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Gender difference in antidiuretic response to desmopressin.
Am J Physiol Renal Physiol. 2011 May; 300(5):F1116-22.AJ

Abstract

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 μg than for men. The ED(50) for men was modeled to be 43.2 μg and 16.1 μg for women, with the ED(50) 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 μg 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-μg melt is an efficacious and safe dose, while for women a dose of 25 μg 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.

Authors+Show Affiliations

Ferring Pharmaceuticals, Copenhagen S, Denmark. kvj@ferring.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase I
Clinical Trial, Phase III
Comparative Study
Controlled Clinical Trial
Journal Article

Language

eng

PubMed ID

21367921

Citation

Juul, Kristian Vinter, et al. "Gender Difference in Antidiuretic Response to Desmopressin." American Journal of Physiology. Renal Physiology, vol. 300, no. 5, 2011, pp. F1116-22.
Juul KV, Klein BM, Sandström R, et al. Gender difference in antidiuretic response to desmopressin. Am J Physiol Renal Physiol. 2011;300(5):F1116-22.
Juul, K. V., Klein, B. M., Sandström, R., Erichsen, L., & Nørgaard, J. P. (2011). Gender difference in antidiuretic response to desmopressin. American Journal of Physiology. Renal Physiology, 300(5), F1116-22. https://doi.org/10.1152/ajprenal.00741.2010
Juul KV, et al. Gender Difference in Antidiuretic Response to Desmopressin. Am J Physiol Renal Physiol. 2011;300(5):F1116-22. PubMed PMID: 21367921.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gender difference in antidiuretic response to desmopressin. AU - Juul,Kristian Vinter, AU - Klein,Bjarke Mirner, AU - Sandström,Rikard, AU - Erichsen,Lars, AU - Nørgaard,Jens Peter, Y1 - 2011/03/02/ PY - 2011/3/4/entrez PY - 2011/3/4/pubmed PY - 2011/7/2/medline SP - F1116 EP - 22 JF - American journal of physiology. Renal physiology JO - Am J Physiol Renal Physiol VL - 300 IS - 5 N2 - 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 μg than for men. The ED(50) for men was modeled to be 43.2 μg and 16.1 μg for women, with the ED(50) 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 μg 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-μg melt is an efficacious and safe dose, while for women a dose of 25 μg 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. SN - 1522-1466 UR - https://www.unboundmedicine.com/medline/citation/21367921/Gender_difference_in_antidiuretic_response_to_desmopressin_ L2 - https://journals.physiology.org/doi/10.1152/ajprenal.00741.2010?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -