Androgen Replacement

[Michael Scally MD]

Donatucci C, Cui Z, Fang Y, Muram D. Long-Term Treatment Patterns of Testosterone Replacement Medications. The Journal of Sexual Medicine. http://onlinelibrary.wiley.com/doi/10.1111/jsm.12608/abstract

Introduction Testosterone replacement therapy (TRT) is prescribed to men diagnosed with hypogonadism to alleviate symptoms, improve quality of life, and improve overall health. However, most men use TRT for only a short duration.

Aim To evaluate the long-term treatment patterns in hypogonadal men using topical TRT or short-lasting TRT injections.

Methods Using the Truven MarketScan® Database, 15,435 men who received their first (index) topical TRT prescription and 517 men who received their short-lasting TRT injection index prescription in 2009 were followed from 12 to 30 months after treatment initiation.

Treatment interruption was defined as a medication gap of >30 days. Patients who remained off treatment were classified as having discontinued treatment. Patients who restarted therapy after 30 days were classified as cyclic users. Patients were required to have continuous insurance coverage during 1 year prior to treatment initiation and at least 1 year afterward.

Main Outcome Measures Main outcome measures were length of therapy, discontinuation, and restarts of topical TRT or short-lasting TRT injections.

Results The patient characteristics were similar for patients who received topical TRT or short-lasting TRT injections.

Of the patients who discontinued therapy during the follow-up period, the percentages of patients who were still on therapy after 3 months were 52% and 31% for topical TRT and short-lasting TRT users, respectively. For cyclic users, there was an attrition rate of approximately 40% to 50% of patients in each cycle.

For both topical TRT and short-lasting TRT injections, the gap between stopping and restarting therapy tended to decrease over time.

Conclusions In this analysis, high discontinuation rates were observed. The treatment pattern of TRT may be related to the disease state rather than dosing, daily use, or mode of administration.

 

[Michael Scally MD]

Men’s Health Weak?
http://www.evidentlycochrane.net/testosterone/

Hard to believe it is already Men’s Health Week. It seems like just yesterday when it was Women’s Check-Up day (or Hand Hygiene Day, or Ultraviolet Light Safety Month or National Mediterranean Diet Month or Every Kid Healthy Week) – the US calendar has hundreds of official national health observances.

The goal of Men’s Health Week (or month – June is designated as both in the US) is to “heighten the awareness of preventable health problems and encourage early detection and treatment of disease among men and boys”.

While the week may be billed as a campaign to "heighten the awareness of preventable health problems" among men and boys, to Drs. Steven Woloshin and Lisa Schwartz, the event--sponsored by AbbVie (ABBV) and Pfizer (PFE), key manufacturers of testosterone replacement products--is also a convenient way for companies to promote Low-T testing and sign more men on to therapies.

 

[Michael Scally MD]

Matsuda Y, Hisasue S-i, Kumamoto Y, et al. Correlation between Erection Hardness Score and Nocturnal Penile Tumescence Measurement. The Journal of Sexual Medicine. http://onlinelibrary.wiley.com/doi/10.1111/jsm.12617/abstract

Introduction The Erection Hardness Score (EHS) and the Sexual Health Inventory for men (SHIM) are patient-reported outcome scoring systems for erectile function. It is unclear which is more reliable for predicting the objective erectile function.

Aim The aim of this study was to evaluate whether the EHS could predict objective erectile function by measuring the maximal penile circumferential change (MPCC) with an erectometer.

Methods The study included 98 patients who visited our clinic from 2005 to 2010. The erectile function was evaluated using the SHIM, EHS, and MPCC. The MPCC was measured with the largest circumferential change of three consecutive occurrences of nocturnal penile tumescence (NPT) determined using the erectometer.

Main Outcome Measures We defined erectile dysfunction (ED) as MPCC < 20 mm and carried out multivariate analysis using logistic regression analysis to clarify the predictors for ED, with the variables including age, the SHIM score, and the EHS. We compared the tendency for MPCC ≥ 20 mm when EHS was 3 or more with that when EHS was 2 or less.

