Disorders of the sex hormones metabolism in obesity

A. L. Zagayko, D. V. Lytkin

Abstract


Topicality. Modern epidemiological situation related to the incidence of obesity, is rather unfavorable: the prevalence of the disease has reached critical values and continues the exponential growth in the population of many countries
around the world, regardless of their index of living standards and economic advancement. Increased body fat mass is correlated with the development of insulin resistance, metabolic syndrome, cardiovascular pathologies and disorders
of the endocrine system, it is violated the patient’s blood and tissues hormones ratio (including sex hormones).
Aim. To analyzed the published data on the correlation between obesity and the abnormality of sex hormones homeostasis.
Results and Discussion. According to modern concepts, one of the main factors influencing the total steroid hormones production and their ratio in the organism in obesity is the activation of steroid metabolism in adipocytes and stromal fat cells. The concentration change of sex hormone-binding globulin bonds sex hormones with body mass index, which normally maintains a balance between free and bound fractions of estrogens and androgens.
Conclusions. Estrogen and androgen hormonal status change fundamentally according to age and gender norms of hormones metabolism in the patients with obesity.


Keywords


androgens; estrogens; obesity

References


Aronne, L. J. Classification of obesity and assessment of obesity–related health risks / L. J. Aronne // Obes. Res. – 2002. – Vol. 10, Issue S12. –

P. 105–115. doi: 10.1038/oby.2002.203

Overweight and obesity [Internet] // Global Health Observatory (GHO) data. – 2014. – Available at : http://www.who.int/gho/ncd/risk_factors/

overweight_text/en/.

Pi–Sunyer, X. The Medical Risks of Obesity / Xavier Pi–Sunyer // Postgrad. Med. – 2009 – Vol. 121 (6). – P. 21–33.

Effect of weight reduction on insulin sensitivity, sex hormone–binding globulin, sex hormones and gonadotrophins in obese children / N. H. Birkebeak,

A. Lange, P. Holland–Fischer et al. // Eur. J. of Endocrinol. – 2010. – Vol. 163, Issue 6. – P. 895–900. doi: 10.1530/eje-10-0538

Kirschner, M. A. Obesity, hormones, and cancer / M. A. Kirschner, N. Ertel, G. Schneider // Cancer Res. – 1981. – Vol. 41, Issue,9, Pt. 2. – P. 3711–3717.

Kokkoris, P. Obesity and endocrine disease / P Kokkoris, Xavier Pi–Sunyer // Endocrinology & Metabolism Clinics of North America. – 2004. –

Vol. 32, Issue 4. – P. 895–914.

Abdominal and gynoid fat mass are associated with cardiovascular risk factors in men and women / P. Wiklund, F. Toss, L. Weinehall et al. // Clin.

Endocrinol. Metab. – 2008. – Vol. 93, Issue 11. – P. 4360–4366. doi: 10.1210/jc.2008-0804

The biology of white adipocyte proliferation / D. B. Hausman, M. DiGirolamo, T. J. Bartness et al. // Obes. Rev. – 2001. – Vol. 2, Issue 4. – P. 239–254.

doi: 10.1046/j.1467-789x.2001.00042.x

Gender differences in the regulation of P450 aromatase expression and activity in human adipose tissue / P. G. McTernan, A. Anwar, M. C. Eggo et

al. // Intern. J. of Obesity. – 2000 – Vol. 24, Issue 7. – P. 875–881. doi: 10.1038/sj.ijo.0801254

Zahid, H. Inflammation, dysregulated metabolism and aromatase in obesity and breast cancer / H. Zahid, E. R. Simpson, K. A. Brown // Curr Opin

Pharmacol. – 2016. – Vol. 31. – P. 90–96. doi: 10.1016/j.coph.2016.11.003

Schneider, J. Effects of obesity on estradiol metabolism: decreased formation of nonuterotropic metabolites / J. Schneider, H. L. Bradlow, G. Strain //

J. Clin. Endocrinol. Metab. – 1983. – Vol. 56, Issue 5. – P. 973–978. doi: 10.1210/jcem-56-5-973

The relationship between sex steroids and sex–hormone–binding globulin in plasma in physiological and pathological conditions / S. K. Cunningham,

