Masculine Vitality: Pros and Cons of Testosterone in Treating the Andropause

As our population ages, concerns about frailty and disability, as well as the all-too-human desire to remain young for as long as possible have led increasing numbers of women and men to the questionable practice of restoring diminishing hormone levels. Hundreds of thousands of American men are creating a massive uncontrolled and possibly life-threatening experiment by taking so called "anti-aging" testosterone replacement therapies

Evaluating the cardiovascular risk of testosterone replacement therapy in men with late-onset hypogonadism

As the major circulating androgen in men, testosterone holds a significant role in the maturation and maintenance of male characteristics. Some of its effects include inducing significant growth of the penis and testes early in development, producing sperm, and contributing to bone mass and muscle strength. Testosterone is synthesized in the testes and released into the circulation where it exerts its effects across the body. Its negative feedback on the hypothalamus and pituitary glands serve as regulation of the hypothalamic-pituitary-testosterone axis. Starting around age 30, testosterone levels have been shown to annually decline approximately 1-2% in men. Decline may eventually lead to a deficiency, presenting as reduced sex drive, erectile dysfunction, low sperm count, or decreased muscle bulk and strength. Many symptoms of testosterone deficiency coincide with old age. Also, the threshold of low testosterone at which symptoms manifest can vary from person to person. For these reasons, diagnosing testosterone deficiency has proven difficult. Nevertheless, certain guidelines have defined late-onset hypogonadism (LOH) as testosterone levels below about 200-300 ng/dl with the simultaneous presentation of at least one related symptom. Increasing diagnosis of late-onset hypogonadism, colloquially known as "Low T", has led to the enormous growth of the testosterone replacement therapy (TRT) market. Testosterone replacement therapy is the administration of either synthetic or endogenous testosterone to restore "above threshold" testosterone levels and improve the negative symptoms associated with deficiency. TRT comes in a wide variety of formulations and its use has risen steeply over the past decade, with a market currently worth around $1.8 billion. Reports estimate that the market for TRT may surpass$5 billion by 2018. However, there is plenty of cause for concern. In its current state, LOH is a loosely defined phenomenon whose treatment with TRT has not been confirmed in the research-standard large, randomized, placebo-controlled, trial. Furthermore, two recent retrospective database studies by Vigen et al. (2013) and Finkle et al. (2014) have reported increases in cardiovascular disease risk and mortality with TRT use in men with LOH. These studies were preceded with a meta-analysis by Xu et al. (2013) reviewing cardiovascular risk of TRT as well as another study measuring TRT effectiveness in elderly men by Basaria et al. (2010), which was prematurely halted due to an unsafe number of adverse events. The four studies above were analyzed and evaluated as the argument against TRT and its potential risk to cardiovascular health. On the other hand, there is plenty of evidence associating low endogenous testosterone levels with adverse effects and the benefits of TRT in treating LOH. This study summarized and evaluated the available evidence of the effects of endogenous testosterone levels and testosterone replacement therapy on cardiovascular health, including coronary artery disease, congestive heart failure, factors of atherosclerosis, and risk factors of cardiovascular disease such as obesity, type 2 diabetes mellitus, dyslipidemia, and inflammatory markers. Additionally, this thesis was written in the midst of a recent controversy concerning the field of TRT. Mainstream reporting on the results of the aforementioned studies by Vigen et al. (2013) and Finkle et al. (2014) led to increasing public concern about the safety of testosterone therapy. The results of these studies were met with heavy criticism by the medical field due to their shortcomings in design and conduct. The consumer rights advocacy group Public Citizen petitioned the FDA to add a black box warning of cardiovascular risk to TRT medications on the market. The Androgen Study Group, a group of medical experts and societies committed to accurate reporting of information about androgens, countered with a letter of their own to the FDA as well as a letter to JAMA requesting that they retract the article by Vigen et al (2013). The FDA is currently evaluating these requests as well as the overall risk of testosterone replacement therapy on cardiovascular health and mortality. The analysis of this thesis proved the argument against testosterone replacement therapy unreliable. The four studies contained significant flaws in methodology, substandard presentation of data, and were initially built upon a weak foundation of evidence. Current evidence shows that low endogenous testosterone levels are associated with increased cardiovascular risk, while the results of testosterone replacement therapy in treating LOH are predominantly positive. Many of these studies are epidemiological in nature, have small sample sizes, and vary in methodology and potential confounding factors. Thus, although the advantages reported for testosterone replacement therapy seems to trend positive, the need for randomized controlled trial(s) still remains. Diagnosis of LOH and prescription of TRT should be approached with caution and on an individualized basis