Results The median age of the patients was 59.5 years (range 18–83). In logistic regression analysis, the EHS was the only predictor for ED with MPCC < 20 mm. The mean EHS in the MPCC < 20 mm group was 1.64 ± 0.20 (mean ± SEM) and that in the MPCC ≥ 20 mm group was 2.46 ± 0.13 (P = 0.0018). There was a correlation between the EHS and the MPCC (correlation coefficient = 0.33). In comparison with the group having an EHS of 2 or less, that with an EHS of 3 or more tended to have MPCC ≥ 20 mm (P = 0.013).

Conclusions The EHS was correlated with the MPCC. The EHS represents the objective erectile function shown by the measurement of NPT.

 

[Michael Scally MD]

Glueck CJ, Wang P. Testosterone therapy, thrombosis, thrombophilia, cardiovascular events. Metabolism. https://www.sciencedirect.com/science/article/pii/S0026049514001450

There are similar time intervals between starting testosterone therapy (TT) and development of thrombotic (~4.5months) or cardiovascular (CVD) events (~3months) which may, speculatively, reflect a shared pathophysiology. We have described thrombotic events 5months (median) after starting TT in 38 men and 4 women, including 27 with deep venous thrombosis-pulmonary embolism, 12 with osteonecrosis, 1 with central retinal vein thrombosis, 1 with amaurosis fugax, and 1 with spinal cord infarction. In 8 men whose TT was continued, second thrombotic events occurred despite adequate anticoagulation with Coumadin in 8 men, 3 of whom had a third thrombotic event. Of these 42 cases, 40 had measures of thrombophilia-hypofibrinolysis, and 39 were found to have previously undiagnosed thrombophilia-hypofibrinolysis. Before beginning TT, especially in men with previous history of thrombotic events, we suggest that, at a minimum, measurements be made for the Factor V Leiden and Prothrombin mutations, Factors VIII and XI, and homocysteine, to identify men who should not receive TT. We need prospective data focused on whether there should be pre-TT screening based on history of previous venous thromboembolism or for all subjects for major gene thrombophilias. To better resolve questions about TT and all cause and cardiovascular morbidity and mortality and thrombosis, a long term, prospective, randomized, blinded study following the example of the Women's Health Initiative is needed. While we wait for prospective placebo-controlled TT outcome data, TT should be restricted to men with well-defined androgen deficiency syndromes.

 

[Michael Scally MD]

Scovell J, Ramasamy R, Kovac JR. A critical analysis of testosterone supplementation therapy and cardiovascular risk in elderly men. Can Urol Assoc J 2014;8(5-6):E356-7. http://journals.sfu.ca/cuaj/index.php/journal/article/view/1962/1661

Currently, the exact mechanisms for increased CVAEs in men on TST remain unknown.

Testosterone stimulates erythropoiesis in a dose-dependent manner – an effect that is more prominent in elderly men. TST also induces a hypercoagulable state via increases in thromboxane A2 and platelet thromboxane A2 receptor density with decreases in prosta- glandins.

In the Tampere Adult Population Cardiovascular Risk study (TAMRISK), the authors demonstrated a relationship between borderline polycythemia and an increased risk of cardiovascular mortality.

Taken together, it is tempting to speculate that TST may exacerbate cardiac risks in men with atherosclerosis by increasing blood viscosity and platelet counts leading to CVAEs in susceptible elderly patients.

A further factor to consider is the level of serum testosterone in the aging male since it appears that both sub-, and supra-physiological levels of testosterone carry risk.

This was illustrated in the population-based cohort study recently done on 3690 men. The authors found that men whose serum testosterone was in the middle 2 quartiles (Q2 and Q3; testosterone 283 ng/dL to 453 ng/dL) of the population had the lowest incidence of death from any cause (Q2 vs. Q1, adjusted hazard ratio

---

0.82; Q3 vs. Q1, HR 0.78; Q4 vs. Q1, HR 0.86).

