Low-Dose Testosterone May Be Helpful in Severe AN Cases

Low doses of testosterone may be beneficial for women with severe cases of anorexia nervosa (AN), according to researchers at Massachusetts General Hospital and Harvard Medical School, Boston (J Clin Endocrinol Metab 2005;1428). This small controlled study showed low doses of testosterone were effective for treating severe bone loss and for improving depression in AN patients.

Previous studies have demonstrated that bone formation increases in postmenopausal women receiving testosterone plus estrogen, compared to women receiving supplemental estrogen alone. The authors believe their study is the first to test the effects of testosterone, without estrogen supplementation, on bone formation.

The patient group included 33 women with AN and relative testosterone deficiency, who were randomized to receive transdermal testosterone (Intrinsa®), in dosages of 150 mcg or 300 mcg/day, or placebo, for 3 weeks. Serum testosterone levels were then measured by column chromatography. At baseline, there were no differences between patients who received placebo and those who were given testosterone in age, weight, body mass index, percent of ideal body weight, duration of amenorrhea, free or total testosterone markers of bone metabolism, bone density, severity of depression, or special cognition.

After three weeks, serum total and free testosterone levels increased significantly in the patients who had the testosterone patches. About half of the patients randomized to receive 150 mcg/day and 67% of those who received 300 mcg/day of testosterone experienced an increase in free testosterone to levels that were higher than those reported as the upper limit of the normal premenopausal woman. Estradiol, serum hormone-binding globulin, dehydroepiandosterone sulfate, and IGF-1 did not change. Lower-weight patients who received testosterone had a smaller increase in serum free testosterone than did higher-weight subjects. Weight did not change during the three-week study in any of the three groups.

Bone changes

Levels of the bone marker C-terminal propeptide of type 1 collagen (PICP) were higher during testosterone administration than with placebo. Changes in PICP correlated with changes in free testosterone over 3 weeks. Other bone markers, serum osteocalcin, bone-specific alkaline phosphatase and serum N-telopeptide levels, did not change significantly over the 3 weeks of treatment in the group receiving testosterone, compared with placebo.

Improved mood and spatial orientation

Depressed patients receiving testosterone had improved mood, compared with patients receiving the placebo. The mean Beck Depression Inventory score at baseline improved from the severely depressed range into the moderately depressed range after 3 weeks of testosterone. There was no change in use of antidepressants among any of the patients during the 3-week trial. After 3 weeks, those treated with testosterone also did better on the Mental Rotations Test than did those receiving placebo. This test evaluates a person’s ability to judge spatial changes in rotated figures.

Side effects

The testosterone patches were generally well tolerated. Three subjects in the testosterone groups and one in the placebo group developed mild skin irritation at the patch site, but they chose not to drop out of the study. There was no increase in hirsutism. One subject randomized to the testosterone treatment, who had a history of affective disorder, reported increased depression and anxiety after 10 days of treatment; this improved when a benzodiazepine was given. Others reported episodes of mild fatigue and vertigo.

Limits of the study

The authors did point out several limitations of their study. First, it involved a small group followed for only 3 weeks. Also, because only one of three bone formation markers responded during the study, they feel that further studies are needed to determine whether testosterone increases bone formation and bone density in persons with severe AN.