Androgen Replacement

Basaria S. Testosterone Therapy in Older Men with Late-Onset Hypogonadism: A Counter-Rationale. Endocr Pract 2013:1-40. Testosterone Therapy in Older Men with Late-Onset Hypogonadism: A Counter-Rationale - Endocrine Practice - American Association of Clinical Endocrinologists / http://www.metapress.com/content/w150n23807479n31/fulltext.pdf

Objective: The past decade has seen a surge in the number of older men being referred to endocrinologists for consideration of testosterone therapy for late-onset hypogonadism (LOH) to treat symptoms such as fatigue, sexual dysfunction and decreased vitality. As a result, the prescription sales of testosterone have increased 20-fold, mainly due to a sophisticated marketing campaign by the industry and the failure of clinicians to distinguish organic hypogonadism from LOH. The objective of this review is to provide a counter-rationale of testosterone therapy in LOH.

Methods: A retrospective review of seminal English-language epidemiologic studies and clinical trials related to testosterone and older men. Review articles and their references were also reviewed and included where relevant.

Results: Population studies reporting on LOH have several shortcomings such as use of multiple numeric definitions, use of testosterone assays not considered standard and measurement of testosterone at a single time point. In contrast to the higher prevalence based solely on numeric values, the syndromic prevalence of LOH is only 2%. Although attrition of testicular Leydig cells and slowing of the GnRH neurons contribute to LOH, obesity and other co-morbidities strongly influence testosterone levels, suggesting that testosterone is a biomarker of health. Testosterone therapy in LOH has consistently shown improvement in muscle mass and strength, however, improvement in physical function is limited to a few trials. Similarly, efficacy of testosterone therapy on falls and fracture rates remain unknown. In terms of risks, erythrocytosis remains the most common adverse effect of testosterone therapy in older men while long-term risks on the prostate and cardiovascular system remain unclear.

Conclusion: Considering the paucity of data on clinically meaningful outcomes, uncertain risks and the fact that modifiable risk factors adversely influence testosterone levels, healthy lifestyle and treatment of co-morbidities might attenuate age-related decline in testosterone levels.
 
Cunningham GR. Andropause or Male Menopause? Rationale for Testosterone Replacement Therapy in Older Men with Low Testosterone Levels. Endocr Pract 2013:1-18. http://www.metapress.com/content/wu1633t82648g73r/fulltext.pdf / Andropause or Male Menopause? Rationale for Testosterone Replacement Therapy in Older Men with Low Testosterone Levels - Endocrine Practice - American Association of Clinical Endocrinologists

Objective: To provide rationale for testosterone replacement therapy of older men with low testosterone levels and symptoms consistent with testosterone deficiency.

Methods: The relevant literature has been reviewed using PubMed.

Results: Cross-sectional and longitudinal population-based studies indicate total and free T levels fall with aging, and they may be accompanied by symptoms consistent with androgen deficiency. Testosterone treatment of younger men with very low testosterone levels and hypothalamic, pituitary or testicular disease is associated with improvement in symptoms, body composition, bone density and hematocrit/hemoglobin. Studies evaluating testosterone treatment of older men with low testosterone levels are limited, but suggest some increase in fat free mass, some decrease in fat mass and some increase in bone density of the lumbar spine and femoral neck.

Conclusion: The Testosterone Trial should provide definitive information regarding potential benefits of testosterone replacement therapy in men >/=65 years of age. If efficacy is confirmed, we will still need more information regarding risks of TRT in older men.
 
Kang S, Park HJ, Park NC. Serum total testosterone level and identification of late-onset hypogonadism: a community-based study. Korean J Urol 2013;54(9):619-23. Serum Total Testosterone Level and Identification of Late-Onset Hypogonadism: A Community-Based Study / :: KJU :: Korean Journal of Urology

PURPOSE: Late-onset hypogonadism (LOH) in aging males is a clinical and biochemical syndrome characterized by a decline in serum testosterone levels. LOH results in various physical and mental disabilities. We evaluated the relationship between serum testosterone levels and symptoms of LOH.

