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