Hormone Therapy for Men
Symptoms of testosterone deficiency affect approximately 1 in 200 men and may include:
- weakness
- fatigue
- reduced libido
- osteoporosis
This condition is commonly referred to as “Andropause” and less often as “Androgen Deficiency in the Aging Male” (ADAM).
A man may be considered hypogonadal at any age if total testosterone is less than 200 ng/dl, or bioavailable testosterone is less than 60 ng/dl. Basaria and Dobs of Johns Hopkins University recommend that elderly men with symptoms of hypogonadism and a total testosterone level < 300 ng/dl should be started on hormone replacement.
Testosterone USP has been approved by the United States Pharmacopoeia and is available as a bulk chemical. Upon a prescription order, compounding pharmacists can use Testosterone USP to prepare numerous dosage forms.
Natural Testosterone Replacement is central to the treatment of all facets of andropause. The term “testosterone” is often used generically when referring to numerous synthetic derivatives, as well as personalized testosterone. Confusion is responsible for conflicting data in the medical literature about the benefits and risks of testosterone therapy. Studies must be reviewed carefully to determine the form of testosterone that was used. Natural testosterone must not be confused with synthetic derivatives or “anabolic steroids,” which when used by athletes and body builders have caused disastrous effects. For example, administration of synthetic non-aromatizable androgens, like stanozolol or methyltestosterone, causes profound decreases in HDL-C (“good cholesterol”) and significant increases in LDL-C (“bad cholesterol”). Yet, hormone replacement with aromatizable androgens, such as testosterone, results in lower total cholesterol and LDL cholesterol levels while having little to no impact on serum HDL cholesterol levels. Proper monitoring of laboratory values and clinical response are essential when prescribing testosterone replacement therapy.
The only absolute contraindications to androgen replacement therapy are the presence of prostate or breast cancer. “Although it is known that the clinical course of prostate cancer is accelerated by testosterone, its incidence is not increased by [testosterone] administration… There is even no clear evidence that testosterone replacement accelerates the development of BPH.”
Drugs & Aging 1999 Aug;15(2):131-42
- Improvement in erectile dysfunction
- Improvement in libido
- Increased muscle mass
- Increased strength and stature
- Preservation of bone mass
- Possible decrease in cardiovascular risk
- Improvement in psychological well-being and mood
A man may be considered hypogonadal at any age if total testosterone is less than 200 ng/dl, or bioavailable testosterone is less than 60 ng/dl. Basaria and Dobs of Johns Hopkins University recommend that elderly men with symptoms of hypogonadism and a total testosterone level < 300 ng/dl should be started on hormone replacement.
In men, relative levels of free circulating estrogens increase with age which can increase estrogenic action in the prostate gland. Bioavailable testosterone levels decline in the aging male due to decreased production by the testes and increased sex hormone binding globulin (SHGB) levels which result in lower free circulating testosterone. Also, an age-related increase in body weight and adipose (fat) cells can result in high levels of aromatase which peripherally converts androgens to estrogen. It has been proposed that increased estrogenic stimulation of the prostate in the aging male may lead to reactivation of growth and subsequent neoplastic transformation. Estrogen effects on the prostate gland may also be indirectly mediated through alterations in other serum hormones. Estrogens stimulate the pituitary release of PRL and some, but not all, of estrogenic effects have been attributed to direct PRL action on the prostate. Furthermore, estradiol exerts negative feedback on the hypothalamic-hypophyseal-testicular axis, blocking luteinizing hormone (LH) secretion and testicular steroidogenesis of androgens (i.e. chemical castration). This feedback regulation was the basis for high-dose estrogen therapy of prostate cancer for several decades.
Steroids. 2008 March; 73(3): 233–244.
The Role of Estrogens and Estrogen Receptors in Normal Prostate Growth and Disease
Prins GS and Korach KS.
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.
Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C.
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 normalization of the patient’s testosterone, luteinizing hormone and follicle-stimulating hormone levels, suppression of serum estradiol levels, and to normalization of spermatogenesis and fertility.”
Nat Clin Pract Endocrinol Metab. 2008 Jul;4(7):415-9.
Treatment of male infertility secondary to morbid obesity.
Roth MY, Amory JK, Page ST.
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.
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).
Click here to access the PubMed abstract of this article.
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.
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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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.
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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.
http://www.medscape.com/viewarticle/576267 (accessed 1/13/2012)
This research at UCLA concluded that transdermal testosterone (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.
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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.
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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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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.
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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.
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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.
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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.
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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
This study concludes: “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.
Warning: Patients using testosterone should seek medical attention immediately if symptoms of a heart attack or stroke are present, such as: Chest pain, Shortness of breath, trouble breathing, weakness in one part or one side of the body, or slurred speech.
