DEA Telemedicine Compliance

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What Is a Normal Testosterone Level for Young Men?

Rethinking the 300 ng/dL Cutoff for Testosterone Deficiency in Men 20-44 Years Old

Viagra Lowers the Risk of Alzheimer’s by Almost 70%, Study Finds

Viagra Lowers the Risk of Alzheimer’s by Almost 70%, Study Finds

Testosterone Eliminates Negative Choices in Men

Testosterone eliminates strategic prosocial behavior through impacting choice consistency in healthy males - A study by Nature.

TRT and Mortality in Older Men

This review demonstrates there are benefits to treating older men with TRT to improve sexual function, increase lean muscle mass and strength, improve mood and cognitive function, and reduce frailty and osteoporosis. This article confirms that there is no evidence that TRT is associated with increased risk of prostate cancer or symptomatic benign prostatic hyperplasia.  The author also notes that TRT reduced all-cause mortality. The author mentions that although injections may be associated with decreased cardiovascular risk, the transdermal route may be associated with potentially relatively greater risk because of conversion to dihydrotestosterone (DHT) by the effect of 5-alpha reductase in the skin.

Cardiovascular Benefits and Risks of TRT in Older Men with Low T

This meta-analysis of 58 research papers regarding TRT and heart health demonstrates that TRT is safe and is associated with prevention of CVD and strokes in hypogonadal men. These studies have have also demonstrated that normal T levels or the normalization of low T levels with testosterone replacement therapy (TRT) is associated with decreased incidence of heart attacks, diabetes, and strokes, besides improving sexual function and the quality of life.

TRT & Heart Health

This meta-analysis demonstrates a reduced cardiovascular risk with higher endogenous T concentration, improvement of known cardiovascular risk factors with TRT therapy, and reduced mortality in testosterone deficient men who underwent TRT replacement therapy versus untreated men. TRT improves myocardial ischemia in men with coronary artery disease, improve exercise capacity in patients with congestive heart failure,, and improve serum glucose levels and insulin resistance in men with diabetes and prediabetes. This review of 40 scientific articles suggests that testosterone therapy offers benefits to heart health.

Testosterone vs Clomiphene Citrate

This study compared traditional TRT with testosterone injections vs. alternative therapy with clomiphene to raise testosterone.  This study showed men treated with TRT showed significant increases in libido, erectile function, and sports performance over men taking clomiphene. Among the men who received clomiphene libido was lower during treatment, indicating that Clomid has an adverse effect on libido in hypogonadal men.

Hypogonadal Men Treated with Clomiphene Citrate vs TRT

Purpose: 

Enclomiphene Citrate Stimulates Testosterone Production While Preventing Oligospermia

Objective: 

Alternatives to Testosterone Replacement: Testosterone Restoration

The European Male Aging Study has demonstrated that the hypogonadism of male aging is predominantly secondary. Theoretically with appropriate stimulation from the pituitary, the aging testis should be able to produce eugonadal levels of testosterone. The strategies for the treatment of late onset hypogonadism (LOH) have focused on replacement with exogenous testosterone versus restoration of endogenous production. The purpose of this article is to review existing peer-reviewed literature supporting the concept of restoration of endogenous testosterone in the treatment of LOH. In view of the EMAS studies, secondary hypogonadism accounts for over 85% of LOH. Ample evidence exists for a deficiency in GTP stimulation with the older men and the ability of the testes to respond to increased GTP production. We currently have several generic medications that accomplish an increase in GTP and normalization of serum testosterone with a favorable side-effect profile. Though shown to be efficacious and well-tolerated in a number of trials, none of the restorative strategies are FDA approved and caution must be advised in their off-label use. Hopefully, future trials will be undertaken to establish a long-term efficacy and safety restorative therapies. Early clinical trials of the compound enclomiphene are encouraging and hopefully will lead to a change in paradigm from TREP to TRES.

Testosterone in Men with Hypogonadism and Transgender Males

This review article compared different formulations of testosterone; gels, patches, and injection with different esters.  It found that patient satisfaction seems to be in favor of long-acting i.m. injections due to the low injection frequency with stable testosterone levels and no daily confrontation with treatment/disease. Patient satisfactory is lower with the use of gel, which is easy in use, but daily application is needed with daily confrontation with treatment and the risk of less compliance, possibly resulting in less stable values, and the least with short-acting injections due to the high injection frequency but especially due to the large fluctuations with concomitant swings in mood, sexual desire, and energy level.

Erythrocytosis Following Testosterone Therapy

Introduction

Evaluation and Management of Testosterone Deficiency: AUA Guideline

This is the American Urological Association’s Guideline for diagnosis and treatment of low testosterone.  

