Hypogonadism%20in%20males%20-%20late-onset Treatment

• Prior to the start of testosterone substitution, there should be confirmation of low serum testosterone & a confirmation of need based on clinical findings
• Only if the potential benefit exceeds the risk, then replacement testosterone should be started
• During hormone replacement therapy (HRT), serum testosterone level should be close to normal throughout the day & should ideally follow the normal diurnal pattern
• It is recommended that a baseline digital rectal examination (DRE) & prostate specific antigen (PSA) level be obtained before starting testosterone therapy

Natural Testosterone Preparations

• Only preparations of natural testosterone should be used
• 17-α-alkylated androgen preparations are not recommended
  
  • These can cause poor androgen effects, adverse lipid changes, & hepatic side effects
• There is not enough evidence of benefit to recommend DHT, DHEA, DHEA-S, hCG, androstenediol or androstenedione in older men w/ hypogonadism

Product Selection

• Some authorities recommend the use of short-acting preparations of testosterone so that if a complication develops, rapid discontinuation can be achieved
• Oral, parenteral, transdermal gel & implantable preparations of testosterone are available in Southeast Asia (transdermal patches are available elsewhere)
• Product selection should be agreed upon between the clinician & patient prior to the start of therapy
• Testosterone undecanoate is the most widely used & safest oral mode of administration
  
  • Rarely causes increase in testosterone levels above the mid-range
  • Oral preparation resorption of testosterone is influenced by intake of fatty food
• A long-acting IM inj testosterone undecanoate is also available given in intervals of 3 months
  
  • Ensures normal testosterone serum concentration for the entire 3 month period
• Testosterone cypionate & enanthate are available as short-acting IM
  
  • May cause fluctuations in serum testosterone from high levels to subnormal levels
• Transdermal testosterone preparations are available as skin patches or gel
  
  • Provides uniform & normal serum testosterone level for 24 hours
  • Gel have advantages of less incidence of skin irritation compared w/ the patch, invisibility of application & flexibility of dosing
  • Gel has the risk of interpersonal transfer (eg to partner or another person who is in close contact)
• Sublingual & buccal testosterone tablets are effective & well-tolerated delivery systems that can provide a rapid & uniform achievement of physiological testosterone level w/ daily administration
• Subdermal depots need to be implanted every 5-7 months & offer a long period of action w/o significant serum fluctuation of the testosterone level
  
  • There is a risk of infections & extrusions

Potential Benefits of Therapy

Effects on Body Composition

• Androgen supplementation in elderly men has been shown to moderately increase muscle mass
• Fat mass may be modestly decreased
• Reports of increase in strength have been inconsistent
  
  • Testosterone treatment seems to improve perception of physical function

Skeletal Effects

• Bone mineral density has been shown to increase
  
  • The lower the pre-treatment testosterone, the greater effect testosterone treatment seems to have on bone mineral density
• Reports of treatment effects on biochemical markers of bone turnover have been inconsistent

Libido & Erectile Function

• Testosterone appears to have a moderate to large favorable effect on libido
• Testosterone use in elderly men may have a minimal to small favorable effect on erectile dysfunction
• As some men w/ erectile dysfunction & low serum testosterone levels may not respond adequately to testosterone, addition of a phosphodiesterase-5 inhibitor may be indicated

Cognition

• There are limited observations of beneficial effects of testosterone treatment on cognitive function in elderly men

Mood & Quality of Life

• Studies have not shown consistently that there is improvement in mood or quality of life in elderly men treated w/ androgens

Glycemic & Lipid Control

• Studies have shown positive effects on glycemic & lipid control, insulin resistance & visceral adiposity in hypogonadal men w/ impaired glucose tolerance & lipid profiles
  
  • Thus, there is a consequent decrease in the cardiovascular risk

Adverse Effects

Prostate

• It is not known if testosterone supplementation in the older male promotes the development or acceleration of prostate cancer
• Testosterone supplementation in older men seems to induce only a small increase in the volume of the prostate w/ an eventual moderate increase in the prostate specific antigen (PSA) level

Hematology

• Testosterone stimulates erythropoiesis
• A significant rise in blood cell mass & hemoglobin can occur from testosterone therapy in older men
• If the hematocrit rises to >50%, withholding therapy may be indicated or in some cases phlebotomy may be necessary

Sleep Apnea

• Testosterone may increase the risk of sleep apnea

Gynecomastia

• Testosterone may be associated w/ the development of gynecomastia from the aromatization of testosterone to estrogen

Lipid & Cardiovascular Safety

• Data are insufficient to determine whether testosterone supplementation would increase, decrease or have no effect on CV disease

• Suspected or confirmed carcinoma of the prostate or breast is an absolute contraindication to testosterone replacement
  
  • Suspected are those w/ palpable prostate nodule or induration or PSA of 4 ng/mL or PSA 3 ng/mL in men at high risk of prostate cancer (eg African Americans or men w/ first-degree relatives w/ prostate cancer)
• Testosterone substitution should be avoided in men w/ significant polycythemia, untreated sleep apnea, severe heart failure, infertility, hematocrit >50%, severe lower urinary tract symptoms due to benign prostatic hyperplasia or significant bladder outlet obstruction