Incidence of Coronary Artery Disease and Testosterone Replacement Therapy

In the United States, males see a decrease in testosterone levels around the age of 40, potentially leading to a condition known as hypogonadism. Testosterone administration is the leading treatment for symptomatic hypogonadism. Testosterone Replacement Therapy (TRT) has increased in popularity amongst practicing healthcare providers. This literature review aims to investigate differences in incidence rates of cardiovascular events in males receiving testosterone therapy compared to untreated males with hypogonadism. Given the conflicting evidence regarding the association between exogenous testosterone and cardiovascular risk, published studies and meta-analysis were reviewed to prove this relationship. A comprehensive literature review was performed using electronic databases such as the American Endocrine Association, Pub-Med, Clinical Key, Cochrane library, and the American Journal of Medicine. A review of the literature shows conflicting data. Various studies showed cardioprotective benefits of TRT, while other studies show an increased incidence of cardiovascular disease. The largest meta-analysis to date revealed no increased cardiovascular risk in men who received testosterone and reduced cardiovascular risk among those with metabolic disease. However, the following studies were limited in duration, dosages, administration routes, and subject population. Because of the inferior quality of evidence, it is challenging to produce a definitive conclusion on cardiovascular disease in males on TRT. Therefore, given the challenge of varied study controls and protocols to assess for rare outcomes, further studies are needed to clarify the association between the duration of TRT and primary adverse cardiovascular effects

Testosterone Therapy and Cardiovascular Risk

Endogenous testosterone levels are inversely associated with cardiovascular risk in older men and men with cardiovascular disease. Current data on cardiovascular outcomes of testosterone therapy include only observational studies and adverse event monitoring in short-term trials that were not designed to measure cardiovascular outcomes. These studies have yielded conflicting results, and some have raised concerns that testosterone therapy may increase cardiovascular risk. A well-designed, adequately powered, prospective trial will ultimately be required to clarify whether testosterone therapy impacts cardiovascular outcomes. This review describes the findings and limitations of recent studies of cardiovascular risk in older men on testosterone therapy and discusses some of the mechanisms through which testosterone may modify cardiovascular risk

Testosterone Replacement Therapy: Long-Term Safety and Efficacy.

Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG) or late-onset hypogonadism (LOH). The former is the consequence of congenital or acquired “organic” damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T) therapy (TTh). In addition, concerns related to cardiovascular (CV) safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an “ex-juvantibus” criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented

Internet Transparency of Local Men’s Health Clinics in Nebraska

An overview of Men’s Health Clinics offering Testosterone Therapy in a Midwest State. Introduction/ Background – Since 2001, there has been a 300% increase in the use of Testosterone therapy. However, there remains limited published data on the demographics of facilities and providers that advertise this service. This study aims to look at such demographics of advertised Men’s health clinics in Nebraska. Methods/ Materials – An internet search was conducted with the phrases “Nebraska Male health clinics, Nebraska Low T/testosterone, Nebraska Hormone Replacement Therapy”. All clinics that were found offering Testosterone therapy with Men’s health in their mission statement were included. Data was gathered using 6 questions, with answers obtained from the public website or by calling the office. Results – 19 different facilities were found that self-identified as Men’s Health clinics. 5/19 facilities were nationally corporate owned, 13/19 were individually owned, and 1 was an academic university. All offered Testosterone Therapy. Of the 19 facilities, 10/19 branded themselves primarily as Men’s Health Clinics. 6/10 out of those offered testosterone therapy, Plasma infusion, and Penile Shockwave Therapy. Those that offered services other than Men’s health were marketed as Medical Spas and Aesthetic centers, offering hormone replacement therapy, aesthetics, and anti-aging treatments. 10/19 Clinics had no MD listed and visits would be with a mid-level provider (NP or PA). Only 1/19 provided prices online, others required consultation before prices would be given. Of the 19 facilities, only 6 accept insurance and the rest are cash-pay clinics only. Conclusions – Of the Nebraska clinics that self-identify as men’s health clinics, many are individually owned clinics with a focus on hormone replacement or aesthetics. Of those clinics, many were run entirely by mid-levels or with a supervising MD overseeing mid-levels. Less than 1/3rd of facilities accept insurance and there is a lack of price transparency

