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Hypogonadism guidelines endocrine society logo – Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline

PLoS Genet.

William Thompson
Saturday, August 3, 2019
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  • Measuring bioavailable T concentrations using ammonium sulfate precipitation is technically challenging.

  • For example, men with primary testicular damage often have normal testosterone levels but high LH.

  • Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial.

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  • Wake Research T concentrations in some T-deficient men may be in the low-normal range; these men may need applications of two patches daily; skin irritation at the application site occurs frequently in many patients. Klinefelter syndrome: expanding the phenotype and identifying new research directions.

Summary of Recommendations

Hypogonadidm, R. Pocket Guidelines. Hypogonadotropic hypogonadism HH or secondary hypogonadism is defined as a clinical syndrome that results from gonadal failure due to abnormal pituitary gonadotropin levels. The European Medicines Agency concluded that there is no consistent evidence of an increased risk of coronary heart disease associated with T therapy in hypogonadal men

Patient characteristics associated with testosterone prescribing in the Veteran Affairs system: a cross-sectional study. The increase in hematocrit during T administration and the frequency of erythrocytosis is higher in older men than in young men Front Diabetes. Secondary hypogonadism results in low T concentrations, impairment of spermatogenesis, and low or inappropriately normal gonadotropin levels. Based on the updated Endocrine Society guidelines, 2 Dr. Diagnostic venepuncture should always be performed in the fasted state?

  • Therefore, screening for hypogonadism does not fulfill the necessary criteria to justify population-level screening 33 ,

  • Society panels take a close look at the latest clinical trials and other studies and use that evidence to develop recommendations. Drug Alcohol Depend.

  • The Endocrine Society best hypogonadusm update and the AUA guidelines concur on many key points, 1,2 including:. Linked to each recommendation is a description of the evidence and the values that the task force considered in making the recommendation; in some instances, there are remarks, a section in which the task force offers technical suggestions for testing conditions, dosing, and monitoring.

  • Sex hormone binding globulin deficiency due to a homozygous missense mutation.

  • Managing the risks of prostate disease during testosterone replacement therapy in older men: recommendations for a standardized monitoring plan.

Clinicians should measure FT using the equilibrium dialysis method performed under standardized conditions. There have been no RCTs that were large enough or long losing loved ones to determine the effects of T-replacement therapy on major adverse cardiovascular events MACE. More importantly, recovery of reproductive function and reversibility of HH have been reported after aggressive venesection therapy [ 4546 ]. In hypogonadal men whose baseline PSA is between 2. This information is not designed to replace a physician's independent judgment about the appropriateness or risks of a procedure for a given patient. Cochrane Database Syst Rev.

LH and FSH assays are susceptible to biotin interference 47 that can cause falsely high or low guideelines accordingly, clinicians should stop biotin supplements for at least 72 hours before testing. If secondary, check prolactin and hypogonadism guidelines endocrine society logo MRI of the pituitary gland if prolactin is high. Scardino PT. Local laboratories usually do not have accurate and reliable assays for FT measurement. Nevertheless, in recent years, accumulation of misleading information online has triggered a global tsunami of testosterone prescriptions. Conditions that lower SHBG [ e. 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.

TAKE-HOME MESSAGE

Follow-up by PSA tests at three, six and twelve months and thereafter annually. The aim of testosterone treatment is to restore physiological androgen dependent functions and to improve QoL, e. Indeed, the GnRH test provides no extra diagnostic information relative to baseline gonadotropin levels.

Most organizations that provide guidelines for prostate cancer screening strongly encourage informing the patient of the potential benefits and risks and engaging him in shared decision making regarding screening with PSA levels and digital rectal examination DRE Fertil Steril. Find a Provider Subscribe Now. Steady-state testosterone level without fluctuation. Eriksson, J.

In contrast, for younger men with anemia, or low bone density, achieving a higher level is probably justified [ 21 ]. Uncontrolled studies show that gonadotropin therapy can reinitiate spermatogenesis in men with hypogonadotropic hypogonadism who have been treated previously with T-replacement therapy T therapy is associated with a significant but small decrease in high-density lipoprotein cholesterol levels 87 Further investigation is needed to determine the preferred method for routinely estimating FT concentrations in clinical populations Men who have a prostate nodule or induration require a urological evaluation. Risk of venous thromboembolism in men receiving testosterone therapy.

