Менопаузальная гормональная терапия и риски сердечно-сосудистых заболеваний: современный взгляд

1. Менопаузальная гормонотерапия и сохранение здоровья женщин в зрелом возрасте (клинические рекомендации Минздрава России), 2015. / Menopauzalnaya gormonoterapiya i sohranenie zdorovya zhenshin v zrelom vozraste (klinicheskie rekomendacii Minzdrava Rossii), 2015. [in Russian]
2. Baber RJ, Panay N, Fenton A the IMS Writing Group. 2016 IMS Recommendations on women's midlife health and menopause hormone therapy. Climacteric 2016; 19 (2): 109–50.
3. Santen RJ, Allred DC, Ardoin SP et al. Endocrine Society. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab 2010; 95 (7 Suppl. 1): s1–s66. DOI: 10.1210/jc.2009-2509
4. Harlow SD, Gass M, Hall JE et al. STRAW+10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging. Climacteric 2012; 15 (2): 105–14. DOI: 10.3109/13697137.2011.650656
5. Harlow SD, Gass M, Hall JE et al. STRAW + 10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Fertil Steril 2012; 97 (4): 843–51. DOI: 10.1016/j.fertnstert.2012.01.128
6. Yoon PW, Bastian B, Anderson RN et al. Centers for Disease Control and Prevention (CDC). Potentially preventable deaths from the five leading causes of death – United States, 2008–2010. MMWR Morb Mortal Wkly Rep 2014; 63 (17): 369–74.
7. Кваша Е.А., Харькова Т.Л., Юмагузин В.В. Смертность от внешних причин в России за полвека. Демографическое обозрение. 2014; 1 (4): 68–95. / Kvasha E.A., Harkova T.L., Yumaguzin V.V. Smertnost ot vneshnih prichin v Rossii za polveka. Demograficheskoe obozrenie. 2014; 1 (4): 68–95. [in Russian]
8. Nicholson CJ, Sweeney M, Robson SC, Taggart MJ. Estrogenic vascular effects are diminished by chronological aging. Sci Rep 2017; 7 (1): 12153. DOI: 10.1038/s41598-017-12153-5
9. Masood DE, Roach EC, Beauregard KG, Khalil RA. Impact of sex hormone metabolism on the vascular effects of menopausal hormone therapy in cardiovascular disease. Curr Drug Metab 2010; 11 (8): 693–714.
10. Иловайская И.А. Кардиоваскулярные аспекты действия половых гормонов и их клиническое значение в постменопаузе. Гинекология. 2012; 14 (4): 68–71. / Ilovajskaya I.A. Kardiovaskulyarnye aspekty dejstviya polovyh gormonov i ih klinicheskoe znachenie v postmenopauze. Gynecology. 2012; 14 (4): 68–71. [in Russian]
11. Abdulnour J, Doucet E, Brochu M et al. The effect of the menopausal transition on body composition and cardiometabolic risk factors: a Montreal-Ottawa New Emerging Team group study. Menopause 2012; 19 (7): 760–7.
12. Davis SR, Castelo-Branco C, Chedraui P et al. Writing Group of the International Menopause Society for World Menopause Day 2012. Understanding weight gain at menopause. Climacteric 2012; 15 (5): 419–29. DOI: 10.3109/13697137.2012.707385
13. Cho GJ, Lee JH, Park HT et al. Postmenopausal status according to years since menopause as an independent risk factor for the metabolic syndrome. Menopause 2008; 15 (3): 524–9.
14. Cagnacci A, Cannoletta M, Palma F et al. Menopausal symptoms and risk factors for cardiovascular disease in postmenopause. Climacteric 2012; 15 (2): 157–62.
15. Szmuilowicz ED, Manson JE, Rossouw JE et al. Vasomotor symptoms and cardiovascular events in postmenopausal women. Menopause 2011; 18 (6): 603–10.
16. Gast GC, Pop VJ, Samsioe GN et al. Vasomotor menopausal symptoms are associated with increased risk of coronary heart disease. Menopause 2011; 18 (2): 146–51.
17. Pines A. Vasomotor symptoms and cardiovascular disease risk. Climacteric 2011; 14 (5): 535–6. DOI: 10.3109/13697137.2011.599058
18. Schierbeck LL, Rejnmark L, Tofteng CL et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: Randomised trial. BMJ 2012; 345: 6409.