Testosterone deficiency and cardiovascular mortality

New concerns have been raised regarding cardiovascular (CV) risks with testosterone (T) therapy (TTh). These concerns are based primarily on two widely reported retrospective studies. However, methodological flaws and data errors invalidate both studies as credible evidence of risk. One showed reduced adverse events by half in T-treated men but reversed this result using an unproven statistical approach. The authors subsequently acknowledged serious data errors including nearly 10% contamination of the dataset by women. The second study mistakenly used the rate of T prescriptions written by healthcare providers to men with recent myocardial infarction (MI) as a proxy for the naturally occurring rate of MI. Numerous studies suggest T is beneficial, including decreased mortality in association with TTh, reduced MI rate with TTh in men with the greatest MI risk prognosis, and reduced CV and overall mortality with higher serum levels of endogenous T. Randomized controlled trials have demonstrated benefits of TTh in men with coronary artery disease and congestive heart failure. Improvement in CV risk factors such as fat mass and glycemic control have been repeatedly demonstrated in T-deficient men treated with T. The current evidence does not support the belief that TTh is associated with increased CV risk or CV mortality. On the contrary, a wealth of evidence accumulated over several decades suggests that low serum T levels are associated with increased risk and that higher endogenous T, as well as TTh itself, appear to be beneficial for CV mortality and risk

Testosterone And Vitamin D Concentrations In Military Personnel Following Traumatic Brain Injury

Purpose: To investigate testosterone and vitamin D status in service members, with and without a history of traumatic brain injury (TBI). Methods: This retrospective de-identified medical review analyzed hormone assessments ordered for 4,285 active duty and veteran military personnel at Womack Army Medical Center, Fort Bragg, NC from 2016-2018. Results: Overall, 343 (8%) of service members had a medically diagnosed TBI. In all men, 19% were deficient in testosterone (<270 ng/dl), and 10% had a testosterone prescription. Active duty men with a history of TBI had lower testosterone compared to active duty men with no documented head injury, but there was no significant difference in veteran men. More than one-third (38%) of all service members were insufficient in vitamin D (<30 ng/ml). Overall there was a weak positive correlation between testosterone and vitamin D concentrations in men but not in women. Conclusions: Our research does not support evidence for high rates of hypogonadism, testosterone prescription, or vitamin D deficiency after TBI compared to military personnel without prior injury. However, our overall dataset shows a high prevalence of vitamin D insufficiency in service members independent of TBI, further supporting that vitamin D status should be assessed regularly in service members

Testosterone and the Adult Male

Abstract In the last 15 years, prescription testosterone sales have increased almost threefold. Testosterone is a powerful hormone, which has both physiological and behavioral effects on the adult male. These effects vary over a man’s life course and social ecology. In a natural setting, testosterone reaches a peak during early adulthood, declines gradually over midlife, and has exponential drops after the age of 70. Increasing testosterone, through testosterone replacement therapy (TRT), past early adulthood, is an evolutionary novel circumstance for an adult male. To gauge these effects, and the motivations that initiated them, this study conducted a preliminary text analysis of 60 posts, and all replies to them, in Facebook groups related to TRT. Coding of these groups was conducted to find the common themes discussed by TRT patients. TRT patients in these groups most often discussed purchasing and treatment information, treatment details, total testosterone blood levels and perceived risks/side effects. A preliminary analysis of above-50 men in these groups also notably discussed sexual health, comorbidities, and energy. Masculinity, did not seem to be a significant theme in these discussions; this may be due to methodological and coding limitations. This is the first attempt, to my knowledge, to analyze TRT from a patient/consumer perspective. This study found a significant focus on side effects, which were not found in an earlier published content analysis of TRT manufacturer websites. The implications of some of these findings will be discussed. This preliminary analysis offers insights for future attempts to analyze TRT, testosterone, and the aging male