The present study aimed to evaluate the effects of 2 mg drospirenone (DRSP) and 1 mg 17β-estradiol (E2) hormone therapy (HT) in combination with rehabilitation therapy for postmenopausal women with Meniere's disease (MD). The combined drug hormone treatment was denoted as DRSP/E2. A total of 65 postmenopausal female patients with MD and severe distress were enrolled in the present prospective study. A total of 31 women comprised the study group (group A), undergoing HT and rehabilitation therapy, whereas 34 women who opted for rehabilitation therapy alone comprised the control group (group B). Vestibular function and distress associated with MD were assessed by stabilometry and the Dizziness Handicap Inventory (DHI) questionnaire, respectively. The data were collected at baseline and during the 3- and 6-month follow-up visits. The areas of the stabilometric ellipses exhibited a higher reduction in group A compared with group B with regard to the baseline values at both follow-up assessments (P<0.001). At baseline, both groups exhibited severe self-perceived discomfort, with similar DHI scores of 72.3±3.7 (group A) and 70.6±3.9 (group B; P=0.07). At the 3-month follow-up, both groups underwent a gradual improvement, which was significantly higher in group A (47.5±3.7) compared with in group B (64.2±3.3; P<0.001). At the 6-month follow-up, the DHI scores were improved in group A (43.4±3.4) compared with in group B (58.5±3.1; P<0.001). Therefore, DRSP/E2 HT was effective in reducing the fluid overload, which is characteristic of MD. The findings of the present study demonstrated that integrated therapy based on the administration of DRSP/E2 HT and rehabilitation may be more effective compared with rehabilitation alone for the management of postmenopausal exacerbation of MD.