Abstract
Women with nocturia are more sensitive to desmopressin, a synthetic arginine vasopressin (AVP) analogue, with significant antidiuretic responses to desmopressin orally disintegrating tablet (ODT) 25 μg, compared with men who require 58 μg to achieve similar responses. In children the current desmopressin dose recommendation to treat primary nocturnal enuresis (PNE) is the same for boys and girls. This post hoc analysis of data from a randomised, doubleblind single-dose study of 84 children with PNE aged 6 - 12 years explored gender differences in sensitivity to desmopressin in children. Following water loading to suppress endogenous AVP, placebo or desmopres-sin 30, 60, 120, 240, 360 or 480 μg was administered when urinary production reached >0.13 mL/min/kg. The endpoints of urinary osmolality and duration of urinary-concentrating action (DOA) (above three thresholds: 125, 200 and 400 mOsm/kg) were analysed to compare efficacy in boys and girls, in each treatment group. The DOA and urinary osmolality were similar in both genders in the desmopressin 120 - 480 μg groups. Boys receiving desmopressin ODT 30 - 60 μg tended to increased urinary osmolality and experienced 1 - 2 hours longer DOA than girls. The same pattern of higher values in boys compared with girls was seen for all measures of urinary osmolality. Conclusion: In a limited sample of pre-pubertal children the antidiuretic response to desmopressin was largely similar between genders, in contrast to findings in adults.
Highlights
The concept of a gender difference in renal sensitivity to desmopressin has been supported by several studies in adult patients with nocturia
Based on descriptive statistics, this post hoc analysis found no clear difference between the genders in either duration or magnitude of desmopressin antidiuretic action in most dose groups
The desmopressin ED50 values for reduction in nocturnal urine volume estimated for adults were derived in patients with nocturia who had not been water-loaded and this study reports urine osmolality and duration of urinary-concentrating action (DOA) in water-loaded children following desmopressin administration
Summary
The concept of a gender difference in renal sensitivity to desmopressin has been supported by several studies in adult patients with nocturia. Post hoc analyses by gender demonstrated a significantly greater decrease in nocturnal urine volume in women at the lower doses of 10 μg and 25 μg compared with men (ED50 16.1 μg vs 43.2 μg), suggesting significantly higher sensitivity to desmopressin in women [4]. A recent meta-analysis of data from nocturia trials with desmopressin demonstrated a durable gender difference in sensitivity to desmopressin in favour of females. Greater efficacy was observed with desmopressin ODT 25 μg in females compared with males, which endured over the long term (one year or more) [6]. Two physiological mechanisms behind this gender difference in renal sensitivity to desmopressin have been suggested, including the genetic X-inactivation mechanism and the OPEN ACCESS
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