Weight loss in the elderly is associated with increased rates of infection, skin breakdown (pressure ulcers) and death. Weight loss of more than 4 percent is associated with increased mortality, and weight loss of more than 4 lb, 4 oz (2 kg) is associated with more functional disability. Megestrol acetate is a synthetic derivative of a naturally occurring progesterone agent that has been used in patients with cancer and those with acquired immunodeficiency syndrome (AIDS) to promote weight gain. Yeh and colleagues conducted this randomized controlled trial to determine the effects of megestrol acetate on weight gain in nursing home residents.
The study population included patients (women and men) who were at least 55 years of age and resided at one Veterans Administration nursing home. Inclusion criteria included a weight loss of at least 5 percent of the resident's usual body weight during the previous three-month period (acute weight loss). Alternate criteria included a body weight 20 percent below the ideal (chronic weight loss). Residents were also required to have a life expectancy of at least 24 weeks and a Karnofsky performance status of at least 40 percent. Exclusion criteria included serious intercurrent illness, poorly controlled hypertension or congestive heart failure. Residents whose weight loss was determined to be caused by depression or hyperthyroidism were also excluded.
Patients were randomized to receive an oral suspension of 20 mL of placebo or 800 mg of megestrol acetate daily for 12 weeks, given two hours after breakfast. At baseline, each resident had a medical history obtained and a physical examination performed, and underwent a variety of blood tests (including albumin, pre-albumin and a complete blood count with differential). Depression and levels of enjoyment and appetite were also assessed. Primary study end points included significant weight gain (defined as more than 4 lb [1.82 kg]) and improved appetite. Weight was measured every four weeks for the 12-week study period, plus 13 weeks after discontinuation of the study drug.
Of the 69 residents enrolled, 51 completed the study and were included in the analysis (26 in the megestrol acetate group and 25 in the placebo group). At the end of the 12-week period during which the participants received the study drug, those in the megestrol acetate group showed a mean weight gain of 2 lb, 3 oz ± 2 lb, 2 oz (1.05 ± 1.0 kg) compared with 2 lb ± 1 lb, 5 oz (0.91 ± 0.68 kg) in the placebo group. Nine residents (34.6 percent) in the megestrol acetate group and seven residents (28 percent) in the placebo group gained at least 4 lb. At week 20, the difference in weight gain between the two groups was statistically significant and remained significant at the last measurement at week 25. At this measurement, residents in the megestrol acetate group showed a mean weight gain of 6 lb, 5 oz ± 3 lb, 1 oz (2.95 kg ± 1.41 kg); 13 of the 26 in this group gained at least 4 lb. In the placebo group, residents showed a mean weight loss of 1 lb ± 1 lb, 9 oz (0.45 kg ± 0.86 kg); only five of the 25 in this group gained at least 4 lb. The weight gain itself was analyzed and was found to include lean body mass, not just fluid. No increase in body weight occurred in 38 percent of patients in the megestrol acetate group. This group of patients was characterized by the presence of polypharmacy (more than 10 medications), more advanced dementia, more concomitant medical problems and a more wasted condition. Those residents taking megestrol acetate had a significant improvement in appetite and enjoyment. No difference in depression scores between the treatment and placebo groups was observed. Adverse events were similar in each group and none was clearly related to treatment with megestrol acetate.
The authors conclude that megestrol acetate was associated with prolonged weight gain after discontinuation of the medication. Because the patients who did not respond to megestrol acetate were those in a more debilitated condition, it may be that earlier use of megestrol acetate may be more beneficial. Megestrol acetate at a dosage of 800 mg per day improves appetite, enjoyment and weight in elderly patients with weight loss.
editor's note: Studies of varying dosages of megestrol acetate are needed, as are studies that include more women (who represent a larger proportion of residents of non-Veterans Administration nursing homes than seen in this single study site). The authors' comment about the lack of efficacy observed in patients who were more ill or more demented is important to note. Although the etiology of weight loss should be sought, steps should also be taken early in the evaluation process to slow or reverse weight loss while an evaluation is underway. The consequences of a seemingly “small” weight loss (4.4 lb, in one study) may be quite severe, and although pharmacologic intervention for weight loss should not be considered first-line treatment, neither should it be avoided or ignored.—g.b.h.