OBJECTIVE: To study the effect of medroxyprogesterone acetate (MPA) on autonomic cardiac control in respiratory insufficiency in postmenopausal women. DESIGN: A prospective, single-blind study. SUBJECTS: Eighteen postmenopausal women with respiratory insufficiency and eight asymptomatic postmenopausal women with nocturnal hypoxaemia as controls. METHODS: Oral MPA treatment was given at 30 mg twice daily for 2 weeks. All-night polysomnography including a two-channel electroencephalogram, an electro-oculogram, an electromyogram, an electrocardiogram, arterial oxyhaemoglobin saturation, maximum end-tidal CO2 partial pressure, a ballistocardiogram and breathing movements were recorded at baseline and at the end of MPA treatment. Heart rate variability (HRV) was calculated in time and frequency domains during various sleep stages on and off MPA, and the results were correlated to respiratory variables. RESULTS: At baseline, patients had higher heart rate and lower HRV than controls, suggesting increased cardiac sympathetic output. MPA increased HRV in patients, but not in controls. End-tidal CO2 partial pressure decreased, and respiratory rate increased during treatment in both groups. CONCLUSIONS: HRV is compromised in women with respiratory insufficiency. Peroral MPA increases their HRV to levels comparable with those in controls. This suggests an improvement in vagal cardiac control beneficial to cardiovascular health.