Aim: To conduct a systematic review and meta-analysis of all randomized placebo-controlled trials (RCTs) that evaluated the efficacy and safety of desmopressin versus placebo among females with nocturia.

Research protocol
We performed this study following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (14) and the Cochrane Handbook of Systematic Reviews of Interventions. Ethical approval was not needed. The study protocol was not retrospectively recorded in the International Prospective Register of Systematic Reviews (PROSPERO). 

Literature search
We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Web of Science, and Google Scholar databases from inception until November 15, 2022. The specific search strategy included: (desmopressin OR DDAVP OR minirin OR stimate) AND (nocturnal polyuria OR nocturnal enuresis OR nocturia OR overactive bladder) AND (woman OR women OR female OR females) AND (randomized OR randomised OR randomly OR trial). We also screened the reference lists of included RCTs to broaden the literature search.

Eligibility criteria
We included studies that met the following PICOS evidence-based criteria: (i) Patients: females with nocturia; (ii) Intervention: desmopressin irrespective of the dose; (iii) Comparator: placebo; (iv) Outcomes: any of our prespecified endpoints, namely mean change in the number of nocturnal voids, mean change in the duration of the first sleep period, 33% responder rate, and rate of overall adverse events, and (v) Study designs: RCTs. The exclusion criteria included: (i) patients with conditions other than nocturia, (ii) drugs other than desmopressin, and (iii) non-RCT studies including animal reports, reviews, and follow-up studies of RCTs.

Results: Nine RCTs with 2852 patients (desmopressin=1110, placebo=1742) were analyzed. The overall risk of bias was low. Compared with placebo, desmopressin significantly reduced the mean number of nocturnal voids (MD=-0.51, 95% CI [-0.70, -0.31], p<0.001), prolonged the duration of the first sleep period (MD=69.06 min, 95% CI [46.54, 91.59], p<0.001), and increased the 33% responder rate (RR=1.30, 95% CI [1.13, 1.50], p<0.001). 
Subgroup analyses according to desmopressin dose (≤50μg and >50μg) showed similar significant differences compared with placebo. Meta-regression showed less improvement in the number of nocturnal voids with the increased age and BMI. There was no significant difference between both groups regarding the rate of overall adverse events (RR=1.11, 95% [0.94, 1.32], p=0.22).

Subgroup analyses according to desmopressin dose (≤50μg and >50μg) showed similar significant differences compared with placebo. Meta-regression showed less improvement in the number of nocturnal voids with the increased age and BMI. There was no significant difference between both groups regarding the rate of overall adverse events (RR=1.11, 95% [0.94, 1.32], p=0.22).

Conclusion: Desmopressin was safe and effective in improving nocturia among females. Higher dose of desmopressin (>50μg) correlated with better efficacy. Age and BMI impacted the mean number of nocturnal voids.