Supporting Literature

Testosterone | Goals and Therapy | Supporting Literature


Plasma Testosterone and Risk of Ischemic Arterial Event in Elderly Men: The French 3C Cohort Study

Soisson et al. of the Center for Research in Epidemiology and Population Health, Hormones and Cardiovascular Disease Team, University of Paris-Sud (France), concluded that “Optimal range of plasma testosterone may confer cardiovascular protection and these results may have clinical implications in the management of testosterone deficiency.”

Maturitas. 2013 Jul;75(3):282-8.
A J-shaped association between plasma testosterone and risk of ischemic arterial event in elderly men: the French 3C cohort study.
Click here to access the PubMed abstract of this article.


 

Testosterone: The Key to Male Vitality?

Kaplan and Hu of the Department of Urology, David Geffen School of Medicine at UCLA, note that “up to 25% of older men experience hypogonadism [low testosterone levels]. Prevalence is higher in men with comorbid disease and increases with age starting in the fourth decade. Hypogonadal men have lower muscle mass, bone mineral density, and hemoglobin, and are in poorer general health. During the past decade, there has been increasing awareness of the health benefits conferred by testosterone replacement therapy (TRT). TRT for hypogonadism increases muscle mass and bone mineral density, decreases fat mass, and improves mood, libido, and sexual performance. Despite these benefits, there is an historical fear that administration of exogenous testosterone may increase the risk of developing prostate cancer or an aggressive form of the disease.

Urology. 2013 Aug;82(2):321-6.
Use of Testosterone Replacement Therapy in the United States and Its Effect on Subsequent Prostate Cancer Outcomes.
Click here to access the PubMed abstract of this article.


“Goodbye Androgen Hypothesis, Hello Saturation Model”

Observations in humans, animals, and PCa cell lines have led to the Saturation Model, ie, that “androgens have a finite, limited ability to stimulate prostate tissue, malignant or benign. This refinement is simple yet profound. Yes, prostate tissue requires androgens for optimal growth. However, it can only use a relatively small amount, beyond which additional androgen is merely excess. The saturation point is well below physiologic concentrations, which explains why manipulation of serum T into or out of the castrate range produces large changes in prostate biology, whereas normal prostate and PCa appear completely indifferent to variations in serum T from the near-physiologic to supraphysiologic range.”

Eur Urol. 2012 Nov;62(5):757-64
Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the Reduction by Dutasteride of Prostate Cancer Events trial.
Click here to access the PubMed abstract of this article.


 

Serum testosterone and dihydrotestosterone and prostate cancer risk

Muller et al. of Department of Surgery, Duke University School of Medicine found that “baseline serum testosterone and DHT levels were unrelated to PCa detection or grade. Our findings of the lowest testosterone levels being associated with the lowest PCa risk with no further changes with higher testosterone support a saturation model but must be confirmed in future studies…” After the exclusion criteria were applied, their study consisted of 149,354 men with prostate cancer.

Eur Urol. 2012 Nov;62(5):757-64. doi: 10.1016/j.eururo.2012.05.025. Epub 2012 May 18.
Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the Reduction by Dutasteride of Prostate Cancer Events trial.
Click here to access the PubMed abstract of this article.


High estradiol levels can suppress testosterone production, and play a role in Metabolic Syndrome. Aromatase inhibitors such as anastrozole can reduce estradiol and increase serum bioavailable and total testosterone levels to the youthful normal range in older men with mild hypogonadism. Suppression of estradiol in men using low-dose anastrozole has been shown to have a positive effect on testosterone production without adverse effects during short term administration.

J Clin Endocrinol Metab. 2004 Mar;89(3):1174-80.
Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels.
Click here to access the PubMed abstract of this article.


In this case study anastrozole was used to restore fertility in a 29-year-old obese man who presented with a low sperm count in the setting of morbid obesity. Roth et al report “Treatment with an aromatase inhibitor, anastrozole, led to normalisation of the patient’s testosterone, luteinising hormone and follicle-stimulating hormone levels, suppression of serum estradiol levels, and to normalisation of spermatogenesis and fertility.”

Nat Clin Pract Endocrinol Metab. 2008 Jul;4(7):415-9.
Treatment of male infertility secondary to morbid obesity.
Click here to access the PubMed abstract of this article.


Testosterone Replacement Therapy for Men and Treatment of Depression

Testosterone replacement therapy (TRT) may be efficacious treatment for subthreshold depression in older men with hypogonadism.

Dysthymia is a chronic type of depression in which a person’s moods are regularly low. Testosterone replacement may be an effective antidepressant strategy for late-onset male dysthymia.

Ther Clin Risk Manag. 2009 Jun;5(3):427-48.
The benefits and risks of testosterone replacement therapy: a review.
Click here to access the PubMed abstract of this article.

J Clin Psychiatry. 2009 Jul;70(7):1009-16.
A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression).
Click here to access the PubMed abstract of this article.