Summary of Recommendations

The increases were greater in trabecular bone than peripheral bone and greater in the xociety than the hip. Logo is no strong evidence for the association between prostate cancer risk and T concentrations or polymorphisms in genes that encode for proteins involved in androgen action or metabolism — Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. Eugonadal men who develop androgen-sensitive prostate cancer, treated with curative intent, routinely receive androgen-deprivation therapy for a period of 6 to 24 months depending on tumor phenotype [ 48 ] and, therefore, from basic first principles, the same occurrence in a hypogonadal man ought not prompt interruption of testosterone treatment for longer than 2 years. Therefore, assessing men for T deficiency should include a general health evaluation to exclude systemic illness, eating disorders, excessive exercise, sleep disorders, and use of recreational drugs and certain medications e.

One or two patches, designed to nominally deliver 2—4 mg of T during 24 h applied every day on nonpressure areas. The EAU advise that testosterone can be cautiously offered to patients who underwent brachytherapy or external beam radiation for low-risk prostate cancer. The relationship between T concentrations and cardiovascular events in prospective epidemiologic studies is also inconsistent 91 J Clin Psychopharmacol.

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Table 5. J Am Coll Cardiol. In making a diagnosis of hypogonadism, both professional organizations recommend that clinicians order two separate testosterone tests early in the morning on nonconsecutive days, using accurate assays and reliable CDC-approved laboratories. No RCT has been long enough or large enough to have adequate statistical power to determine whether T administration increases the risk of prostate cancer. The American Urological Association AUA issued its first-ever guidelines on the evaluation and management of testosterone deficiency 1 with near simultaneous release of updated best practice recommendations for testosterone therapy in men with hypogonadism 2 from the Endocrine Society. The responsible use of antibiotics for an elevated PSA level.

Statistical study]. Klinefelter syndrome with hypogonadism. A randomised phase II clinical trial detailing the efficacy and safety of Enclomiphene Citrate EC as an alternative to testosterone preparations is available. Decrease in lean body mass and muscle strength. Buchter, D. Rosner, W. Efficacy and safety of testosterone replacement gel for treating hypogonadism in men: phase III open-label studies.

  • N Engl J Med. Similar numbers of men in both treatment groups experienced MACE during the year of treatment or the subsequent year of observation.

  • Similar large interassay and interlaboratory variability occurs with FT measurements. In order to overcome some of the limitations of the analysis of Xu et al.

  • Screening and overdiagnosis: public health implications.

Significance of mutations in the androgen receptor gene in males with idiopathic infertility. Eur Urol. Nevertheless, the FDA mandated pharmaceutical companies to add labeling information about a possible increased risk of cardiovascular events with the use of T. J Bone Miner Metab. Diabetes Care.

Randomized and open-label trials in young men with hypogonadism report a hypogonadism guidelines endocrine society logo frequency of serious adverse hypogonadlsm with replacement doses of T 86— Screening of autosomal gene deletions in patients with hypogonadotropic hypogonadism using multiplex ligation-dependent probe amplification: detection of a hemizygosis for the fibroblast growth factor receptor 1. In some instances, educating patients that obesity or opioids may be contributing to hypogonadism could motivate them to lose weight or discontinue narcotic pain medications. Inactivating KISS1 mutation and hypogonadotropic hypogonadism. Intra-individual variations in serum total testosterone among men presenting for evaluation of hypogonadism. Puhse, G. McLachlan, R.

Case Report

The EAU advise that testosterone can be cautiously offered to patients who underwent brachytherapy or external beam radiation for low-risk prostate cancer. Evaluation and management of testosterone deficiency: AUA guideline. Advanced Search. Massachusetts General Hospital, Boston, Massachusetts. A meta-analysis by Araujo et al.

Twenty-five per cent of men with testicular tumours develop testosterone deficiency after treatment [ ]. Risk of venous thromboembolism in men receiving testosterone therapy. Combined primary and secondary testicular failure results in low testosterone levels and variable gonadotropin levels. Scientists have conducted a great deal of research on testosterone therapy in recent years. Basal hormonal evaluation revealed low serum estradiol 6. The relationship of T and mortality has been heterogeneous across studies MRI can demonstrate a malformation, an expansive or infiltrative disorder of the hypothalamo-pituitary region.

Factors affecting spermatogenesis upon gonadotropin-replacement therapy: a meta-analytic study. Abouassaly, R. Non-necessary Non-necessary. Identifying secondary hypogonadism is of clinical importance, as it can be a consequence of pituitary pathology including prolactinomas and can cause infertility. The advantage of the use of PDE5Is for erectile dysfunction is that these drugs are usually very effective and work fast. Testosterone undecanoate Intramuscular; one injection every ten to fourteen weeks Steady-state testosterone levels without fluctuation.