MATERIALS AND METHODS: During an andropause screening program, we examined responses to the Saint Louis university androgen deficiency in aging males (ADAM) questionnaire and results on the International Index of Erectile Function (IIEF-5) in terms of clinical symptoms and evaluated serum total testosterone levels for a biochemical diagnosis of LOH in healthy community-living volunteers aged over 40 years.

RESULTS: The mean age of the 534 men was 59.1 years (range, 40 to 79 years), and their mean serum testosterone level was 464.1+/-171.9 ng/dL. The serum testosterone level decreased significantly with age. There was a 92.5% positive response rate to the ADAM questionnaire. The percentage of patients whose serum testosterone level was <350 ng/dL among those with a positive response to the ADAM questionnaire was 25.6% (137 patients). The mean serum testosterone level among patients with a positive or negative ADAM questionnaire was 472.4+/-198.5 ng/dL and 487.3+/-165.7 ng/dL, respectively (p>0.05). There was no significant correlation between IIEF-5 scores and serum testosterone levels.

CONCLUSIONS: Among men over 40 years of age, 25.6% met the clinical and biochemical diagnostic criteria for LOH. There was no relationship between serum testosterone levels and symptoms of LOH.
 
Isidori AM, Buvat J, Corona G, et al. A Critical Analysis of the Role of Testosterone in Erectile Function: From Pathophysiology to Treatment-A Systematic Review. Eur Urol. A Critical Analysis of the Role of Testosterone in Erectile Function: From Pathophysiology to Treatment—A Systematic Review

CONTEXT: Androgen modulation of erectile function (EF) is widely accepted. However, the use of testosterone replacement therapy (TRT) in men with erectile dysfunction (ED) has generated an unprecedented debate.

OBJECTIVE: To summarize the relevant data on the incidence, diagnosis, and management of ED coexisting with hypogonadism and to develop a pathophysiology-based treatment algorithm.

EVIDENCE ACQUISITION: We reviewed the relevant medical literature, with a particular emphasis on original molecular studies, prospective observational data, and randomized controlled trials performed in the past 20 yr.

EVIDENCE SYNTHESIS: Testosterone modulates nearly every component involved in EF, from pelvic ganglions to smooth muscle and the endothelial cells of the corpora cavernosa. It also regulates the timing of the erectile process as a function of sexual desire, coordinating penile erection with sex. Epidemiologic studies confirm the significant overlap of hypogonadism and ED; however, most guidelines do not consider the differential diagnosis of hypogonadism or the relevance of subclinical disease. Various clinical tools can help the physician to assess and restore androgen levels in men with ED. Special attention is given to fertility-sparing treatments, due to the increasing number of older men desiring fatherhood. The simultaneous use of phosphodiesterase type 5 inhibitors (PDE5-Is) and TRT has recently been questioned. Originally proposed as a salvage therapy for nonresponders to PDE5-Is, this approach has been inappropriately transformed into a combination therapy. Clinical data are consistent when reinterpreted in the proper framework, whereas molecular evidence remains controversial.

CONCLUSIONS: A body of molecular and clinical evidence supports the use of TRT in hypogonadal patients with ED, although the benefit-risk ratio is uncertain in advanced age. Critical appraisal of this evidence enabled the development of a pathophysiology-oriented algorithm designed to avoid inappropriate treatments and support whether to start with TRT, PDE5-I only, or both. Apparently divergent findings are reconciled when TRT is correctly indicated. An improved diagnosis and individualized management is desirable in light of the many available options.
 
