Menopausal hormone therapy: modern state of the problem

Prof. L.V. Zhuravlyova, T.A. Rogachova.

Kharkiv National Medical University.

The article contains a review of current international guidelines for conducting menopausal hormone therapy (MHT). The problem of inefficiency and risks of MHT associated with impaired metabolism of sex hormones in the elderly and in a number of common pathological conditions, especially in the metabolic syndrome, is discussed. Comparative analysis of the effectiveness and safety of oral and transdermal forms of MHT is carried out. Examination plan to identify indications and contraindications for MHT is presented. The benefits and risks of MHT for various age groups are discussed, as well as in the presence of certain concomitant diseases.

Key words: metabolism of sex hormones in the elderly, menopausal hormone therapy, metabolic


1. Hodis HN, Mack WJ, Henderson VW, et al. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med. 2016; 374: 1221-1231.
2. 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:e6409.
3. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, et al. Menopausal hormone therapy and health outcomes during the intervention and extended posts stopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013;310:1353-1368.
4. Bassuk SS, Manson JE. Menopausal hormone therapy and cardiovascular disease risk: utility of biomarkers and clinical factors for risk stratification. Clin Chem. 2014; 60: 68-77.
5. Wild RA, Wu C, Curb JD, et al. Coronary heart disease events in the Women’s Health Initiative hormone trials: effect modification by metabolic syndrome: a nested case-control study within the Women’s Health Initiative randomized clinical trials. Menopause. 2013; 20: 254-260.
6. Wolff EF, He Y, Black DM, et al. Self-reported menopausal symptoms, coronary artery calcification, and carotid intimamedia thickness in recently menopausal women screened for the Kronos early estrogen prevention study (KEEPS). FertilSteril. 2013; 99: 1385-1391.
7. Thurston RC, Chang Y, Barinas-Mitchell E, et al. Menopausal hot flashes and carotid intima media thickness among midlife women. Stroke. 2016; 47: 2910-2915.
8. Połać I, Borowiecka M, Wilamowska A, Nowak P. Coagulation and fibrinolytic parameters in women and the effects of hormone therapy; comparison of transdermal and oral administration. GynecolEndocrinol. 2013; 29: 165-168.
9. L’Hermite M. HRT optimization using transdermal estradiol plus micronized progesterone, a safer HRT. Climacteric. 2013; 16 (suppl 1):44-53.
10. Sweetland S, Beral V, Balkwill A, et al. Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study. J ThrombHaemost. 2012; 10: 2277-2286.
11. Shufelt CL, Merz CN, Prentice RL, et al. Hormone therapy dose, formulation, route of delivery, and risk of cardiovascular events in women: findings from the Women’s Health Initiative Observational Study. Menopause. 2014; 21: 260-266.
12. Renoux C, Dell’aniello S, Garbe E, Suissa S. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ. 2010;340:c2519.
13. Qureshi AI, Malik AA, Saeed O, Defillo A, Sherr GT, Suri MF. Hormone replacement therapy and the risk of subarachnoid hemorrhage in postmenopausal women. J Neurosurg. 2016:124:45-50.
