a condition that alters sex hormone–binding globulin, we recommend obtaining a free T concentration using either equilibrium dialysis or estimating it using an accurate formula.

In men determined to have androgen deficiency, we recommend additional diagnostic evaluation to ascertain the cause of androgen deficiency.

We recommend T therapy for men with symptomatic T deficiency to induce and maintain secondary sex characteristics and correct symptoms of hypogonadism after discussing the potential benefits and risks of therapy and of monitoring therapy and involving the patient in decision making.

We recommend against starting T therapy in patients who are planning fertility in the near term or have any of the following conditions: breast or prostate cancer, a palpable prostate nodule or induration, prostate-specific antigen level > 4 ng/mL, prostate-specific antigen > 3 ng/mL in men at increased risk of prostate cancer (e.g., African Americans and men with a first-degree relative with diagnosed prostate cancer) without further urological evaluation, elevated hematocrit, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms, uncontrolled heart failure, myocardial infarction or stroke within the last 6 months, or thrombophilia.

We suggest that when clinicians institute T therapy, they aim at achieving T concentrations in the mid-normal range during treatment with any of the approved formulations, taking into consideration patient preference, pharmacokinetics, formulation-specific adverse effects, treatment burden, and cost.

Clinicians should monitor men receiving T therapy using a standardized plan that includes: evaluating symptoms, adverse effects, and compliance; measuring serum T and hematocrit concentrations; and evaluating prostate cancer risk during the first year after initiating T therapy.

Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism. 2018. http://dx.doi.org/10.1210/jc.2018-00229

 

[Michael Scally MD]

The Efficacy and Adverse Events of Testosterone Replacement Therapy in Hypogonadal Men

Context - The efficacy and safety of testosterone replacement therapy (TRT) in hypogonadal men remain incompletely understood.

Objective - To conduct a systematic review and meta-analysis of randomized clinical trials (RCT) to determine the effects of TRT on patient-important outcomes and adverse events in hypogonadal men.

Data Sources - We searched Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, and Scopus from inception to March 2th, 2017.

Study selection - RCTs that assessed the efficacy and adverse events of TRT of at least 12 weeks compared with placebo in adult men with hypogonadism, defined by morning testosterone ≤300 ng/dL and at least one symptom or sign of hypogonadism.

Data extraction - Reviewers working independently and in duplicate assessed the quality of the trials and collected data on patient characteristics, interventions, and outcomes.

Data synthesis - We found 11 publications, reporting on 4 eligible trials (including 1,779 patients) at low risk of bias. Compared to placebo, TRT was associated with a small but significant increase in sexual desire or libido [standardized mean difference (SMD): 0.17, 95% CI 0.01, 0.34] (n=1383), erectile function [SMD: 0.16, 95% CI 0.06, 0.27] (n=1344), and sexual satisfaction [SMD: 0.16, 95% CI 0.01, 0.31] (n=676), but had no effect on energy or mood. TRT was associated with an increased risk of developing erythrocytosis [relative risk: 8.14, 95% CI: 1.87, 35.40] (n=1579) compared to placebo, but had no significant effect on lower urinary tract symptoms (LUTS).

Conclusion - In hypogonadal men TRT improves sexual desire, erectile function, and sexual satisfaction, however it increases the risk of erythrocytosis.

Ponce OJ, Spencer-Bonilla G, Alvarez-Villalobos N, et al. The efficacy and adverse events of testosterone replacement therapy in hypogonadal men: A systematic review and meta-analysis of randomized, placebo-controlled trials. The Journal of Clinical Endocrinology & Metabolism. 2018. http://dx.doi.org/10.1210/jc.2018-00404

 

[Michael Scally MD]

NO data support this overly conservative threshold. Indeed, Eur Male Aging Study reveals total T does not even correspond to symptoms-symptoms follow free T. Science has moved beyond rigid, restrictive total T thresholds that unfairly deprive patients of good care.


AUA guideline suggests total T <300 ng/dL to support a dx of TD based on mean T levels in best available literature to maximize potential benefit and minimize risks of T Rx. http://www.auanet.org/guidelines/evaluation-and-management-of-testosterone-deficiency

 

[Dr JIM]

NO data support this overly conservative threshold. Indeed, Eur Male Aging Study reveals total T does not even correspond to symptoms-symptoms follow free T. Science has moved beyond rigid, restrictive total T thresholds that unfairly deprive patients of good care.