In summary, the preponderance of the evidence suggests that TST should be used judiciously in elderly males, with a paradigm focused on returning serum testosterone levels to normal limits, rather than treating with supra-physiological doses (i.e., injections).

Furthermore, it is essential to choose the proper TST modality and to schedule regular (i.e., every 3 months) visits to monitor hematocrit, platelet and serum estradiol levels with an experienced TST specialist.

 

[Michael Scally MD]

Nudleman E, Witmer MT, Kiss S, Williams GA, Wolfe JD. Central Serous Chorioretinopathy in Patients Receiving Exogenous Testosterone Therapy. Retina. http://journals.lww.com/retinajourn...ROUS_CHORIORETINOPATHY_IN_PATIENTS.98325.aspx

PURPOSE: To report an association between central serous chorioretinopathy (CSCR) and exogenous testosterone therapy.

METHODS: This is a retrospective case series from two institutions. Patients who presented with fluorescein angiography and optical coherence tomography findings consistent with CSCR were included. All patients were concurrently being treated with exogenous testosterone therapy and lacked other known risk factors for CSCR.

RESULTS: Nine patients presented with CSCR after beginning exogenous testosterone therapy. Two patients stopped therapy with resolution of symptoms and subretinal fluid.

CONCLUSION: Exogenous testosterone may be an independent risk factor for the development of CSCR.

 

[Michael Scally MD]

FDA Adding General Warning to Testosterone Products about Potential for Venous Blood Clots
http://www.fda.gov/Drugs/DrugSafety/ucm401746.htm

[06/19/2014] The U.S. Food and Drug Administration (FDA) is requiring manufacturers to include a general warning in the drug labeling of all approved testosterone products about the risk of blood clots in the veins. Blood clots in the veins, also known as venous thromboembolism (VTE), include deep vein thrombosis (DVT) and pulmonary embolism (PE).

The risk of venous blood clots is already included in the labeling of testosterone products as a possible consequence of polycythemia, an abnormal increase in the number of red blood cells that sometimes occurs with testosterone treatment.

Because there have been postmarket reports of venous blood clots unrelated to polycythemia, FDA is requiring a change to drug labeling of all testosterone products to provide a more general warning regarding venous blood clots and to ensure this risk is described consistently in the labeling of all approved testosterone products.

Because these clots occur in the veins, this new warning is not related to FDA’s ongoing evaluation of the possible risk of stroke, heart attack, and death in patients taking testosterone products. We are currently evaluating the potential risk of these cardiovascular events, which are related to blood clots in the arteries and are described in the http://www.fda.gov/Drugs/DrugSafety/ucm383904.htm.

 

[Michael Scally MD]

Being in the NEJM Journal Watch will certainly raise the awareness (and more) regarding the FDA Warning.

FDA: Risk for Venous Thromboembolism with All Testosterone Products
http://www.jwatch.org/fw108966/2014/06/23/fda-risk-venous-thromboembolism-with-all-testosterone

 

[Michael Scally MD]

[NO] Effect of Testosterone Treatment on Constitutional and Sexual Symptoms in Men with Type 2 Diabetes

Gianatti EJ, Dupuis P, Hoermann R, Zajac JD, Grossmann M. Effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes in a randomized, placebo-controlled clinical trial. The Journal of Clinical Endocrinology & Metabolism. http://press.endocrine.org/doi/abs/10.1210/jc.2014-1872

Objective: To assess the effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes (T2D).

Design: Randomized double-blind, parallel, placebo-controlled trial.

Setting: Tertiary referral center.

Patients: Men aged 35-70 years with T2D, a HbA1c < 8.5% and a total testosterone level < 12.0 nmol/L (346 ng/dl) with mild to moderate aging male symptoms and erectile dysfunction.

Intervention: 88 participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n= 45) or matching placebo (n= 43).

Main Outcome Measures: Constitutional symptoms using the aging male symptoms (AMS) score, sexual desire (question 17 AMS score) and erectile function (International Index of Erectile Function-5).