T. Loughlin, M. Culliton, T. J. McKenna // Annals of Clinical Biochemistry: An International Journal of Biochemistry and Laboratory Medicine. –

– Vol. 22, Issue 5. – P. 489–497. doi: 10.1177/000456328502200504

Modulation of SHBG binding to testosterone and estradiol by sex and morbid obesity / M. Grasa, J. Gulfo, N. Camps et al. // Eur. J. of Endocrinol. –

doi: 10.1530/eje-16-0834

Selby, C. Sex hormone binding globulin: origin, function and clinical significance / C. Selby // Annals of Clinical Biochemistry: An International

Journal of Biochemistry and Laboratory Medicine. – 1990. – Vol. 27, Issue 6. – P. 532–541. doi: 10.1177/000456329002700603

Testosterone concentrations in diabetic and nondiabetic obese men / S. Dhindsa, M. G. Miller, C. L. McWhirter et al. // Diabetes Care. – 2010. – Vol. 33, Issue 6. – P. 1186–1192. doi: 10.2337/dc09-1649

Giagulli, V. A. Pathogenesis of the decreased androgen levels in obese men / V. A. Giagulli, J. M. Kaufman, A. Vermeulen // The J. of Clin. Endocrinol.

and Metabolism. – 1994. – Vol. 79, Issue 4. – P. 997–1000. doi: 10.1210/jc.79.4.997

Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men

with type 2 diabetes / C. Wang, G. Jackson, T. H. Jones et al. // Diabetes Care. – 2011. – Vol. 34, Issue 7. – P. 1669–1675. doi: 10.2337/dc10-2339

Regulation of pituitary cell function by adiponectin / F. Rodriguez–Pacheco, A. J. Martinez–Fuentes, S. Tovar et al. // Endocrinol. – 2007. –

Vol. 148, Issue 1. – P. 401–410.

Obesity and male reproductive potential / A. O. Hammoud, M. Gibson, C. M. Peterson et al. // J. of Androl. – 2006. – Vol. 27, Issue 5. – P. 619–626.

doi: 10.2164/jandrol.106.000125

Relationship between BMI, total testosterone, sex hormone–binding–globulin, leptin, insulin and insulin resistance in obese men / J. A. Osuna,

C. R. Gómez–Pérez, G. Arata–Bellabarba, V. Villaroel // Archives of Androl – 2006. – Vol. 52, Issue 5. – P. 355–361. doi: 10.1080/01485010600692017

Relationship between sexual function, body mass index and levels of sex steroid hormones in young men / S. Jastrzębska, R. Walczak–Jędrzejowska,

E. Kramek et al. // Endokrynol Pol. – 2014. – Vol. 65, Issue 3. – P. 203–209.

Correlation between sex hormone levels and obesity in the elderly male / J. Cao, T. M. Chen, W. J. Hao et al. // Aging Male. – 2012. – Vol. 15, Issue 2. –

P. 85–89. doi: 10.3109/13685538.2012.666585

Clinical study changes in testosterone levels and sex hormone–binding globulin levels in extremely obese men after bariatric surgery [Internet] /

P. Boonchaya–anant, N. Laichuthai, P. Suwannasrisuk et al. // Intern. J. of Endocrinol. – 2016. doi: 10.1155/2016/1416503

Age as a predictive factor of testosterone improvement in male patients after bariatric surgery: preliminary results of a monocentric prospective

study / E. Facchiano, S. Scaringi, M. Veltri et al. // Obesity Surgery. – 2013. – Vol. 23, Issue 2. – P. 167–172. doi: 10.1007/s11695-012-0753-6

Erectile dysfunction and hormonal imbalance in morbidly obese male is reversed after gastric bypass surgery: a prospective randomized controlled

trial / L. O. Reis, W. J. Favaro, G. C. Barreiro et al. // Intern. J. of Androl. – 2010. – Vol. 33, Issue 5. – P. 736–744. doi: 10.1111/j.1365-2605.2009.01017.x

Obesity and reproductive disorders in women / R. Pasquali, C. Pelusi, S. Genghini et al. // Human Reproduction Update. – 2003. – Vol. 9, Issue 4. –

P. 359–372. doi: 10.1093/humupd/dmg024

Central obesity in women and its association with serum level of testosterone and estradiol / M. Maddah, A. Jazayery, R. Mirdamadi, M. R. Eshraghiyan // J. Reprod. Infertil. – 2002. – Vol. 3, Issue 4. – P. 14–20.

