Men's Health & HRT
Bio-identical Hormone Replacement Therapy achieves the sustained levels of testosterone that would be produced by normally functioning testicles. This form of therapy is the only kind that produces the natural level of this hormone. Because the testosterone used is totally natural, it is ideal for men wanting the benefits of a bio-identical hormone, without the drawbacks of a synthetic.
Symptoms of testosterone deficiency in men include fatigue, lack of mental acuity, loss of libido, and difficulty achieving or sustaining an erection.
Why bio-identical hormone therapy for men? Hormonal needs for men have received national attention, but with marginal treatment options available. Synthetic hormonal treatments for men can be expensive, require daily use, and in many cases, need to be carefully timed with their partner’s needs for normal sexual activities and pleasure.
Current medical research now defines the male equivalent to menopause as andropause. Men experience a more gradual decline in hormone levels. They lose approximately one percent of their testosterone and 2.5 percent of their DHEA per year beginning at age 30.
Men find themselves lacking in sexual desire, gaining weight, losing muscle mass, and feeling sluggish, depressed, and irritable. Yet, they believe they must endure these body and hormonal changes as part of aging.
Introduction To Male Testosterone
Testosterone is responsible for the normal growth and development of male sex organs and the maintenance of secondary sex characteristics. It is the primary androgenic hormone.
When the testes fail to produce normal levels of testosterone, testosterone deficiency results. Hypogonadism is caused by primary testicular failure. Testosterone levels are low and pituitary gonadotropins are elevated. In hypogonadism, there is inadequate secretion of pituitary gonadotropins. In addition to a low testosterone level, LH and FSH levels are low or low-normal. The development of hypogonadism after puberty frequently results in complaints such as diminished libido, erectile dysfunction, infertility, gynecomastia, changes in body composition, reductions in body and facial hair, and osteoporosis. Hypogonadal men report higher levels of anger, confusion, and depression.
There are now a variety of products available to treat testosterone deficiency. Successful management of testosterone replacement therapy requires appropriate evaluation and an understanding of the benefits and risks of treatment.
Proper Diagnosis of Testosterone Deficiency
There are many causes of testosterone deficiency. A medical history, physical exam, and proper laboratory evaluation are imperative. The medical history should include questions regarding abnormalities at birth, the current status of sexual function, and secondary sexual 
characteristics, such as beard growth, muscular strength, and energy level. Hypogonadal men have statistically significant reductions in the incidence of nocturnal erections, the degree of penile rigidity during erection, and the frequency of sexual thoughts, feelings of desire, and sexual fantasies. Furthermore, alterations in body composition, changes in adipose tissue, increases in percent body fat, and reduction in muscle mass, are frequently seen in hypogonadal men.
Proper labs should be drawn to determine a diagnosis. The following levels should be drawn in the morning: FSH, LH, SHBG, Total and Free Testosterone, Estradiol, and Estrone.
The Clinical Rationale for Testosterone Replacement Therapy
Testosterone replacement should, in theory, approximate the natural endogenous production of the hormone. The average male produces 4-7 mg of testosterone per day in a circadian pattern, with maximal plasma levels attained in the early morning and minimal levels in the evening.
The clinical rationale for treatment of testosterone deficiency may include:
- increasing bone density
- enhancing body composition by increasing muscle strength and reducing adipose tissue
- improving energy and mood
- improving libido and erectile function
Types of Testosterone Replacement Therapy
Ideal testosterone replacement therapy produces and maintains physiologic serum concentrations of the hormone and its active metabolites without significant side effects or safety concerns. Several different types of testosterone replacement are currently marketed, including tablets, injectables, sublingual, transdermal, and pellet insertion.
Oral agents
Oral agents may cause elevations in liver function tests and abnormalities at liver scan and biopsy. Both modified and unmodified oral testosterone preparations are available. Unmodified testosterone is rapidly metabolized by the liver, making satisfactory serum concentrations difficult to achieve. Modified 17-alpha alkyltestosterones, such as methyltestosterone or fluoxymesterone, also require relatively large doses that must be taken several times a day.
Intramuscular injection
Testosterone cypionate is frequently used in parenteral preparation that provides a safe means of hormone replacement. In men, 20-50 years of age, an intramuscular injection of 200 mg of testosterone cypionate is generally sufficient to produce serum testosterone levels that are supranormal initially and fall into the normal ranges over the next 14 days. Fluctuations in testosterone levels may yield variations in libido, sexual function, energy, and mood. Some patients may be inconvenienced by the need for frequent testosterone injections.