19. Hodis HN, Mack WJ, Shoupe D et al. Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal hormone timing hypothesis. Menopause 2015; 22 (4): 391–401. DOI: 10.1097/GME.0000000000000343
20. Hodis HN, Mack WJ. The "window of opportunity": the reduction of coronary heart disease and total mortality with menopausal therapies is age- and time-dependent. Brain Res 2011; 1379: 244–52. DOI: 10.1016/j.brainres.2010.10.076
21. Rocca WA, Grossardt BR, Shuster LT. Oophorectomy, estrogen, and dementia: a 2014 update. Mol Cell Endocrinol 2014; 389 (1–2): 7–12. DOI: 10.1016/j.mce.2014.01.020
22. Canonico M, Oger E, Plu-Bureau G et al. Estrogen and Thromboembolism Risk (ESTHER) Study Group. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 2007; 115 (7): 840–5.
23. Smith NL, Blondon M, Wiggins KL et al. Lower risk of cardiovascular events in postmenopausal women taking oral estradiol compared with oral conjugated equine estrogens. JAMA Intern Med 2014; 174 (1): 25–31.
24. Blondon M, van Hylckama Vlieg A, Wiggins KL et al. Differential associations of oral estradiol and conjugated equine estrogen with hemostatic biomarkers. J Thromb Haemost 2014; 12 (6): 879–86. DOI: 10.1111/jth.12560
25. Schindler AE. The "newer" progestogens and postmenopausal hormone therapy (HRT). J Steroid Biochem Mol Biol 2014; 142: 48–51. DOI: 10.1016/j.jsbmb.2013.12.003
26. Dinger J, Bardenheuer K, Heinemann K. Drospirenone plus estradiol and the risk of serious cardiovascular events in postmenopausal women. Climacteric 2016; 19 (4): 349–56. DOI: 10.1080/13697137.2016.1183624
27. De Franciscis P, Mainini G, Labriola D et al. Low-dose estrogen and drospirenone combination: effects on metabolism and endothelial function in postmenopausal women with metabolic syndrome. Clin Exp Obstet Gynecol 2013; 40 (2): 233–5.
28. Schindler AE, Campagnoli C, Druckmann R et al. Classification and pharmacology of progestins. Maturitas 2008; 61 (1–2): 171–80.
29. Caprio M, Zennaro MC, Fève B et al. Potential role of progestogens in the control of adipose tissue and salt sensitivity via interaction with the mineralocorticoid receptor. Climacteric 2008; 11 (3): 258–64. DOI: 10.1080/13697130802162608
30. Ronconi V, Turchi F, Appolloni G et al. Aldosterone, mineralocorticoid receptor and the metabolic syndrome: role of the mineralocorticoid receptor antagonists. Curr Vasc Pharmacol 2012; 10 (2): 238–46.
31. Archer DF, Thorneycroft IH, Foegh M et al. Long-term safety of drospirenone-estradiol for hormone therapy: a randomized, double-blind, multicenter trial. Menopause 2005; 12: 716–27.
32. Bell RJ, Davison SL, Papalia MA et al. Endogenous androgen levels and cardiovascular risk profile in women across the adult life span. Menopause 2007; 14 (4): 630–8.
33. Kim C, Harlow SD, Zheng H et al. Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and estrone over the menopausal transition. Womens Midlife Health 2017; 3. DOI: 10.1186/s40695-017-0028-4
34. Simon JA, Davis SR, Althof SE et al. Sexual well-being after menopause: An International Menopause Society White Paper. Climacteric 2018: 1–13. DOI: 10.1080/13697137.2018.1482647
35. Wåhlin-Jacobsen S, Kristensen E, Pedersen AT et al. Androgens and Psychosocial Factors Related to Sexual Dysfunctions in Premenopausal Women: 2016 ISSM Female Sexual Dysfunction Prize. J Sex Med 2017; 14 (3): 366–79. DOI: 10.1016/j.jsxm.2016.12.237
36. Parish SJ, Hahn SR. Hypoactive Sexual Desire Disorder: A Review of Epidemiology, Biopsychology, Diagnosis, and Treatment. Sex Med Rev 2016; 4 (2): 103–20. DOI: 10.1016/j.sxmr.2015.11.009
37. Jiménez MC, Sun Q, Schürks M et al. Low dehydroepiandrosterone sulfate is associated with increased risk of ischemic stroke among women. Stroke 2013; 44 (7): 1784–9. DOI: 10.1161/STROKEAHA.111.000485
38. Rexrode KM, Manson JE, Lee IM et al. Sex hormone levels and risk of cardiovascular events in postmenopausal women. Circulation 2003; 108: 1688–93.
39. Christodoulakos G, Lambrinoudaki I, Panoulis C et al. Serum androgen levels and insulin resistance in postmenopausal women: association with hormone therapy, tibolone and raloxifene. Maturitas 2005; 50 (4): 321–30.
