A symposium entitled "Testosterone Replacement Therapy in Men: Emerging Clinical Issues" was held in conjunction with the 82nd Annual Meeting of The Endocrine Society, June 21-24, 2000 in Toronto, Canada. Dr. Glenn Cunningham, Baylor College of Medicine, Houston, was the moderator of the symposium and highlighted the fact that probably 4-5 million men in the USA are testosterone deficient, but less than 1 million currently receive testosterone replacement therapy (TRT).
The first speaker was Dr. Peter Snyder, University of Pennsylvania, Philadelphia, who spoke on "Prevalence, Symptoms, Signs, Consequences, and Diagnosis of Hypogonadism in the Adult Male". He emphasized that the actions of testosterone were multifold and either could be a direct effect or the result of metabolism to estradiol or dihydrotestosterone in specific target tissues. Using examples from his own TRT study, he reviewed the time course of testosterone effects. Improvement in energy, libido, mood and hot flashes occur within a few weeks of the onset of TRT, while increases in muscle mass, development of gynecomastia, or elevations in red blood cell mass take months to occur. Increases in muscle strength or bone mineral density, or the development of azospermia take even longer. His suggestions for the general evaluation for hypogonadism in men with signs or symptoms suggestive of testosterone deficiency included a morning serum total testosterone level, LH and FSH levels (to check for primary or secondary hypogonadism), and, in certain cases, additional tests of the pituitary (prolactin, thyroid, and adrenal studies). He felt there were two scenarios where a measurement other than total testosterone probably should be used to diagnose "testosterone deficiency"; these were ones where alterations in SHBG levels often occur, namely, in men who are older or obese.
The second speaker was Dr. Ronald Swerdloff, UCLA School of Medicine, Torrance, California, who presented "Pharmacodynamics of Androgen Replacement Therapy in Middle-aged and Older Men". He noted that availability of SARMs (selective androgen receptor modulators) to treat testosterone deficient men would be at least 10 years away and that what has occurred in TRT over the past years has been development of new testosterone delivery systems. He reported on the result of a recently completed open label dose response and bioefficacy study of two doses (50 mg/d and 100 mg/d) of a testosterone gel (AndroGel), or transdermal testosterone patch (Androderm, 5mg/d) given for a period of up to 180 days in 227 hypogonadal men (mean age 51 yrs). Average 24 hour T levels were highest in the 100mg T gel group (1.9 and 1.4 fold higher than the T patch or 50 mg T gel groups), but both T and estradiol levels remained within the normal range for all replacement doses. In terms of study outcomes, sexual motivation and self assessment of sexual performance normalized fully at 30 days (or even earlier) with all T dosages. By as early as 90 days of therapy, improvement in lean body mass was noted on DXA scan, and changes seemed to be dose related (the higher T gel dose giving the most change). The same dose-response seemed to occur for the decrease in body fat, and bone mineral density, but not strength, which increased similarly across groups. Bone turnover markers showed early changes, with an increase in osteocalcin levels, followed by a decrease back to baseline; PTH levels increased over the 6 months of the study and urinary N-telopeptides tended to decrease with time. Increases in hematocrit also were dose related. No change in HDL-cholesterol was noted in any group nor did prostate symptoms occur. There was a small, but statistically significant, increase in PSA over the 6 months of treatment, the magnitude of which was dose related.
The third speaker was Dr. J. Lisa Tenover, Emory University, Atlanta, who spoke on "Special Considerations for Androgen Replacement in Older Men." She spoke about issues in regards to potential TRT adverse effects and choice of treatment modality that were particularly relevant to older men. In terms of adverse effects, the following points were made: the transient fluid retention that can occur at the onset of therapy are real but might only be of concern in men with problems such as congestive heart failure; gynecomastia is not common, but occurs more frequently in the older man and usually can be controlled by lowering the T dose; screening (by history) for sleep apnea is important because TRT may exacerbate the symptoms in some men; TRT can result in exaggerated erythropoiesis and development of polycythemia in older men; and studies to date show that with proper baseline screening to eliminate men at high risk, up to 5 years of TRT results in no obvious increase in lower urinary tract symptoms or detectable prostate cancer, but study evaluation times have been limited and the number of men studied small so that the longer term effects of TRT on prostate disease development are unknown. In considering the modality of T replacement for older men, certain factors should be weighed, including: (1) the sex steroid levels achievable, since some older men seeking TRT do not have frank hypogonadism at baseline; (2) patient's acceptance of method of delivery; (3) cost to the patient, especially since the national health system in the US (Medicare) does not pay for medications; and (4) the risk of development of erythropoiesis (methods resulting in more even serum levels of T usually do not increase red blood cell mass as much as do methods that give high peak T levels).
Lisa Tenover, USA