Sublingual
Sublingual testosterone is placed under the tongue and is usually in the form of a square or circle, depending on strength of the troche. A sublingual dose is given twice a day. It by-passes the liver and takes about 2 to 3 minutes to dissolve. The taste is generally bitter but the compounding pharmacies will flavor it to mask the bitterness. Testosterone levels will rise and fall on this therapy which is why it would be best to be administered two or three times a day in smaller doses.
Transdermal Vehicle
Clinical studies of transdermal systems demonstrate their efficacy in providing adequate testosterone replacement therapy.3,4 Transdermal therapy can be made in a cream or gel by a compounding pharmacy. Different strengths are used, ranging from 10mg to 200mg per ml. A daily dose is given in the early morning hours. For best results of maintaining physiologic testosterone levels you would want to administer testosterone twice a day early am (5 am to 7 am) and again around 1 to 4 pm.
Monitoring Patients on Testosterone Replacement
Patients on testosterone replacement therapy should be monitored to ensure that testosterone levels are within normal levels. The prescribing physician should evaluate any changes in the clinical signs and symptoms of testosterone deficiency and should assess for acne and increase in 
breast size and tenderness. Serum testosterone levels should be checked between 5 to 7 hours after administration of topical or sublingual delivery systems.
A prostate-specific antigen (PSA) should be checked in all men before initiating treatment, repeated at three to six months, and then annually in men >40 years of age. A confirmed increase in PSA >2 ng/mL, or a total PSA >4.0 ng/mL requires urologic evaluation. The hematocrit level should also be checked at baseline, at three to six months, and then annually. A hematocrit >55% warrants evaluation for hypoxia, sleep apnea, and/or a reduction in the dose of testosterone therapy. Measurement of the bone mineral density of the lumbar spine and/or the femoral necks at one year may be considered in hypogonadal men with osteopenia.
Benefits of Testosterone Replacement Therapy
Benefits of testosterone replacement therapy include better mood, increased energy levels, and libido. Testosterone replacement has also been shown to enhance libido, the frequency of sexual acts, and sleep-related erections.5 Transdermal testosterone replacement therapy, in particular, has been linked to positive effects on fatigue, mood, and sexual function.6 More specifically, testosterone replacement therapy has been shown to improve positive mood parameters, such as feelings of friendliness, and reduce negative mood parameters, such as anger and irritability.7
Testosterone replacement therapy is also associated with positive changes in body composition. In hypogonadal men, testosterone replacement therapy has demonstrated a number of effects, including an increase in lean body mass, decrease in body fat,8, and increases in muscle size.9
Testosterone replacement with transdermal testosterone delivery systems in HIV-infected men with low testosterone levels has been associated with statistically significant gains in lean body mass (p=0.02), increased red cell counts, and reductions in emotional distress.10Transdermal testosterone has also been administered to HIV-positive women, yielding positive trends in weight gain and quality of life.11
Improvements in bone density have also been shown with testosterone replacement therapy. Increases in spinal bone density have been realized in hypogonadal men,12 with most treated men maintaining bone density above the fracture threshold.13
Contraindications to Testosterone Replacement Therapy
Testosterone replacement is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate as it may cause rapid growth of these tumors. Hormone therapy is also inappropriate in men with severe benign prostatic hypertrophy (BPH)-related bladder outlet obstruction. The use of testosterone to improve athletic performance or correct short stature is potentially dangerous and inappropriate.
Lipid Abnormalities
Physiologic testosterone replacement is known to reduce total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. Some authorities recommend that lipid values be followed closely in men receiving testosterone replacement therapy.
Prostate Changes
Although PSA is not specific to prostate cancer, it is a good surrogate for judging the effects of androgens on the prostate. In one study of testosterone-treated men, PSA rose to normal levels but no higher than in the controls, leading the authors to conclude that testosterone-induced prostate growth should not preclude hypogonadal men from testosterone replacement therapy. Indeed, another study indicates that even men who achieved supraphysiologic levels of serum testosterone had no significant changes in PSA levels.14
The effects of transdermal testosterone replacement on prostate size and PSA levels in hypogonadal men have also been evaluated.15 Prostate size during therapy with transdermal testosterone was comparable to that reported in normal men, and PSA levels were within the normal range.
