Course Authors
John E. Morley, M.D.
During the last three years, Dr. Morley has received grant/research support from Vivus, Merck & Co., Pharmacia, B. Braun McGaw, Bayer Corp and Nestec, Ltd. He has also served on the Speakers' Bureau for LXN, Organon, Ross, Pharmacia, GlaxoSmithKline, Aventis, Searle, Roche, Bristol-Myers Squibb, Novartis, Pratt, B.Braun McGaw, Pfizer and Solvay.
Estimated course time: 1 hour(s).
Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.
Upon completion of this Cyberounds®, you should be able to:
Discuss the high prevalence of hypogonadism in older men
Describe the approach to diagnosing andropause
Employ the tools to treat andropause.
Mr. B is a 73-year-old male who fell while on a walking tour in the Venezuelan Andes. He was going up a relatively steep, rocky incline when he lost his footing and fell forward. He did not fracture any bones, but, on returning to the U.S.A., Mr. B decided to consult his physician concerning a general decrease in strength which had affected, among other things, his tennis game. Mr. B had also reported that he was often mildly fatigued, more grumpy than in the past, had diminished enthusiasm for sex and was less excited about planning future travel.
If this patient were younger, below 50, the primary physician might first suspect some kind of emotional explanation for this patient's complaints; but, because the patient was well past 50 and had reported a decreased interest in sex, low testosterone syndrome was considered. The patient gave the following answers to the St. Louis University Low Testosterone Syndrome Survey(1):
- Do you have a decrease in libido? Yes
- Do you have a lack of energy? Yes
- Do you have a decrease in strength and/or endurance? Yes
- Do you have a decreased enjoyment of life? No
- Are you sad? No
- Are you grumpy? Yes
- Are your erections less strong? Yes
- Have you noticed a recent deterioration in your ability to play sports? Yes
- Are you falling asleep earlier after dinner? No
- Has there been a recent deterioration in your work performance? No
If a male over 50 answers yes to the first question or yes on any three other questions, the low testosterone syndrome should be considered in the differential diagnosis..
On physical examination, we noted that Mr. B was two inches shorter than his stated measured height at 20 years of age. Laboratory tests revealed normal thyroid function and prolactin. The patient's bioavailable testosterone at 50 ng/dl was low (normal 70-300 ng/dl), and he had a LH in the normal range. Mr. B was started on intramuscular injections of testosterone enanthate 200 mg every two weeks with improvement in energy and libido.
The Low Testosterone Syndrome
As is shown in Figure 1, nearly half of healthy males over 50 years of age have bioavailable (weakly bound) testosterone levels less than those seen in normal young males.(2) The FDA has estimated that 4 to 5 million men have hypogonadism with only about 300,000 men receiving treatment.
Figure 1.
Testosterone values decline less rapidly as sex hormone binding globulin (SHBG) levels increase with age. In our analysis of the New Mexico Process Study, we found, using longitudinal data, that there is a decline in total testosterone of 100 mg/dl/decade.(3) This has subsequently been confirmed by three other studies.(4),(5),(6) Bioavailable testosterone measures the free testosterone and that bound to albumin which is tissue available. It does not measure the testosterone bound to SHBG which is not available to tissues. Total testosterone is a poor measure of hypogonadism in older men. Free testosterone assays done by many commercial labs utilize the analog method. This does not measure free testosterone.(7)
The decline in testosterone occurs without the expected rise in luteinizing hormone, suggesting that it is due predominantly to a failure of the hypothalamic-pituitary unit (secondary hypogonadism) rather than testicular failure (primary hypogonadism) (Fig. 2). In the old-old, there is a tendency for the LH levels to rise, and true primary hypogonadism is seen in this group.
Figure 2.
Epidemiological studies have suggested the following effects may be associated with decline in testosterone:
- Decreased libido (enthusiasm for sex, sexual thoughts, etc.)(8)
- Decreased muscle mass (unpublished data by Baumgartner from the New Mexico Process Study)
- Decreased memory (unpublished data from St. Louis University)
- Osteopenia (highly controversial and difficult to tease out from age effects)
- Increased cardiovascular disease (reviewed by Barrett-Connor at the 1996 International Congress of Endocrinology)
There have not been a large number of international studies with testosterone in older persons and many of them lack adequate controls. Studies worth noting are:
- Three studies have shown increased strength(9),(10),(11) and others increased muscle.(12),(13)
- A number of studies have demonstrated improved visual spatial cognition and verbal fluency.(14),(15)
- Studies have shown increased bone and lean body mass.
(16),(17) - One study found decreased levels of leptin (the fat hormone.(11)
The major side effect of testosterone therapy is an increased hematocrit. When the hematocrit reaches greater than 55%, testosterone needs to be discontinued or the patient needs to be venesected! Hematocrit should be followed every three months. Other side effects include:
- gynecomastia (testosterone is aromatized to estrogen)
- water retention leading to hypertension or congestive heart failure
- possible accelerated growth of prostatic cancer (digital rectal examination and Prostate Specific Antigen need to be done every six months)
- sleep apnea (data is not good for this)
Available studies suggest that in older persons enlargement of benign prostatic hypertrophy is not produced by testosterone. Also, in this group, testosterone either has no effect or mild beneficial effects on cholesterol.(18)
Methods of Testosterone Administration
Testosterone can be administrated intramuscularly. Usually 200 mg of testosterone enanthate or cypionate is given every two weeks. Patients can be taught to self-inject at home.
Two testosterone patches are available. Testoderm® is placed on the shaved scrotum, while Androderm® is placed directly on the skin. Androderm® has a high rate of skin allergies (~ 30%). Both of these approaches are substantially more expensive than the injections.
Androgel is a gel that is applied daily.(19) It has a low incidence of skin irritation. It has had a high acceptability among men in the United States and accounts for over half of the new prescriptions.
In Canada and Europe, testosterone undecenoate (Organon) is an oral form of testosterone that is absorbed through the lymphatics and thus does not have to first pass through the liver and is less potentially hepatotoxic than the other orally available forms of testosterone.
Finally, intramuscular implantation of testosterone pellets represents a depot delivery system.
Conclusion
The potential of testosterone therapy of the male meno(viro)pause is outlined in Figure 3 and, hopefully, will be confirmed by on-going double-blind placebo studies.
Figure 3.
