Hormone Replacement Therapy for Men

March 8, 2017

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 < 300ng/dl should be started on hormone replacement.

Testosterone

What is the Optimal Form of Testosterone for Replacement Therapy?

Testosterone USP is natural bio-identical testosterone that 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 natural bio-identical 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

Goals and Therapy

Goals of Testosterone Replacement Therapy in Adult Hypogonadal Men (age 50 or older)

Improvement in psychological well-being and mood
Improvement in erectile dysfunction
Improvement in libido
Increased muscle mass
Increased strength and stature
Preservation of bone mass
Possible decrease in cardiovascular risk

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 < 300ng/dl should be started on hormone replacement.

Supporting Literature

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

Arch Gen Psychiatry. 2008 Mar;65(3):283-9
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 (accessed 10/08)

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.

Wang C, Swedloff RS, Iranmanesh A, Dobs A, Snyder PJ, Cunningham G, Matsumoto AM, Weber T, Berman N.
Department of Medicine, Harbor-University of California-Los Angeles Medical Center and Research and Education Institute, Torrance 90509, USA.

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.

Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G, Dlewati A, Santanna J, Loh L, Lenrow DA, Holmes JH, Kapoor SC, Atkinson LE, Strom BL.
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

Click here to access the PubMed abstract

Am J Med 2001 May;110(7):563-72

Hypogonadism and androgen replacement therapy in elderly men.

Basaria S, Dobs AS.
Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Click here to access the PubMed abstract

Drugs Aging 1999 Aug;15(2):131-42

Risks versus benefits of testosterone therapy in elderly men.

Basaria S, Dobs AS.
Division of Endocrinology and Metabolism, Johns Hopkins University, Baltimore, Maryland 21287, USA.

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.

Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB.New England Research Institutes, Watertown, Massachusetts, USA.

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.

Sternbach H.
Department of Psychiatry, UCLA-Neuropsychiatric Institute, Los Angeles, USA.

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.

Cohen PG.

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.

Barrett-Connor E, Von Muhlen DG, Kritz-Silverstein D.

Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0607

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.

Reiter WJ, Pycha A, Schatzl G, Klingler HC, Mark I, Auterith A, Marberger M.

Department of Urology, University of Vienna, Vienna, Austria.

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

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.