Z.Sh. Pavlova – Ph.D. (Med.), Endocrinologist, University Hospital, Medical Scientific  and Educational Center of M.V. Lomonosov Moscow State University (Moscow, Russia) E-mail: zukhra73@gmail.com

I.I. Golodnikov – Student, Faculty of Basic Medicine, 

M.V. Lomonosov Moscow State University (Moscow, Russia)

E-mail: golodnikov@fbm.msu.ru

A.A. Kamalov – Dr. Sc. (Med.), Urologist, Director of the Medical Scientific and Educational Center  of M.V. Lomonosov Moscow State University (Moscow, Russia); 

E-mail: armais.kamalov@rambler.ru

Based on the data that demonstrate a lower prevalence of nephrolithiasis in women of the reproductive period, compared with men, it is logical to assume that it is estrogens that have a protective effect. After the menopause, and even more so after a few years, the number of women and men with nephrolithiasis is almost equalized, which again can increase the confidence of scientists who suggest the presence of a protective effect of estrogen against kidney stone disease (KSD).

It is logical to assume that hormone replacement therapy (HRT) in postmenopausal women should have a protective effect against urolithiasis. Researchers in the USA who conducted the study “Women's Health” from 1993 to 1998 in 40 clinical centers in America were puzzled by the same idea. The following conclusions can be drawn from this study

1. The use of HRT significantly increased the risk of urolithiasis in both groups, using only estrogen or in combination with progesterone, compared with placebo.
2. The presence of a history of KSD increased the risk of recurrence of urolithiasis by 5 times. In this case, scientists did not reveal a significant effect of estrogen.
3. The authors also did not find a reliable relationship between the risk of developing urolithiasis in postmenopausal patients and the use of estrogen or a combination of estrogen / progesterone and age, body mass index, ethnicity, the use of thiazide diuretics, or regular coffee consumption.

In addition, very important data in a number of studies demonstrate the different mineral and organic composition of urine in people with obesity and normal composite body composition. The concentrations of oxalates, citrate, phosphates, potassium and the same uric acid differed.

We can`t reduce the ubiquitous role of insulin, which is significantly altered in the body of a person who has excessively developed adipose tissue, to the state of insulin resistance. With the development of insulin resistance, the buffer capacity of urine decreases, the synthesis of ammonium and, accordingly, the pH of the urine changes in the acidic direction. In addition, insulin resistance helps to reduce the concentration of citrate, and this is one of the leading endogenous factors that counteract the development of urolithiasis.

As a result, there is no doubt about the effect of estrogen on urolithiasis. An unambiguous conclusion cannot be made from the data available today. There is no complete understanding of the role of estrogens in the pathogenesis of urolithiasis, either in the male population or among women. But, a lot of information that forms the understanding that urolithiasis is a multifactorial and complex process and the addition of estrogens or a combination of estrogens and progesterone does not solve the problem of nephrolithiasis and does not protect, in this case, women, from the development or relapse of KSD. Moreover, according to the available and presented data, it probably even contributes to the development of stones in the genitourinary tract in postmenopausal women. Unfortunately, for now, we cannot take into account all the factors involved in the process of urolithiasis, and of course, the drugs themselves that were used in the studies probably have certain drawbacks, with corresponding results. In other words, by adding estrogens or estrogens and progesterone we cannot restore the biochemical balance of biological substances that women have at their reproductive age. The influence of excessively developed adipose tissue on the KSD is convincingly presented in a large number of works. But, the effect of excessively developed adipose tissue with a change in the balance of estrogens and their metabolites in relation to the KSD remains to be studied.

Pavlova Z.Sh., Golodnikov I.I., Kamalov A.A. Do estrogens protect us from nephrolithiasis? (Review). Technologies of living systems. 2020. V. 17. № 4. P. 5–13. DOI: 10.18127/j20700997-202004-01 (In Russian).

