Menopausal hormone therapy for rheumatic diseases (gout)

Panevin T.S., Yureneva S.V.

1) V.A. Nasonova Research Institute of Rheumatology, Ministry of Science and Education of the Russian Federation, Moscow, Russia; 2) Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, Moscow, Russia
The perimenopausal and postmenopausal period is characterized by the development of many diseases of great sociomedical significance, as well as metabolic disorders, including those of purine metabolism. Despite the fact that gout is traditionally considered to be a disease that predominantly affects males, the prevalence of hyperuricemia (HU) and gout significantly increases in females when menopause occurs. The available data on the association of gout with the postmenopausal period, as well as its frequent combination with other metabolic syndrome components actualize the possible additional positive effects of menopausal hormone therapy (MHT) for GU and gout in females during perimenopause and postmenopause. The review considers the results of prospective versus large retrospective studies of the impact of MHT on changes in uric acid (UA) levels and on the risk of gout. The biological mechanism underlying the relationship between menopause, estrogen action, MHT, and serum UA levels is assumed to be an inhibitory effect of estrogens on UA reabsorption in the renal tubules. In addition, estrogen deficiency favors the development of metabolic disorders, such as abdominal obesity, insulin resistance, and dyslipidemia. The anti-inflammatory effect of estrogens may be the basis for reducing the risk of gout when using MHT.
Conclusion: MHT can lead to a decrease in the level of UA and in the risk of gout. However, the decrease in the production of estrogens and progestogens only partially explains the higher risk of HU and gout. The protective effect against gout is probably due not only to the estrogenic, but also progestogenic component of MHT. It may be promising to study the impact of MHT not only on the risk, but also on the course of gout.