Pasquali, R. Obesity and androgens: facts and perspectives / R. Pasquali // Fertil. Steril. – 2006. – Vol. 85, Issue 5. – P. 1319–1340. doi: 10.1016/j.

fertnstert.2005.10.054

Age, insulin, SHBG and sex steroids exert secondary influence on plasma leptin level in women / T. Milewicz, J. Krzysiek, A. Janczak–Saif et al. //

Endokrynol. Pol. – 2005. – Vol. 56, Issue 6. – P. 883–890.

Inhibitory effect of obesity on gonadotropin, estradiol and inhibin b levels in fertile women / G. De Pergola, S. Maldera, M. Tartagni et al. // Obesity.

– 2006. – Vol. 14, Issue 11. – P. 1954–1960. doi: 10.1038/oby.2006.228

Baglietto, L. Circulating steroid hormone concentrations in postmenopausal women in relation to body size and composition / L. Baglietto, D. R.

English, J. L. Hopper // Breast Cancer Res. Treat. – 2009. – Vol. 115, Issue 1. – P. 171–179. doi: 10.1007/s10549-008-0069-3

Obesity and reproductive hormone levels in the transition to menopause / E. W. Freeman, M. D. Sammel, H. Lin, C. R. Gracia // Menopause. – 2010. –

Vol. 17, Issue 4. – P. 718–726. doi: 10.1097/gme.0b013e3181cec85d

Relationship of obesity–related disturbances with LH/FSH ratio among post–menopausal women in the United States / H. Beydoun, M. Beydoun,

N. Wiggins, L. Stadtmauer // Maturitas. – 2012. – Vol. 71, Issue 1. – P. 55–61. doi: 10.1016/j.maturitas.2011.10.010

Mah, P. M. Obesity and testicular function / P. M. Mah, G. A. Wittert // Molecular and Cellular Endocrinol. – 2009. – Vol. 316. – P. 180–186.

Androgens before and after weight loss in obese children / T. Reinehr, G. de Sousa, C. L. Roth, W. Andler // J. of Clin. Endocrinol. and Metabolism. –

– Vol. 90. – P. 5588–5595.

Maturation of luteinizing hormone secretion across puberty: evidence for altered regulation in obese peripubertal girls / C. R. McCartney, K. A. Prendergast, S. K. Blank et al. // J. of Clin. Endocrinol. and Metabolism. – 2009. – Vol. 94, Issue 1. – P. 56–66. doi: 10.1210/jc.2008-1252


GOST Style Citations


1. Aronne, L. J. (2002). Classification of obesity and assessment of obesity-related health risks. Obesity Research, 10 (S12), 105S–115S. doi: 10.1038/
oby.2002.203

2. Global Health Observatory (GHO) data. (2014). Overweight and obesity. Available at: http://www.who.int/gho/ncd/risk_factors/overweight_text/en/.

3. Pi–Sunyer, X. (2009). The Medical Risks of Obesity. Postgrad. Med., 121 (6), 21–33.

4. Birkebaek, N. H., Lange, A., Holland-Fischer, P., Kristensen, K., Rittig, S., Vilstrup, H. et al. (2010). Effect of weight reduction on insulin sensitivity,
sex hormone-binding globulin, sex hormones and gonadotrophins in obese children. European Journal of Endocrinology, 163 (6), 895–900. doi:
10.1530/eje-10-0538

5. Kirschner, M. A., Ertel, N., Schneider, G. (1981). Obesity, hormones, and cancer. Cancer Res., 41 (9 (2)), 3711–3717.

6. Kokkoris, P., Pi–Sunyer, Xavier. (2004). Obesity and endocrine disease. Endocrinology & Metabolism Clinics of North America, 32 (4), 895–914.