Nevertheless, if a normal Society logo has been demonstrated, then organic MH becomes improbable and, indeed, testosterone treatment will create a risk of infertility that was not previously present. Nat Clin Pract Urol. Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. That HH whether organic or functional is not necessarily a final diagnosis, but potentially the first manifestation of another disease, is regrettably overlooked by some guidelines. J Am Coll Cardiol.

Publication types

Basin shared the following highlights with EndocrineWeb :. Practice Update ADA Testosterone plus lifestyle program reduced risk of type 2 diabetes in overweight and obese men [Internet] Amsterdam: Elsevier; c Postgrad Med J.

In fact, older or obese men receiving testosterone therapy outside the umbrella of organic hypogonadism may be at society logo of developing secondary polycythemia, CV disease and detection of subclinical prostate cancer [ 2223 ], not to mention androgen-induced hypogonadotropic infertility. Therefore, screening for hypogonadism does not fulfill the necessary criteria to justify population-level screening 33 Abstract Objective. T therapy suppresses spermatogenesis and is not appropriate in men with hypogonadotropic hypogonadism who desire fertility in the next 6 to 12 months. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. Postgrad Med J.

Br J Haematol, In this guideline, the task force made several statements to emphasize the importance of: informing the patient regarding potential benefits and risks of testosterone treatment and of monitoring treatment; shared decision making; general preventive care measures; and basic principles of androgen deficiency screening, diagnosis, and treatment. There is good evidence that testosterone deficiency, as well as erectile dysfunction, are both independent biomarkers, but not necessarily the cause, of cardiovascular disease and also for all-cause and cardiovascular mortality [ ]. Genetic determinants of serum testosterone concentrations in men. Although some clinicians have suggested considering patients with a history of organ-confined prostate cancer for T replacement on an individualized basis—if they have undergone radical prostatectomy, have undetectable PSA, and no detectable residual disease 2 or more years after surgery —the lack of data from RCTs precludes a general recommendation. Formulation-specific adverse effects. Shores, M.

Effects on liver and cholesterol b. The responsible use of antibiotics for an elevated PSA level. Hypogonadism is more prevalent in older men, in men with endocrine society logo, those with comorbidities, and in men with poor health status. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. Table 4. Oestradiol is also essential for bone mineralisation in men [ 21 ]. The most important symptom is the constitutional delay of puberty: it is the most common cause of delayed puberty pubertas tarda [ 36 ].

Guidelines

Common side-effects are the risk of interpersonal transfer if appropriate precautions are not taken [loogo. Bulliard J-LChiolero A. Kalinchenko, S. Berookhim B, et al. A small number of epidemiologic studies have reported a negative relationship between T concentrations and measures of subclinical atherosclerosis, such as common carotid artery intima—media thickness 92 ,

Abouassaly, R. A diagnosis of male hypogonadism must comprise both persistent clinical symptoms and biochemical evidence of testosterone deficiency [ 9 ]. In these patients hormonal stimulation with hCG and FSH or alternatively pulsatile GnRH treatment can induce puberty, restore fertility in most cases and normalise bone mineralisation [ 428182 ]. Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men.

In one RCT in men with opioid-induced T deficiency, T administration improved society logo sensitivity, sexual desire, body composition, and some aspects of quality of life These cookies do not store any personal information. Irwig, M. There is considerable variation in T concentrations in hypogonadal men who are receiving T therapy 8; this variation is even greater in hypogonadal men being treated with transdermal gels or with oral T undecanoate. Her bone age was 13 years. Definition: male hypogonadism is a clinical syndrome caused by androgen deficiency which may adversely affect multiple organ functions and quality of life QoL [ 8 ]. Both immuno-assay and mass spectrometry based assays can produce reliable results, as long as they are well-validated.

Background

Adverse events associated with testosterone administration. Analysis of variation in prostate-specific antigen values. J Clin Oncol. Prevalence of symptomatic androgen deficiency in men. Diagnostic and treatment recommendations are the same as for patients with classical testosterone deficiency.

Hypogonadism guidelines endocrine society logo men whose total Hypogonaism is near the lower limit of normal or who have a condition that alters sex hormone—binding globulin, we recommend llgo a free T concentration using either equilibrium dialysis or estimating it using an accurate formula. The benefits and risks of testosterone replacement therapy: a review. Christou, M. She had 2 older brothers with a history of normal pubertal development. Table 3: Clinical symptoms and signs suggestive for androgen deficiency Clinical symptoms and signs suggestive for androgen deficiency: Reduced testis volume Male-factor infertility Decreased body hair Gynaecomastia Decrease in lean body mass and muscle strength Visceral obesity Metabolic syndrome Insulin resistance and type 2 diabetes mellitus Decrease in bone mineral density osteoporosis with low trauma fractures Mild anaemia Sexual symptoms: Reduced sexual desire and sexual activity Erectile dysfunction Fewer and diminished nocturnal erections Cognitive and psychovegetative symptoms: Hot flushes Changes in mood, fatigue and anger Sleep disturbances Depression Diminished cognitive function The most prevalent symptoms of male hypogonadism in ageing men are reduced sexual desire and sexual activity, erectile dysfunction, loss of vigour and changes in mood [ 1252 ]. For each recommendation within the guidelines there is an accompanying online strength rating form which addresses a number of key elements namely:. Two RCTs in community-dwelling older men did not find significant improvements in memory or multiple other domains of cognitive function with T treatment 84 ,

Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone: a controlled clinical trial. Identification of late-onset hypogonadism in middle-aged and elderly men. High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. Other studies suggest that hypogonadism guidelines endocrine with erectile dysfunction and low T may have an increased risk of cardiovascular disease and all-cause mortality, but we cannot infer a causal association The recommendation not to treat asymptomatic older men with age-related declines in T concentration places a higher value on avoiding unknown long-term risks and a lower value on the limited evidence of the potential benefits of T therapy. T therapy may increase the risk of serious adverse effects in men with some conditions Table 7 ; we recommend against using T therapy in patients with these disorders. This is indeed an area that is ripe for a truly multidisciplinary review of the evidence.

INTRODUCTION

Similar large interassay and interlaboratory variability occurs with FT measurements. Common side-effects are the risk of interpersonal transfer if appropriate precautions are not taken []. Organizational Financial.

Morales A. The responsible use of antibiotics for an elevated PSA level. Nevertheless, the FDA mandated pharmaceutical companies to add labeling information about a possible guideelines risk of cardiovascular events with the use of T. Central defects of the hypothalamus or pituitary cause secondary testicular failure. Effects of testosterone replacement in middle-aged men with dysthymia: a randomized, placebo-controlled clinical trial. Financial Support: This guideline was supported by the Endocrine Society. Effects on QoL, and also on depressive mood, may become detectable within one month, but the maximum effect may take longer [ 88 ].

Google Scholar PubMed. The suggestion not to treat asymptomatic men with T2DM places a lower value on the unproven potential benefits of T therapy with regard to glycemic control and a higher value eneocrine avoiding the burdens of T administration, monitoring, and cost, as well as the unknown long-term risks of T therapy. A harmonized reference range for FT has not been established, so reference ranges may vary considerably depending on the specific equilibrium dialysis method or the algorithm used to calculate FT. Uncompensated Leadership. Clinicians should maintain serum testosterone concentrations during treatment in the mid-normal range for healthy young men Table 9.

Long-acting preparation that cannot allow drug withdrawal in case of onset of side-effects [ ]. In men who have conditions that alter sex hormone—binding globulin SHBG Table 2or whose initial total testosterone concentrations are at or near the lower limit of the normal range Fig. 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.

  • T therapy can cause fluid retention and edema and potentially worsen edema associated with heart failure or other edematous states. Free testosterone should hypogonadism guidelines endocrine society logo measured when sex hormone—binding globulin SHBG levels may be abnormal, such as in obesity, diabetes, nephrotic syndrome, hypothyroidism, acromegaly, and in patients taking steroids or progestins decreased SHBG levels ; or in older age, HIV disease, cirrhosis and hepatitis, hyperthyroidism, and in patients taking certain anticonvulsants or those taking estrogen increased SHBG levels.

  • Testosterone therapy is not recommended for men who would like to father a child in the near future.

  • We hope this review will allow clinicians to navigate the field of MH with greater confidence and, thereby, offer the most appropriate and safe advice and management subject to limitations of the existing evidence base.

Endcorine, both guidelines stress that a number indicative of a low testosterone must be combined with symptoms and signs of a testosterone deficiency in order to make a formal diagnosis of hypogonadism as opposed to a natural decline in testosterone due to aging. If untreated, MH can lead to sexual dysfunction, anemia, osteoporosis and fracture, myopathy and frailty, tender gynecomastia, psychosocial impairments and reduced quality of life. Indeed, there are persisting concerns relating to CV disease that may relate to a counterbalancing risk arising from greater propensity to arterial thrombosis with rising hematocrit. J Clin Epidemiol. T concentrations may be affected by acute illness, nutritional deficiency, and by certain medications e.

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High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The androgen receptor Testosterone exerts its action through the AR, located in the cytoplasm and nucleus of target cells. Fluctuation of testosterone levels []. Permissions Icon Permissions. Oncol Rep,

Soisson, V. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. Locally advanced or metastatic hypogonadism guidelines endocrine society logo cancer. Men who have a prostate nodule or induration require a urological evaluation. Differentiate the two forms of hypogonadism primary and secondary hypogonadism by determining luteinising hormone and follicle-stimulating hormone levels, as this has implications for patient evaluation and treatment and makes it possible to identify patients with associated health problems and infertility. Khera, M.

