Gender difference in antidiuretic response to desmopressin

Juul KV, Klein BM, Sandstrom R, Erichsen L, Norgaard JP. Gender difference in antidiuretic response to desmopressin. Am J Physiol Renal Physiol 300: F1116-F1122, 2011. First published March 2, 2011; doi:10.1152/ajprenal.00741.2010.-Increased age and female gender are well-known risk factors for the development of desmopressin-induced hyponatremia. However, little focus has been on exploring gender differences in the antidiuretic response to desmopressin. Based on an exploratory analysis from three clinical trials, we report a significant gender difference in the effects of desmopressin on nocturnal urine volume that could not be explained by pharmacokinetic differences. Mean desmopressin concentration profiles were tested for covariates, and age and gender were not statistically significant and only weight was significant for log(C-max) (P = 0.0183) and borderline significant for log(AUC) (P = 0.0571). The decrease in nocturnal urine volume in nocturia patients treated with desmopressin over 28 days was significantly larger for women at the lower desmopressin melt doses of 10 and 25 mu g than for men. The ED50 for men was modeled to be 43.2 mu g and 16.1 mu g for women, with the ED50 men/women estimated to be 2.7 (1.3-8.1 95% CI), corresponding to significantly higher sensitivity to desmopressin in women. An increasing incidence of hyponatremia with increasing dose was found, and at the highest dose level of 100 mu g decreases in serum sodium were approximately twofold greater in women over 50 yr of age than in men. A new dose recommendation stratified by gender is suggested in the treatment of nocturia: for men, 50- to 100-mu g melt is an efficacious and safe dose, while for women a dose of 25 mu g melt is recommended as efficacious with no observed incidences of hyponatremia. Areas for further research are proposed to uncover pathophysiological mechanism(s) behind these gender differences.