Elevated Hematocrit (erythrocytosis)

The most frequently reported adverse reaction to testosterone replacement therapy is erythrocytosis, an abnormal elevation of hemoglobin (greater than 18.5 g/dL) or hematocrit (greater than 52%).  However, no studies to date have demonstrated a link between testosterone replacement therapy-induced erythrocytosis and cardiovascular (CV) events or venous thromboembolism (VTE or “blood clots”).

TRT and Prostate Cancer

Evidence suggests that testosterone replacement therapy does not support an increased risk.  This meta-analysis of TRT and prostate risk demonstrates a short-term increase in PSA and prostate volume.  However, there was no increased risk of prostate cancer or prostate-related events in patients on testosterone replacement therapy.

TRT and Sexual Function - Current Approach to Treatment

Androgens are essential for the development of the penis and it is well known that testosterone play a critical role in the physiology of erectile function. From animal studies, testosterone insufficiency disrupts cellular-signaling pathways and induces pathologic alterations in penile tissues leading to erectile dysfunction. In human, the testosterone threshold for maintaining erection is low which explains the reason why some contracted men still have an erection due to the androgens produced by the adrenal gland. Testosterone alone can improve erectile function in hypogonadic patients. Associated with PDE5-I, testosterone supplementation is a treatment for the hypogonadic patients non responders to therapy. The article reviews the different aspects of the testosterone role in the pathophysiology of erection.

TRT and Sexual Function - Endocrinological Control

Introduction

TRT and Sexual Function - Androgens

Sexual symptoms are the most specific determinants of low 

Testosterone and Erectile Dysfunction

Aging is associated with a decline in several important health factors in men, including libido. Serum testosterone concentrations also decrease with age, and many age-related clinical features are closely associated with androgen deficiency, including erectile function (ED). Approximately 70% of ED is of organic origin, with the major risk factors being diabetes mellitus, hypercholesterolemia, smoking and chronic medical illnesses. These are also established risk factors for atherosclerosis, which is the predominant predisposing factor of vasculogenic ED. The introduction of phosphodiasterase-5 (PDE-5) inhibitors for the treatment of ED made a significant impact both in terms of clinical efficacy, and increasing the awareness of the condition. In spite of this, some patients fail to respond to PDE-5 inhibitors alone. Both animal and clinical studies indicate that testosterone therapy improves both erectile function and the response to PDE-5 inhibitors in patients with ED and hypogonadism. Indeed, interventional studies demonstrate that testosterone replacement therapy improves erectile function in hypogonadal men who have previously failed to respond to PDE-5 inhibitors alone. Furthermore, it has been demonstrated that the full therapeutic potential of PDE5 inhibitors will only become manifest in a eugonadal state. Recent studies have demonstrated a close relationship between testosterone and ED and suggest that testosterone therapy may be a valuable option for an increasing number of affected men. European guidelines recommend that all men presenting with ED should have their testosterone concentrations measured.

Erectile Dysfunction and Testosterone Deficiency

A definitive role of testosterone in erectile function has been controversial; however, recent evidence is becoming available which substantiates a key function for this hormone. Testosterone deficiency is associated with a decline in erectile function and testosterone levels are inversely correlated with increasing severity of erectile dysfunction. Erectile dysfunction can be caused by multifactorial pathologies. In particular, erectile dysfunction may be the first symptom of cardiovascular disease. Animal studies have demonstrated that castration causes vascular smooth muscle cell atrophy, venous leakage, adipocytes in the subtunical space, loss of elastic fibers and increase in collagen deposition. Testosterone increases the expression of nitric oxide synthase and phosphodiesterase type 5, both principal enzymes involved in the erectile process. Testosterone replacement alone in hypogonadal men can restore erectile function. A significant proportion of men who fail to respond to a PDE5 inhibitor are testosterone deficient. Testosterone replacement therapy can convert over half of these men into phosphodiesterase type 5 responders. It is now recommended that testosterone levels should be assessed in all patients with erectile dysfunction.

Cardiovascular Disease, Hypogonadism and ED: Early Detection, Prevention and the Positive Effects of Long-Term TRT

In this prospective longitudinal study of 622 men on TRT: erectile function increased significantly, average weight loss was 23.6 ± 0.6 kg after 8 years, blood glucose readings improved and several patients with diabetes went into remission.  Cholesterol levels improved significantly and systolic blood pressure decreased by 33±1 mmHg on average.

TRT Improves Erectile Function and Libido in Hypogonadal Men

Purpose of Review

Andropause: Introducing the Concept of ‘Relative Hypogonadism’ in Aging Males

Andropause affects many organ systems including the brain, heart, bones, muscle, adipose tissue, and blood vessels besides the sexual organs. The authors state that the prevalence of hypogonadism in aging males is not well established. There are many epidemiological studies that point towards a decline of testosterone with aging.

