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HYPOGONADISM IN MALES - LATE-ONSET
Late onset hypogonadism is defined as clinical and biochemical syndrome characterized by older age, set of typical symptoms, and deficiency in serum testosterone levels.
The quality of life may be decreased and multiple organ systems may be adversely affected.
Prior to the start of testosterone substitution, there should be confirmation of low serum testosterone and a confirmation of need based on clinical findings.
Only if the potential benefit exceeds the risk, then replacement testosterone should be started.

Principles of Therapy

  • 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

Pharmacotherapy

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

Contraindications to Testosterone Administration

  • 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
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