Referral to endocrinology is recommended for patients with thyroid, adrenal, pituitary or hypothalamic dysfunction. The urologist should be aware that aging men with ED may show a variety of symptoms when hypogonadism coexists: low libido, depression, decreased intellectual abilities, decreased lean body mass, decreased bone mineral density, decreased skin turgor, changes in body hair distribution, changes in sleep patterns, and increased visceral fat. This discussion is limited to treatment of hypogonadism and hyperprolactinemia as they relate to ED.
In the patient with documented hypogonadism and ED, it is reasonable to initiate androgen therapy. Parenteral depo-preparations of testosterone such as testosterone cypionate and enanthate are the cheapest form of androgen supplementation and are effective in restoring serum levels of testosterone to normal. They are administered through deep intramuscular injection; resulting in supraphysiologic levels of testosterone for 72 h with gradual steady decline over 2-3 weeks. Enanthate and cypionate are generally administered every 2-4 weeks at dosages of 200-400 mg. Testosterone propionate has a shorter half-life requiring dosing every other day. Transcutaneous dosing more closely simulates normal circadian levels of testosterone if patients apply the patch in the morning.
There are currently 3 FDA-approved preparations available in the United States: Testoderm/Testoderm TTS (Alza Pharmaceuticals), Androderm (GlaxoSmithKline), and AndroGel (Unimed Pharmaceuticals, Inc). Testoderm comes in 2 sizes, delivering 4 mg/d or 6 mg/d. Physiologic blood levels can be achieved in 65% of patients who apply the system to the scrotum. Testoderm TTS may be applied daily as a 5-mg patch to the arm, back, or upper buttocks, avoiding the inconveniences of scrotal therapy. Androderm comes as a patch that delivers 2.5 mg or 5 mg. The most common adverse reactions to both Testoderm TTS and Androderm are itching, chronic skin irritation, and allergic contact dermatitis. Patients should alternate sites of application and avoid sun-exposed sites, and they may be helped by local application of cortisone cream to irritated skin. Androgel 1% is a cream designed to deliver 50 mg of testosterone, applied once daily in the morning to clean, dry skin over the shoulders, upper arms, or abdomen. It is supplied in packets of 25 mg and 50 mg. The most common adverse reaction is also skin-site irritation. The oral forms available in the United States are 17α-methyl testosterone preparations. When taken orally, these preparations are largely rendered metabolically inactive during the “first pass” circulation through the liver. These preparations are toxic to the liver and can lead to hepatitis, cholestatic jaundice, hepatomas, hemorrhagic liver cysts, and hepatocarcinoma (Bagatell and Bremner, 1996). Testosterone undecenoate is an oral testosterone ester relatively free of liver toxicity but is not available in the United States.
- Physiology of Penile Erection
- Male Sexual Dysfunction
- Male Sexual Dysfunction Epidemiology
- Diagnosis & Treatment
- Nonsurgical Treatment of Erectile Dysfunction
A discussion of potential adverse effects is in order. In a young hypogonadal man, testosterone replacement is clearly the treatment of choice. However, the risks may outweigh the benefits in some patients. Supraphysiologic levels of testosterone will suppress luteinizing hormone and follicle-stimulating hormone production and can result in infertility, breast tenderness, and gynecomastia. Erythrocytosis is the most common laboratory alteration noted with long-term therapy. Androgens may also induce or worsen sleep apnea. Cardiovascular risks are increased in some patients by increases in red cell mass and thromboxane A2 as well as platelet aggregation (Ajayi, Mathur, and Halushka, 1995). Many practitioners have raised concerns about the potential risks of androgen therapy in elderly patient with prostate symptoms or occult prostate cancer. Several studies in the literature suggest that androgen replacement does not induce prostate cancer in men with normal prostates, and placebo-controlled studies show little difference in prostate volume, prostate-specific antigen levels, and obstructive symptoms (Cooper et al, 1998; Nomura et al, 1998). The fear of exacerbating an occult cancer of the prostate remains a major concern. Nevertheless, there are some older hypogonadal patients whose libido and erectile function can be restored by testosterone therapy and who should not be denied the option. When a patient desires this, we routinely perform a digital rectal examination and obtain a serum prostate-specific antigen level. When one is in doubt, ultrasound-guided biopsy is also done before androgen therapy is given. The presence of prostate or breast cancer is an absolute contraindication to androgen supplementation. Patients are followed up every 6 months with a rectal examination and serum prostate-specific antigen test as long as they are receiving therapy. Laboratory surveillance should also include hemoglobin/hematocrit levels, liver function tests, and a cholesterol and lipid profile. The efficacy of testosterone supplementation is reasonably determined by clinical response rather than blood level of testosterone.
In patients with hyperprolactinemia with or without hypogonadism, testosterone therapy does not improve sexual function. Treatment should first be aimed at eliminating the offending drugs, such as estrogens, morphine, sedatives, or neuroleptics. Bromocriptine is a dopamine agonist that lowers the prolactin level and restores testosterone to normal. It is used to reduce tumor size of a prolactin-secreting adenoma. Neurosurgery may occasionally be needed if the response is not satisfactory or if there are changes in the visual field secondary to optic nerve compression.
Revision date: July 3, 2011
Last revised: by Janet A. Staessen, MD, PhD