Results: Testosterone treatment did not substantially improve aging male symptoms (mean adjusted difference (MAD) in change over 40 weeks across the testosterone and placebo groups in AMS total score, -0.9 [95% CI -4.1, 2.2], p=0.67), or sexual desire (MAD in question 17 AMS, -0.3 [95% CI -0.8, 0.2], p=0.17). While compared to placebo, erectile function in men assigned to testosterone was reduced (MAD in IIEF-5, -2.0 [95% CI -3.4, -0.6], p<0.02), there was no significant difference between baseline and 40 week IIEF-5 scores if both groups were analyzed separately. At baseline, symptoms were worse in men with depression and microvascular complications, but did not correlate with testosterone levels.

Conclusions: In this trial, testosterone treatment did not substantially improve constitutional or sexual symptoms in obese, aging men with T2D with mild to moderate symptoms and modest reduction in testosterone levels typical for the vast majority of such men.

 

[Michael Scally MD]

Men Who Have Sustained DVT-PE While Taking Testosterone

Dr. Glueck Offers Assistance – cjglueck@health-partners.org or sonar16@gmail.com. Dr. Glueck will answer questions and advise. Attached are lab orders good at both Quest and LabCorp nationally to get the full screening in men on TT with thrombosis. Also, attached is a testosterone thrombosis outcome questionnaire.

 

[Michael Scally MD]

Miner M, Barkin J, Rosenberg MT. Testosterone deficiency: myth, facts, and controversy. Can J Urol 2014;21(3):39-54. http://canjurol.com/abstract.php?ArticleID=2783&PMID=&version=1.0

Testosterone deficiency (TD) afflicts approximately 30% of men ages 40-79 years, with an increase in prevalence strongly associated with aging and common medical conditions including obesity, diabetes, and hypertension.

There appears to be a strong relationship between TD and metabolic syndrome, though the relationship is not certain to be causal. Several studies have suggested that repletion of testosterone in deficient men with these comorbidities may indeed reverse or delay their progression.

While testosterone repletion has been largely thought of in a sexual realm, we discuss its potential role in general men's health concerns: metabolic, body composition, and its association with decreased all-cause mortality.

Recent guidelines and studies have suggested variable prevalence statistics and expanded uses of testosterone repletion in certain populations with both biochemical and clinical signs of testosterone deficiency. Yet, this is not done without risk.

A recent randomized placebo-controlled trial of testosterone repletion in elderly frail men with limited mobility has suggested potential negative cardiovascular risks in this older, sicker group of men. Two more recent retrospective studies of variable clinical design and interpretation suggest testosterone poses an increased cardiovascular risk in older men than 65 years and younger men with heart disease.

This review examines these and other studies, with practical recommendations for the diagnosis of testosterone deficiency and repletion in middle aged and older men, including an analysis of treatment modalities and areas of concern and uncertainty.

 

[Michael Scally MD]

Baillargeon J, Urban RJ, Kuo Y-F, et al. Risk of Myocardial Infarction in Older Men Receiving Testosterone Therapy. Annals of Pharmacotherapy. http://aop.sagepub.com/content/early/2014/06/20/1060028014539918.full

Background: Testosterone therapy for older men has increased substantially over the past decade. Research on the effects of testosterone therapy on cardiovascular outcomes has yielded inconsistent results.

Objective: To examine the risk of myocardial infarction (MI) in a population-based cohort of older men receiving intramuscular testosterone.

Methods: Using a 5% national sample of Medicare beneficiaries, we identified 6355 patients treated with at least 1 injection of testosterone between January 1, 1997, and December 31, 2005. We matched this cohort to 19 065 testosterone nonusers at a 1:3 ratio based on a composite MI prognostic score. Patients were followed until December 31, 2005, or until they lost coverage from Medicare, enrolled in a health maintenance organization, experienced a MI, or died.