Relative Hypogonadism and Metabolic Syndrome in Newly Diagnosed Adult Male Patients with Impaired Glucose Tolerance or Type 2 Diabetes Mellitus

Sex steroid hormones are known to be important regulators of the lipid and glucose metabolism. Lower levels of testosterone (T) or sex hormone-binding globulin (SHBG) have been reported in men with type 2 diabetes. On the other hand, the relationship between relative hypogonadism and metabolic syndrome has not yet to be thoroughly studied. Ninety-eight Japanese adult (age 20-64) male patients with impaired glucose tolerance (IGT) or type 2 diabetes mellitus were divided into either an metabolic syndrome group (n = 42) or a non- metabolic syndrome (n = 56) group according to the definition of metabolic syndrome from WHO, or into three tertiles according to their sex hormone index level. The metabolic syndrome group had a significantly lower T/estradiol (E(2)) and SHBG level (p < 0.01). The age and subcutaneous fat surface area (SFA) were significantly different within the tertiles in SHBG and T/E(2). Logistic regression analyses were performed to investigate the association between the sex steroid hormone index level and the incidence of metabolic syndrome. Regarding the highest tertiles as a criterion, lower SHBG, T/E(2) or free T/E(2) had a higher odds ratio of prevalence of metabolic syndrome even after adjusting for age and SFA. Relative hypogonadism was strongly associated with the prevalence of metabolic syndrome in Japanese adult men who were newly diagnosed to have IGT or type 2 diabetes.

TRT & Weight Loss for Men with Newly Diagnosed Diabetes

Men with the metabolic syndrome (MetS) and type 2 diabetes (T2D) often have low testosterone levels. Elevating low testosterone levels may improve features of the MetS and glycemic control. In a single blind, 52-week randomized clinical trial, the effects of supervised diet and exercise (D&E) with or without transdermal testosterone administration on components of the MetS in hypogonadal men with the MetS and newly diagnosed T2D were assessed. A total of 32 hypogonadal men (total testosterone <12.0 nmol/L) with newly diagnosed T2D and with the MetS as defined by the Adult Treatment Panel III and the International Diabetes Federation received supervised D&E, but 16 received it in combination with testosterone gel (50 mg) once daily (n = 16). No glucose-lowering agents were administered prior to or during the study period. Outcome measures were components of the MetS as defined by the Adult Treatment Panel III and the International Diabetes Federation. Serum testosterone, glycosylated hemoglobin (HbA(1c)), fasting plasma glucose, high-density lipoprotein cholesterol, triglyceride concentrations, and the waist circumference improved in both treatment groups after 52 weeks of treatment. Addition of testosterone significantly further improved these measures compared with D&E alone. All D&E plus testosterone patients reached the HbA(1c) goal of less than 7.0%; 87.5% of them reached an HbA(1c) of less than 6.5%. Based on Adult Treatment Panel III guidelines, 81.3% of the patients randomized to D&E plus testosterone no longer matched the criteria of the MetS, whereas 31.3% of the D&E alone participants did. Additionally, testosterone treatment improved insulin sensitivity, adiponectin, and high-sensitivity C-reactive protein. Addition of testosterone to supervised D&E results in greater therapeutic improvements of glycemic control and reverses the MetS after 52 weeks of treatment in hypogonadal patients with the MetS and newly diagnosed T2D.

Testosterone and Obesity

Testosterone is a key hormone in the pathology of metabolic diseases such as obesity. Low testosterone levels are associated with increased fat mass (particularly central adiposity) and reduced lean mass in males. These morphological features are linked to metabolic dysfunction, and testosterone deficiency is associated with energy imbalance, impaired glucose control, reduced insulin sensitivity and dyslipidaemia. A bidirectional relationship between testosterone and obesity underpins this association indicated by the hypogonadal-obesity cycle and evidence weight loss can lead to increased testosterone levels. Androgenic effects on enzymatic pathways of fatty acid metabolism, glucose control and energy utilization are apparent and often tissue specific with differential effects noted in different regional fat depots, muscle and liver to potentially explain the mechanisms of testosterone action. Testosterone replacement therapy demonstrates beneficial effects on measures of obesity that are partially explained by both direct metabolic actions on adipose and muscle and also potentially by increasing motivation, vigour and energy allowing obese individuals to engage in more active lifestyles. The degree of these beneficial effects may be dependent on the treatment modality with longer term administration often achieving greater improvements. Testosterone replacement may therefore potentially be an effective adjunctive treatment for weight management in obese men with concomitant hypogonadism.

Testosterone and Weight Loss: The Evidence

Purpose of review