Transient PSA elevations are common and may be due to test—retest variability or other disorders, such as prostatitis, benign prostatic hyperplasia, prostate trauma, hypoggonadism tract infections, or assay variability. It should be noted that patients with high BMI may require higher doses since obesity seems to affect the pharmacokinetics of transdermal testosterone preparations []. In this guideline, the task force made several statements to emphasize the importance of: informing the patient regarding potential benefits and risks of testosterone treatment and of monitoring treatment; shared decision making; general preventive care measures; and basic principles of androgen deficiency screening, diagnosis, and treatment. T concentrations also are affected by age, obesity, diabetes, sleep disorders including obstructive sleep apnea OSAand health status 10 ,

Long duration and constant serum testosterone level. Am J Kidney Dis, Hypogonadism guidelines endocrine society logo as a risk factor for cardiovascular mortality in men: a meta-analytic study. Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. Uncommon adverse events for which there is weak evidence of association with T administration. The MrOS osteoporotic fractures in men study in Sweden. The review only included trials that used testosterone or its esters.

  • Organic male hypogonadism—usually permanent—is well-established, but aging men may also exhibit lower serum testosterone levels; principally due to burden of extra-gonadal comorbidities such as obesity, diabetes and metabolic syndrome, but with an underlying intact hypothalamo-pituitary-testicular HPT axis capable of springing back into operation once comorbidities are addressed. Accessed April 17,

  • Testosterone therapy. El Osta, R.

  • Therefore, clinicians should use a reliable reference laboratory for these tests. If this is not possible then an endocrinology referral is warranted to discuss the risks and benefits of any suggested intervention.

  • Endocrine Society committees and members and the cosponsoring organization were invited to review and comment on preliminary drafts of the guideline. Clinical characteristics and incidences of benign and malignant insulinoma using a national inpatient database in Japan.

Acquired causes of HH are mostly due to structural or functional abnormalities involving the hypothalamic-pituitary axis, and most of these patients have multiple pituitary hormone hypogonasism. Advance article alerts. Testosterone can also be metabolised into oestradiol by aromatase, present in fat tissue, the prostate, the testes and bone. Contributors to the substantial variation in on-treatment testosterone levels in men receiving transdermal testosterone gels in randomized trials. Prostate biopsy may be associated with adverse effects such as pain, fever, bleeding, infection, transient urinary difficulties, the psychological harm of false-positive test results, and overdiagnosis

An optimal monitoring schedule for serum testosterone level is loog dependent on the formulation of testosterone used. Primary testicular failure is the endocrine society frequent cause of hypogonadism and results in low testosterone levels, impairment of spermatogenesis and elevated gonadotropins high LH and FSH. The precise and early diagnosis of HH can prevent negative physical and psychological sequelae, preserve normal peak bone mass, and restore the fertility in affected patients. The benefits and adverse consequences of long-term T therapy on patient-important outcomes in asymptomatic men with low T concentrations remain unclear. Effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes in a randomized, placebo-controlled clinical trial. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis.

Publication types

Permissions Icon Permissions. Puhse, G. Hypothalamic—pituitary—testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. The effect of erythropoiesis may become evident at three months and peaks at twelve months [ 88 ].

  • Most of the circulating T is bound to SHBG and albumin and, to a lesser extent, to cortisol-binding globulin and orosomucoid; only 2. Uncommon adverse events for which there is weak evidence of association with T administration.

  • Kelly, D. Testosterone treatment and cognitive function in older men with low testosterone and age-associated memory impairment.

  • Therefore, assessing men for T deficiency should include a general health evaluation to exclude systemic illness, eating disorders, excessive exercise, sleep disorders, and use of recreational drugs and certain medications e.

  • J Acquir Immune Defic Syndr.

  • This strategy places a relatively lower value on avoiding the burden and cost of tests with unknown yield.

Table 2. Grossmann, M. Considerable heterogeneity across trials, varying degrees of weight loss and disease severity, variable T regimens and treatment durations, and imprecision all limited the strength of inferences. Suppression of gonadotropins e. Association of low testosterone levels with all-cause mortality by different cut-offs from recent studies.

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It arises due to non-disjunction during paternal or maternal meiotic division of germ cells [ 29 ]. Pituitary, Hypogknadism laboratories usually do not have accurate and reliable assays for FT measurement. Select Format Select format. Strong Use short-acting preparations rather than long-acting depot administration when starting the initial treatment, so that therapy can be adjusted or stopped in case of adverse side-effects. What has also been labelled as late-onset hypogonadism and age-related hypogonadism is comprised of these two types of hypogonadism [ ].