40. Weinberg ME, Manson JE, Buring JE et al. Low sex hormone-binding globulin is associated with the metabolic syndrome in postmenopausal women. Metabolism 2006; 55: 1473–80.
41. Sutton-Tyrrell K, Wildman RP, Matthews KA et al SWAN Investigators. Sex hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the Study of Women Across the Nation (SWAN). Circulation 2005; 111: 1242–9.
42. Brand JS, van der Schouw YT. Testosterone, SHBG and cardiovascular health in postmenopausal women. Int J Impot Res 2010; 22 (2): 91–104. DOI: 10.1038/ijir.2009.64
43. Davis SR, Robinson PJ, Moufarege A, Bell RJ. The contribution of SHBG to the variation in HOMA-IR is not dependent on endogenous oestrogen or androgen levels in postmenopausal women. Clin Endocrinol (Oxf) 2012; 77 (4): 541–7. DOI: 10.1111/j.1365-2265.2011.04301.x
44. Janse F, Tanahatoe SJ, Eijkemans MJ, Fauser BC. Testosterone concentrations, using different assays, in different types of ovarian insufficiency: a systematic review and meta-analysis. Hum Reprod Update 2012; 18 (4): 405–19. DOI: 10.1093/humupd/dms013
45. Zang H, Davis SR. Androgen replacement therapy in androgen-deficient women with hypopituitarism. Drugs 2008; 68 (15): 2085–93.
46. Wierman ME, Arlt W, Basson R et al. Androgen therapy in women: a reappraisal: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2014; 99 (10): 3489–510. DOI: 10.1210/jc.2014-2260
47. Schmidt J, Brännström M, Landin-Wilhelmsen K, Dahlgren E. Reproductive hormone levels and anthropometry in postmenopausal women with polycystic ovary syndrome (PCOS): a 21-year follow-up study of women diagnosed with PCOS around 50 years ago and their age-matched controls. J Clin Endocrinol Metab 2011; 96 (7): 2178–85. DOI: 10.1210/jc.2010-2959
48. Markopoulos MC, Rizos D, Valsamakis G et al. Hyperandrogenism in women with polycystic ovary syndrome persists after menopause. J Clin Endocrinol Metab 2011; 96 (3): 623–31. DOI: 10.1210/jc.2010-0130

________________________________________________

1. Menopauzalnaya gormonoterapiya i sohranenie zdorovya zhenshin v zrelom vozraste (klinicheskie rekomendacii Minzdrava Rossii), 2015. [in Russian]
2. Baber RJ, Panay N, Fenton A the IMS Writing Group. 2016 IMS Recommendations on women's midlife health and menopause hormone therapy. Climacteric 2016; 19 (2): 109–50.
3. Santen RJ, Allred DC, Ardoin SP et al. Endocrine Society. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab 2010; 95 (7 Suppl. 1): s1–s66. DOI: 10.1210/jc.2009-2509
4. Harlow SD, Gass M, Hall JE et al. STRAW+10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging. Climacteric 2012; 15 (2): 105–14. DOI: 10.3109/13697137.2011.650656
5. Harlow SD, Gass M, Hall JE et al. STRAW + 10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Fertil Steril 2012; 97 (4): 843–51. DOI: 10.1016/j.fertnstert.2012.01.128
6. Yoon PW, Bastian B, Anderson RN et al. Centers for Disease Control and Prevention (CDC). Potentially preventable deaths from the five leading causes of death – United States, 2008–2010. MMWR Morb Mortal Wkly Rep 2014; 63 (17): 369–74.
7. Kvasha E.A., Harkova T.L., Yumaguzin V.V. Smertnost ot vneshnih prichin v Rossii za polveka. Demograficheskoe obozrenie. 2014; 1 (4): 68–95. [in Russian]
8. Nicholson CJ, Sweeney M, Robson SC, Taggart MJ. Estrogenic vascular effects are diminished by chronological aging. Sci Rep 2017; 7 (1): 12153. DOI: 10.1038/s41598-017-12153-5
9. Masood DE, Roach EC, Beauregard KG, Khalil RA. Impact of sex hormone metabolism on the vascular effects of menopausal hormone therapy in cardiovascular disease. Curr Drug Metab 2010; 11 (8): 693–714.
10. Ilovajskaya I.A. Kardiovaskulyarnye aspekty dejstviya polovyh gormonov i ih klinicheskoe znachenie v postmenopauze. Gynecology. 2012; 14 (4): 68–71. [in Russian]
11. Abdulnour J, Doucet E, Brochu M et al. The effect of the menopausal transition on body composition and cardiometabolic risk factors: a Montreal-Ottawa New Emerging Team group study. Menopause 2012; 19 (7): 760–7.