1. John B.S., Patel U., Anson K. What radiation exposure can a patient expect during a sin-gle stone episode? J. Endourol. 2008. V. 22. № 3.  P. 419–22.
2. Stamatelou K.K., Francis M.E., Jones C.A., Nyberg L.M., Curhan G.C. Time trends in re-ported prevalence of kidney stones in the United States: 1976–1994. Kidney Int. 2003. V. 63. № 5. P. 1817–23.
3. Romero V., Akpinar H., Assimos D.G. Kidney stones: a global picture of prevalence, in-cidence, and associated risk factors. Rev Urol. 2010. V. 12.
4. Fisang C., Anding R., Muller S.C., Latz S., Laube N. Urolithiasis--an interdisciplinary di-agnostic, therapeutic and secondary preventive challenge. Dtsch Arztebl Int. 2015. V. 112. № 6. P. 83–91.
5. Pearle M.S., Calhoun E.A., Curhan G.C. Urologic diseases in America project: urolithia-sis. J. Urol. 2005. V. 173. № 3. P. 848–57.
6. Rule A.D., Bergstralh E.J., Melton L.J., 3rd, Li X., Weaver A.L., Lieske J.C. Kidney stones and the risk for chronic kidney disease. Clin. J. Am. Soc. Nephrol. 2009. V. 4. № 4. P. 804–11.
7. Grundy S.M., Cleeman J.I., Daniels S.R., Donato K.A., Eckel R.H., Franklin B.A., Gor-don D.J., Krauss R.M., Savage P.J., Smith S.C., Jr., Spertus J.A., Costa F. Diagnosis and man-agement of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005. V. 112. № 17. P. 2735–52.
8. Kryuchkov I.A., Chekhonackaya M.L., Rossolovskij A.N., Bobylev D.A. Mochekamennaya bolezn': etiologiya i diagnostika (obzor literatury). Sbornik nauchnyh trudov NII fundamental'noj i klinicheskoj uronefrologii Saratovskogo GMU im. V.I. Razumov-skogo «Aktual'nye problemy fundamental'noj i klinicheskoj uronefrologii – 2017». Saratov. 2017 (In Russian).
9. Suslyaeva N.M., Zavadovskaya V.D., Shul'ga O.S. Vozmozhnosti ul'trazvukovogo is-sledovaniya v diagnostike visceral'nogo ozhireniya. Ul'trazvukovaya i funkcional'naya diagnostika. 2012. № 4. C. 24–29 (In Russian).
10. Simmons R.K., Alberti K.G., Gale E.A., Colagiuri S., Tuomilehto J., Qiao Q., Rama-chandran A., Tajima N., Brajkovich Mirchov I., Ben-Nakhi A., Reaven G., Hama Sambo B., Mendis S., Roglic G. The metabolic syndrome: useful concept or clinical tool? Report of a WHO Expert Consultation. Diabetologia. 2010. V. 53. № 4. P. 600–5.
11. Heller H.J., Sakhaee K., Moe O.W., Pak C.Y. Etiological role of estrogen status in renal stone formation. J Urol. 2002. V. 168. № 5. P. 1923–7.
12. Marshall V., White R.H., De Saintonge M.C., Tresidder G.C., Blandy J.P. The natural history of renal and ureteric calculi. Br. J. Urol. 1975. V. 47. № 2. P. 117–24.
13. Johnson C.M., Wilson D.M., O'Fallon W.M., Malek R.S., Kurland L.T. Renal stone epi-demiology: a 25-year study in Rochester, Minnesota. Kidney Int. 1979. V. 16. № 5. P. 624–31.
14. Maalouf N.M., Sato A.H., Welch B.J., Howard B.V., Cochrane B.B., Sakhaee K., Rob-bins J.A. Postmenopausal hormone use and the risk of nephrolithiasis: results from the Women's Health Initiative hormone therapy trials. Arch. Intern. Med. 2010. V. 170. № 18. P. 1678–85.
15. Rossouw J.E., Anderson G.L., Prentice R.L., LaCroix A.Z., Kooperberg C., Stefanick M.L., Jackson R.D., Beresford S.A., Howard B.V., Johnson K.C., Kotchen J.M., Ockene J. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. Jama. 2002. V. 288. № 3. P. 321–33.
