Effectiveness of early start of menopausal hormone therapy in the menopausal transition: comparative analysis of therapy

Gasparyan S.A., Chotchaeva A.M., Karpov S.M.

Stavropol State Medical University, Ministry of Health of Russia, Stavropol, Russia
Objective: To optimize preventive and therapeutic measures aimed at reducing the severity of menopausal symptoms as well as preserving cognitive function to improve the quality of life in perimenopausal women.
Materials and methods: The study included 120 women aged 40–50 years with signs of hypoestrogenism. There were the following study groups: group 1 included patients who received systemic menopausal hormone therapy (MHT) in the form of a combination of 1 mg of estradiol/ 10 mg of dydrogesterone orally (n=30); group 2 consisted of patients receiving a combination of 1 mg of estradiol/10 mg of dydrogesterone orally and intramuscular injections of polypeptides of the pineal gland of cattle (10 mg, lyophilizate for intravenous administration) (n=30); group 3 included those who received 17-β estradiol transdermally in the form of a 0.06% gel in combination with 52 mg of LNG-IUD (n=30); group 4 consisted of patients who did not receive treatment (n=30). The duration of the study was 12 months. Baseline indicators were evaluated using the Greene climacteric scale, Beck Depression Inventory, Montreal Cognitive Assessment test and laboratory levels of nerve growth factor followed by dynamic control of these indicators on days 180 (6 months) and 360 (12 months).
Results: The frequency and severity of vasomotor symptoms in the group 1 were 0.79±0.68 and were reduced by 88.3% for 12 months in comparison with the baseline. Group 2 showed a decrease by 76.8%. Groups 1 and 2 showed a comparable decrease in overall menopausal indicators over 12 months; the decrease in vasomotor symptoms was less severe in group 3. According to the severity of depressive symptoms, the results of the follow-up showed a decrease by 49.9% (7.80±2.01 vs. 15.57±4.27) and 65.9% (5.90±2.08 vs. 17.30±5.85) respectively, in groups 1 and 2. In group 3 the decrease was less severe and amounted to 15.3% (11.86±4.01 vs. 14.00±4.31). Improvements were noted only in groups 1 and 2 in patients receiving fixed combined MHT. Groups 1 and 2 demonstrated an improvement in rheological properties of blood. There was positive dynamics of clotting parameters in both study groups.
Conclusion: Early initiation of cyclic combined MHT (1 mg of estradiol, 10 mg of dydrogesterone) contributed to the decrease of menopausal symptoms and restored cognitive function, however, this was not observed in the group of patients receiving transdermal therapy of 17-β estradiol in the form of a gel in combination with LNG-IUD or in the absence of therapy. Moreover, there was a positive dynamics of hemostasis indicators in patients receiving MHT with dydrogesterone. The obtained data make it possible to improve preventive and therapeutic measures, to personalize therapy for perimenopausal women.

Authors’ contributions: Gasparyan S.A. – developing the concept and design of the study, editing the manuscript significantly in order to increase the scientific value of the article; Chotchaeva A.M. – obtaining and performing data analysis, interpreting the results, writing the article; Karpov S.M. – developing the concept and design of the study, editing the manuscript significantly in order to increase the scientific value of the article.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The study was carried without sponsorship.
Ethical Approval: The study was approved by the Ethical Review Board of Stavropol State Medical University, Ministry of Health of Russia (Protocol No. 107 dated 17.03.2022).
Patients’ Consent for Publication: The patients provided an informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Gasparyan S.A., Chotchaeva A.M., Karpov S.M. Effectiveness of early start
of menopausal hormone therapy in the menopausal transition: comparative analysis of therapy.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (4): 162-169 (in Russian)


menopausal hormone therapy
polypeptides of epiphysis (pineal gland) of cattle
transdermal estradiol


  1. Beard J.R., Officer A., de Carvalho I.A., Sadana R., Pot A.M. et al. The World report on ageing and health: a policy framework for healthy ageing. Lancet. 2016;387(10033):2145-54. https://dx.doi.org/10.1016/S0140-6736(15)00516-4.
  2. Maki P.M., Thurston R.C. Menopause and brain health: hormonal changes are only part of the story. Front. Neurol. 2020; 11: 562275.https://dx.doi.org/10.3389/fneur.2020.562275.
  3. Rudnicka E., Napierała P., Podfigurna A., Męczekalski B., Smolarczyk R., Grymowicz M. The World Health Organization (WHO) approach to healthy ageing. Maturitas. 2020; 139: 6-11. https://dx.doi.org/10.1016/j.maturitas.2020.05.018.
  4. Министерство здравоохранения Российской Федерации. Менопауза и климактерическое состояние у женщины. Клинические рекомендации. M.; 2021. 45 с. [Ministry of Health of the Russian Federation. Menopause and the menopausal state in women. Clinical guidelines. Moscow; 2021. 45 p.(in Russian)].
  5. Федеральная служба государственной статистики. Демография. (rosstat.gov.ru). Дата доступа 05.07.2022. [Federal State Statistics Service. Demography (rosstat.gov.ru). Date of access 05.07.2022. (in Russian)].
  6. Baber R.J., Panay N., Fenton A.; IMS Writing Group. 2016 IMS Recommendations on women's midlife health and menopause hormone therapy. Climacteric. 2016; 19(2):109-50. https://dx.doi.org/10.3109/13697137.2015.1129166.
  7. Slopien R., Wender-Ozegowska E., Rogowicz-Frontczak A., Meczekalski B., Zozulinska-Ziolkiewicz D. et al. Menopause and diabetes: EMAS clinical guide. Maturitas. 2018; 117: 6-10. https://dx.doi.org/10.1016/j.maturitas.2018.08.009.
  8. ФГУ «Научный центр акушерства, гинекологии и перинатологииим. В.И. Кулакова Росмедтехнологий», Российская Ассоциация по менопаузе. Практические рекомендации. Ведение женщин в пери- и постменопаузе. M.; 2010: 18-28. [V.I. Kulakov Scientific Center for Obstetrics, Gynecology and Perinatology, Rosmedtechnology, Russian Menopause Association. Practical guidelines. Management of women in peri- and postmenopause. Moscow; 2010: 18-28. (in Russian)].
  9. Salpeter S.R., Walsh J.M., Ormiston T.M., Greyber E., Buckley N.S., Salpeter E.E. Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome ipostmenopausal women. Diabetes Obes. Metab. 2006; 8(5): 538-54. https://dx.doi.org/10.1111/j.1463-1326.2005.00545.x.
  10. Ткачева О.Н., Доброхотова Ю.Э., Дудинская Е.Н., Котовская Ю.В., Рунихина Н.К., Хашукоева А.З. Профилактика преждевременного старения у женщин. Методические рекомендации. М.; 2018: 12-4. [Tkacheva O.N., Dobrokhotova Yu.E., Dudinskaya E.N., Kotovskaya Yu.V., Runikhina N.K., Khashukoeva A.Z. Prevention of premature aging in women. Methodological guidelines. Мoscow; 2018: 12-4. (in Russian)].
  11. Manson J.E., Aragaki A.K., Bassuk S.S., Chlebowski R.T., Anderson G.L. et al. Menopausal estrogen-alone therapy and health outcomes in women with and without bilateral oophorectomy: A randomized trial. Ann. Intern. Med. 2019; 171(6): 406-14. https://dx.doi.org/10.7326/M19-0274.
  12. Chu J.H., Michos E.D., Ouyang P., Vaidya D., Blumenthal R.S., Budoff M.J., Blaha M.J., Whelton S.P. Coronary artery calcium and atherosclerotic cardiovascular disease risk in women with early menopause: The Multi-Ethnic Study of Atherosclerosis (MESA). Am. J. Prev. Cardiol. 2022; 11:100362. https://dx.doi.org/10.1016/j.ajpc.2022.100362.
  13. Hodis H.N., Mack W.J., Shoupe D., Azen S.P., Stanczyk F.Z., Hwang-Levine J.,Budoff M.J., Henderson V.W. 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.https://dx.doi.org/10.1097/GME.0000000000000343.
  14. Karlamangla A.S., Lachman M.E., Han W., Huang M., Greendale G.A. Evidence for cognitive aging in midlife women: study of women's health across the nation. PLoS One. 2017; 12(1):e0169008. https://dx.doi.org/10.1371/journal.pone.0169008.