14. Fournier A, Fabre A, Mesrine S, et al. Use of different postmenopausal hormone therapies and risk of histology and hormone receptor-defined invasive breast cancer. J ClinOncol. 2008;26:1260-1268.
15. Allen NE, Tsilidis KK, Key TJ, et al. Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition. Am J Epidemiol. 2010;172:1394-1403.
16. Stanczyk FZ, Hapgood JP, Winer S, Mishell DR Jr. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr Rev. 2013;34:171-208.
17. Stuenkel CA. Menopause hormone therapy and diabetes. Climacteric. 2017; 20: 11-21.
18. Sharifi M, Lewiecki EM. Conjugated estrogens combined with bazedoxifene: the first approved tissue selective estrogen complex therapy. Expert Rev ClinPharmacol. 2014; 7: 281-291.
19. Goodman NF, Cobin RH, Ginzburg SB, et al. AACE medical guidelines for clinical practice for diagnosis and treatment of menopause. EndocrPract. 2011; 17(suppl 6).
20. Baber RJ, 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): 109-150.
21.De Villiers TJ, Hall JE, Pinkerton JV, Cerdas Perez S, Rees M, Yang C, Pierroz DD. Revised Global Consensus Statement on Menopausal Hormone Therapy.Climacteric. 2016; 19:313-315.
22. Mychka VB, Tolstov SN, Prohorova JuV, Salov IA, Vertkin AA. Zhenshhina na ambulatornom prieme: chto dolzhen znat’ terapevt? Doktor.Ru. 2014;55,9: 67-75. Russian.
23. Ovsjannikova TV, Kulikov TV. Individual’nyj vybormenopauzal’noj gormonal’noj terapii. Ginekologija. 2016;4:59-62. Russian.
24. Ilovajskaja IA, Vojtashevskij KV. Molodil’nye jabloki XXI stoletija. Menopauzal’naja gormonal’naja terapija:vozmozhnost’ i riski. StatusPraesens. 2015;5:80-86. Russian.
25. Baranova EI, Bol’shakova OO, Zazerskaja IE, Jusipova TH. Vlijanie zamestitel’noj terapii s drospirenonom na strukturno-funkcional’nye parametry serdechno-sosudistoj sistemy u zhenshhin s gipertonicheskoj bolezn’ju i abdominal’nym ozhireniem v postmenopauze. Arterial’naja gipertenzija. 2015;4:372-377. Russian.
26. Grigorjan OR. Menopauzal’nyj sindrom u zhenshhin s saharnym diabetom. Saharnyj diabet. 2013;3:103-108. Russian.
27. Pestrikova T Ju, Jurasova EA, Jachinskaja TV, Kovaleva TD. Menopauzal’naja gormonal’naja terapija ili negormonal’noe lechenie: racional’nyj vybor. Ginekologija. 2015;3:94-39. Russian.
28. Jureneva SV, Il’ina LM, Jakushevskaja OV. Menopauzal’naja gormonal’naja terapija v postmenopauze: kachestvo zhizni segodnja i v dolgosrochnoj perspektive. Ginekologija. 2016; 1: 24-29. Russian.
29. Menopauzal’naja gormonoterapija i sohranenie zdorov’ja zhenshhin zrelogo vozrasta. Klinicheskie rekomendacii (Protokol lechenija). Pis’mo Ministerstva zdravoohranenija RF ot 02.10.2015; 15, 4, 10, 2:5804. Russian.
30. Madjanov IV, Madjanova T S. Menopauzal’naja gormonal’naja terapija: chto dolzhen znat’ vrach-terapevt? Lechashhij Vrach. 2017;3:44-47. Russian.
31. Kuznecova LV, Pavlovskaja EA, Zazerskaja IE. Vlijanie jestrogen-gestagennoj terapii na klinicheskie projavlenija sustavnogo sindroma u zhenshhin v klimaktericheskom periode . Farmateka. 2016;3:57-61. Russian.
32. Popkova A S, Cherkashina AV, Chachiashvili MV, Smetneva NS. Vlijanie menopauzal’noj gormonal’noj terapii na soderzhanie citokinov i immunoglobulinov pri komorbidnosti saharnogo diabeta II i HOBL v period menopauzal’nogo perehoda. Allergologija i immunologija. 2016;4: 242-245. Russian.