12. Davis SR, Castelo-Branco C, Chedraui P et al. Writing Group of the International Menopause Society for World Menopause Day 2012. Understanding weight gain at menopause. Climacteric 2012; 15 (5): 419–29. DOI: 10.3109/13697137.2012.707385
13. Cho GJ, Lee JH, Park HT et al. Postmenopausal status according to years since menopause as an independent risk factor for the metabolic syndrome. Menopause 2008; 15 (3): 524–9.
14. Cagnacci A, Cannoletta M, Palma F et al. Menopausal symptoms and risk factors for cardiovascular disease in postmenopause. Climacteric 2012; 15 (2): 157–62.
15. Szmuilowicz ED, Manson JE, Rossouw JE et al. Vasomotor symptoms and cardiovascular events in postmenopausal women. Menopause 2011; 18 (6): 603–10.
16. Gast GC, Pop VJ, Samsioe GN et al. Vasomotor menopausal symptoms are associated with increased risk of coronary heart disease. Menopause 2011; 18 (2): 146–51.
17. Pines A. Vasomotor symptoms and cardiovascular disease risk. Climacteric 2011; 14 (5): 535–6. DOI: 10.3109/13697137.2011.599058
18. Schierbeck LL, Rejnmark L, Tofteng CL et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: Randomised trial. BMJ 2012; 345: 6409.
19. Hodis HN, Mack WJ, Shoupe D et al. Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal hormone timing hypothesis. Menopause 2015; 22 (4): 391–401. DOI: 10.1097/GME.0000000000000343
20. Hodis HN, Mack WJ. The "window of opportunity": the reduction of coronary heart disease and total mortality with menopausal therapies is age- and time-dependent. Brain Res 2011; 1379: 244–52. DOI: 10.1016/j.brainres.2010.10.076
21. Rocca WA, Grossardt BR, Shuster LT. Oophorectomy, estrogen, and dementia: a 2014 update. Mol Cell Endocrinol 2014; 389 (1–2): 7–12. DOI: 10.1016/j.mce.2014.01.020
22. Canonico M, Oger E, Plu-Bureau G et al. Estrogen and Thromboembolism Risk (ESTHER) Study Group. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 2007; 115 (7): 840–5.
23. Smith NL, Blondon M, Wiggins KL et al. Lower risk of cardiovascular events in postmenopausal women taking oral estradiol compared with oral conjugated equine estrogens. JAMA Intern Med 2014; 174 (1): 25–31.
24. Blondon M, van Hylckama Vlieg A, Wiggins KL et al. Differential associations of oral estradiol and conjugated equine estrogen with hemostatic biomarkers. J Thromb Haemost 2014; 12 (6): 879–86. DOI: 10.1111/jth.12560
25. Schindler AE. The "newer" progestogens and postmenopausal hormone therapy (HRT). J Steroid Biochem Mol Biol 2014; 142: 48–51. DOI: 10.1016/j.jsbmb.2013.12.003
26. Dinger J, Bardenheuer K, Heinemann K. Drospirenone plus estradiol and the risk of serious cardiovascular events in postmenopausal women. Climacteric 2016; 19 (4): 349–56. DOI: 10.1080/13697137.2016.1183624
27. De Franciscis P, Mainini G, Labriola D et al. Low-dose estrogen and drospirenone combination: effects on metabolism and endothelial function in postmenopausal women with metabolic syndrome. Clin Exp Obstet Gynecol 2013; 40 (2): 233–5.
28. Schindler AE, Campagnoli C, Druckmann R et al. Classification and pharmacology of progestins. Maturitas 2008; 61 (1–2): 171–80.
29. Caprio M, Zennaro MC, Fève B et al. Potential role of progestogens in the control of adipose tissue and salt sensitivity via interaction with the mineralocorticoid receptor. Climacteric 2008; 11 (3): 258–64. DOI: 10.1080/13697130802162608
30. Ronconi V, Turchi F, Appolloni G et al. Aldosterone, mineralocorticoid receptor and the metabolic syndrome: role of the mineralocorticoid receptor antagonists. Curr Vasc Pharmacol 2012; 10 (2): 238–46.
31. Archer DF, Thorneycroft IH, Foegh M et al. Long-term safety of drospirenone-estradiol for hormone therapy: a randomized, double-blind, multicenter trial. Menopause 2005; 12: 716–27.
32. Bell RJ, Davison SL, Papalia MA et al. Endogenous androgen levels and cardiovascular risk profile in women across the adult life span. Menopause 2007; 14 (4): 630–8.
