International hormone society on repla***ent T
Consensus # 7 Testosterone Therapy of Partial Androgen Deficiency in Men
De***ber 05, 2006
After a careful literature review and discussions with physicians from all over the world who are experienced in treating endocrine disorders, we, the members of the Consensus Group of Experts of the International Hormone Society, think it is time to treat testosterone deficiency in aging men.
Since the chemical structure of testosterone and a method to synthesize it were discovered in the 1930?s, a significant number of studies have shown testosterone and other androgens to be essential hormones for optimum male health. The level of bio-available testosterone, along with levels of other androgens, declines as men age. Androgens decrease gradually and their decline is associated with various signs and symptoms such as fatigue, depressed mood, loss of sexual desire, impotency, loss of muscle mass, increase in fat mass, and many other manifestations generally attributed to aging. Persistent androgen deficiency may increase the risk of age-related conditions such as obesity, diabetes and cardiovascular disease. Although this age-related androgen decline does not affect men as brutally as menopause impacts women, it may nonetheless impair a man?s quality of life, his health, and perhaps his lifespan. The age-related decrease of androgen activity in men is variously known as andropause, male climacteric, PADAM (partial androgen deficiency in aging men), ADAM (androgen deficiency in aging men), age-related hypogonadism, male menopause, and penopause.
Men are treated much less frequently for testosterone deficiency than postmenopausal women are treated with female hormones for ovarian deficiency. Men endure a pre-andropause progressing to andropause, just as women undergo perimenopause, followed by menopause. This concept of a male equivalent to ovarian deficiency and failure is currently not fully accepted, yet we see no valid reason for the distinction.
Opponents of treating age-related androgen decline cite rare, conflicting, and often weak studies. Some of these studies show no significant difference in androgen levels of young and old men, others suggest that testosterone might increase the proliferation of prostate cancer (at least in vitro), and others suggest that testosterone repla***ent at low doses does not have significant effects. These atypical studies are generally contradicted by a larger number of studies that show the opposite, and, in particular, a neutral or protective effect of testosterone against prostate cancer.
A global review of the literature does not provide any conclusive evidence that treatment with testosterone or its derivatives increases the risk of prostate cancer in vivo. On the contrary, men with low testosterone levels appear to have a higher risk of more aggressive prostate cancer, atherosclerosis and poor quality of life. Moreover, prostate cancer patients whose androgen levels are drastically lowered by anti-androgen therapy, which does not appear to increase the survival in these men.
IHS recommendation for Diagnosis of Partial Testosterone Deficiency in men: To diagnose a mild to moderate testosterone insufficiency, physicians should do a thorough clinical evaluation noting all the suggestive signs and symptoms. These include a loss of libido in varying degrees, impotence, fatigue, depression, sarcopenia, abdominal obesity and gynaecomastia. Laboratory tests are also essential. We recommend testing the patient for total and free testosterone, SHBG (sex hormone binding globulin), dihydrotestosterone or androstanediol glucuronide (the major metabolite of dihydrotestosterone), FSH and LH. It is also important to test for serum estradiol and possibly estrone because high levels of estrogen can block androgen activity. Testing for prolactin is indicated when hyperprolactinemia is suspected, as this may block the action of male hormones.
IHS recommendation for Treatment of Partial Testosterone Deficiency in men: Because of its adverse impact on health, we recommend that physicians treat any persistent testosterone deficiency, even if moderate, with androgens, preferably testosterone or a close derivative, unless there is a contraindication. All men who live long enough can expect to need supplemental testosterone. Significant declines usually occur between the ages of 30 and 50, although there are exceptions in which supplementation may be needed earlier or later.
Only physiological doses of testosterone or another suitable androgen should be given, in doses that bring testosterone levels into the reference range of 21-30, or perhaps 31-40, year old men. The best routes of testosterone delivery appear to be via a transdermal gel or intramuscular injections.
Caution: Testosterone can convert into estradiol, high levels of which have adverse effects in men. These include gynecomastia, benign prostatic hypertrophy (in particular prostate stromal hyperplasia), and possibly myocardial infarction. Therefore, we recommend that physicians avoid excess serum estrogen levels during testosterone treatment. Dietary measures, such as avoiding daily alcohol and caffeine intake, can help keep estrogens low. Avoiding obesity is also important because fat tissue, rich in the enzyme aromatase, catalyzes the conversion of testosterone to estradiol. When these measures are not adequate, the use of an aromatase inhibitor or progesterone may be indicated. Progesterone enhances the conversion of estradiol, the most potent estrogen, into estrone, a weak estrogen.
Contra-indication: Prostate cancer may constitute a major contra-indication. However, there appears to be very little solid supporting evidence, despite the body of research on this issue. Some studies support the conclusion that patients with prostate cancer, who also suffer from a severe androgen deficiency that impairs their health and quality of life, may have benefits from low dose testosterone treatment that outweigh the potential risk of stimulating the prostate cancer.
In conclusion, we have found no compelling evidence against the use of physiological doses of testosterone in adult men presenting with borderline to overtly low androgen levels, particularly testosterone. On the contrary, as such repla***ent therapy may offer significant beneficial effects, we recommend the use of physiological doses of testosterone, or one of its close derivatives, to correct well–diagnosed testosterone deficiencies in men in a program where they are regularly followed.