33. Uspenskaja JuB, Kuznecova IV. Gormony i fitogormony: pol’za i risk dlja pecheni. Ginekologija. 2014;1:35-40. Russian.
34. Maslova AS. Medikamentoznye porazhenija pecheni pri lechenii narushenij reproduktivnoj funkcii u zhenshhin. Svitmedicini ta biologii. 2015;3,51:136-142. Russian.
35. Di Martino V, Lebray P, Myers RP. et al. Progression of liver fibrosis in women infected with hepatitis C: long-term benefit of estrogen exposure. Hepatology. 2004;40(6):1426-1433.
36. Codes L, Asselah T, Cazals-Hatem D. et al. Liver fibrosis in women with chronic hepatitis C: evidence for the negative role of the menopause and steatosis and the potential benefit of hormone replacement therapy. Gut. 2007;5:390-395. .
37. Gavrilova NP, Seliverstov PV, Tatarova NA, Radchenko VG. Podhody k terapii pacientok s klimaktericheskimi rasstrojstvami, oslozhnennymi menopauzal’nym metabolicheskim sindromom s holestazom. Eksperimental’naja i klinicheskaja gastrojenterologija. 2014;108,8:34-40. Russian.
38. Radzinskij VE, Eremichev RJu. ZGT i ekstragenital’nye zabolevanija. Dokazannoe k 2013 godu. Medicinskij sovet. 2013;8:20-21. Russian.
39. Prilepskaja VN. Klimaktericheskij sindrom: innovacii v menopauzal’noj terapii. RMZh. 2017;2: 105-108. Russian.
40. Tolstov SN, Salov IA, Rebrov AP. Narushenija funkcional’noj aktivnosti jendotelija i vozmozhnosti ih korrekcii u zhenshhin v rannej postmenopauze. Racional’naja farmakoterapija v kardiologii. 2017;13,2:191-196. Russian.
41. Pestrikova TJu, Jurasova EA, Jachinskaja TV, Kovaleva TD. Menopauzal’naja gormonal’naja terapija ili negormonal’noe lechenie: racional’nyj vybor. Ginekologija. 2015;3:94-39. Russian.
42. Subhankulova AF, Volchkova NS. Rol’ menopauzal’noj gormonoterapii v lechenii arterial’noj gipertenzii. V kn.: Arterial’naja gipertonija 2017 kak mezhdisciplinarnaja problema. Sbornik tezisov XIII Vserossijskogo kongressa. 2017. 52 p. Russian.
43. Tolstov SN, Salov IA, Rebrov AP. Kardiometabolicheskie faktory riska u zhenshhin klimaktericheskogo perioda, vozmozhnosti korrekcii vyjavlennyh narushenij. Dnevnik kazanskoj shkoly. 2017;2,16:25-32. Russian.
44. Lesnaja OA, Sturov NV, Vyhristjuk JuV. Personificirovannaja medicina: v fokuse vnimanija serdechno-sosudistaja patologija u zhenshhin v periode menopauzal’nogo perehoda i v postmenopauze. Trudnyj pacient. 2017;1,2:30-34 Russian.
45. Kuznecova IV, Pokul’ LV, Burchakov DI, Burchakova MN, Berishvili MV, Chugunova NA. Terapija i profilaktika narushenij zdorov’ja u zhenshhin starshe 40 let: ucheb. Posobie. Moskwa: Indeks Med Media; 2017. Russian.
46. Tolstov SI, Salov IA, Rebrov AP. Vyrazhennost’ abdominal’nogo ozhirenija i narushenij uglevodnogo obmena u zhenshhin v rannej postmenopauze i vozmozhnosti korrekcii vyjavlennyh narushenij. Farmateka. 2017;3:36-40. Russian.
47. RadoslawSlopiena, EwaWender-Ozegowskab, Anita Rogowicz-Frontczakc et al. Menopause and diabetes: EMAS clinical guide 2018. Maturitas. 2018;117:6-10. .
48. Petra Stutea, IulianaCeausub, Herman Depypere et al. Maturitas. 2016;92:1-6. DOI:
49. Rhoda H. Cobin, Neil F. Goodman. American association of clinical endocrinologists and American college of endocrinology position statement on menopause – 2017 update. AACE Journals. Endocrine Practice. 2017;23:7.