Ultra-low dose estradiol plus dydrogesterone: a role in prevention of the development and progression of atherosclerosis

Abstract

Active development of the "anti-aging medicine", attempts to slow down biological (including vascular) aging led to the creation of new pharmaceuticals including menopausal hormone therapy. The vascular wall protective mechanism of the hormones is not completely clear, but it was shown that natural estrogens are able to control the condition of the vascular wall, prevent platelet adhesion, control a range of metabolic and trophic and energy processes in the endothelium of the vascular wall, producing antithrombogenic factors, namely their inhibition contributes to the development of atherosclerosis. It is known that standard and low-dose estrogen may restore the impaired antithrombogenic potential of the vascular wall, provided its initial reduction does not exceed 20%. The issue of the role and possibilities of correction of the antithrombogenic activity of the vascular wall with ultra-low dose estradiol remained unresolved. As a "clinical model" for the study of this issue, we formed 2 groups of patients: in the study group patients received ultra-low dose estradiol plus dydrogesterone, subjects from the control group received beta-alanine. Three-year follow-up showed a decrease in antithrombogenic activity of the vascular wall in control subjects after 2 and 3 years of follow-up according to the M.V. Baluda's test versus subjects treated with ultra-low dose estrogen plus dydrogesterone. The decrease of the relative risk of reduction of the antithrombogenic activity of the vascular wall with the use of ultra-low dose estrogen plus dydrogesterone during the first two years was 2.3 times, and during the 3 years of follow-up — 3.8 times versus control. Thus, prescribing only ultra-low dose estradiol plus dydrogesterone for patients with normal antithrombogenic activity of the vessel wall at baseline reliably lowers the risk of long-term reduction of antithrombogenic potential of the vascular wall.

Keywords

vascular aging / menopausal hormone therapy / antithrombogenic activity of the vascular wall / dydrogesterone / beta-alanin / atherosclerosis / anti-aging medicine / ultra-low dose

References

[1] Potter B. Menopause. P. Care. 2018;4:625–641.

[2] Potter B. Menopause // P. Care. 2018, No. 4. P. 625–641.

[3] Kryukov EV, Panevin TS. Antitrombogenic vascular wall activity in women with climacteric myocardiodystrophy while menopause. Bulletin of Pirogov National Medical and Surgical Center. 2020;15(2):67–70. (In Russ.)

[4] Крюков Е.В., Паневин Т.С. Антитромбогенная активность сосудистой стенки в период пери- и постменопаузы у женщин с климактерической миокардиодистрофией // Вестник национального медико-хирургического центра им Н.И. Пирогова. 2020. Т. 15, № 2. С. 67–70.

[5] Tapilskaya NI, Glushakov RI. Principally, my friends, may brains not to get old. Potential of menopausal hormone therapy in brain aging prevention. StatusPraesens. Gynecology, obstetrics, infertility. 2019;(4):74–78. (In Russ.)

[6] Тапильская Н.И., Глушаков Р.И. Главное, ребята, мозгом не стареть. Возможности менопаузальной гормональной терапии в профилактике старения головного мозга // StatusPraesens. Гинекология, акушерство, бесплодный брак. 2019. № 4. С. 74–78.

[7] Chester RC, Kling DM, Manson DI. What the Women's Health Initiative has taught us about menopausal hormone therapy. Clin Cardiol. 2018;41(2):247–252. doi: https://doi.org/10.1002/clc.22891

[8] Chester R.C., Kling D.M., Manson D.I. What the Women's Health Initiative has taught us about menopausal hormone therapy // Clin Cardiol. 2018. Vol. 41, No. 2. P. 247–252. doi: https://doi.org/10.1002/clc.22891

[9] Piróg M Jach R, Kacalska-Janssen O. Differential effect of the ultra-low dose and standard estrogen plus dydrogesterone therapy on thrombin generation and fibrinolysis in postmenopausal women. Acta Obstet Gynecol Scand. 2017;96(12):1438–1445.

[10] Piróg M. Jach R., Kacalska-Janssen O. Differential effect of the ultra-low dose and standard estrogen plus dydrogesterone therapy on thrombin generation and fibrinolysis in postmenopausal women // Acta Obstet Gynecol Scand. 2017. Vol. 96, No. 12. P. 1438–1445.