AUA guideline suggests total T <300 ng/dL to support a dx of TD based on mean T levels in best available literature to maximize potential benefit and minimize risks of T Rx. http://www.auanet.org/guidelines/evaluation-and-management-of-testosterone-deficiency

While important as a therapeutic guide the focus should be placed on the PATIENTS signs and symptoms and NOT the level
per se.

JIM

 

[Michael Scally MD]

Variance in Peak and Trough Testosterone Levels in Men Using Intramuscular Testosterone
http://www.jurology.com/article/S0022-5347(18)42186-6/fulltext

INTRODUCTION AND OBJECTIVES - In men using intramuscular testosterone (IM T), clinical experience shows us that, despite stable dosing and frequency, total testosterone peak (Tp) and trough (Tt) levels are highly variable, thus challenging the clinician to make a decision regarding dose adjustments. The goal of this study was to define the variability in T levels in a population of men on IM T.

METHODS - Patients with 3 consecutive Tp and Tt levels available, while on a stable dose and interval of IM T cypionate were analyzed.

All patients were instructed as follows:
· Tp levels to checked 18 hours after IM T injection, and
· Tt levels to be drawn the following week on the day of injection, prior to injecting the next dose.

We report on Tp, Tt and Δ (Tp-Tt). T level was measured using LC/MS-MS. To assess for T level variation across the 3 cycles, we calculated mean change in Tp and Tt as well as maximal change in Tp and Tt. Distribution analysis was performed to assess for variance distribution.

RESULTS - 29 patients met the inclusion criteria equating to 174 total T levels analyzed. Mean age was 52±28y. Dose distribution was: 3% receiving 40mg, 10% 60mg, 35% 80mg, 38% 100mg, 7% 120mg and 7% receiving other dose. 83% were injecting every 7 days.

Averaged over 3 cycles, mean Tp was 910±165 ng/dl; mean Tt 558±80ng/dl, mean Δ 352±154. Mean Tp variance was 210±99ng/dl representing a 23% change from cycle to cycle. Mean Tt variance = 102±63ng/dl (17.5% change). Averaged over all patients, maximum Tp change was 315±148ng/dl and maximum Tt change was 152±94ng/dl, representing a maximum change of 37% and 26% respectively. In distribution analysis, 25% of patients had a maximum Tp change greater than 51% and maximum Tt change of 35%.

CONCLUSIONS - In our population of patients on stable IM T dose, there was a wide mean variation in both Tp (23%) and Tt (17.5%). In addition to that, 25% of patients had a maximum Tp change greater than 50% and maximum Tt change greater than 35%. Clinicians should be aware of this high variability in levels when deciding on dose adjustment.

 

[Dr JIM]

And this study was based upon TRT dosages.

Pity E/2 levels were not also measured bc if they were folk might then understand it’s time to cease chasing that cat tail, esp when CYCLING aromatizable AAS.

Jim

 

[Dr JIM]

Variance in Peak and Trough Testosterone Levels in Men Using Intramuscular Testosterone
http://www.jurology.com/article/S0022-5347(18)42186-6/fulltext

INTRODUCTION AND OBJECTIVES - In men using intramuscular testosterone (IM T), clinical experience shows us that, despite stable dosing and frequency, total testosterone peak (Tp) and trough (Tt) levels are highly variable, thus challenging the clinician to make a decision regarding dose adjustments. The goal of this study was to define the variability in T levels in a population of men on IM T.

METHODS - Patients with 3 consecutive Tp and Tt levels available, while on a stable dose and interval of IM T cypionate were analyzed.

All patients were instructed as follows:
· Tp levels to checked 18 hours after IM T injection, and
· Tt levels to be drawn the following week on the day of injection, prior to injecting the next dose.

We report on Tp, Tt and Δ (Tp-Tt). T level was measured using LC/MS-MS. To assess for T level variation across the 3 cycles, we calculated mean change in Tp and Tt as well as maximal change in Tp and Tt. Distribution analysis was performed to assess for variance distribution.

RESULTS - 29 patients met the inclusion criteria equating to 174 total T levels analyzed. Mean age was 52±28y. Dose distribution was: 3% receiving 40mg, 10% 60mg, 35% 80mg, 38% 100mg, 7% 120mg and 7% receiving other dose. 83% were injecting every 7 days.