menopausal hormone therapy
uric acid


  1. Szoeke C.E., Cicuttini F.M., Guthrie J.R., Dennerstein L. The relationship of reports of aches and joint pains to the menopausal transition: a longitudinal study. Climacteric. 2008; 11(1): 55-62.
  2. Sievert L.L., Goode-Null S.K. Musculoskeletal pain among women of menopausal age in Puebla, Mexico. J. Cross Cult. Gerontol. 2005; 20(2): 127-40.
  3. Ho S.C., Chan S.G., Yip Y.B., Cheng A., Yi Q., Chan C. Menopausal symptoms and symptom clustering in Chinese women. Maturitas. 1999; 33(3): 219-27.
  4. Насонова В.А., Барскова В.Г. Ранние диагностика и лечение подагры – научно обоснованное требование улучшения трудового и жизненного прогноза больных. Научно-практическая ревматология. 2004; 42(1): 5-7. [Nasonova V.A., Barskova V.G. Early diagnostic and treatment of gout – is scientifically based reguirements for improvement of labour and living prognosis of patients. Rheumatology Science and Practice. 2004; 42(1): 5-7. (in Russian)].
  5. McQueen F.M., Chhana A., Dalbeth N. Mechanisms of joint damage in gout: evidence from cellular and imaging studies. Nat. Rev. Rheumatol. 2012; 8(3): 173-81.
  6. Loeb J.N. The influence of temperature on the solubility of monosodium urate. Arthritis Rheum. 1972; 15(2): 189-92.
  7. Zhu Y., Pandya B.J., Choi H.K. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum. 2011; 63(10): 3136-41.
  8. Lally E.V., Ho G., Kaplan S.R. The clinical spectrum of gouty arthritis in women. Arch. Intern. Med. 1986; 146(11): 2221-5.
  9. Елисеев М.С., Чикаленкова Н.А., Денисов И.С., Барскова В.Г. Факторы риска подагры: половые различия. Научно-практическая ревматология. 2011; 49(6): 28-31. [Eliseyev M.S., Chikalenkova N.A., Denisov I.S., Barskova B.G. Risk factors for gout: Gender differences. Nauchno-prakticheskaya revmatologiya/Rheumatology Science and Practice. 2011; 49(6): 28-31. (in Russian)].
  10. Meyers O.L., Monteagudo F.S. A comparison of gout in men and women. A 10-year experience. S. Afr. Med. J. 1986; 70(12): 721-3.
  11. Harrold L.R., Yood R.A., Mikuls T.R., Andrade S.E., Davis J., Fuller J. et al. Sex differences in gout epidemiology: evaluation and treatment. Ann. Rheum. Dis. 2006; 65(10): 1368-72.
  12. Елисеев М.С., Чикаленкова Н.А., Барскова В.Г. Клинические особенности подагры у женщин: результаты сравнительного исследования. Научно-практическая ревматология. 2014; 52(2): 178-82. [Eliseev M.S., Chikalenkova N.A., Barskova V.G. Clinical features of gout in women: the results of a comparative study. Rheumatology Science and Practice. 2014; 52(2): 178-82. (in Russian)].
  13. De Souza A., Fernandes V., Ferrari A.J. Female gout: clinical and laboratory features. J. Rheumatol. 2005; 32(11): 2186-8.
  14. Mumford S.L., Dasharathy S.S., Pollack A.Z., Perkins N.J., Mattison D.R., Cole S.R. et al. Serum uric acid in relation to endogenous reproductive hormones during the menstrual cycle: findings from the BioCycle study. Hum. Reprod. 2013; 28(7): 1853-62.
  15. Wen X., Perrett D., Jones N., Tozer A.J., Docherty S.M., Iles R.K. High follicular fluid adenosine levels may be pivotal in the metabolism and recycling of adenosine nucleotides in the human follicle. Metabolism. 2010; 59(8): 1145-55.
  16. Lavy G., Behrman H.R., Polan M.L. Purine levels and metabolism in human follicular fluid. Hum. Reprod. 1990; 5(5): 529-32.
  17. Turner R.E., Frank M.J., van Ausdal D., Bollet A.J. Some aspects of the epidemiology of gout. Sex and race incidence. Arch. Intern. Med. 1960; 106: 400-6.
  18. Yü T.F. Some unusual features of gouty arthritis in females. Semin. Arthritis Rheum. 1977; 6(3): 247-55.
  19. Puig J.G., Michán A.D., Jiménez M.L., Pérez de Ayala C., Mateos F.A., Capitán C.F. et al. Female gout. Clinical spectrum and uric acid metabolism. Arch. Intern. Med. 1991; 151(4): 726-32.
  20. Khosla U.M., Zharikov S., Finch J.L., Nakagawa T., Roncal C., Mu W. et al. Hyperuricemia induces endothelial dysfunction. Kidney Int. 2005; 67(5): 1739-42.
  21. Mercuro G., Vitale C., Cerquetani E., Zoncu S., Deidda M., Fini M., Rosano G.M. Effect of hyperuricemia upon endothelial function in patients at increased cardiovascular risk. Am. J. Cardiol. 2004; 94(7): 932-5.
