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Department of Internal Medicine, Division of Geriatric Medicine, St. Louis University Health Sciences Center, St. Louis, Missouri 63104
Address all correspondence and requests for reprints to: Dr. John E. Morley, Department of Internal Medicine, Division of Geriatric Medicine, St. Louis University Health Sciences Center, 1402 S. Grand Boulevard, Room M238, St. Louis, Missouri 63104.
Abstract |
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Top Abstract Introduction Subjects and Methods Results Discussion References |
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There was no significant difference in the initial blood tests in the two groups. At 2 yr follow-up, only the hematocrit showed a statistically significant increase in the testosterone-treated group compared to the control group (P < 0.001). A decrease in the urea nitrogen to creatinine ratio and an increase in the prostate-specific antigen concentration was not statistically significant. Eleven (24%) of the testosterone-treated subjects developed polycythemia sufficient to require phlebotomy or the temporary withholding of testosterone, one third of which occurred less than 1 yr after starting testosterone treatment. There was no significant difference in the incidence of new illness in the two groups during the 2-yr follow-up. Alhough self-assessment of libido was dramatically improved in the testosterone-treated group (P < 0.0001), approximately one third of the subjects discontinued therapy.
In conclusion, testosterone replacement therapy appears to be well tolerated by over 84% of the subjects. Long term testosterone replacement to date appears to be a safe and effective means of treating hypogonadal elderly males, provided that frequent follow-up blood tests and examinations are performed.
Introduction |
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Top Abstract Introduction Subjects and Methods Results Discussion References |
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Subjects and Methods |
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Top Abstract Introduction Subjects and Methods Results Discussion References |
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Results |
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Top Abstract Introduction Subjects and Methods Results Discussion References |
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The 2 yr changes in serum and hematocrit values of the two groups are compared in Table 2. There were no significant differences in the prostate-specific antigen concentration. The urea nitrogen to creatinine ratio dropped in the study group, but the change was not statistically significant. Only hematocrit showed a significant increase in the testosterone-treated group compared to that in controls. Eleven subjects (24%) in the testosterone group developed polycythemia (hemoglobin, >17 g/dL; hematocrit, >52%), warranting temporary withdrawal of testosterone therapy or phlebotomy. Of these, the first occurrence of polycythemia was within the first year of therapy in six (33%) subjects, between 12 yr in 3 (6.7%) subjects, and beyond 2 yr in two (4.4%) subjects.
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Discussion |
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Top Abstract Introduction Subjects and Methods Results Discussion References |
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As prostate cancer has been associated with hormone-responsive growth (34), and as benign prostatic hypertrophy and declining testosterone levels both occur in the aging population, there has long been a concern among clinicians that chronic testosterone replacement might have an adverse effect on the prostate. Recent studies indicate that the clinical course of prostate cancer is accelerated by testosterone, but the incidence is not increased by it (17, 29). In other words, testosterone does not appear to cause prostate cancer. Although prostate carcinoma is a clear contraindication for testosterone replacement therapy, there is no clinical evidence that testosterone accelerates BPH (17, 24, 35). In fact, in this study, subjects receiving testosterone had fewer complaints of bladder outlet obstruction symptoms than those in the control group, although the difference was not statistically significant. The frequent follow-up visits in men taking testosterone, which included a rectal exam and serum prostate-specific antigen measurement, may be an effective screening mechanism that is not operative in men not taking testosterone, who may have much less frequent primary care checkups. Consequently, it is possible that should new prostate cancer occur, it may be diagnosed earlier in this group, resulting in a more favorable outcome.
The adverse effect of testosterone on the lipid profile has been documented in younger men, although the long term effect of the change on mortality and morbidity is uncertain. Although a drop in serum high density lipoprotein cholesterol of 1015% has been shown to occur in many studies in younger men (17, 36, 37), other studies were unable to confirm a decline in high density lipoprotein cholesterol or an increase in total cholesterol in older men (18, 38, 39). The long term clinical significance is not clear, as in our experience there is no increase in angina, myocardial infarctions, or strokes in patients receiving testosterone for up to 3 yr. Furthermore, total cholesterol in the testosterone-treated group and the control group did not significantly differ in this study.
Sleep apnea, associated with testosterone, has been reported previously (40). In this study only one subject reported worsening sleep apnea, leading to discontinuation of testosterone. In general, however, most subjects who reported a favorable response to testosterone also report better sleep habits as part of their overall sensation of well-being associated with testosterone.
It is not surprising that testosterone has a minimal mineralocorticoid effect, because steroid compounds differ in quantitative, rather that absolute, qualitative effects. No significant weight gain, fluid retention, or sodium retention were noted in this study. Short term studies have indicated a decrease in the urea nitrogen to creatinine ratio (18). This difference was not found to be significant in this study. It is possible that an early change in sodium levels and fluid shifts are overcome with the long term use of testosterone.
Conclusion
Testosterone replacement therapy was well tolerated in 69% of the subjects in this study. Approximately one third of the subjects discontinued therapy, most of which occurred soon after starting the treatment (18% within 1 yr). The most common reason for discontinuing testosterone replacement therapy was the lack of noticeable improvement in the presenting symptom, or the inconvenience of therapy and frequent follow-up visits. Of those who continued therapy, most reported an improvement in libido, energy, mood, and sleep. The only strict contraindications for testosterone use are prostate cancer, allergic hypersensitivity to the testosterone preparation (41), or an elevated hematocrit. In the absence of these, long term testosterone replacement therapy to date appears to be safe and effective. Frequent follow-up visits and blood testing (hematocrit and prostate-specific antigen) are essential, however, for proper management of the hypogonadal older male.
Received April 1, 1997.
Revised July 30, 1997.
Accepted August 5, 1997.
References |
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