Averaged over 3 cycles, mean Tp was 910±165 ng/dl; mean Tt 558±80ng/dl, mean Δ 352±154. Mean Tp variance was 210±99ng/dl representing a 23% change from cycle to cycle. Mean Tt variance = 102±63ng/dl (17.5% change). Averaged over all patients, maximum Tp change was 315±148ng/dl and maximum Tt change was 152±94ng/dl, representing a maximum change of 37% and 26% respectively. In distribution analysis, 25% of patients had a maximum Tp change greater than 51% and maximum Tt change of 35%.

CONCLUSIONS - In our population of patients on stable IM T dose, there was a wide mean variation in both Tp (23%) and Tt (17.5%). In addition to that, 25% of patients had a maximum Tp change greater than 50% and maximum Tt change greater than 35%. Clinicians should be aware of this high variability in levels when deciding on dose adjustment.

View attachment 88934

The problem w TT level studies they only rarely correlate and collate reproducible symptomatic
patient data for use in the clinical setting.

I mean any TRT doc knows there’s a high degree of variability
between and amoung patients and the dosages selected but how does this effect management unlees the avoidance of SP levels is the primary objective.

The signs and symptoms of hypogonadism are just to varied to rely upon “a level” as the therapeutic standard.

 

[Michael Scally MD]

Risk Factors For Late-Onset Hypogonadism

The European Male Aging Study (EMAS) has recently defined strict diagnostic criteria for late-onset hypogonadism (LOH) including the levels of serum total testosterone (TT), free testosterone (FT) and three sexual symptoms. However, there is no report on risk factors for LOH using these criteria.

In this study, we investigated risk factors for LOH based on these criteria. We recruited 277 men (aged 36-80 years) who completed both a health check-up and two questionnaires (a health and lifestyle questionnaire, and a sexual function questionnaire).

Data on parameters, such as systolic blood pressure (SBP), glucose, triglyceride (TG) and high-density lipoprotein (HDL), were obtained from medical records of the hospital in Shantou. TT and sex hormone-binding globulin (SHBG) were measured by chemiluminescent immunoassay, and FT was calculated.

TT, FT, age, waist circumference, SBP and glucose showed significant differences between LOH-positive and LOH-negative individuals. Univariate regression analyses showed that age, waist circumference, SBP, glucose and health status were risk factors for LOH. Pearson's correlation analysis revealed that TT was inversely correlated with waist circumference, glucose and SBP, and FT was inversely correlated with age, SBP and health status.

In conclusion, age, waist circumference, SBP, glucose and health status were risk factors for LOH.

Yang QT, Wu KS, Li ZJ, et al. Risk factors for late-onset hypogonadism. Andrologia 2018:e13016. https://onlinelibrary.wiley.com/doi/abs/10.1111/and.13016

 

[Michael Scally MD]

[French] Androgens and Cardiovascular Risk: A Series of Case Report in The French and Canadian Pharmacovigilance Databases

Introduction - Age-related androgenic deficiency (DALA) is a pathology that is increasingly cited in recent publications. The cardiovascular risk of testosterone is debated: present for the FDA, absent for the European Medicines Agency in 2015. Our objective was to analyze the association between androgens and vascular pathologies in adverse reactions reported in pharmacovigilance databases.

Material and method - We conducted a retrospective case series study of the French and Canadian pharmacovigilance databases for the period 2005–2015. Cases were defined as the association of the occurrence of a cardiovascular event (myocardial infarction or stroke) and the presence of testosterone in the treatment of patients.

Results - Of the 10 years analyzed, 12 French cases and 6 Canadian cases (representing 13 MIs and 5 strokes) were recorded in men aged 55 years on average. All were doubtful: differential diagnoses were possible (2.4 confounding conditions on average per patient) and overall cardiovascular risk was high for the majority of cases.

Conclusion - Our study shows a very low report of cardiovascular effects under testosterone, all doubtful. Pending further studies, it seems reasonable to consider the cardiovascular risk of patients who are candidates for hormone therapy for age-related androgen deficiency.

Rochoy M, Thomas R, Béné J, et al. Androgens and cardiovascular risk: A series of case report in the French and Canadian pharmacovigilance databases. Progrès en Urologie 2018. Androgènes et risque cardiovasculaire : série de cas dans les bases de pharmacovigilance française et canadienne - ScienceDirect

 

[Michael Scally MD]

Testosterone Therapy and Medical Hysteria

A recent study has shown a decline in testosterone prescriptions since media reports of potential increased cardiovascular risk in 2014. The phenomenon of medical hysteria accounts for this reduced prescribing, as numerous subsequent studies provide substantial evidence of reduced cardiovascular risk and other important benefits with testosterone therapy for men with testosterone deficiency.