Ruige JB, Ouwens DM, Kaufman J-M. Beneficial and Adverse Effects of Testosterone on the Cardiovascular System in Men. Journal of Clinical Endocrinology & Metabolism. http://jcem.endojournals.org/content/early/2013/09/23/jc.2013-1970.abstract (Beneficial and Adverse Effects of Testosterone on the Cardiovascular System in Men)

Context: The widespread use of T therapy, particularly in aging males, necessitates knowledge of the relationship between T and the cardiovascular system.

Evidence Acquisition: The review is based on a 1970 to 2013 PubMed search with terms related to androgens in combination with cardiovascular disease, including T, dihydrotestosterone, trial, mortality, cardiovascular disease, myocardial infarction, blood pressure, endothelial function, dyslipidemia, thrombosis, ventricular function, and arrhythmia. Original articles, systematic reviews and meta-analyses, and relevant citations were screened.

Evidence Synthesis: Low T has been linked to increased blood pressure, dyslipidemia, atherosclerosis, arrhythmia, thrombosis, endothelial dysfunction, as well as to impaired left ventricular function. On the one hand, a modest association is suggested between low endogenous T and incident cardiovascular disease or cardiovascular mortality, implying unrecognized beneficial T effects, residual confounding, or a relationship with health status. On the other hand, treatments with T to restore “normal concentrations” have so far not been proven to be beneficial with respect to cardiovascular disease; neither have they definitely shown specific adverse cardiovascular effects. The cardiovascular risk-benefit profile of T therapy remains largely evasive in view of a lack of well-designed and adequately powered randomized clinical trials.

Conclusions: The important knowledge gap as to the exact relationship between T and cardiovascular disease would support a cautious, restrained approach to T therapy in aging men, pending clarification of benefits and risks by adequately powered clinical trials of sufficient duration.
 
Hayes LD, Grace FM, Sculthorpe N, Herbert P, Kilduff LP, Baker JS. Does chronic exercise attenuate age-related physiological decline in males? Res Sports Med 2013;21(4):343-54. An Error Occurred Setting Your User Cookie

Alteration in body composition, physical function, and substrate metabolism occur with advancing age. These changes can be attenuated by exercise. This study evaluated whether master athletes (MA [n = 20]) would have improved exercise capabilities, anthropometry, and hormone profiles when compared with age-matched sedentary counterparts (S [n = 28]).

The MA group was predominantly aerobically trained with some resistance exercise incorporated in their routine. The VO2max, peak power output, and salivary testosterone was significantly higher (p < 0.05) in the MA group, while diastolic blood pressure, systolic blood pressure, and body fat percentage were lower (p < 0.05). Cortisol, fat free mass, (FFM) and total body mass were not significantly different between groups. Salivary testosterone correlated positively with VO2max (r (2) = .320), suggesting that increased aerobic capacity is linked with higher concentrations of testosterone.

These results suggest that life-long exercise is associated with favorable body composition and attenuation of the age related decline in testosterone.
 
Glintborg D, Christensen LL, Kvorning T, et al. Strength Training and Testosterone Treatment Have Opposing Effects on Migration Inhibitor Factor Levels in Ageing Men. Mediators Inflamm. 2013:539156. Strength Training and Testosterone Treatment Have Opposing Effects on Migration Inhibitor Factor Levels in Ageing Men

Background. The beneficial effects of testosterone treatment (TT) are debated.

Methods. Double-blinded, placebo-controlled study of six months TT (gel) in 54 men aged 60-78 with bioavailable testosterone (BioT) <7.3 nmol/L and waist >94 cm randomized to TT (50-100 mg/day, n = 20), placebo (n = 18), or strength training (ST) (n = 16) for 24 weeks. Moreover, the ST group was randomized to TT (n = 7) or placebo (n = 9) after 12 weeks.

Outcomes. Chemokines (MIF, MCP-1, and MIP-1 alpha ) and lean body mass (LBM), total, central, extremity, visceral, and subcutaneous (SAT) fat mass established by DXA and MRI.

