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Avoid contact with females or children (see package insert) in patients applying gel preparations.
Oral therapy is not recommended due to significant hepatotoxicity.
The FDA has cautioned that testosterone is approved for men with confirmed low testosterone by laboratory testing and caused by certain medical conditions, NOT just due to aging.
Despite prior data showing no clear association between testosterone replacement therapy (TRT) and CV disease, there have been several recent papers suggesting that TRT use puts patients at an increased risk for CV disease. These papers have been criticized widely for being flawed due to comparison of unequal groups, short and inaccurate endpoints, flawed laboratory testing, erroneous exclusion criteria, and atypical statistical analysis. Despite this, an FDA panel concluded that there is a possible increased CV risk associated with testosterone use.
Testosterone replacement therapy (FDA approved)
Topical gels/solutions
Multiple FDA-approved formulations
Most frequently prescribed in United States
Mimics normal daily circadian rhythm
Good absorption, but 15 " “20% are nonresponders
Transfer concern to children and women
Dosage adjustments to obtain optimal results
Gel application: arms, back, axilla, and groin
Testosterone pellets (Testopel)
Minor office procedure with mild discomfort
Long-acting formulation, 3 to 4 months
1 " “2% risk of infection or pellet extrusion
Transdermal patch (Androderm)
Achieves less robust levels
Convenient over gels, no risk of transference
High incidence of skin irritation
Testosterone cypionate and enanthate (short acting)
Injectable (IM), inexpensive
Inconvenient: injections every 1 to 3 weeks
Starting dose: 100 mg/week, or 200 mg/2 weeks
Roller coast effect: levels rise and fall
Testosterone undecanoate (long acting)
Injectable, expensive, convenient
Small risk of oil embolism, needs observation in office for 30 minutes postinjection
Given approximately every 8 to 12 weeks
Buccal application (Striant)
Adheres to gum line, irritation in 16.3%
Poor compliance, every 12 hours application
Nasal gel (Natesto)
OFF LABEL TREATMENT
Human chorionic gonadotropin (hCG)
Structure similar to LH, mimicks its actions
Frequent, 3 times per week starting at 1,500 IU SC
Poor compliance
Maintenance of testicular volume and fertility
Used in men wanting to preserve fertility
Clomiphene citrate: oral agent
Increases T by interfering with negative feedback, resulting in increased LH and FSH
Starting dose of 25 mg daily 3 to 7 times weekly
Used in men wanting to preserve fertility
Aromatase inhibitors (Arimidex): oral agent
Blocks conversion of T to estradiol
Does not negatively impact spermatogenesis and testicular volume
Utilized in cases of low T/estradiol ratio
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ISSUES FOR REFERRAL
- Elevated PSA and/or abnormal prostate exam should be referred to urology.
- Worsening symptoms of BPH or increasing IPSS
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Necessary to monitor effectiveness of therapy as well as for adverse effects: Initially 3 to 6 months after treatment initiation and then annually
- Measure hematocrit at baseline, at 3 to 6 months, and then annually. If hematocrit >54% or symptomatic, stop therapy until hematocrit decreases to a safe level. Treatment includes phlebotomy, blood donation, or adjustment of dose.
- Evaluate patient for hypoxia or sleep apnea.
- Monitor bone mineral density after 1 to 2 years of therapy in these men with osteoporosis or low trauma fracture.
- Changes in voiding symptoms
- Prostate exam done regularly every 6 to 12 months.
- Refer to urology when increase in PSA >0.7 ng/mL within any 12-month period of T treatment or detection of prostatic abnormality on prostate exam.
DIET
Healthy diet and weight reduction if obese ‚
PATIENT EDUCATION
- TD is chronic and likely to need lifelong therapy.
- T replacement comes with many risks, and it is very important to regularly monitor outcomes.
- Women and children must not be allowed to come in contact with T-replacement gel products.
PROGNOSIS
- Sustained reversal of symptoms can be achieved when serum levels of T fall in the normal range.
- Adverse health effects seen in many with chronically low levels of T
COMPLICATIONS
Complications of testosterone replacement ‚
- Decreased testicular volume and azoospermia
- Fluctuations in mood or libido
- Gynecomastia and growth of breast cancer
- Acne and oily skin
- Erythrocytosis (increased hemocrit)
- Exacerbation of sleep apnea
- Hepatotoxicity with prolonged oral use
- Possible prostate enlargement with or without worsening symptoms of BPH
- Unknown cardiovascular risks
REFERENCES
11 Conners ‚ WPIII, Morgentaler ‚ A. The evaluation and management of testosterone deficiency: the new frontier in urology and men 's health. Curr Urol Rep. 2013;14(6):557 " “564.22 Paduch ‚ DA, Brannigan ‚ RE, Fuchs ‚ EF, et al. The laboratory diagnosis of testosterone deficiency. Urology. 2014;83(5):980 " “988.33 Bhasin ‚ S, Cunningham ‚ GR, Hayes ‚ FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536 " “2559.44 Jenkins ‚ LC, Mulhall ‚ JP. Editor 's comment " ”how dangerous is testosterone supplementation? Int Braz J Urol. 2015;41(2):195 " “198.
ADDITIONAL READING
- Buvat ‚ J, Maggi ‚ M, Guay ‚ A, et al. Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment. J Sex Med. 2013;10(1):245 " “284.
- Vigen ‚ R, O 'Donnell ‚ CI, Bar ƒ ³n ‚ AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829 " “1836.
CODES
ICD10
- E29.1 Testicular hypofunction
- E89.5 Postprocedural testicular hypofunction
ICD9
- 257.2 Other testicular hypofunction
- 257.1 Postablative testicular hypofunction
SNOMED
- 111551000 Testicular hypofunction
- 190552005 Postablative testicular hypofunction
- 38825009 Deficiency of testosterone biosynthesis (disorder)
- 48723006 male hypogonadism (disorder)
- 236813004 Post-chemotherapy testicular hypofunction (disorder)
- 20615009 Postirradiation testicular hypofunction (disorder)
CLINICAL PEARLS
- Testosterone deficiency is common and prevalence increases with age.
- Testosterone deficiency can have negative adverse impact on many bodily systems.
- Symptomatic men with sexual dysfunction, obesity, and metabolic diseases should be tested for testosterone deficiency and treated.
- Initial test of choice is a morning total and free testosterone; if low, repeat measurements.
- Testosterone replacement therapy in the appropriately selected population can increase lean mass, reduce fat mass, increase bone density, improve libido, and improved erections.