Results: In a Cox regression analysis adjusting for demographic and clinical characteristics, receipt of testosterone therapy was not associated with an increased risk of MI (hazard ratio

---

= 0.84; 95% CI = 0.69-1.02). In this analysis, there was an interaction between receipt of testosterone and quartile of risk of MI (P = 0.023). For men in the highest quartile of the MI prognostic score, testosterone therapy was associated with a reduced risk of MI (HR = 0.69; 95% CI = 0.53-0.92), whereas there was no difference in risk for the first (HR = 1.20; 95% CI = 0.88-1.67), second (HR = 0.94; 95% CI = 0.69-1.30), and third quartiles (HR = 0.78; 95% CI = 0.59-1.01).

Conclusions: Older men who were treated with intramuscular testosterone did not appear to have an increased risk of MI. For men with high MI risk, testosterone use was modestly protective against MI.

 

[Millard]

Conclusions: Older men who were treated with intramuscular testosterone did not appear to have an increased risk of MI. For men with high MI risk, testosterone use was modestly protective against MI.

Given all the recent negative TRT reports, the irony is that doctors will be most likely to withhold TRT from "men with high MI risk"!

 

[Michael Scally MD]

Corona G, Rastrelli G, Maseroli E, et al. Low testosterone syndrome protects subjects with high cardiovascular risk burden from major adverse cardiovascular events. Andrology. http://onlinelibrary.wiley.com/doi/10.1111/j.2047-2927.2014.00241.x/abstract

The role of testosterone (T) in the cardiovascular (CV) health of men is controversial. Some data suggest that hypogonadism is associated with CV mortality but not morbidity, however, recent evidence shows that hypogonadal subjects treated with T replacement therapy have a higher incidence of new CV events.

The aim of this study is to analyse whether gonadal status might predict new CV event incidence according to a patient's previous history of CV events, in a cohort of subjects complaining of sexual dysfunction.

A consecutive series of 1687 patients was followed-up for a mean time of 4.3 ± 2.6 years for new occurrence of CV events, detecting 139 events. Hypogonadism (total T < 12 nmol/L) was not associated with an increased incidence of new CV events in the entire cohort. However, when considering patients with a previous history of CV events, hypogonadism was associated with a reduced risk of new CV events, even after adjusting for confounders (hazard ratios – HR = 0.498 [0.240; 0.996]; p = 0.049), whereas no relationship was observed in subjects free of previous CV events.

Similar results were observed when reduced testis volume (TV) was considered as a predictor of new CV events in subjects with previous CV events (HR = 0.486 [0.257; 0.920]; p = 0.027). In patients with a history of previous CV events, but not in those without previous CV events, having both low T and low TV was associated with a lower incidence of new CV events as compared with subjects with only one or none of these conditions, even after adjusting for confounders (HR = 0.514 [0.306; 0.864]; p for trend < 0.02). Notably, CV risk estimated with risk engines based on traditional risk factors was not different between hypogonadal and eugonadal subjects.

In conclusion, hypogonadism could be interpreted as a protective mechanism in unhealthy conditions, such as previous CV events, to avoid fatherhood and spare energy.

 

[Michael Scally MD]

Dupree JM, Langille GM, Khera M, Lipshultz LI. The safety of testosterone supplementation therapy in prostate cancer. Nat Rev Urol;advance online publication. http://www.nature.com/nrurol/journal/vaop/ncurrent/full/nrurol.2014.163.html

Patients with prostate cancer can present with hypogonadism and experience health and quality-of-life declines related to low testosterone levels.

Despite generations of urological dogma suggesting that testosterone supplementation therapy (TST) for hypogonadism causes prostate-cancer progression, a review of the contemporary literature provides evidence to the contrary.

The prostate saturation model suggests that the androgen receptor (AR) is saturated at serum testosterone levels of 150-200 ng/dl, and that additional serum testosterone above this level has limited, if any, effects within the prostate.

Indeed, studies in the modern era of PSA assessments indicate that TST does not affect prostate size, intraprostatic testosterone levels, or prostate-cancer progression, provided the baseline serum testosterone level is greater than this AR saturation point.

