Megestrol Acetate Has Limited Benefit for Anorexia-Cachexia Syndrome

Article

The female hormone megestrol acetate (MA) improves appetite and is associated with slight weight gain in patients with cancer, AIDS, and other underlying pathology, but comes with significant adverse events.

The female hormone megestrol acetate (MA) improves appetite and is associated with slight weight gain in patients with cancer, AIDS, and other underlying pathology, concluded an intervention review conducted by the Cochrane Pain, Palliative and Supportive Care Group, but comes with significant adverse events1
   
The FDA initially approved MA, a synthetic derivative of progesterone, in the 1950s as a contraceptive agent. However, weight gain was a common side effect, and the contraceptive drug eventually was discontinued. The known orexigenic effects of MA led to the approval of the drug in 1993 for the treatment of anorexia, cachexia, and significant unexplained weight loss in patients with AIDS. It has since been used to help ameliorate these symptoms in patients with other illnesses, such as cancer, although the mechanism of action is unknown.
   
For this review, the researchers included studies that assessed MA compared with placebo or other drug treatments in patients with anorexia-cachexia syndrome related to cancer, AIDS, or another underlying pathology. They identified 35 trials-different from those used in a previous review2-that included 3,963 patients in those focusing on effectiveness and 3,180 patients in those addressing safety.1
   
The results of a meta-analysis showed that compared with placebo, MA improves appetite and has a small effect on weight gain in patients with AIDS, cancer, and other underlying conditions. However, the use of MA had no benefit when compared with other drugs. The optimal dose of MA is unknown, but assessment of different doses of MA indicated that higher doses had greater association with weight gain than lower doses. Patients with cancer or AIDS who were given MA had a marginal improvement in quality of life compared with placebo. When compared with other drugs, however, there was no noted improvement in quality of life among either patient group.
   
MA is associated with significant adverse effects. In the 35 trials included in this review, more than 40 adverse effects were identified. Edema, thromboembolism or thromboembolic phenomena, and death occurred more often in patients treated with MA, making the side-effect profile a significant consideration when prescribing the drug.
   
In clinical practice, these findings mean that about 1 in 4 patients who receive MA will have an increased appetite, about 1 in 12 patients will gain weight, and about 1 in 23 will die. The safety data for MA, especially long-term use of MA, remain limited.

Pertinent Points:
- Megestrol acetate (MA) helps improve appetite and has a small effect on weight gain in patients with anorexia-cachexia syndrome.
- Overall, the use of MA does not improve quality of life.
- Compared with placebo and other drugs, MA is associated with more adverse effects.
 

References:

1. Ruiz Garcia V, Lopez-Briz E, Sanchis RC, et al. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2013;3:CD004310. doi: 10.1002/14651858.CD004310.pub3.
2. Berenstein G, Ortiz Z. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2005;2:CD004310. doi: 10.1002/14651858.CD004310.pub2.

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