Testosterone replacement in men with age-related hormone deficiency

Findings by SBU Alert

Version: 1

Technology and target group

The production of male sex hormones (androgens) in the body declines with advancing age. Reduced levels may have negative effects on health. Therefore, androgen replacement has been tested on a smaller scale by administering testosterone, the most important of the male sex hormones. Potential health benefits include an increase in bone density, increased muscle mass, greater libido, and enhanced well-being. Testosterone can be administered in three principal ways: intramuscular injections, patches, and tablets. Depending on the treatment criteria used, the potential target group would be estimated to range from 5 percent to somewhat over 30 percent of all males above 60 years of age. This would mean treating between 45 000 and 200 000 males per year.

Patient benefit

Several double-blind controlled studies have shown that treatment can have positive effects on libido and mood. The effects on bone density have been investigated in nine smaller, uncontrolled studies. Several of these studies reported a positive effect, while others found no difference between the control group and the study group. Testosterone injections have been shown to yield a 3 percent to 5 percent increase in muscle mass and an increase in muscle strength. In summary, testosterone therapy for age-related hormone deficiency appears to have some effect. However, there is uncertainty about the clinical relevance of this finding and its importance for the patients quality of life. No studies have assessed the effects on sexual function. The effects of long-term treatment are unknown. In the short term, treatment has few side effects. There is no documentation on long-term side effects. A theoretical, but unconfirmed, increase in the risk for benign prostatic hyperplasia and prostate cancer may exist.

Ethical aspects

Because of the uncertain benefits of androgen replacement therapy in older men, it is important for the patient to be adequately informed about the uncertainty of the treatments benefits and its side effects.

Economic aspects

No health economic assessments have been identified. The cost effectiveness of treatment is difficult to determine since it is unclear what effects treatment might have on quality of life or what its long-term effects are. If 10 percent of males over 60 years of age would be candidates for treatment, using the least expensive treatment alternative, the annual cost to the health services for drugs alone would be approximately 80 million SEK. Additional costs would include the cost for physician visits and the cost for needles and syringes (injection treatment).

Scientific evidence

Currently there is poor* scientific documentation on the benefits and risks associated with androgen replacement therapy in older males. There is no* scientific documentation on the long-term effects nor on the cost effectiveness. In Sweden testosterone replacement is not approved for treatment of age-related hormone deficiency. Hence, it is available for use only within the framework of scientific studies. A prioritization-related concern is where the health services should draw the line for intervention, and if interventions should cover conditions that are associated with natural aging. Such issues should be considered as topics for health policy discussions.

*This assessment by SBU Alert uses a 4-point scale to grade the quality and evidence of the scientific documentation. The grades indicate: (1) good, (2) moderate, (3) poor, or (4) no scientific evidence on the subject.

This summary is based on a report prepared at SBU in collaboration with Prof. Aleksander Giwercman, Malmö University Hospital. It has been reviewed by Assoc. Prof. Leif Abramsson, Norrland University Hospital, Umeå.

The complete report is available only in Swedish.

Alert is a joint effort by the Swedish Council on Technology Assessment in Health Care (SBU), the Medical Products Agency, the National Board of Health and Welfare, and the Federation of Swedish County Councils.

References

1. Bhasin S, Bagatell CJ, Bremner WJ, Plymate SR, Tenover JL, Korenman SG et al. Therapeutic perspective. Issues in testosterone replacement in older men. J Clin Endocrinol Metab 1998;83(10):3435-48.
2. Hajjar RR, Kaiser RE, Morley JE. Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. J Clin Endocrinol Metab 1997;82(11):3793-6.
3. Kenny AM, Prestwood KM, Gruman CA, Marcello KM, Raisz LG. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 2001;56(5):M266-72.
4. Ly LP, Jimenez M, Zhuang TN, Celermajer DS, Conway AJ, Handelsman DJ. A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. J Clin Endocrinol Metab 2001;86(9):4078-88.
5. Morley JE, Perry HM 3rd. Androgen deficiency in aging men. Med Clin North Am 1999;83(5):1279-89, vii. Review.
6. Tenover JL. Male hormone replacement therapy including "andropause". Endocrinol Metab Clin North Am 1998;27(4):969-87, x. Review.
7. Tenover JL. Experience with testosterone replacement in the elderly. Mayo Clin Proc 2000;75 Suppl:S77-81; discussion S82. Review.
8. Vermeulen A. Environment, human reproduction, menopause, and andropause. Environ Health Perspect 1993;101 Suppl 2:91-100. Review.
9. Vermeulen A. Andropause. Maturitas 2000;34(1):5-15. Review.