In my clinic, it is not unusual for patients with reduced libido and testosterone deficiency to ask for an alternative to testosterone therapy, as they have been informed by their cardiologist or other physician that testosterone is bad for the heart. This widespread belief is a prime example of a phenomenon that some of my colleagues and I have termed ‘medical hysteria’. In this phenomenon, medical opinion can be hijacked by media stories that distort science by only emphasizing studies that are deemed newsworthy1

…

Testosterone therapy seems to offer cardiovascular benefits, not harms. Recognizing the effect of the media on medical decision- making is important1. At a time when most clinicians struggle to find the time to read journal articles, we increasingly learn about the latest medical news from the media. What is inadequately appreciated is how journals and the media work together to select the most newsworthy study results among the hundreds published daily. Unexpected serious risks of a popular treatment qualify as newsworthy.

Media companies compete for clicks, journals for impact factor. The reader is, therefore, provided with a highly selected set of results, without opportunity to vet their reliability. Notably, none of the important criticisms regarding the Vigen2 study received media attention, nor did the correction, nor did subsequent studies revealing cardiovascular benefits associated with testosterone therapy. Reassuring results are not nearly as newsworthy as unexpected risks.

Testosterone deficiency is a real condition affecting real men. Testosterone therapy in these men is effective and supported by level 1 evidence. Indeed, every clinician experienced with testosterone therapy has had the remarkable experience of having a treated patient sincerely thank them. The testosterone therapy controversies have distracted us from one of the most exciting stories in all of medicine — the powerful potential of testosterone therapy to improve quality of life and general health.

Morgentaler A. Testosterone therapy and medical hysteria. Nature Reviews Urology 2018. Testosterone therapy and medical hysteria

 

[Dr JIM]

It’s unfortunte the cardiac event rate posed by TRT has been sensationalized in the lay press and extrapolated by the medical media from those at high risk to all comers.

An sefdentary obese diabetic male w HTN is obviously at greater risk than a male w isolated hypogonadism.

And IME it should be no surprise the majority of patients
who are involved in TRT litigation
have multiple risk factors, but allege physiologic TT levels are
responsible for all that woes them, from depression to death.

Yet much like junk science enabled attorneys to gouge billions from the silicone breast implant debacle, it seems a similar course will be followed by TRT.

Jim

 

[Michael Scally MD]

Testosterone Therapy: Do American and European Clinicians Have Different Approaches?

Despite its discovery nearly 100 years ago, testosterone remains a controversial and often poorly understood topic. Given the wide discrepancies in opinions on testosterone, the current commentary provides a contrasting discussion on opinions and practice patterns of Europe and the United States.

Although it is clearly impossible to accurately and thoroughly categorize entire regions, the current commentaries will attempt to highlight key social and political differences that ultimately serve to mold public opinions, practice patterns, and research biases.

Trost L, Zitzmann M. Testosterone Therapy: Do American and European Clinicians Have Different Approaches? The Journal of Sexual Medicine. https://www.jsm.jsexmed.org/article/S1743-6095(18)31093-2/abstract

 

[Michael Scally MD]

The Association of Cardiorespiratory Fitness, Body Mass Index, and Age with Testosterone Levels at Screening of Healthy Men Undergoing Preventive Medical Examinations.

Highlights
· Testosterone levels did not decline with age up to 80 years, were inversely associated with body mass index, and were directly associated with cardiorespiratory fitness.
· Lower testosterone levels are not an inevitable consequence of aging.
· Cardiorespiratory fitness may be an important factor in helping to maintain normal testosterone levels at older age, when weight gain and chronic disease become more prevalent.

Background Currently, exogenous hormone replacement is used in many men with hypogonadism without clear organic cause. This study examines the contribution of modifiable health behaviors, i.e., physical activity and weight control, to the maintenance of testosterone levels with aging.

Methods In a cross-sectional study of 2994 healthy men aged 50-79 years examined at a preventive medicine clinic from January 2012 to March 2016, screening morning total testosterone levels were measured and categorized as low (<250 ng/dL), low normal (250-399 ng/dL), and normal (>400 ng/dL). Cardiorespiratory fitness (fitness) was estimated from a maximal exercise treadmill test. Multiple logistic regression models were used to test the associations between low testosterone levels and age, body mass index (BMI), and fitness.