Results. From 0 to 24 weeks, MIF and SAT decreased during ST + placebo versus placebo, whereas BioT and LBM were unchanged. TT decreased fat mass (total, central, extremity, and SAT) and increased BioT and LBM versus placebo. MIF levels increased during TT versus ST + placebo. ST + TT decreased fat mass (total, central, and extremity) and increased BioT and LBM versus placebo. From 12 to 24 weeks, MCP-1 levels increased during TT versus placebo and MCP-1 levels decreased during ST + placebo versus placebo.

Conclusion. ST + placebo was associated with decreased MIF levels suggesting decreased inflammatory activity. TT may be associated with increased inflammatory activity.
 
Schooling CM. Androgen activity, ischaemic heart disease and risk factors among men in NHANES III. Eur J Clin Invest. Androgen activity, ischaemic heart disease and risk factors among men in NHANES III - Schooling - 2013 - European Journal of Clinical Investigation - Wiley Online Library

AIM: Observationally, low serum testosterone among men is associated with cardiovascular diseases and its risk factors, but it is unclear whether raising endogenous androgens would be protective. To clarify the role of androgens, the association of two different androgen biomarkers (serum testosterone and androstanediol glucuronide) with cardiovascular disease risk factors and mortality was examined in a nationally representative sample of US men.

RESEARCH DESIGN AND METHODS: Multivariable linear and proportion hazards regression were used to examine the adjusted associations of serum testosterone and androstanediol glucuronide with cardiovascular disease risk factors and death from major cardiovascular diseases in 1460 men from NHANES III phase 1 (1988-1991) followed-up through 2006.

RESULTS: Serum testosterone and androstanediol glucuronide were weakly correlated (0.13). Serum testosterone was associated with healthier values of most cardiovascular disease risk factors but not with death from ischaemic heart disease or stroke, adjusted for age, education, race/ethnicity, smoking and alcohol use. Similarly adjusted, androstanediol glucuronide was associated with unhealthier values of some cardiovascular risk factors and death from ischaemic heart disease (hazard ratio 1.16, 95% confidence interval 1.003-1.33 per standard deviation).

CONCLUSIONS: Androgen biomarkers had inconsistent associations with cardiovascular disease risk factors and ischaemic heart disease. Androstanediol glucuronide, rather than serum testosterone, had associations with cardiovascular disease risk factors more similar to those seen in randomized controlled trials of testosterone therapy, with corresponding implications for raising androgens.
 
http://www.nytimes.com/2013/10/16/u...l=1&adxnnlx=1381864021-SbuzpW6D79KWI2a8zaYkig

The barrage of advertisements targets older men. “Have you noticed a recent deterioration of your ability to play sports?” “Do you have a decrease in sex drive?” “Do you have a lack of energy?”

If so, the ads warn, you should “talk to your doctor about whether you have low testosterone” — “Low T,” as they put it.

In the view of many physicians, that is in large part an invented condition. Last year, drug makers in the United States spent $3.47 billion on advertising directly to consumers, according to FiercePharma.com. And while ever-present ads like those from AbbVie Pharmaceuticals have buoyed sales of testosterone gels, that may be bad for patients as well as the United States’ $2.7 trillion annual health care bill, experts say.

Sales of prescription testosterone gels that are absorbed through the skin generated over $2 billion in American sales last year, a number that is expected to more than double by 2017. Abbott Laboratories — which owned AbbVie until Jan. 1 — spent $80 million advertising its version, AndroGel, last year.

Once a niche treatment for people suffering from hormonal deficiencies caused by medical problems like endocrine tumors or the disruptive effects of chemotherapy, the prescription gels are increasingly being sold as lifestyle products, to raise dipping levels of the male sex hormone as men age.

“The market for testosterone gels evolved because there is an appetite among men and because there is advertising,” said Dr. Joel Finkelstein, an associate professor at Harvard Medical School who is studying male hormone changes with aging. “The problem is that no one has proved that it works and we don’t know the risks.”

