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Objectives: A prospective, open-labeled study to assess the antihypertensive effect of monotherapy with rilmenidine and its impact on quality of life (QoL), as well as on biochemical parameters in perimenopausal women with essential hypertension., Design and Methods: Fifty-five perimenopausal women with mild to moderate essential hypertension (mean age 51.4+/-2.4 years) were enrolled. At baseline and after 12-week monotherapy with rilmenidine, we assessed: systolic (SBP) and diastolic (DBP) blood pressure (BP), heart rate (HR), fasting glucose, serum creatinine and total cholesterol levels. QoL was also assessed at baseline and at 12 weeks by two standardized questionnaires: the Short Form - 36 (SF-36) and the Subjective Symptoms Assessment Profile (SSAP). Statistical analysis was performed using Student's t-test to compare changes in BP, QoL and biochemical parameters during therapy with rilmenidine., Results: After 12 weeks of therapy, there was a significant decrease in BP and HR. Normalization of BP was observed in 46 (84%) women. Rilmenidine did not influence serum creatinine, fasting glucose and lipid profile. Treatment was very well tolerated by the patients and no side-effects were noted. Both the SF-36 and the SSAP demonstrated improvement in general QoL. We observed a significant improvement in all SF-36 subscales. In the SSAP, a similar significant improvement was found, except dizziness subscale. Improvement in QoL was not related to reduction of BP., Conclusions: Monotherapy with rilmenidine is safe and effective in BP treatment and significantly improves QoL in perimenopausal women with essential hypertension.