[11] Pinkerton JV, James AH. Management of Menopausal Symptoms for Women Who Are at High Risk of Thrombosis. Clin Obstet Gynecol. 2018;61(2):260–268. doi: https://doi.org/10.1097/GRF.0000000000000358

[12] Pinkerton J.V., James A.H. Management of Menopausal Symptoms for Women Who Are at High Risk of Thrombosis // Clin Obstet Gynecol. 2018. Vol. 61, No. 2. P. 260–268. doi: https://doi.org/10.1097/GRF.0000000000000358

[13] Godo S, Shimokawa H. Endothelial functions Arterioscler Thromb. Vasc Biol. 2017;(37):108–114.

[14] Godo S., Shimokawa H. Endothelial functions Arterioscler Thromb // Vasc Biol. 2017, No. 37. P. 108–114.

[15] Kryukov EV, Panevin TS, Popova LV. Aging of hemostasis. Clinical Medicine. 2020;98(1):9–12. (In Russ.)

[16] Крюков Е.В., Паневин Т.С., Попова Л.В. Возрастные изменения системы гемостаза // Клиническая медицина. 2020. Т. 98, № 1. C. 9–12.

[17] Konukoglu D, Uzun H. Endothelial Dysfunction and Hypertension Adv Exp Med Biol. 2017;(956):511–540.

[18] Konukoglu D., Uzun H. Endothelial Dysfunction and Hypertension // Adv Exp Med Biol. 2017, No. 956. P. 511–540.

[19] Baluda VP, Baluda MV, Deyanov II, et al. Physiology of hemostasis: study guide. Moscow, 1995. (In Russ.)

[20] Балуда В.П., Балуда М.В., Деянов И.И., и др. Физиология системы гемостаза: учеб. пособие. М., 1995. 245 с.

[21] Panevina AS, et al. Alterations of proinflamatory cytokines and antitrombogenic vascular wall activity in case of menopausal hormone therapy use. Clinical medicine. 2018;96(11):1029–1033. (In Russ.)

[22] Паневина А.С., и др. Изменение профиля провоспалительных цитокинов и антитромбогенной активности стенки сосудов под влиянием менопаузальной гормональной терапии // Клиническая медицина. 2018. Т. 96, № 11. С. 1029–1033.

[23] Dinger J, Bardenheuer K, Heinemann K. Drospirenone plus estradiol and the risk of serious cardiovascular events in postmenopausal women. Climacteric. 2016;19(4):349–356.

[24] Dinger J., Bardenheuer K., Heinemann K. Drospirenone plus estradiol and the risk of serious cardiovascular events in postmenopausal women // Climacteric. 2016. Vol. 19, No. 4. P. 349–356.

[25] Ivanova OY, Tugarinova MS, Maltseva NV, Timofeenko AI. Clinical case of pregnancy complicated by cardiomyopathy. StatusPraesens. Gynecology, obstetrics, infertility. 2020;(2/3)[65/67]:143–145. (In Russ.)

[26] Иванова О.Ю., Тугаринова М.С., Мальцева Н.В., Тимофеенко А.И. Клинический случай беременности, осложненной кардиомиопатией // Status Praesens. Гинекология, акушерство, бесплодный брак. 2020. № 2/3 [65/67]. C. 143–145.

[27] Maisch B, Volker R. Cardiomyopathies: classification, diagnosis, and treatment. Heart Fail Clin. 2012;8(1):53–78.

[28] Maisch B., Volker R. Cardiomyopathies: classification, diagnosis, and treatment // Heart Fail Clin. 2012. Vol. 8, No. 1. P. 53–78.

[29] Yarmolinskaya MI, Makletsova SA, Ipastova ID. Comdined estrogen and gestogen contraceptives and thrombosis: view of actualist. StatusPraesens. Gynecology, obstetrics, infertility. 2017;38(2):69–78. (In Russ.)

[30] Ярмолинская М.И., Маклецова С.А., Ипастова И.Д. Комбинированные эстроген-гестагенные контрацептивы и тромбозы: взгляд реалиста // StatusPraesens. Гинекология, акушерство, бесплодный брак. 2017. Т. 38, № 2. С. 69–78.

RIGHTS & PERMISSIONS

Kryukov E.V., Popova L.V., Vasiliev S.V., Panevin T.S., Panevina A.S., Stromskaya U.A., Samoilova N.V., Makarov O.E.