Dr. Eric Topol, a cardiologist and chief academic officer at Scripps Health in San Diego, is alarmed by the high percentage of patients he sees who use the roll-on prescription products, achieving testosterone levels that he described as “ridiculously high.”

The gels are of questionable medical benefit for many of the millions of men who now take them, he and other doctors say, and their side effects may well prove dangerous.

“These medicines come with a risk of coronary artery disease,” Dr. Topol said.

“When I ask patients why they’re on it, the instant response, is, ‘I have low T.’ I ask, ‘Why would you even get tested for that?’ There isn’t really a normal,” he said. Other side effects include an enlarged prostate, he added.

Nevertheless, many insurers cover the cost of the high-priced hormone treatments, requiring only a small co-payment from patients. AndroGel and another popular testosterone gel, Axiron, by Eli Lilly & Company, sell for more than $500 a month retail, and about $400 with pharmacy coupons.

Many experts say that pharmaceutical advertising promotes excessive and inappropriate drug use by convincing patients that they are ill — or have a more serious condition than is genuinely the case — and need medicine to treat it. While television viewers are barraged with advertising warning men they may have “low T,” Dr. Finkelstein said, “There is no such disease.”

Such advertising also leads patients to seek out more expensive treatments, rather than cheaper ones that are often equally effective. Drugs that are advertised are almost always the ones that are costly.

In response to an article Sunday in The New York Times on prescription drug costs for asthma medicines in the United States, a number of readers complained about the high price of inhalers, and that the costs were inflated by the millions of dollars pharmaceutical companies spend on advertising for them.

Jack D. from Philadelphia, for example, wrote that he mail-ordered his prescription steroid nasal spray from overseas, for 20 percent of the price in the United States. “I refuse to pay for ads featuring talking bees with Spanish accents,” he wrote. Merck spent $46.3 million last year advertising Nasonex, its popular steroid spray.

Patients of any age may benefit from testosterone replacement if their levels are severely low because of serious medical problems, experts say. But testosterone normally declines as men age — just as estrogen does in women.

The F.D.A. has approved the gels “for use in men who either no longer produce the male sex hormone testosterone or produce it in very low amounts.” But that directive is ambiguous, and the F.D.A. office did not respond to questions because of the government shutdown.

Should testosterone be replaced in older men, and will it safely redress frequent ordinary symptoms of male aging, like decreased muscle mass and libido? And what constitutes a very low amount?

Dr. Finkelstein said, “Until there are big long-term studies to address the issues of testosterone replacement, we’re not ready to make recommendations on that.”


But drug companies defend their efforts to reach out to potential users. Testosterone deficiency is “a recognized clinical condition, with signs/symptoms that can impact millions of patients,” said Morry B. Smulevitz, a director of communications for Lilly, which makes Axiron. While he said the company did not condone the use of medicine for purposes other than those approved by the F.D.A., it “encouraged patients to talk to their physicians to weigh the risks and benefits.”

David Freundel, director of public affairs for AbbVie, which makes AndroGel, said the company’s “low testosterone efforts” were “developed to educate men who may be at risk for, or have, low testosterone, so they can have the appropriate dialogue with their physician to determine if testing and treatment may be appropriate.”

Studies are just beginning to yield results to address the appropriate use of the drug in older men. For example, scientists have found that age-related male changes in body fat depend on a different hormone, estradiol, which also decreases with age. Likewise, while strength and libido do decrease with falling testosterone levels, that effect may not be significant until testosterone levels are very low, Dr. Finkelstein said. Low testosterone is rarely the main cause of erectile dysfunction.

Finally, he added, no one has really defined what is a “normal” or “physiological” testosterone level. And yet, physicians often order tests for “low T.”

A survey this year by CMI/Compass found that more than half of physicians felt that pharmaceutical advertising to consumers should be scaled back, and 63 percent said it misinformed patients.

