Rational Pharmacotherapy in Cardiology

Advanced search


Full Text:


Aim. To evaluate the nature of the dysfunction of the endothelium in postmenopausal women with climacteric syndrome, peculiarities of its changes during long-term use of a fixed low-dose combination of 17β-estradiol 1 mg/drosperidone 2 mg daily (Е2 1 mg/DRSP 2 mg). Material and methods. A non-randomized, uncontrolled study included 162 women in early postmenopausal period with climacteric syndrome. Patients were divided into 2 groups. Patients of the main group (n=84) received menopausal hormone therapy (MHT) with the fixed combination of Е2 1 mg/DRSP 2 mg. Patients of the control group (n=78) did not receive MHT. The duration of the follow-up was 5.2 years. The endothelium dependent vasodilation (EDVD) of brachial artery was assessed by reactive hyperemia. Endothelial dysfunction (ED) markers - plasma levels of endothelin-1 (ET-1), NO metabolites, asymmetric dimethylarginine (ADMA) and von Willebrand factor antigen (vWF:Ag) - were studied by a highly sensitive quantitative enzyme-linked immunosorbent assay. Results. The examined postmenopausal women with climacteric syndrome had significant increase in the concentration of ET-1 up to 1.0 (0.7-1.3) fmol/ml, increased levels of vWF:Ag up to 0.835 (0.760-0.990) U/ml and reduction in the level of the total content of stable metabolites of nitric oxide (NOx) to 39.2 (35.4-43.7) μmol/l. Disorders of EDVD of the brachial artery were observed in 50 (59.5%) women of the main group and in 45 (57.6%) women of the control group (p=0.7). The relationships between EDVD parameters and levels of ADMA (r=-0.31, p=0.029) and NOx (r=0.31, p=0.002) were revealed. In patients with impaired EDVD, a significant decrease in the level of stable NO metabolites and an increase in ADMA and ET-1 levels were detected. A significant increase in the EDVD of the brachial artery was observed throughout the follow-up period. Besides an increase in NO metabolites level, and decrease in the ET-1 and ADMA levels were found by the 12th month of MHT. Conclusions. Disorders of endothelial function were found in the majority of women in early postmenopausal period, the most marked changes were in patients with impaired vasoreactivity of brachial artery. Favorable changes in vascular endothelium function were observed during long-term MHT with the fixed combination of Е2 1 mg/DRSP 2 mg.

About the Authors

S. N. Tolstov
Saratov State Medical University named after V. I. Razumovsky
Russian Federation

Sergey N. Tolstov - MD, PhD, Candidate for a Doctor's Degree, Chair of Therapy 

B.Kazachya ul. 112, Saratov, 410012

I. A. Salov
Saratov State Medical University named after V. I. Razumovsky
Russian Federation

Igor A. Salov - MD, PhD, Head of Chair of Obstetrics and Gynecology 

B.Kazachya ul. 112,Saratov, 410012

A. P. Rebrov
Saratov State Medical University named after V. I. Razumovsky
Russian Federation

Andrey P. Rebrov - MD, PhD, Head of Chair of Therapy 

B.Kazachya ul. 112,Saratov, 410012


1. Shabrov A.V., Apresjan A.G., Dobkes A.L., et al. Current Methods of Endothelial Dysfunction Assessment and their Possible Use in the Practical Medicine. Rational Pharmacotherapy in Cardiology. 2016;12(6):733-42. (In Russ.) [Шабров А.В., Апресян А.Г., Добкес А.Л. и др. Современные методы оценки эндотелиальной дисфункции и возможности их применения в практической медицине. Рациональная Фармакотерапия в Кардиологии. 2016;12(6):733-42].

2. Anichkov D.A., Shostak N.A. Menopause and cardiovascular risk. Rational Pharmacotherapy in Cardiology 2005;1:37-42. (In Russ.) [Аничков Д.А., Шостак Н.А. Менопауза и сердечно-сосудистый риск. Рациональная Фармакотерапия в Кардиологии 2005;1:37-42].

3. Szmuilowicz E.D., Manson J.E., Rossouw J.E., et al. Vasomotor symptoms and cardiovascular events in postmenopausal women. Menopause. 2011;18(6):603-10.

4. de Villiers T.J., Pines A., Panay N., et al. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric. 2013;16(3):316-37.

5. Salov I.A., Tolstov S.N., Mychka V.B., et al. Menopausal metabolic syndrome and hormone replacement therapy. Akusherstvo i Ginekologija. 2011;2:24-31. (In Russ.) [Салов И.А., Толстов С.Н., Мычка В.Б. и др. Менопаузальный метаболический синдром и заместительная гормональная терапия. Акушерство и Гинекология. 2011;2:24-31].

6. Arnal J.F., Fontaine C., Billon-GaleЂs A., et al. Estrogen receptors and endothelium. Arterioscler Thromb Vasc Biol. 2010;30:1506-12.

7. Cagnacci A., Tarquini R., Perfetto F., et al. Endothelin-1 and nitric oxide levels are related to cardiovascular risk factors but are not modified by estradiol replacement in healthy postmenopausal women. A cross-sectional and a randomized cross-over study. Maturitas. 2003;44(2):117-24.

8. Baber R.J., Panay N., Fenton A. and the IMS Writing Group NS 2016. IMS Recommendations on women’s midlife health and menopause hormone therapy. Climacteric. 2016;19(2):109-50.

9. Verhoeven M.O., Hemelaar M., Van der Mooren M.J., et al. Oral, more than transdermal, oestrogen therapy lowers asymmetric dimethylarginine in healthy postmenopausal women: a randomized, placebocontrolled study. J Intern Med. 2006;259(2):199-208.

10. Maffei S., Mercuri A., Zucchelli G.C., Vassalle C. Estrogen therapy effects on different vasoactive factors in recent postmenopausal healthy women. Int J Cardiol. 2006;107(2):194-9.

11. Silvestri A., Gambacciani M., Vitale C., et al. Different effect of hormone replacement therapy, DHEAS and tibolone on endothelial function in postmenopausal women with increased cardiovascular risk. Maturitas. 2005;50(4):305-11.

12. Gambacciani M., Rosano G., Cappagli B., et al. Clinical and metabolic effects of drospirenone-estradiol in menopausal women: a prospective study. Climacteric. 2011;14(1):18-24. 13. Simoncini T., Fu X.D., Caruso A., et al. Drospirenone increases endothelial nitric oxide synthesis via a combined action on progesterone and mineralocorticoid receptors. Hum Reprod. 2007;22(8):232534.


For citations:

Tolstov S.N., Salov I.A., Rebrov A.P. ENDOTHELIAL DYSFUNCTIONS AND THEIR CORRECTION IN WOMEN WITH EARLY POSTMENOPAUSE. Rational Pharmacotherapy in Cardiology. 2017;13(2):191-196. (In Russ.)

Views: 507

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)