Testosterone Therapy: Monitor Estradiol and DHT Levels
As men age, testosterone levels progressively fall and inflammatory biomarkers increase. The gradual decline in testosterone production with aging, known as andropause, is common and may have deleterious effects on men including decreased overall well-being, increased risk of cardiovascular disease and sarcopenia, reduced sexual function, and bone loss.
Occasionally, physicians may discourage male patients from getting testosterone replacement therapy based on a few recent studies indicating the therapy causes cardiovascular events, including myocardial infarctions. Yet, an extensive review of the testosterone replacement therapy literature reveals that the majority of clinical studies show that properly administered testosterone replacement therapy, in which estradiol and dihydrotestosterone levels are also controlled, has no adverse effects on myocardial infarction risk.
While testosterone is available in many forms, compounded troches offer several benefits:
- Convenience – easier than pellets or injections
- Decreased risk of cross contamination – men need not be concerned about others contacting the site of application, such as the arm or leg when a child or pet is held
- Rapid buccal or sublingual absorption means the dose can be a fraction of that required for topical forms of testosterone
- Patients can quickly achieve peak levels when desired
The testosterone controversy stems largely from poorly designed clinical studies in which patients were subjected to testosterone replacement therapy without having their estradiol and dihydrotestosterone levels properly controlled.
Int J Pharm Compd. 2015 May-Jun;19(3):195-203.
Compounded Testosterone Troches TO OPTIMIZE HEALTH AND THE TESTOSTERONE CONTROVERSY.
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Asian J Androl. 2016 Jan-Feb;18(1):25-34.
Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism: a multicenter randomized controlled trial in Japan (EARTH Study).
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Korean J Urol. 2015 Apr;56(4):310-7.
Elderly men over 65 years of age with late-onset hypogonadism benefit as much from testosterone treatment as do younger men.
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Testosterone Therapy and Cardiovascular Mortality
Testosterone therapy is recommended for men with symptomatic androgen deficiency and unequivocally low testosterone levels. Tanna et al. concluded from the study that testosterone therapy can be safely considered in men with appropriately diagnosed clinical androgen deficiency and increased cardiovascular risk after a thorough discussion of potential risks and with guideline-recommended safety monitoring.
Curr Atheroscler Rep. 2015 Mar;17(3):490.
The role of testosterone therapy in cardiovascular mortality: culprit or innocent bystander?
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Testosterone Therapy in Men with Crohn’s Disease May Improve the Clinical Course
Crohn’s disease is an inflammatory chronic bowel disease characterized by an imbalanced production of pro-inflammatory mediators (tumor necrosis factor-α) and an increased recruitment of leukocytes to the site of inflammation. Low serum testosterone is associated with an increase in inflammatory factors, while testosterone administration reduces them. There is evidence for an immunomodulatory effect of testosterone on differentiation of regulatory T cells.
The study concluded that normalizing serum testosterone in men who have low testosterone levels had a positive effect on the clinical course of Crohn’s disease.
Horm Mol Biol Clin Investing. 2015 Jun;22(3):111-7.
Testosterone therapy in men with Crohn’s disease improves the clinical course of the disease: data from long-term observational registry study.
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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.
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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.
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“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.
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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.
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.
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.
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Nat Clin Pract Endocrinol Metab. 2008 Jul;4(7):415-9.
Treatment of male infertility secondary to morbid obesity.
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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.
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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).
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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.
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Arch Gen Psychiatry. 2008 Mar;65(3):283-9
Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men.
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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.
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.
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J Clin Endocrinol Metab 2000 Aug;85(8):2670-7
Effects of testosterone replacement in hypogonadal men.
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Am J Med 2001 May;110(7):563-72
Hypogonadism and androgen replacement therapy in elderly men.
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Drugs Aging 1999 Aug;15(2):131-42
Risks versus benefits of testosterone therapy in elderly men.
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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.
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Am J Psychiatry 1998 Oct;155(10):1310-8
Age-associated testosterone decline in men: clinical issues for psychiatry.
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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.
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J Clin Endocrinol Metab 1999 Feb;84(2):573-7
Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study.
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Oxytocin Therapy for Male Sexual Function
MacDonald and Feifel of the University of California, San Diego Medical Center Department of Psychiatry, published a case report on a male treated with a course of intranasal oxytocin treatment for social anxiety. The patient had significant, broad-spectrum improvements in sexual function, including libido, erection, and orgasm, and oxytocin was well tolerated.
J Sex Med. 2012 May;9(5):1407-10.
Dramatic improvement in sexual function induced by intranasal oxytocin.
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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.
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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.
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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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