16. Anderson G.L., Limacher M., Assaf A.R., Bassford T., Beresford S.A., Black H., Bonds D., Brunner R., Brzyski R., Caan B., Chlebowski R., Curb D., Gass M., Hays J., Heiss G., Hen-drix S., Howard B. V., Hsia J., Hubbell A., Jackson R., Johnson K. C., Judd H., Kotchen J. M., Kuller L., LaCroix A. Z., Lane D., Langer R.D., Lasser N., Lewis C.E., Manson J., Margolis K., Ockene J., O’Sullivan M.J., Phillips L., Prentice R.L., Ritenbaugh C., Robbins J., Rossouw J.E., Sarto G., Stefanick M.L., Van Horn L., Wactawski-Wende J., Wallace R., Wassertheil-Smoller S. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Wom-en's Health Initiative randomized controlled trial. Jama. 2004. V. 291.  № 14. P. 1701–12.
17. Mattix Kramer H.J., Grodstein F., Stampfer M.J., Curhan G.C. Menopause and post-menopausal hormone use and risk of incident kidney stones. J. Am. Soc. Nephrol. 2003. V. 14. № 5. P. 1272–7.
18. 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. V. 85. № 1. P. 198–208.
19. Nicholls A., Snaith M.L., Scott J.T. Effect of oestrogen therapy on plasma and urinary levels of uric acid. Br. Med. J. 1973. V. 1. № 5851. P. 449–51.
20. Pavlova Z.S., Golodnikov I.I., Kamalov A.A., Nizov A.N. A role of fructose in urinary stone formation. Urologiia. 2019. № 1. P. 114–18.
21. Gallagher J.C., Riggs B.L., DeLuca H.F. Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J. Clin. Endocrinol. Metab. 1980. V. 51. № 6. P. 1359–64.
22. McKane W.R., Khosla S., Burritt M.F., Kao P.C., Wilson D.M., Ory S.J., Riggs B.L. Mechanism of renal calcium conservation with estrogen replacement therapy in women in early postmenopause--a clinical research center study. J. Clin. Endocrinol. Metab. 1995. V. 80. № 12. P. 3458–64.
23. Carter M.R., Green B.R. Renal calculi: emergency department diagnosis and treatment. Emerg. Med. Pract. 2011. V. 13. № 7. P. 1–17; quiz 18.
24. Shine S. Urinary calculus: IVU vs. CT renal stone? A critically appraised topic. Abdom Imaging. 2008. V. 33. № 1. P. 41–3.
25. Saklayen M.G. The Global Epidemic of the Metabolic Syndrome. Curr Hypertens Rep. 2018. V. 20. № 2. P. 12.
26. National Center for Health Statistics, Division of Health Interview Statistics. Crude and age-adjusted percentage of civilian, noninstitutionalized adults with diagnosed diabetes, United States, 1980-2010. National Center for Chronic Disease Prevention and Health Promotion. Ed. Atlanta, GA, Center for Disease Control and Prevention, Division of Diabetes Translation. 2012.
27. Palaniappan L.P., Wong E.C., Shin J.J., Fortmann S.P., Lauderdale D.S. Asian Ameri-cans have greater prevalence of metabolic syndrome despite lower body mass index. Int. J. Obes. (Lond). 2011. V. 35. № 3. P. 393–400.
28. Simonova G.I., Pechenkina E.A., ShCherbakova L.V. Rasprostranennost' metaboli-cheskogo sindroma i ego komponentov v Sibiri. Tezisy dokladov konferencii «Aktu-al'nye voprosy diagnostiki i lecheniya metabolicheskogo sindroma». M. 2006. № 17. C. 45 (In Russian).
29. Romancova T.I., Poluboyarinova I.V., Roik O.V. Dinamika sostoyaniya zhirovoj tkani po dannym MP-tomografii u bol'nyh ozhireniem na fone lecheniya Reduksinom. Ozhirenie i metabolizm. 2012. № 4. C. 39–43 (In Russian).
30. Butrova S.A., Berkovskaya M.A. Sovremennye aspekty terapii ozhireniya. Poli-klinika. 2012. № 5. C. 24–26 (In Russian).
31. Mandeville J.A., Gnessin E., Lingeman J.E. Imaging evaluation in the patient with renal stone disease. Semin Nephrol. 2011. V. 31. № 3. P. 254–8.
32. Rosa M., Usai P., Miano R., Kim F.J., Finazzi Agro E., Bove P., Micali S. Recent find-ing and new technologies in nephrolitiasis: a review of the recent literature. BMC Urol. 2013. V. 13. P. 10.
33. Dedov I.I., Mel'nichenko G.A., Fadeev V.F. Ozhirenie: etiologiya, patogenez, klinicheskie aspekty. OOO «Med. Inform. agentstvo». 2006. C. 456 (In Russian).