However, the body of data on this subject comes from a small number of cases, and TST should only be administered to patients with prostate cancer after thorough discussions of the risks and benefits, with subsequent careful monitoring.

 

[Michael Scally MD]

Eisenberg ML, Li S, Herder D, Lamb DJ, Lipshultz LI. Testosterone therapy and mortality risk. Int J Impot Res. http://www.nature.com/ijir/journal/vaop/ncurrent/abs/ijir201429a.html

Recent data suggest an increased risk of cardiovascular events and mortality in men on testosterone therapy (TT). To date, there are no long-term, prospective studies to determine safety. In such cases, retrospective observational studies can be helpful.

We examined our patient database to determine whether TT altered the risk of all-cause mortality in men. We queried our hormone database for all men with a serum testosterone level and then examined charts to determine testosterone status.

In all, 509 men had charts available for review. We linked our patient records to the National Death Index to determine mortality. Of the 509 men who met inclusion criteria, 284 were on TT and 225 did not use testosterone. Age (mean 54 years) and follow-up time (mean 10 years) were similar for both groups.

In all, 19 men died-10 (4.4%) men not on TT and 9 (3.2%) men on TT. After adjusting for age and year of evaluation, there was no significant difference in the risk of death based on TT (hazard ratio 0.92, 95% confidence interval 0.36-2.35, P=1.0).

There appears to be no change in mortality risk overall for men utilizing long-term testosterone therapy.

 

[Michael Scally MD]

“Low T” and Prescription Testosterone: Public Viewing of the Science Does Matter
http://blogs.plos.org/everyone/2014...n-testosterone-public-viewing-science-matter/

On January 29th 2014, researchers from UCLA, NCI, and Consolidated Research, Inc. published an observational study in PLOS ONE detailing increased cardiovascular risks associated with men taking testosterone therapy.

Only three days later, on January 31st, this study in combination with another, published in JAMA in November 2013 with similar findings, triggered a Food and Drug Administration (FDA) Drug Safety Communication and evaluation that is currently ongoing.

Since then, lawsuits against testosterone drug makers have been filed in both the US and Canada, and the FDA has set up a joint advisory committee who will meet this fall to evaluate potential health risks associated with testosterone therapies to determine whether any regulatory measures are required.

For matters relating to public health, this study is both relevant and controversial due to the skyrocketing of testosterone prescriptions to men, an industry now valued at $2 billion USD.

Unfortunately, testosterone is often prescribed without a blood test for the medical diagnosis that warrants its use (hypogonadism), as it is also claimed to have other health benefits, including improved sex drive, mood, energy levels, and anti-aging effects.

While it’s clear that this PLOS ONE article impacted the actions of regulatory agencies and issues pertaining to public health, we wondered whether this influence was reflected in the paper’s article-level metrics (ALMs).

Or, as Roli Roberts asked in a recent PLOS Biologue post, “how do you know when you’ve published a great paper?” Or even a good paper?

More at the link ...

 

[Michael Scally MD]

Morgentaler A, Benesh JA, Denes BS, Kan-Dobrosky N, Harb D, Miller MG. Factors Influencing Prostate-Specific Antigen Response among Men Treated with Testosterone Therapy for 6 Months. The Journal of Sexual Medicine. http://onlinelibrary.wiley.com/doi/10.1111/jsm.12657/abstract

Introduction Factors influencing prostate-specific antigen (PSA) changes in men undergoing testosterone (T) therapy have not been well studied.

Aim The aim of this study was to assess the influence of selected variables on PSA changes in hypogonadal men administered with 1.62% testosterone gel (T-gel) for 6 months.

Methods A double-blind, placebo-controlled study of 274 (234 T-gel, 40 placebo) hypogonadal men >18 years of age, with baseline T concentrations <300 ng/dL, PSA ≤2.5 ng/mL, and negative digital rectal examination. Subjects received once-daily T-gel for T therapy.