7. Wiklund, P., Toss, F., Weinehall, L., Hallmans, G., Franks, P. W., Nordström, A., Nordström, P. (2008). Abdominal and gynoid fat mass are associated with cardiovascular risk factors in men and women. The Journal of Clinical Endocrinology & Metabolism, 93 (11), 4360–4366. doi: 10.1210/jc.2008-0804

8. Hausman, D. B., DiGirolamo, M., Bartness, T. J., Hausman, G. J., Martin, R. J. (2001). The biology of white adipocyte proliferation. Obesity Reviews, 2 (4),
239–254. doi: 10.1046/j.1467-789x.2001.00042.x

9. McTernan, P. G., Anwar, A., Eggo, M. C., Barnett, A. H., Stewart, P. M., Kumar, S. (2000). Gender differences in the regulation of P450 aromatase
expression and activity in human adipose tissue. International Journal of Obesity, 24 (7), 875–881. doi: 10.1038/sj.ijo.0801254

10. Zahid, H., Simpson, E. R., Brown, K. A. (2016). Inflammation, dysregulated metabolism and aromatase in obesity and breast cancer. Current Opinion in Pharmacology, 31, 90–96. doi: 10.1016/j.coph.2016.11.003

11. Schneider, J., Bradlow, H. L., Strain, G., Levin, J., Anderson, K., Fishman, J. (1983). Effects of obesity on estradiol metabolism: decreased formation
of nonuterotropic metabolites. The Journal of Clinical Endocrinology & Metabolism, 56 (5), 973–978. doi: 10.1210/jcem-56-5-973

12. Cunningham, S. K., Loughlin, T., Culliton, M., McKenna, T. J. (1985). The Relationship between Sex Steroids and Sex-Hormone-Binding Globulin
in Plasma in Physiological and Pathological Conditions. Annals of Clinical Biochemistry: An International Journal of Biochemistry and Laboratory
Medicine, 22 (5), 489–497. doi: 10.1177/000456328502200504

13. Grasa, M., Gulfo, J., Camps, N., Alcalá, R., Monserrat, L., Moreno-Navarrete, J. M. et al. (2017). Modulation of SHBG binding to testosterone and
estradiol by sex and morbid obesity. European Journal of Endocrinology, EJE–16–0834. doi: 10.1530/eje-16-0834

14. Selby, C. (1990). Sex hormone binding globulin: origin, function and clinical significance. Annals of Clinical Biochemistry: An International Journal of Biochemistry and Laboratory Medicine, 27 (6), 532–541. doi:10.1177/000456329002700603

15. Dhindsa, S., Miller, M. G., McWhirter, C. L., Mager, D. E., Ghanim, H., Chaudhuri, A., Dandona, P. (2010). Testosterone Concentrations in Diabetic and
Nondiabetic Obese Men. Diabetes Care, 33 (6), 1186–1192. doi: 10.2337/dc09-1649

16. Giagulli, V. A. (1994). Pathogenesis of the decreased androgen levels in obese men. Journal of Clinical Endocrinology & Metabolism, 79 (4), 997–1000.
doi: 10.1210/jc.79.4.997

17. Wang, C., Jackson, G., Jones, T. H., Matsumoto, A. M., Nehra, A., Perelman, M. A. et al. (2011). Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care, 34 (7), 1669–1675.
doi:10.2337/dc10-2339

18. Rodriguez–Pacheco, F., Martinez–Fuentes, A. J., Tovar, S. et al. (2007). Regulation of pituitary cell function by adiponectin. Endocrinology, 148 (1), 401–410.

19. Hammoud, A. O., Gibson, M., Peterson, C. M. et al. (2006). Obesity and male reproductive potential. Journal of Andrology, 27 (5), 619–626. doi:
10.2164/jandrol.106.000125
20. Osuna C., J. A., Gómez-Pérez, R., Arata-Bellabarba, G., Villaroel, V. (2006). Relationship between bmi, total testosterone, sex hormonebindingglobulin, leptin, insulin and insulin resistance in obese men. Archives of Andrology, 52 (5), 355–361. doi: 10.1080/01485010600692017

21. Jastrzębska, S., Walczak–Jędrzejowska, R., Kramek, E. et al. (2014). Relationship between sexual function, body mass index and levels of sex steroid
hormones in young men. Endokrynol Pol., 65 (3), 203–209.