Influence of implantation site and track geometry on the extrusion rate and pharmacology of testosterone implants. An optimal monitoring schedule for serum testosterone level is society logo dependent on the formulation of testosterone used. Safety and efficacy of testosterone gel in the treatment of male hypogonadism. Repeat total testosterone on at least two occasions with a reliable method. Select Format Select format. Pharmacokinetics and safety of long-acting testosterone undecanoate injections in hypogonadal men: an week phase III clinical trial. The recent genetics of hypogonadotrophic hypogonadism—novel insights and new questions.

Available trials failed to demonstrate a similar effect at the femoral neck. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. We recommend T therapy pogo 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. Two RCTs in community-dwelling older men did not find significant improvements in memory or multiple other domains of cognitive function with T treatment 84 ,

Volume The TTrials observed men for adverse outcomes endocrine society logo the year of treatment and the year after treatment 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 commissioned meta-analysis showed that T treatment was associated with a significantly higher frequency of erythrocytosis vs placebo.

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Physicians should recognize that there is hypogohadism disagreement among experts on this issue due to incomplete evidence. A UK epidemic of testosterone prescribing, — Testosterone increased hemoglobin in both men with anemia of a known cause and in those having unexplained anemia. The response of metastatic adenocarcinoma of the prostate to exogenous testosterone. Most studies of T therapy in young, hypogonadal men were open label and did not include a placebo group. Therefore, screening for hypogonadism does not fulfill the necessary criteria to justify population-level screening 33 Provides flexibility of dosing, ease of application, good skin tolerability; less erythrocytosis than injectable T.

We recommend making a diagnosis giidelines losing loved ones only in men with symptoms and signs consistent with testosterone T deficiency and unequivocally and consistently low serum T concentrations. This Endocrine Society clinical practice guideline makes recommendations regarding testosterone therapy among adult men with hypogonadism. Nearly all opioids in doses equivalent to 30 mg of methadone suppress endogenous T production, although longer acting opioids induce greater and more sustained suppression of T concentrations. The role of long-acting parenteral testosterone undecanoate compound in the induction of secondary sexual characteristics in males with hypogonadotropic hypogonadism.

Although firmly believing hypogonadism guidelines endocrine society logo greater interdisciplinary consensus is required in this area, we do not routinely perform DRE in our patients, but we do monitor PSA. Front Diabetes. Conditions that are associated with decreased SHBG concentrations. This recommendation places high value on identifying men with secondary hypogonadism who might have disorders of the pituitary gland or hypothalamus that require management in addition to T treatment.

Clin Endocrinol Metab. Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction: a systematic review and meta-analysis. Cardiovascular risks of exogenous testosterone use among men: a systematic review and meta-analysis. Typical Starting Doses. Advanced practice in endocrinology nursing.

Conditions that lower SHBG [ e. Most clinical laboratories measure LH and FSH gudielines using immunometric assays that have sufficient sensitivity to distinguish between normal and low levels. Summary of Recommendations. Sexual symptoms:. Testosterone treatment is contraindicated in men with severe chronic cardiac failure as fluid retention may lead to an exacerbation of the condition. Preventive Services Task Force. J Endocrinol Invest,

The possibility of nutritional disorders or an undiagnosed chronic illness that may affect the hypothalamic GnRH pulse generator should be evaluated in patients with HH. Guidelinse randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal endocrine society logo men with subthreshold depression dysthymia or minor depression. Age Ageing, Bone mineral density of the lumbar spine, femoral neck, and hip is recommended at the initial diagnosis of HH and after 1 to 2 years of sex steroid therapy in hypogonadal patients with osteoporosis or low trauma fracture Congenital idiopathic hypogonadotropic hypogonadism: evidence of defects in the hypothalamus, pituitary, and testes. Behre, H. In a systematic review, the average PSA increase after initiating T therapy was 0.

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

The contraindications to treatment are outlined. Multiple daily intranasal dosing required; local hypogonadisk side effects, not appropriate for men with nasal disorders. All included trials tested transdermal therapy with a duration of therapy that ranged from 12 to 52 weeks. Studies were placebo-controlled trials that used randomization or allocation-by-minimization with low-to-moderate risk of bias. T does not significantly improve sexual function and activity in men who do not have low T concentrations in the hypogonadal range However, EMAS also found the overwhelming contribution to the apparent age-related decline in T levels to reside not in chronological aging per sebut rather in the accumulation of age-associated co-morbidities, such as obesity, resulting in suppression of LH secretion [ 8 ].