Prostate Cancer
There appears to be little association between testosterone replacement therapy and the development of prostate cancer. The etiology of prostate cancer is apparently multifactorial and dietary, geographic, genetic, and other influences are all thought to play a role in the development of the disease. Recent studies indicate that testosterone levels have no apparent systematic relationship to the incidence of prostate cancer.16,17.
References
1. McClure, R.D., Oses, R. and Ernest, M.L.: Hypogonadal impotence treated by transdermal testosterone. Urology, 37(3):224, 1991.
2. Snyder, P.J. and Lawrence, D.A.: Treatment of male hypogonadism with testosterone enanthate. J Clin Endocrinol Metab, 51:1335, 1980.
3. Cofrancesco, J. and Dobs, A.S.: Transdermal testosterone delivery systems. The Endocrinologist, 6:207, 1996.
4. Yu, Z., Gupta, S.K., Hwang, S.S., Kipnes, M.S., Mooradian, A.D., Snyder, P.J. and Atkinson, L.E.: Testosterone pharmacokinetics after application of an investigational transdermal system in hypogonadal men. J Clin Pharmacol, 37:1139, 1997.
5. Shabsigh, R.: The effects of testosterone on the cavernous tissue and erectile function. World J Urol, 15:21, 1997.
6. Meikle, A.W., Arver, S., Dobs, A.S., Sanders, S.W. and Mazer, N.A.: Androderm: A permeation-enhanced, non-scrotal testosterone transdermal
7. Alexander, G.M., Swerdloff, R.S., Wang, C., Davidson, T., McDonald, V., Steiner, B. and Hines, M.: Androgen-behavior correlations in hypogonadal men II. Cognitive abilities. Horm Behav, 33:85, 1998.
8. Tenover, J.S.: Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab, 75:1092, 1992.
9. Bhasin, S., Storer, T.W., Berman, N., Yarasheski, K.E., Clevenger, B., Phillips, J., Lee, W.P., Bunnell, T.J. and Casaburi, R.: Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab, 82:407, 1997.
10. Bhasin, S., Storer, T.W., Asbel-Sethi, N., Hays, R., Sinha-Hikim, I., Shen, R., Arver, S. and Beall, G.: Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. J Clin Endocrinol Metab, 83:3155, 1998.
11. Miller, K., Corcoran, C., Armstrong, C., Caramelli, K., Anderson, E., Cotton, D., Basgoz, N., Hirschhorn, L., Tuomala, R., Schoenfeld, Daugherty, C., Mazer, N. and Grinspoon, S.: Transdermal testosterone administration in women with acquired immunodeficiency syndrome wasting: a pilot study. J Clin Endocrinol Metab, 83:2717, 1998.
12. Finkelstein, J.S., Klibanski, A., Neer, R.M., Dopplet, S.H., Rosenthal, D.I., Segre, G.V. and Crowley, W.F.: Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab, 69:776, 1989.
13. Behre, H.M., Kliesch, S., Leifke, E., Link, T.M. and Nieschlag, E.: Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab, 82:2386, 1997.
14. Cooper, C.S., MacIndoe, J.H., Perry, P.J., Yates, W.R. and Williams, R.D.: The effect of exogenous testosterone on total and free prostate-specific antigen levels in healthy young men. J Urol, 156:438, 1996.
15. Meikle, A.W., Arver, S., Dobs, A.S., Adolfsson, J., Sanders, S.W., Middleton, R.G., Stephenson, R.A., Hoover, D.R., Rajaram, L. and Mazer, NA. Prostate size in hypogonadal men treated with a nonscotal permeation-enhanced testosterone transdermal system. Urology 1997; 49:191-6.
16. Ebling DW, Ruffer J, Whittington R, Vanarsdalen K, Broderick GA,
Malkowicz SB, Wein AJ. Development of prostate cancer after pituitary dysfunction: A report of 8 patients. Urology 1997;49:564-568.
17. Gustafsson O, Norming U, Gustafsson S, Eneroth P, Astrom G, Nyman CR. Dihydrotestosterone and testosterone levels in men screened for prostate cancer: a study of a randomized population. Br J Urol 1996;77:433-440.