Main Outcome Measures Changes in mean serum PSA, percentage of free PSA (%fPSA), and T from baseline to 6 months (182 days).

Results Mean age was 53.5 years and baseline mean values were total T 247 ng/dL, PSA 0.9 ng/mL, and %fPSA 24.6%. Among men treated with T-gel, T increased to 499 ng/dL and PSA increased by 0.1 ng/mL (P = 0.0012). PSA increased ≥0.3 ng/mL in 26.3%, <0.3 ng/mL in 73.7%, including a decline from baseline in 33.0%. In the placebo group, T increased 29 ng/dL to 274 ng/dL, and PSA decreased 0.1 ng/mL, compared with baseline. A greater increase in PSA was noted in men ≥60 years old than in men <60 years old (0.4 vs. 0.05 ng/mL, respectively; P = 0.0006). Mean PSA did not change in men with baseline serum T >250 ng/dL, whereas it increased by 0.2 ng/mL in men with T ≤250 ng/dL (P = 0.0031). PSA increased 0.3 ng/mL in men with baseline %fPSA <20% and 0.1 ng/mL in men with %fPSA ≥20%.

Conclusions Overall, T-gel treatment was associated with a minor increase in PSA, of questionable clinical significance. Factors predicting greater PSA increases included age ≥60 years, baseline T ≤250 ng/dL, and %fPSA <20%. Men with T >250 ng/dL and age <60 years demonstrated minimal or no PSA change.

 

[Michael Scally MD]

Corona G, Maseroli E, Rastrelli G, et al. Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert Opin Drug Saf 2014:1-25. http://informahealthcare.com/doi/abs/10.1517/14740338.2014.950653

Introduction: Recent reports have significantly halted the enthusiasm regarding androgen-boosting; suggesting that testosterone supplementation (TS) increases cardiovascular (CV) events.

Areas covered: In order to overcome some of the limitations of the current evidence, the authors performed an updated systematic review and meta-analysis of all placebo-controlled randomized clinical trials (RCTs) on the effect of TS on CV-related problems. Out of 2747 retrieved articles, 75 were analyzed, including 3016 and 2448 patients in TS and placebo groups, respectively, and a mean duration of 34 weeks. Our analyses, performed on the largest number of studies collected so far, indicate that TS is not related to any increase in CV risk, even when composite or single adverse events were considered. In RCTs performed in subjects with metabolic derangements a protective effect of TS on CV risk was observed.

Expert opinion: The present systematic review and meta-analysis does not support a causal role between TS and adverse CV events. Our results are in agreement with a large body of literature from the last 20 years supporting TS of hypogonadal men as a valuable strategy in improving a patient's metabolic profile, reducing body fat and increasing lean muscle mass, which would ultimately reduce the risk of heart disease.

 

[Michael Scally MD]

Jarow JP, Troiani J, McNellis D, Wiederhorn R, Fang G, Handelsman H. Use of Biomarkers to Assess Tissue Specific Androgen Adequacy: Defining Male Hypogonadism. J Urol. https://www.sciencedirect.com/science/article/pii/S0022534712048379

PURPOSE: The criteria for normal testosterone have been established by expert consensus rather than by evidence. We determined whether a cutoff point for normal could be established using biomarkers.

MATERIALS AND METHODS: We performed an exploratory investigation of 1,492 hypogonadal men pooled from 7 registration trials. Serum testosterone, prostate specific antigen and hematocrit were measured at baseline and after 90 days of continuous testosterone replacement therapy.

RESULTS: Baseline prostate specific antigen, percent change in prostate specific antigen and hematocrit appeared to be most strongly related to baseline serum testosterone. Subgroup analysis and visual inspection of linear spline fit of these data suggested an approximate serum testosterone cutoff for normal of 300 ng/dl for percent change in hematocrit, and 200 ng/dl for baseline prostate specific antigen and percent change in prostate specific antigen.

CONCLUSIONS: This exploratory study revealed considerable variation among individuals and target tissues in individuals. Further study should be performed using standardized assays in a broader population.