22. Cao, J., Chen, T., Hao, W., Li, J., Liu, L., Zhu, B., Li, X. (2012). Correlation between sex hormone levels and obesity in the elderly male. The Aging Male, 15 (2), 85–89. doi: 10.3109/13685538.2012.666585

23. Boonchaya–anant, P., Laichuthai, N., Suwannasrisuk, P., Houngngam, N., Udomsawaengsup, S., Snabboon T. (2016). Clinical study changes in testosterone levels and sex hormone–binding globulin levels in extremely obese men after bariatric surgery [Internet]. International Journal of Endocrinology. doi: 10.1155/2016/1416503

24. Facchiano, E., Scaringi, S., Veltri, M., Samavat, J., Maggi, M., Forti, G. et al. (2012). Age as a predictive factor of testosterone improvement in male patients after bariatric surgery: preliminary results of a monocentric prospective study. Obesity Surgery, 23 (2), 167–172. doi: 10.1007/s11695-012-0753-6

25. Reis, L. O., Favaro, W. J., Barreiro, G. C., De Oliveira, L. C., Chaim, E. A., Fregonesi, A., Ferreira, U. (2010). Erectile dysfunction and hormonal imbalance
in morbidly obese male is reversed after gastric bypass surgery: a prospective randomized controlled trial. International Journal of Andrology, 33 (5),
736–744. doi: 10.1111/j.1365-2605.2009.01017.x

26. Pasquali, R. (2003). Obesity and reproductive disorders in women. Human Reproduction Update, 9 (4), 359–372. doi: 10.1093/humupd/dmg024

27. Maddah, M., Jazayery, A., Mirdamadi, R., Eshraghiyan, M. R. (2002). Central obesity in women and its association with serum level of testosterone
and estradiol. J. Reprod. Infertil., 3 (4), 14–20.

28. Pasquali, R. (2006). Obesity and androgens: facts and perspectives. Fertility and Sterility, 85 (5), 1319–1340. doi: 10.1016/j.fertnstert.2005.10.054

29. Milewicz, T., Krzysiek, J., Janczak–Saif, A. et al. (2005). Age, insulin, SHBG and sex steroids exert secondary influence on plasma leptin level in
women. Endokrynol. Pol., 56 (6), 883–90.

30. De Pergola, G., Maldera, S., Tartagni, M., Pannacciulli, N., Loverro, G., Giorgino, R. (2006). Inhibitory effect of obesity on gonadotropin, estradiol,
and inhibin b levels in fertile women. Obesity, 14 (11), 1954–1960. doi: 10.1038/oby.2006.228

31. Baglietto, L., English, D. R., Hopper, J. L., MacInnis, R. J., Morris, H. A., Tilley, W. D. et al. (2009). Circulating steroid hormone concentrations in postmenopausal women in relation to body size and composition. Breast Cancer Research and Treatment, 115 (1), 171–179. doi: 10.1007/s10549-008-0069-3

32. Freeman, E. W., Sammel, M. D., Lin, H., Gracia, C. R. (2010). Obesity and reproductive hormone levels in the transition to menopause. Menopause., 17 (4), 718–726. doi: 10.1097/gme.0b013e3181cec85d

33. Beydoun, H. A., Beydoun, M. A., Wiggins, N., Stadtmauer, L. (2012). Relationship of obesity-related disturbances with LH/FSH ratio among postmenopausal women in the United States. Maturitas, 71 (1), 55–61. doi: 10.1016/j.maturitas.2011.10.010

34. Mah, P. M., Wittert, G. A. (2009). Obesity and testicular function. Molecular and Cellular Endocrinology, 316, 180–186.

35. Reinehr, T., de Sousa, G., Roth, C.L., Andler, W. (2005). Androgens before and after weight loss in obese children. Journal of Clinical Endocrinology
and Metabolism, 90, 5588–5595.

36. McCartney, C. R., Prendergast, K. A., Blank, S. K., Helm, K. D., Chhabra, S., Marshall, J. C. (2009). Maturation of Luteinizing Hormone (Gonadotropin-
Releasing Hormone) Secretion across Puberty: Evidence for Altered Regulation in Obese Peripubertal Girls. The Journal of Clinical Endocrinology
& Metabolism, 94 (1), 56–66. doi: 10.1210/jc.2008-1252





DOI: https://doi.org/10.24959/ubphj.17.90

Abbreviated key title: Ukr. bìofarm. ž.

ISSN 2519-8750 (Online), ISSN 2311-715X (Print)