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Testosterone in Aging Men
The article entitled "Current Status of Testosterone Replacement Therapy in Men" by Winters,1 published recently in the ARCHIVES, is the most up-to-date presentation I have had the pleasure of reading in my ongoing review of the literature on this subject. My experience with this kind of patient prompts me to comment on Dr Winters' recommendations and to add other information that should interest your readers.
Dr Winters recommends testing any man with "suspicious symptoms," while admitting that symptoms might be vague. Since testosterone (T) may begin to decrease before age 30 years,2 it seems to me that it would be prudent to begin routine testing of men by age 55 years at the latest. The importance of identifying a T deficiency at an early stage in men is certainly as important as identifying an estrogen deficiency in women. Early treatment has proven prophylactic benefits.
In well-established states of T deficiency, easily recognized physical signs can alert the examiner to pursue this diagnosis, even when symptoms are vague.3
Testosterone blood levels are raised by vigorous exercise of skeletal muscles. Since T can elevate depressed moods, this may be why people feel better after a good workout. The narrow hips, menstrual irregularity, and delayed bone calcification seen so frequently in young female athletes could all be explained by relatively high T levels suppressing normal estrogen production (increased testosterone-estrogen ratio).
Testosterone lessens exertional fatigue by improving oxygen use in heart and skeletal muscles, where T receptors are most highly concentrated.4 The high concentrations of T receptors in the heart muscle likely indicate a strong need for T throughout a person's lifetime.
Dr Winters mentions the use of natural T buccal lozenges, but is concerned about the wide fluctuations in T blood levels that occur with this product. In my experience, depo forms of T are a much greater problem in this regard. The natural form of T, aside from being the type of T the body normally makes, has the advantage of being readily aromatized to estradiol when the dose of T is too high. This is in contrast to alkylated forms of T that cannot be aromatized and, therefore, remain in the system long enough to cause serious liver problems, elevation of low-density lipoprotein cholesterol levels, and lowering of high-density lipoprotein cholesterol levels.3 I agree that free T blood levels only help to confirm that the patient is actually taking the medication. However, estradiol levels that are in the normal range 12 hours after dissolution of the lozenge indicate that the dose of T is probably correct. With the T lozenges, serum T levels will be supraphysiologic in the first hour, but back to baseline by 6 hours. This contrasts with depo forms of T that may be supraphysiologic for a week or more. Even with only 1 dose per day, the lozenges appear to saturate T receptors. Ultimately, the gold standard for determining adequacy of dose is still clinical response: the return of normal libido, muscle strength, and a feeling of well-being.
W. V. Applegate, MD, DABFP
La Mesa, Calif
1. Winters SJ. Current status of testosterone replacement therapy in men. Arch Fam Med. 1999;8:257-263.
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2. Barrett-Connor EL. Testosterone and risk factors for cardiovascular disease in men. Diabetes Metab. 1995;21:156-161.
3. Hypogonadism Task Force. AACE clinical practice guidelines for the evaluation and treatment of hypogonadism in adult male patients [American Association of Clinical Endocrinologists Web site]. 1998:1-24. Available at: http://www.aace.com/clinguideindex.htm. Accessed December 9, 1999.
4. Mooradian AD, Morley JE, Korenman SG. Biological actions of androgens. Endocr Rev. 1987;8:1-28.
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I agree with Dr Applegate that buccal administration of natural testosterone represents a potential alternative to intramuscular injections or transdermal testosterone replacement. No commercial preparations for buccal administration are currently available, however, and the possibility of batch-to-batch variation is of substantial concern with delivery systems prepared by individual pharmacists. Moreover, there is almost no published information on the efficacy and safety of testosterone when it is absorbed via the oral or buccal route, and the appropriate dose and frequency of treatment are unknown. Therefore, I cannot recommend this approach to testosterone replacement therapy at this time.
Stephen J. Winters, MD
Pittsburgh, Pa
Arch Fam Med. 2000;9:221.
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