Both testosterone and 5α-DHT are metabolized mainly in the liver. Approximately 50% of testosterone is metabolized via conjugation into testosterone glucuronide and to a lesser extent testosterone sulfate by glucuronosyltransferases and sulfotransferases, respectively. An additional 40% of testosterone is metabolized in equal proportions into the 17-ketosteroids androsterone and etiocholanolone via the combined actions of 5α- and 5β-reductases, 3α-hydroxysteroid dehydrogenase, and 17β-HSD, in that order. Androsterone and etiocholanolone are then glucuronidated and to a lesser extent sulfated similarly to testosterone. The conjugates of testosterone and its hepatic metabolites are released from the liver into circulation and excreted in the urine and bile. Only a small fraction (2%) of testosterone is excreted unchanged in the urine.
There are relatively few contraindications to the use of vacuum devices. Some conditions can predispose to priapism or perhaps bleeding with constriction, such as sickle cell disease, polycythemia, and other blood dyscrasias. Patients taking anticoagulants can safely use vacuum constriction devices but need to accept a higher risk of bleeding (ecchymosis). Good manual dexterity is also needed to use the device; if manual dexterity is impaired, a willing sexual partner can learn to apply the device.
Male hypogonadism becomes more common with increasing age and is currently an under-treated condition. The diagnosis of hypogonadism in the aging male requires a combination of symptoms and low serum testosterone levels. The currently available testosterone preparations can produce consistent physiological testosterone levels and provide for patient preference.
Erectile dysfunction is known to be associated with general health status, thus, lifestyle modification improves erectile function and decreases the rate of decline of function with aging. One year after discontinuation of smoking, patients were found to have a 25% improvement in erectile quality.16 In addition, multivariate analysis found obesity is associated with erectile dysfunction with an approximately 50% increase in ED in obese men as compared with normal weight men.17
The main surgical treatment of ED involves insertion of a penile implant (also called penile prostheses). Because penile vascular surgery is not recommended for aging males who have failed oral PDE5 inhibitors, ICI or IU therapies, implants are the next step for these patients. Although placement of a penile implant is a surgery which carries risks, they have the highest rates of success and satisfaction among ED treatment options.
The use of anabolic steroids (manufactured androgenic hormones) shuts down the release of luteinising hormone and follicle stimulating hormone secretion from the pituitary gland, which in turn decreases the amount of testosterone and sperm produced within the testes. In men, prolonged exposure to anabolic steroids results in infertility, a decreased sex drive, shrinking of the testes and breast development. Liver damage may result from its prolonged attempts to detoxify the anabolic steroids. Behavioural changes (such as increased irritability) may also be observed. Undesirable reactions also occur in women who take anabolic steroids regularly, as a high concentration of testosterone, either natural or manufactured, can cause masculinisation (virilisation) of women.
Important future developments will include selective androgen receptor modulators (SARMs). These drugs will be able to produce isolated effects of testosterone at androgen receptors. They are likely to become useful clinical drugs, but their initial worth may lie in facilitating research into the relative importance of testosterone’s action at the androgen receptor compared to at other sites or after conversion to other hormones. Testosterone will remain the treatment of choice for late onset hypogonadism for some time to come.
In males, testosterone is synthesized primarily in Leydig cells. The number of Leydig cells in turn is regulated by luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In addition, the amount of testosterone produced by existing Leydig cells is under the control of LH, which regulates the expression of 17β-hydroxysteroid dehydrogenase.
Of particularly concern are antihypertensive medications for CVD (eg, digoxin, disopyramide [Norpace], gemfibrozil [Lopid]), anxiety, depression (eg, lithium, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants), or psychosis (eg, chlorpromazine, haloperidol, pimozide [Orap], thioridazine, thiothixene). Antihypertensive drugs, such as diuretics (eg, spironolactone, thiazides) and beta blockers, may be associated with ED. Discontinuation or switching to alternative drugs, such as angiotensin-converting enzyme inhibitors or calcium channel blockers (eg, diltiazem, nifedipine, amlodipine), may reduce ED. The newer angiotensin II receptor antagonists may be less problematic with respect to ED, but long-term data is needed to evaluate this.
One study examined the role of testosterone supplementation in hypogonadal men with ED. These men were considered nonresponders to sildenafil, and their erections were monitored by assessing nocturnal penile tumescence (NPT). After these men were given testosterone transdermally for 6 months, the number of NPTs increased, as did the maximum rigidity with sildenafil.  This study suggests that a certain level of testosterone may be necessary for PDE5 inhibitors to function properly.
Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.
In addition to its role as a natural hormone, testosterone is used as a medication, for instance in the treatment of low testosterone levels in men and breast cancer in women. Since testosterone levels decrease as men age, testosterone is sometimes used in older men to counteract this deficiency. It is also used illicitly to enhance physique and performance, for instance in athletes.
Type 2 diabetes is an important condition in terms of morbidity and mortality, and the prevalence is increasing in the developed and developing world. The prevalence also increases with age. Insulin resistance is a primary pathological feature of type 2 diabetes and predates the onset of diabetes by many years, during which time raised serum insulin levels compensate and maintain normoglycemia. Insulin resistance and/or impaired glucose tolerance are also part of the metabolic syndrome which also comprises an abnormal serum lipid profile, central obesity and hypertension. The metabolic syndrome can be considered to be a pre-diabetic condition and is itself linked to cardiovascular mortality. Table 1 shows the three commonly used definitions of the metabolic syndrome as per WHO, NCEPIII and IDF respectively (WHO 1999; NCEPIII 2001; Zimmet et al 2005).