  22. Трошина Е.А., Покусаева В.Н., Андреева Е.Н. Ожирение у женщин. Мельниченко Г.А., Никифоровский Н.К., ред. М.: МИА; 2017. [Troshina E.A., Pokusaeva V.N., Andreeva E.N. Obesity in women. Ed. by Mel'nichenko G.A., Nikiforovskiy N.K. Moscow: Medical Information Agency; 2017. (in Russian)].
  23. Simon J.A., Lin F., Vittinghoff E., Bittner V.; Heart and Estrogen-Progestin Replacement Study (HERS) Research Group. The relation of postmenopausal hormone therapy to serum uric acid and the risk of coronary heart disease events: the Heart and Estrogen-Progestin Replacement Study (HERS). Ann. Epidemiol. 2006; 16(2): 138-45.
  24. Sumino H., Ichikawa S., Kanda T., Nakamura T., Sakamaki T. Reduction of serum uric acid by hormone replacement therapy in postmenopausal women with hyperuricaemia. Lancet. 1999; 354(9179): 650.
  25. Hak A.E., Choi H.K. Menopause, postmenopausal hormone use and serum uric acid levels in US women--the Third National Health and Nutrition Examination Survey. Arthritis Res. Ther. 2008; 10(5): R116.
  26. Дедов И.И., Шестакова М.В., Мельниченко Г.А., Мазурина Н.В., Андреева Е.Н., Бондаренко И.З., Гусова З.Р., Дзгоева Ф.Х., Елисеев М.С., Ершова Е.В. и др. Междисциплинарные клинические рекомендации «Лечение ожирения и коморбидных заболеваний». Ожирение и метаболизм. 2021; 18(1): 5-99. [Dedov I.I., Shestakova M.V., Melnichenko G.A. et al. Interdisciplinary Clinical Practice Guidelines "Management of obesity and its comorbidities". Obesity and metabolism. 2021; 18(1): 5-99 (in Russian)].
  27. Hak A.E., Curhan G.C., Grodstein F., Choi H.K. Menopause, postmenopausal hormone use and risk of incident gout. Ann. Rheum. Dis. 2010; 69(7): 1305-9.
  28. Colditz G.A., Manson J.E., Hankinson S.E. The Nurses' Health Study: 20-year contribution to the understanding of health among women. J. Womens Health. 1997; 6(1): 49-62.
  29. Bachmann G. Physiologic aspects of natural and surgical menopause. J. Reprod. Med. 2001; 46(3, Suppl.): 307-15.
  30. Bruderer S.G., Bodmer M., Jick S.S., Meier C.R. Association of hormone therapy and incident gout: population-based case-control study. Menopause. 2015; 22(12): 1335-42.
  31. Lawson D.H., Sherman V., Hollowell J. The General Practice Research Database. Scientific and Ethical Advisory Group. QJM. 1998; 91(6): 445-52.
  32. Meier C.R., Jick H. Omeprazole, other antiulcer drugs and newly diagnosed gout. Br. J. Clin. Pharmacol. 1997; 44(2): 175-8.
  33. Jung J.H., Song G.G., Lee Y.H., Kim J.H., Hyun M.H., Choi S.J. Serum uric acid levels and hormone therapy type: a retrospective cohort study of postmenopausal women. Menopause. 2018; 25(1): 77-81.
  34. Adamopoulos D., Vlassopoulos C., Seitanides B., Contoyiannis P., Vassilopoulos P. The relationship of sex steroids to uric acid levels in plasma and urine. Acta Endocrinol. (Copenh). 1977; 85(1): 198-208.
  35. Stanczyk F.Z., Hapgood J.P., Winer S., Mishell D.R. Jr. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr. Rev. 2013; 34(2): 171-208.
  36. Bodel P., Dillard G.M. Jr., Kaplan S.S., Malawista S.E. Anti-inflammatory effects of estradiol on human blood leukocytes. J. Lab. Clin. Med. 1972; 80(3): 373-84.
  37. Weissmann G., Rita G.A. Molecular basis of gouty inflammation: interaction of monosodium urate crystals with lysosomes and liposomes. Nat. New Biol. 1972; 240(101): 167-72.
  38. Spilberg I. Current concepts of the mechanism of acute inflammation in gouty arthritis. Arthritis Rheum. 1975; 18(2): 129-34.

Received 17.05.2021

Accepted 01.06.2021

About the Authors

Taras S. Panevin, Ph.D., endocrinologist, V.A. Nasonova Research Institute of Rheumatology, Ministry of Health of Russia, +7(914)207-43-67,,, 115522, Russia, Moscow, Kashirskoye Shosse, 34A.
Svetlana V. Yureneva, Dr. Med. Sci., Leading Researcher at the Department of Gynecological Endocrinology, NMRC for OG&P, Ministry of Health of Russia,,, 117997, Russia, Moscow, Ac. Oparina str., 4.

Authors' contributions: Panevin T.S. – pilot study; writing and editing the text; Yureneva S.V. – writing and editing the text; final approval of the manuscript.
Conflicts of interest: The authors declare that there are no possible conflicts of interest.
Funding: The pilot and analytical study has not been sponsored.

For citation: Panevin T.S., Yureneva S.V. Menopausal hormone therapy for rheumatic diseases: Gout.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2021; 9: 36-41 (in Russian)

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