Former abusers of anabolic androgenic steroids exhibit decreased testosterone levels and hypogonadal symptoms years after cessation: a case-control study. A hypogonadism guidelines endocrine society logo for clarity, consistency, and helpfulness: state-of-the-art clinical practice guidelines in endocrinology using the grading of societ, assessment, development, and evaluation system. Nonspecific symptoms and signs associated with testosterone deficiency. Contributors to the substantial variation in on-treatment testosterone levels in men receiving transdermal testosterone gels in randomized trials. Causes of secondary hypogonadism include hyperprolactinemia; severe obesity; iron overload syndromes; the use of opioids, glucocorticoids, or androgen-deprivation therapy with gonadotropin-releasing hormone agonists; androgenic—anabolic steroid AAS withdrawal syndrome; idiopathic hypogonadotropic hypogonadism; hypothalamic or pituitary tumors or infiltrative disease; head trauma; and pituitary surgery or radiation. Gonadal steroid-dependent effects on bone turnover and bone mineral density in men.

Also, a man with a missense mutation of the SHBG gene who had complete deficiency of SHBG and very low TT concentrations was reported to have normal FT and gonadotropin levels, normal male reproductive development, and normal testes size and spermatogenesis, suggesting a limited role of SHBG in male sexual development and spermatogenesis Normalisation of testosterone levels after testosterone replacement therapy also seems to be associated with decreased incidence of atrial fibrillation [ ]. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Moreover, AAS use is associated with persistent changes in sperm characteristics weeks following discontinuationreduction in testicular volume up to 16 weeks following discontinuation and gynecomastia often irreversible [ ]. Spitzer M, et al. Male hypogonadism due to defects of androgen target organs These forms are primarily rare defects and will not be further discussed in detail in these guidelines.

HPG axis suppression due to co-morbidities such as obesity: should it be considered a form of HH like any other, and treated accordingly with testosterone; a form of functional, or non-organic HH, not usually treated with T, or is it instead socisty described as physiological NGI-effect for which a logical basis for testosterone prescribing, along with data on risks and benefits, are all notably lacking? In patients who agree to prostate cancer monitoring, clinicians should evaluate PSA levels and perform a digital prostate examination at baseline and at 3 to 12 months after starting testosterone treatment. T directly stimulates bone formation and inhibits bone resorption through multiple mechanisms that involve estrogen receptor— and androgen receptor—mediated processes 14 Weekly Insulin is Close to Becoming a Reality.

In cases of mild forms of secondary hypogonadism or in selected cases of guidelinea hypogonadism induction of testosterone synthesis by hCG alone may lead to suppression of FSH negative feedback wociety testosterone production and has consequently also to be combined with FSH treatment if necessary. Pituitary mass, radiation to the pituitary region, or hypogonadism guidelines endocrine society logo diseases of the sellar region Treatment with medications that affect T production or metabolism, such as opioids and glucocorticoids Withdrawal from long-term AAS use HIV-associated weight loss Infertility Osteoporosis or low trauma fracture Low libido or erectile dysfunction. Testosterone and Aging: Clinical Research Directions. Juan P Brito. In the Testosterone Trials TTrials which we describe in greater detail later in this articleno statistically significant improvement was observed in fatigue with T treatment vs placebo 68 ; this was confirmed in the commissioned systematic review and meta-analysis. Also, a man with a missense mutation of the SHBG gene who had complete deficiency of SHBG and very low TT concentrations was reported to have normal FT and gonadotropin levels, normal male reproductive development, and normal testes size and spermatogenesis, suggesting a limited role of SHBG in male sexual development and spermatogenesis

There is also an inherent risk of vulnerable normal men being encouraged to seek testosterone treatment in the belief that hypogonadism guidelines endocrine society logo may harbor some unspecified resistance to testosterone-action. Primary Care Written by. Table 2. Free testosterone should be measured when sex hormone—binding globulin SHBG levels may be abnormal, such as in obesity, diabetes, nephrotic syndrome, hypothyroidism, acromegaly, and in patients taking steroids or progestins decreased SHBG levels ; or in older age, HIV disease, cirrhosis and hepatitis, hyperthyroidism, and in patients taking certain anticonvulsants or those taking estrogen increased SHBG levels.

Muraleedharan, V. Delayed puberty. It places a low value on the potential benefits of early detection and treatment of T deficiency in men who have not sought medical attention. Testosterone treatment and mortality in men with low testosterone levels.

  • Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study.

  • Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism.

  • Using the lower limit of the range established in local laboratories may not accurately identify men with hypogonadism.

  • The contraindications to treatment are outlined.

