Population pharmacokinetic/pharmacodynamic evaluation of low-dose drospirenone with 17β-estradiol in postmenopausal women with moderate to severe vasomotor symptoms

Author(s):  
Gabriele Sutter ◽  
Thomas Schmelter ◽  
Kerstin Gude ◽  
Matthias Schaefers ◽  
Christoph Gerlinger ◽  
...  
2018 ◽  
Vol 132 (1) ◽  
pp. 161-170 ◽  
Author(s):  
Rogerio A. Lobo ◽  
David F. Archer ◽  
Risa Kagan ◽  
Andrew M. Kaunitz ◽  
Ginger D. Constantine ◽  
...  

Author(s):  
James A. Simon ◽  
Andrew M. Kaunitz ◽  
Robin Kroll ◽  
Shelli Graham ◽  
Brian Bernick ◽  
...  

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S N Tolstov ◽  
I A Salov ◽  
A P Rebrov

Abstract Introduction This is the first pilot study to assess the functional state of the vascular wall in postmenopausal women on the background of ultra low-dose menopausal hormone therapy (MHT). Purpose To evaluate the protective effects on endothelial function of ultra-low-dose MHT 0.5 mg of 17β-estradiol (E2) and 0.25 mg of drospirenone (DRSP) in postmenopausal women. Methods The study included 115 previously examined postmenopausal women. Group 1 (n=25) included patients who started receiving MGT with DRSP during the menopausal transition; in the 2nd group (n=31), women who started receiving MGT with DRSP in the early postmenopausal period. Women of the 1st and 2nd groups made the transition to a combination of 0.5 mg E2/0.25 mg DRSP. The control group (n=59) of women not taking MGT. The duration of therapy is 1.0 (0.9; 1.2) years. The age of women was 56.8±1.6 years, 57.1±2.8 years and 57.3±1.7 years (p>0.05). Endothelium-dependent vasodilation (EDV) of the brachial artery, levels of endothelin-1 (ET-1), metabolites of nitric oxide (NO), asymmetric dimethylarginine (ADMA), von Willebrand factor antigen (vWF: Ag) in plasma were evaluated. Results In the control group EDV 8.6±5.1% of the original and 7.4±4.5% by the end of the study (p=0.08); in women of the 1st group 12.5±3.8% and 12.2±4.4; in women of the 2nd group11.1±8.5% and 10.5±0.2% (p=0.07 between women of the 1st and 2nd groups by the end of the study). The level of NO metabolites in women of the 1st group 43.4 (28.6; 45.9) at baseline and 40.7 (34.4; 41.5) μmol/l by the end of the study, in women of the 2nd group 38.8 (36.5; 44.9) and 35.2 (32.8; 38.9) μmol/l (p=0.04 between the women of the 1st and 2nd groups). In the control group 34.6 (30.4; 38.2) and 27.8 (24.5; 34.9) μmol/l (p<0.001 for women of the 1st and 2nd groups). In women of the 1st group a significant increase in ET-1 was detected from 1.02±0.26 initially to 1.18±0.24 fMol/ml by the end of the study; levels of vWF:Ag with 0.839 (0.695; 0.940) and 0.900 (0.782; 0.925) U/ml. The level of ADMA did not change significantly 0.43±0.10 and 0.45±0.10 μmol/L. In women of the 2nd group a significant increase ET-1 was detected from 1.08±0.42 to 1.29±0.59 fMol ml; vWF:Ag from 0.841 (0.718; 0.960) to 0.829 (0.811; 0.984) U/ml and ADMA from 0.43±0.10 to 0.48±0.15 μmol/l (p>0.05). In the the control group a significant increase in the level of ET-1 was observed from 1.40±0.43 to 1.74±0.34 fMol/ml by the end of the study; vWF levels:Ag 0.860 (0.743; 0.941) and 0.960 (0.850; 1.025) U/ml, ADMA 0.48±0.16 and 0.60±0.18 μmol/l (p<0.01 compared with women of the 1st and 2nd groups). Conclusions Revealed protective effects on endothelial function of ultra low-dose MHT in postmenopausal women. Early and prolonged MHT has an additional positive effect on the functional state of the vascular wall. Acknowledgement/Funding None


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