Medroxyprogesterone Acetate Attenuates and Tibolone Prevents the Development of Monocrotaline‐Induced Pulmonary Hypertension.

Abstract

Pulmonary hypertension (PH) is predominantly a female disease, yet little is known regarding the effects of female hormones in PH, and oral contraceptives and hormone replacement therapy have been suggested as potential risk factors for PH. Recently we have shown that progesterone attenuates the development of monocrotaline (MCT)-induced PH in ovariectomized (OVX) rats. Therefore, we investigated the effects of medroxyprogesterone acetate (MPA, a synthetic progestin) and tibolone (TIB, a combined steroidal progestogenic and estrogenic compound) on the development of MCT-induced PH. OVX rats were randomly administered either saline (CONT, n=7), MCT (60mg/kg i.p., n=10), MCT+MPA (10mg/kg/day, s.c.; MPA group; n=8) or MCT+TIB (2mg/kg/day, p.o.; TIB group; n=8). After 35 days the right ventricular peak systolic pressure (RVPSP) was assessed. MCT significantly elevated RVPSP (58.1±2.6 vs. 28.6±1.1 mmHg, MCT vs. CONT) and increased right ventricle/left ventricle+septum ratio (RV/LV+S: 0.411±0.0210 vs. 0.247±0.007, MCT vs. CONT; p<0.001). MPA attenuated the development of PH and tibolone prevented MCT from inducing PH (RVPSP: 40.1±3.7 and 33.0±3.5 mmHg; RV/LV+S: 0.327±0.023 and 0.260±0.015; MPA and TIB, respectively). MCT induced a 30% mortality, with no mortality in MPA or TIB groups. This study suggests that progestins and combined progestin/estrogen compounds may have protective effects in PH and warrants further investigation of the progestin estrogen interactions in pulmonary hypertension. (Supported by AHA Award #0455778U)