“I really don’t understand why it’s tolerated at a time we’re struggling with health care costs,” Dr. Topol said. “A lot of people bounce their legs in meetings, but that doesn’t mean you have restless leg syndrome, and you shouldn’t be taking drugs for that.”
 
I think we're very clearly seeing the effects of the low T marketing here. Every guy with low libido, low energy who doesn't feel like himself with ED and brain fog must have low T.....in spite of their 600+ tT.

When my tT was 150 I felt like death and now I feel great. TRT has been the single best medical intervention in my life and I credit it for saving my life. I wasn't suicidal but I had zero quality of life and now I feel alive!
 
“When I ask patients why they’re on it, the instant response, is, ‘I have low T.’ I ask, ‘Why would you even get tested for that?’ There isn’t really a normal"

This guy is a moron,every test on your bloodwork up has a low,normal and high range :confused: He is just singling out tetosterone levels and being an ASS..........
 
I think we're very clearly seeing the effects of the low T marketing here. Every guy with low libido, low energy who doesn't feel like himself with ED and brain fog must have low T.....in spite of their 600+ tT.

When my tT was 150 I felt like death and now I feel great. TRT has been the single best medical intervention in my life and I credit it for saving my life. I wasn't suicidal but I had zero quality of life and now I feel alive!

I'm not sure that I get the point of your first paragraph. Judging by comments on forums, many guys have difficulty getting scripts even with marginal levels.
 
I'm not sure that I get the point of your first paragraph. Judging by comments on forums, many guys have difficulty getting scripts even with marginal levels.

Point is we very clearly get psych patients here with normal labs across the board who are fucking batt shit crazy but they've seen so many low T commercials they convince themselves that MUST be the problem. When this board suggests to look elsewhere they throw a temper tantrum because it MUST be low T.....that's my point. This is getting progressively worse with time IMO and it directly correlates with the number of low T commercials.

My other point is if you have a tT of 600+ with all those symptoms....it isn't LOW T. See you have to have low T to be diagnosed with low T.
 
Point is we very clearly get psych patients here with normal labs across the board who are fucking batt shit crazy but they've seen so many low T commercials they convince themselves that MUST be the problem. When this board suggests to look elsewhere they throw a temper tantrum because it MUST be low T.....that's my point. This is getting progressively worse with time IMO and it directly correlates with the number of low T commercials.

My other point is if you have a tT of 600+ with all those symptoms....it isn't LOW T. See you have to have low T to be diagnosed with low T.

Fuck You!!! For my age, the testosterone level should be 5,000.
 
Point is we very clearly get psych patients here with normal labs across the board who are fucking batt shit crazy but they've seen so many low T commercials they convince themselves that MUST be the problem. When this board suggests to look elsewhere they throw a temper tantrum because it MUST be low T.....that's my point. This is getting progressively worse with time IMO and it directly correlates with the number of low T commercials.

My other point is if you have a tT of 600+ with all those symptoms....it isn't LOW T. See you have to have low T to be diagnosed with low T.

Fair enough. In defense of those guys, though, the low T commercials are likely the only thing that acknowledges their symptoms. They're just looking for a solution and their doctors tell them its all in their heads.
 
Fair enough. In defense of those guys, though, the low T commercials are likely the only thing that acknowledges their symptoms. They're just looking for a solution and their doctors tell them its all in their heads.

That's because for many of them it IS all in their heads......
 
You seem to have quite a bit of contempt for people who are only, as George Clooney might say, looking for answers.

It's the same thing every time and most of us here have seen it so many times we just wish these people would listen. Yeah yeah I know what is normal or there is no normal or it's whatever is normal for you? Yeah yeah you read the normal tT for a 37 yo is 950. Yeah yeah it must be low DHEA.....etc, etc, etc. We know they are perusing a dead end road and what's best for THEM is to look elsewhere.

I have no dog in these fights....if someone wants to insist their problem is low T when EVERY single objective measure says it not and they don't get better it's no skin off my nose.
 
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