  15. Reuben R., Karkaby L., McNamee C., Phillips N.A., Einstein G. Menopause and cognitive complaints: are ovarian hormones linked with subjective cognitive decline? Climacteric. 2021; 24(4): 321-32. https://dx.doi.org/10.1080/13697137.2021.1892627.
  16. Turner R.J., Kerber I.J. A theory of eu-estrogenemia: a unifying concept. Menopause. 2017; 24(9):1086-97. doi: 10.1097/GME.0000000000000895.
  17. Greene J.G. Constructing a standard climacteric scale. Maturitas. 2008; 61(1-2): 78-84. https://dx.doi.org/10.1016/j.maturitas.2008.09.011.
  18. Nasreddine Z.S., Phillips N.A., Bédirian V., Charbonneau S., Whitehead V.,Collin I., Cummings J.L., Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J. Am. Geriatr. Soc. 2005; 53(4): 695-9. https://dx.doi.org/10.1111/j.1532-5415.2005.53221.x.
  19. Beck A.T., Ward C.H., Mendelson M., Mock J., Erbaugh J. An inventory for measuring depression. Arch. Gen. Psychiatry. 1961; 4: 561-71.https://dx.doi.org/10.1001/archpsyc.1961.01710120031004.
  20. Sims S.K., Wilken-Resman B., Smith C.J., Mitchell A., McGonegal L., Sims-Robinson C. Brain-derived neurotrophic factor and nerve growth factor therapeutics for brain injury: the current translational challenges in preclinical and clinical research. Neural Plast. 2022; 2022: 3889300.https://dx.doi.org/10.1155/2022/3889300.
  21. Blondon M., Timmons A.K., Baraff A.J., Floyd J.S., Harrington L.B., Korpak A.M., Smith N.L. Comparative venous thromboembolic safety of oral and transdermal postmenopausal hormone therapies among women Veterans. Menopause. 2021; 28(10):1125-9. https://dx.doi.org/10.1097/GME.0000000000001823.
  22. Anagnostis P., Bitzer J., Cano A., Ceausu I., Chedraui P. et al. Menopause symptom management in women with dyslipidemias: An EMAS clinical guide. Maturitas. 2020; 135: 82-8. https://dx.doi.org/10.1016/j.maturitas.2020.03.007.
  23. Vinogradova Y., Coupland C., Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019; 364: k4810.https://dx.doi.org/10.1136/bmj.k4810.
  24. Fornili M., Perduca V., Fournier A., Jérolon A., Boutron-Ruault M.C., Maskarinec G., Severi G., Baglietto L. Association between menopausal hormone therapy, mammographic density and breast cancer risk: results from the E3N cohort study. Breast Cancer Res. 2021; 23(1): 47. https://dx.doi.org/10.1186/s13058-021-01425-8.
  25. Cordina-Duverger E., Truong T., Anger A., Sanchez M., Arveux P., Kerbrat P., Guénel P. Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France. PLoS One. 2013; 8(11): e78016. https://dx.doi.org/10.1371/journal.pone.0078016.
  26. Lyytinen H., Pukkala E., Ylikorkala O. Breast cancer risk in postmenopausal women using estradiol-progestogen therapy. Obstet Gynecol. 2009; 113(1): 65-73. https://dx.doi.org/10.1097/AOG.0b013e31818e8cd6.
  27. Vinogradova Y., Coupland C., Hippisley-Cox J. Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases. BMJ. 2020; 371: m3873.https://dx.doi.org/10.1136/bmj.m3873.

Received 19.04.2023

Accepted 27.04.2023

About the Authors

Susanna A. Gasparyan, Dr. Med. Sci., Professor, Professor at the Department of Obstetrics and Gynecology, Stavropol State Medical University, Ministry of Health of Russia, https://orcid.org/0000-0001-8284-8117, Russia, Stavropol, Tukhachevskogo str., 17.
Alina M. Chotchaeva, postgraduate student, Department of Obstetrics and Gynecology, Stavropol State Medical University, Ministry of Health of Russia,
chotchaeva.alina96@gmail.com, https://orcid.org/0000-0002-1455-8473, Russia, Stavropol, Tukhachevskogo str., 17.
Sergey M. Karpov, Dr. Med. Sci., Professor, Head of the Department of Neurology, Neurosurgery and Medical Genetics, Stavropol State Medical University,
Ministry of Health Care of Russia, https://orcid.org/0000-0002-0163-8335, Russia, Stavropol, Tukhachevskogo str., 17.
Corresponding author: Alina M. Chotchaeva, chotchaeva.alina96@gmail.com

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.