EFFECTS OF HYDROXYUREA ADMINISTRATION ON THE BODY-WEIGHT, BODY-COMPOSITION AND EXERCISE PERFORMANCE OF PATIENTS WITH SICKLE-CELL-ANEMIA

1. As an ancillary study carried out during the recently completed Mul ticenter Study of Hydroxyurea, we examined the effect of hydroxyurea o n the body weight, body composition and exercise capacity of adult pat ients with sickle-cell anaemia. 2. The subjects received either hydrox yurea (six males and four females) or placebo (eight males and six fem ales). Data for each subject were generated during four separate 24 h admissions to the General Clinical Research Center. These admissions o ccurred at baseline and then at 6, 12 and 18 months after the start of study drug (hydroxyurea or placebo) administration. During each admis sion, body composition was measured by using a dual X-ray absorptiomet er, and exercise testing was performed by cycle ergometry. Anaerobic p erformance was assessed according to a 'Wingate' protocol (20 s at max imal intensity against a cycling resistance of 7.5% body weight). Aero bic performance was examined using a steady state submaximal exercise protocol (10 min cycling time). 3. At baseline, no significant differe nce in any parameter was found between the hydroxyurea- and placebo-tr eated groups. At 18 months, the hydroxyurea-treated subjects exhibited an average weight gain of 3.16 kg. The mean weight gain in the placeb o-treated subjects was 1.82 kg. Body composition analysis showed that the additional weight in both groups involved both lean and fat body m ass components. In anaerobic performance, the subjects given hydroxyur ea showed an increase in peak muscle power of 104.9 W. The placebo gro up also showed an increase, but theirs was a more modest gain of 57.7 W. The most marked improvement in anaerobic performance was observed i n the hydroxyurea-treated men (P < 0.05). In aerobic performance, the hydroxyurea-treated subjects exhibited a decrease in peak heart rate r esponse to a standardized workload of 15.2 beats/min, as compared with a decrease of only 4.3 beats/min in the placebo-treated patients. 4. Taken together, the overall weight gain, combined with increases in bo th anaerobic muscular performance and aerobic cardiovascular efficienc y, provides objective data to support the subjective impression that h ydroxyurea administration produces an improvement in the physical capa city of patients with sickle-cell anaemia.