33. Kim C, Harlow SD, Zheng H et al. Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and estrone over the menopausal transition. Womens Midlife Health 2017; 3. DOI: 10.1186/s40695-017-0028-4
34. Simon JA, Davis SR, Althof SE et al. Sexual well-being after menopause: An International Menopause Society White Paper. Climacteric 2018: 1–13. DOI: 10.1080/13697137.2018.1482647
35. Wåhlin-Jacobsen S, Kristensen E, Pedersen AT et al. Androgens and Psychosocial Factors Related to Sexual Dysfunctions in Premenopausal Women: 2016 ISSM Female Sexual Dysfunction Prize. J Sex Med 2017; 14 (3): 366–79. DOI: 10.1016/j.jsxm.2016.12.237
36. Parish SJ, Hahn SR. Hypoactive Sexual Desire Disorder: A Review of Epidemiology, Biopsychology, Diagnosis, and Treatment. Sex Med Rev 2016; 4 (2): 103–20. DOI: 10.1016/j.sxmr.2015.11.009
37. Jiménez MC, Sun Q, Schürks M et al. Low dehydroepiandrosterone sulfate is associated with increased risk of ischemic stroke among women. Stroke 2013; 44 (7): 1784–9. DOI: 10.1161/STROKEAHA.111.000485
38. Rexrode KM, Manson JE, Lee IM et al. Sex hormone levels and risk of cardiovascular events in postmenopausal women. Circulation 2003; 108: 1688–93.
39. Christodoulakos G, Lambrinoudaki I, Panoulis C et al. Serum androgen levels and insulin resistance in postmenopausal women: association with hormone therapy, tibolone and raloxifene. Maturitas 2005; 50 (4): 321–30.
40. Weinberg ME, Manson JE, Buring JE et al. Low sex hormone-binding globulin is associated with the metabolic syndrome in postmenopausal women. Metabolism 2006; 55: 1473–80.
41. Sutton-Tyrrell K, Wildman RP, Matthews KA et al SWAN Investigators. Sex hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the Study of Women Across the Nation (SWAN). Circulation 2005; 111: 1242–9.
42. Brand JS, van der Schouw YT. Testosterone, SHBG and cardiovascular health in postmenopausal women. Int J Impot Res 2010; 22 (2): 91–104. DOI: 10.1038/ijir.2009.64
43. Davis SR, Robinson PJ, Moufarege A, Bell RJ. The contribution of SHBG to the variation in HOMA-IR is not dependent on endogenous oestrogen or androgen levels in postmenopausal women. Clin Endocrinol (Oxf) 2012; 77 (4): 541–7. DOI: 10.1111/j.1365-2265.2011.04301.x
44. Janse F, Tanahatoe SJ, Eijkemans MJ, Fauser BC. Testosterone concentrations, using different assays, in different types of ovarian insufficiency: a systematic review and meta-analysis. Hum Reprod Update 2012; 18 (4): 405–19. DOI: 10.1093/humupd/dms013
45. Zang H, Davis SR. Androgen replacement therapy in androgen-deficient women with hypopituitarism. Drugs 2008; 68 (15): 2085–93.
46. Wierman ME, Arlt W, Basson R et al. Androgen therapy in women: a reappraisal: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2014; 99 (10): 3489–510. DOI: 10.1210/jc.2014-2260
47. Schmidt J, Brännström M, Landin-Wilhelmsen K, Dahlgren E. Reproductive hormone levels and anthropometry in postmenopausal women with polycystic ovary syndrome (PCOS): a 21-year follow-up study of women diagnosed with PCOS around 50 years ago and their age-matched controls. J Clin Endocrinol Metab 2011; 96 (7): 2178–85. DOI: 10.1210/jc.2010-2959
48. Markopoulos MC, Rizos D, Valsamakis G et al. Hyperandrogenism in women with polycystic ovary syndrome persists after menopause. J Clin Endocrinol Metab 2011; 96 (3): 623–31. DOI: 10.1210/jc.2010-0130

И.А.Иловайская*

1. ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф.Владимирского». 129110, Россия, Москва, ул. Щепкина, д. 61/2;
2. ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И.Евдокимова» Минздрава России. 127473, Россия, Москва, ул. Делегатская, д. 20, стр.1
*irena.ilov@yandex.ru

________________________________________________

I.A.Ilovayskaya*

1. M.F.Vladimirskiy Moscow regional research clinical institute. 129110, Russian Federation, Moscow, ul. Shchepkina, d. 61/2;
2. A.I.Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health of the Russian Federation. 127473, Russian Federation, Moscow, ul. Delegatskaia, d. 20, str. 1
*irena.ilov@yandex.ru