LOS ANGELES — Despite growing interest in the use of androgens among postmenopausal women, there are few clinical data about their efficacy for this population of patients, Carol Havens, M.D., said at the annual meeting of the California Academy of Family Physicians.
“My patients are coming into me all the time with stuff off the Internet or out of magazines such as Ladies' Home Journal and People, promoting the use of androgens for impotence in women, mostly for libido,” said Dr. Havens, a family physician who is director of clinical education for Kaiser Permanente's Northern California region. “There is lots of information out there in the lay press but very little in the medical press. Very few trials have actually been done. There's very little we actually know.”
The theory behind androgen replacement is that androgen deficiency causes clinical symptoms such as dysphoria, fatigue, and low sex drive. However, androgen levels in women are highly variable, and they're not clearly linked to such symptoms, she said.
“Contrary to popular belief, androgen levels don't suddenly go down at the time of menopause like estrogen levels do. They actually decrease gradually,” explained Dr. Havens, who also chairs the California Medical Association's Committee on CME. “The androgen level of a woman at the age of 50 is about half that of a woman at the age of 25.”
Estratest is the only androgen-replacement preparation approved for women in the United States. It contains 0.625/1.25-mg esterified estrogen plus 1.25/2.5-mg methyltestosterone.
Transdermal androgen patches are not appropriately dosed for women. In fact, it's difficult to accurately measure testosterone in women because most of the assays were developed to test men.
“The available assays lack the sensitivity to be able to accurately measure the lower testosterone levels that are found in women,” Dr. Havens said. “The other problem is that testosterone is highly bound to sex hormone-binding globulin and albumin. In women, 1% or less of total testosterone is actually available as free testosterone, which is the biologically active one. The free testosterone index is the test that's been widely advertised as being the most reliable, but your lab may not be able to give you an accurate level of free testosterone.”
Key indications for androgen replacement in postmenopausal women with clinical symptoms of androgen deficiency include adequate estrogen status and having free testosterone levels at or below the lowest quartile for reproductive age. “The objective of replacement is to restore their testosterone levels to that of the mid-range for that of healthy young women,” she said.
The effect of androgens on coronary heart disease is unknown, but oral androgens decrease HDL cholesterol (by up to 20%), LDL cholesterol, and triglycerides. “So they could have a significant effect on lipids,” she noted.
Transdermal androgens, on the other hand, do not appear to affect lipid levels.
Estrogenic effects of androgens may include vaginal bleeding, endometrial hyperplasia, and the stimulation of breast epithelium, but there are no reports of direct links to breast or endometrial cancer.
Androgens appear to increase bone mineral density, but they have an unclear effect on fracture rate, muscle performance, and physical function. They also do not decrease visceral fat. “This is the opposite of what happens in men,” Dr. Havens said. “Androgens in women may actually increase visceral fat.”
As for the effect on sexuality, testosterone levels are not well correlated with libido in women, “although women who take testosterone do report an increase in libido and sexual activity,” she noted. “The increase in sexual activity is pretty limited.”
Other effects may include increases in erythropoiesis, hostility, hirsutism, and acne. (The transdermal form does not seem to affect hirsutism or acne.)
Pregnant and lactating women should not take androgens, nor should those with breast or endometrial cancer or polycythemia. Relative contraindications include moderate to severe acne, moderate to severe hirsutism, androgenic alopecia, and severe insulin resistance.
If you start postmenopausal women on androgens, ask them about their symptoms, and do follow-up lipid tests, liver function tests, and hemoglobin tests, Dr. Havens said.