  • Embase, Medline and the Cochrane Central Register of Controlled Trials databases were searched, with a limitation to reviews or meta-analysis of randomised controlled trials RCTs. Brain Res Mol Brain Res.

Late-onset hypogonadism and mortality in aging men. Osteoporosis in men: an Endocrine Society hypogonadism guidelines endocrine society logo practice guideline. Clinicians should monitor men receiving T therapy guidelunes 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. Arterial and venous thrombosis by high platelet count and high hematocrit: individuals from the Copenhagen General Population Study. Reversibility of hypogonadotropic hypogonadism in a patient with the juvenile form of hemochromatosis.

Nevertheless, the FDA mandated pharmaceutical companies to add labeling information about a possible increased risk of cardiovascular events with the use of T. This information is not designed to replace a physician's independent judgment about the appropriateness or risks of a procedure for a given patient. The classification of hypogonadism as primary or secondary has therapeutic implications. Therefore, clinicians should measure T concentrations in the morning after an overnight fast. Follow us on:. FSH, follicle-stimulating hormone; LH, leutinizing hormone.

Uncompensated Leadership. The ES recommends case detection for men deemed to be at increased risk of having hypogonadism and likely to benefit from T therapy, such as those with low libido, erectile dysfunction, infertility, HIV-associated weight loss, osteoporosis or low-trauma fracture, a history of anabolic steroids use, or using opioids or other drugs or substances that affect T production or metabolism. Google Scholar PubMed. Cochrane Database Syst Rev.

Hypogonadism may be more subtle and not always evident by low testosterone levels. Clinicians should use an accurate and reliable method, optimally, an assay that has been certified by an accuracy-based standardization or quality control program [e. Additionally, no RCT was of sufficient size to evaluate risk.

Available at: www. Effect of transdermal testosterone and oral progesterone on drug-induced qt interval lengthening in older men: a randomized, double-blind, placebo-controlled crossover-design study. Testosterone lab testing and initiation in the United Kingdom ones uypogonadism United States, to Prolonged hypogonadism in males following withdrawal from anabolic-androgenic steroids: an under-recognized problem. Total testosterone concentrations in the borderline zone around the lower limit of the normal range e. Clin Endocrinol Metab. The trials included in these meta-analyses suffered from various limitations, including heterogeneity of eligibility criteria, dosing, formulations, and intervention durations; variability in the quality of adverse event recording; lack of large trial cohorts; failure to prespecify and adjudicate cardiovascular outcomes; and lack of a sufficient number of MACE.

  • The efficacy and adverse events of testosterone replacement therapy in hypogonadal men: a hypogonadksm review and meta-analysis of randomized, placebo-controlled trials. The few RCTs that have reported cardiovascular events were limited by their small size, short intervention durations, variable quality of adverse event reporting, and failure to prespecify and adjudicate cardiovascular events 79—8284 ,

  • Different treatment protocols can be used in male patients with HH. The prevalence of structural pituitary abnormalities by MRI scanning in men presenting with isolated hypogonadotrophic hypogonadism.

  • Testosterone concentrations exhibit significant diurnal and day-to-day variations and may be suppressed by food intake or glucose.

  • Prostate cancer: screening. KAL-1 Xp

  • Journal List Endocrinol Metab Seoul v. Causes of secondary hypogonadism include hyperprolactinemia; severe obesity; iron overload syndromes; the use of opioids, glucocorticoids, or androgen-deprivation therapy with gonadotropin-releasing hormone agonists; androgenic—anabolic steroid AAS withdrawal syndrome; idiopathic hypogonadotropic hypogonadism; hypothalamic or pituitary tumors or infiltrative disease; head trauma; and pituitary surgery or radiation.

Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial. Wociety, T may increase skeletal muscle mass and strength, which may indirectly increase BMD and potentially reduce fall propensity and fracture risk; however, there are no randomized trials that assess the effect of T on fall and fracture prevention. Gonadal function in men with chronic illness. Testosterone vs.

Common drug-related adverse events include acne, oiliness of skin, and breast tenderness Table 8. We recommend measuring fasting morning total Siciety concentrations using an accurate and reliable assay as the initial diagnostic test. Many older men hypogonadism guidelines endocrine society logo small foci of subclinical cancer in their prostate ; we do not know whether T replacement might cause these subclinical cancers to grow and become clinically overt. One or two patches, designed to nominally deliver 2—4 mg of T during 24 h applied every day on nonpressure areas. Measuring bioavailable T concentrations using ammonium sulfate precipitation is technically challenging. Nat Clin Pract Urol. Similar large interassay and interlaboratory variability occurs with FT measurements.

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