J Clin Psychopharmacol. 2009 Jun;29(3):216-21.
Effects of testosterone replacement in middle-aged men with dysthymia: a randomized, placebo-controlled clinical trial.
Click here to access the PubMed abstract of this article.


Low Free Testosterone as a Potentially Treatable Cause of Depression in Older Men

Arch Gen Psychiatry. 2008 Mar;65(3):283-9
Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men.
Click here to access the PubMed abstract of this article.


Low Testosterone Increases Mortality Risk in Men

A population-based cohort study followed 1954 men aged 20 to 89 years for an average of 7.2 years, and has demonstrated a link between low levels of testosterone and increased risk for mortality in adult men of all ages.

http://www.medscape.com/viewarticle/576267


Administration of a transdermal testosterone (T) gel formulation to hypogonadal men provided dose-proportional increases in serum T levels to the normal adult male range. Testosterone 1% gel (50 or 100 mg/day) was compared to the permeation-enhanced T patch. After 180 days, skin irritation was reported in 5.5% of subjects treated with T gel and in 66% of subjects in the permeation-enhanced T patch group. This research at UCLA concluded that T gel replacement improved sexual function and mood, increased lean mass and muscle strength (principally in the legs), and decreased fat mass in hypogonadal men with less skin irritation and discontinuation compared with the recommended dose of the permeation-enhanced T patch.

J Clin Endocrinol Metab. 2000 Aug;85(8):2839-53
Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. Testosterone Gel Study Group.
Click here to access the PubMed abstract.


The following study concluded that replacing testosterone in hypogonadal men increases bone mineral density of the spine and hip, fat-free mass, prostate volume, erythropoiesis, energy, and sexual function. The full effect of testosterone on bone mineral density took 24 months, but the full effects on the other tissues took only 3-6 months.

J Clin Endocrinol Metab 2000 Aug;85(8):2670-7
Effects of testosterone replacement in hypogonadal men.
Click here to access the PubMed abstract

Am J Med 2001 May;110(7):563-72
Hypogonadism and androgen replacement therapy in elderly men.
Click here to access the PubMed abstract

Drugs Aging 1999 Aug;15(2):131-42
Risks versus benefits of testosterone therapy in elderly men.
Click here to access the PubMed abstract


The findings below suggest that low levels of testosterone and SHBG play some role in the development of insulin resistance and subsequent type 2 diabetes.

Diabetes Care 2000 Apr;23(4):490-4
Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study.
Click here to access the PubMed abstract


Manifestations of testosterone deficiency have included depression, anxiety, irritability, insomnia, weakness, diminished libido, impotence, poor memory, reduced muscle and bone mass, and diminished sexual body hair. Although testosterone levels decline with age, there is great interindividual variability.

Am J Psychiatry 1998 Oct;155(10):1310-8
Age-associated testosterone decline in men: clinical issues for psychiatry.
Click here to access the PubMed abstract.


Massive obesity in males is associated with decreased total and free testosterone levels as well as elevated estradiol levels.

Med Hypotheses 1999 Jan;52(1):49-51
The hypogonadal-obesity cycle: role of aromatase in modulating the testosterone-estradiol shunt-a major factor in the genesis of morbid obesity.
Click here to access the PubMed abstract.


These results suggest that testosterone treatment might improve depressed mood in older men who have low levels of bioavailable testosterone.

J Clin Endocrinol Metab 1999 Feb;84(2):573-7
Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study.
Click here to access the PubMed abstract


The following results suggest that until the age of 60 years, the mean serum level of DHEAS is lower in patients with ED than in healthy volunteers.

Urology 2000 May;55(5):755-8
Serum dehydroepiandrosterone sulfate concentrations in men with erectile dysfunction.
Click here to access the PubMed abstract


Sublingual sildenafil in the treatment of erectile dysfunction: faster onset of action with lower dose

Forty consecutive patients with erectile dysfunction (mean age was 55 years) for more than three months were included in this study. Sixty-five percent of patients (13/20) who received sublingual sildenafil achieved satisfying erections and coitus, whereas the rate was 15% in the placebo group (3/20). The mean onset of action with sublingual sildenafil was 15.5 minutes and lasted for an average of 40 minutes. Minimal headaches, sweating and flushing were noted as the side-effects. The conclusion: “20 mg sublingual sildenafil is safe and effective in the treatment of erectile dysfunction. Sublingual administration has some advantages as it is not effected by food ingestion and quickly appears in the circulation. These advantages provide a faster onset of action with a lower dose when compared to oral sildenafil. Sublingual use of sildenafil may be more cost-effective and possibly provides a more predictable onset of action.”


Int J Urol. 2004 Nov;11(11):989-92
Sublingual sildenafil in the treatment of erectile dysfunction: faster onset of action with less dose.
Click here to access the PubMed abstract of this article.

The International Journal of Pharmaceutical Compounding [March/April 2007;11(2):121] reported a formula for Sildenafil 20mg Troches (flavored) with a recommended beyond-use date of 180 days.

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