Findings Mean testosterone levels were in the normal range for each age group (50-59, 60-69, and 70-79). There was a similar prevalence of low testosterone in each age group (11·3%, 10%, and 10·5%, respectively). The prevalence of low testosterone was positively associated with BMI and negatively associated with fitness but was not associated with age.

Interpretation This study found no evidence that low testosterone is an inevitable consequence of aging. Maintenance of healthy weight and fitness may help maintain normal testosterone levels.

DeFina LF, Radford NB, Leonard D, et al. The association of cardiorespiratory fitness, body mass index, and age with testosterone levels at screening of healthy men undergoing preventive medical examinations: The Cooper Center Longitudinal Study. Maturitas 2018. https://www.sciencedirect.com/science/article/pii/S0378512218304249

 

[Dr JIM]

Low T needn’t be a part of the aging process if a reasonable weight is maintained thru diet and exercise.

No surprise, that is the antithesis of darn near all older TRT patients IME.

 

[thrombus]

Low T needn’t be a part of the aging process if a reasonable weight is maintained thru diet and exercise.

No surprise, that is the antithesis of darn near all older TRT patients IME.

What are the reasonable weight targets?

 

[Michael Scally MD]

Clinical Practice Update on Testosterone Therapy for Male Hypogonadism: Contrasting Perspectives to Optimise Care

U.S. Endocrine Society (ES) published a clinical practice guideline on testosterone therapy in men with hypogonadism, and Endocrine Society of Australia (ESA) a position statement on management of male hypogonadism.

Both emphasise the importance of diagnosing men who are androgen deficient due to organic (classical or pathological) hypogonadism arising from disorders of the hypothalamus, pituitary or testes, who assuredly benefit from testosterone therapy.

Both recognise that men with an intact gonadal axis may have low testosterone concentrations, for instance older men or men with obesity or other medical comorbidities.

ES guidelines classify such symptomatic men as having organic (advanced age) or functional (obesity, medical comorbidities) hypogonadism, giving an option for testosterone therapy as a shared decision between clinicians and individual patients. ESA did not recommend testosterone therapy in these men.

ES offers a reference range for total testosterone established in young men, while ESA cites age-standardised reference ranges. ES recommends using free testosterone as well as total testosterone to identify men with hypogonadism in conditions where sex hormone-binding globulin (SHBG) is altered, or when total testosterone is borderline. ESA recommends confirmatory biochemical testing with total testosterone, recognising that this may be lower than expected if SHBG concentrations are low.

Both emphasise the importance of identifying pre-existing prostate and cardiovascular disease prior to initiating testosterone therapy, with ES providing specific recommendations for PSA measurement, deferring testosterone therapy after major cardiovascular events and indications for pituitary imaging.

These contrasting approaches highlight gaps in the evidence base where individualised patient management is required.

Yeap BB, Wu FCW. Clinical practice update on testosterone therapy for male hypogonadism: contrasting perspectives to optimise care. Clinical Endocrinology 2018;0. https://doi.org/10.1111/cen.13888

 

[Michael Scally MD]

Testosterone: From Basic to Clinical Aspects

The goal of this textbook is to revisit the entire universe of testosterone; from its molecule to its accurate use in well-diagnosed endocrinologic diseases. So that every doctor or medical student can take advantage of this work to diagnose and properly treat every patient who seeks us, avoiding the inappropriate use of hormones and iatrogenesis.

Research on testosterone is increasing in many senses; however there is still much controversy regarding its physiology and clinical use. This book addresses these topics, providing a broad overview about testosterone, from its basic features to the most recent evidence of clinical applicability. Also, specific conditions in which testosterone play a pivotal role are discussed in detail, such as hypogonadism, misuse and abuse, puberty, cardiovascular effects and testosterone therapy.

Although not essential for survival, testosterone represents the essence of male biological function, being the important testicular androgen in men. Low serum testosterone levels are associated with cardiovascular morbidity, metabolic syndrome, type 2 diabetes mellitus, atherosclerosis, osteoporosis, sarcopenia, and mortality. Conversely, increased serum levels of testosterone may lead to deleterious events. In general, there is increasing evidence that serum testosterone is a major biomarker status of men’s health in general.

Testosterone: From Basic to Clinical Aspects is an indispensable reference for all those who seek state-of-the-art knowledge regarding this hormone, from basic issues (including pharmacology and physiology) through clinical aspects (related diseases and supplementation therapy).

Hohl A, ed. Testosterone: From Basic to Clinical Aspects. Cham: Springer International Publishing; 2017. Testosterone | SpringerLink