The Endocrine Society is sounding a strong word of caution about androgen therapy with a new clinical practice guideline that recommends against diagnosing and treating androgen deficiency in women.
The guideline cites the “lack of a well-defined clinical syndrome” and the “lack of normative data on total or free testosterone levels across the life span” as reasons why a diagnosis should not be made.
On the issue of treatment, the document acknowledges “evidence for short-term efficacy of testosterone in selected populations, such as surgically menopausal women,” but says that inadequate indications and insufficient evidence of long-term safety means that the “generalized use of testosterone in women” cannot be recommended (J. Clin. Endocrinol. Metab. 2006;91;3697–710).
“Based on [our literature review], we felt that at this time, we could not, as a committee and a society, recommend either for making the diagnosis or for treatment,” said Dr. Margaret E. Wierman, the endocrinologist who chaired the seven-member task force that developed the evidence-based guidelines.
“The quality of the literature was just not up to a standard [needed] to make a global recommendation,” said Dr. Wierman, chief of endocrinology at the Veterans Affairs Medical Center in Denver and professor of medicine, physiology, and biophysics at the University of Colorado, Denver. “The sort of hype that testosterone has been given is not yet based on a lot of scientific fact.”
Earlier this year, the Endocrine Society issued clinical practice guidelines on androgen deficiency in men, recommending against offering testosterone therapy to all older men with low testosterone levels. (See box.)
The new guideline on androgen deficiency in women has a tone and reach that differs from the less conservative “androgen deficiency” section in the American Association of Clinical Endocrinologists' recently updated menopause guidelines.
Dr. Wierman said she hopes that the new guideline—as well as a document to be released by the Endocrine Society in the next 18–24 months on problems with sex steroid assays for both men and women—will drive development of more sensitive and specific assays. “I think the assay issue will soon be improved,” she said.
Physicians must appreciate the fact that the findings on estrogen from the Women's Health Initiative had some impact on the task force, Dr. Wierman said.
“At this point, we felt that the Endocrine Society needs to act as the word of caution so we're not coming back 5 years from now and saying, 'Why weren't we cautious? Why didn't we push our colleagues across academia and research to do the studies to better understand [androgens], so that patients will benefit and won't be harmed?'” she said.
Dr. Steven Petak, president of the American Association of Clinical Endocrinologists, said his organization took a different approach last year in addressing the issue of androgen therapy when updating its menopause guidelines.
“We also were quite cautious, and we agree that long-term safety issues need to be clarified,” he said. “But we still went on and stated that there are some criteria for diagnosis, and we gave some recommendations” for the use of androgen.
The Endocrine Society's guidelines “don't do much for patients whose therapies are being considered now,” said Dr. Petak of the Texas Institute for Reproduction and Endocrinology. “The Endocrine Society's recommendations for further basic and clinical research in the field are of prime importance and we agree wholeheartedly.”
Even With Men, Go Slow With Androgen
The Endocrine Society's earlier guideline on androgen deficiency in men advises physicians to offer testosterone therapy on an individual basis to older men with consistently low testosterone levels on more than one occasion and clinically significant symptoms of androgen deficiency.
The guideline advises against the use of androgen therapy in the general population because of a lack of consensus on the case definition and a lack of data on the public health impact of androgen deficiency.
To establish the diagnosis of androgen deficiency in men, a reliable assay should be used to measure the morning total testosterone level. This should be confirmed either by repeating the measurement of morning total testosterone or by measuring the free or bioavailable testosterone level (J. Clin. Endocrinol. Metab. 2006;91:1995–2010).
Testosterone therapy is appropriate in symptomatic men who have classic androgen deficiency syndromes and low testosterone levels, say the guidelines. It should be used to induce and maintain secondary sex characteristics and to improve sexual function, sense of well-being, muscle mass, strength, and bone mineral density.
Testosterone therapy is not appropriate in patients with metastatic prostate cancer, breast cancer, or a palpable prostate nodule or induration. Patients with a prostate-specific antigen (PSA) greater than 3 ng/mL without further urological evaluation are not candidates for testosterone therapy. Other contraindications include erythrocytosis and hyperviscosity. With a lack of randomized controlled trial data, there was no recommendation on treating men with prostate cancer who have been disease free for 2 years or more.