Endocrine and metabolic disorders in women with polycystic ovary syndrome and new possibilities of their correction

Г. Б. Семенина

Abstract


The article presents the results of a survey of hormonal and exchange-metabolic balance in women with polycystic ovary syndrome (PCOS). Under supervision there were 67 women with PCOS and 30 healthy women (control group). Depending on the body mass index of patients they were also divided into the corresponding subgroups.

Analysis of results of exchange-metabolic surveys revealed that the clinical phenotype of PCOS with overweight characterized by a next combination: insulin resistance on an empty stomach, decreased insulin sensitivity, additive hyperinsulinemia and disorder of glucose utilization, high basal levels of cortisol and its suppression after glucose load, dyslipidemia with increased level of total cholesterol, lipoproteins low and very low density, triglycerides on an empty stomach and after load, and decreased level of high density lipoprotein. The clinical phenotype of PCOS with normal body weight was characterized by a tendency to abdominal accumulation of fat in the absence of excessive body weight, decreased the metabolic clearance of glucose and increased level of the two-hour glucose tolerance test of insulin and glucose on an empty stomach, basal hypercortisolemia and suppression of cortisol on the background of a glucose load, and dyslipidemia in the form of reduced levels of high density lipoproteins.

These changes are possible risk factors for the formation in women with PCOS the cardiovascular diseases, type II diabetes, and during pregnancy – gestational diabetes. In addition, women with PCOS are more likely to develop pregnancy complications such as miscarriage, fetal growth retardation syndrome, hypertension, the induced pregnancy and pre-eclampsia.

In order to prevent pregnancy complications in these women used the combined drug mesix containing a D-Chiro-inositol within 6 months. Evaluation of clinical and laboratory efficacy of treatment showed a positive effect on the menstrual cycle in 57.4%, on the hormonal balance in 78.9% and on exchange-metabolic disorders in 63.2% of patients with PCOS. In this connection, the author points out the need to study the effectiveness of a long-term use of this drug, taking into account its security and economic adequacy.


Keywords


polycystic ovary syndrome; hyperandrogenia; insulin resistance; hyperinsulinemia; D-Chiro-inositol

References


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Asada, H., Yamagata, Y., Taketani, T., et al.

“Potential link between estrogen receptor-alpha gene hypomethylation and uterine fibroid formation.” Mol Hum Reprod 14 (2008): 539–45.

Asuncion, M., Calvo, R.M., San Millan, J.L. “A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain.” J Clin Endocrinol Metab 105 (2010): 4434–38.

Azziz, R., Woods, K.S., Reyna, R. “The prevalence and feautures of the polycystic ovary syndrome in an unselected population.” J Clin Endocrinol Metab 89.6 (2007): 2745–9.

Balen, A.H., Conway, G.S., Kaltsas, G. “Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients.” Hum Reprod 10.8 (2009): 2107–11.

Belosi, C., Guiliani, M., Suriano, R., et al. “Diagnosis of polycystic ovary syndrome.” Minerva Ginecol 56.1 (2009): 7–13.

Carmina, E. “Diagnosis of polycystic ovary syndrome: from NIH criteria to ESHRE-ASRM guidelines.” Minerva Ginecol 56.1 (2011): 1–6.

Cederhоlm, J., Wibell, L. “Insulin release and peripheral sensitivity at the oral glucose tolerance test.” Diab Res Clin Pract 10 (1990): 167–75.

Cate, R.L., Mattaliano, R.J., Hession, C., et al. “Isolation of the bovine and human genes for Mullerian inhibiting substance and expression of the human gene in animal cells.“ Cell 45 (1986): 685–98.

Diamanti-Kandarakis, E., Kouli, C.R., Bergiele, A.T., et al. “A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile.” J Clin Endocrinol Metab 104 (2009): 4006–11.

Draveska, I., Lazurova, I., Kraus, V. “Obesity in the major factor determining an insulin sensitivity and androgen production in women with anovulatory cycles.” Bratisl Lek Listy 104.12 (2009): 393–9.

Drivsholm, T., Hansen, T., Urhammer, S.A., et al. “Assessment of insulin-sensitivity and beta-cell function from an oral glucose tolerance test.” Diabetologia 42.1 (1999): 185.

Dunaif, A. Diabetes mullitus and PCOS. Blackwell Sci Publ (2002): 238–347.

Durlinger, A.L, Visser, J.A. Themmen, A.P. “Regulation of ovarian function: the role of anti-Mullerian hormone.” Reprod 124 (2008): 601–9.

Geleijnse, Y.M., et al. ”Dietary intake of menaquinones is associated with a reduced risk of coronary heart disease.” Nutr Metab Cardiovas Dis 190 (2009): 1195–207.

Goverde, A.J., van Koert, A.J., Eijkemans, M.J., et al. “Indicators for metabolic disturbances in anovulatory women with polycystic ovary syndrome diagnosed according to the Rotterdam consensus criteria.“ Hum Reprod 24.3 (2009): 710–7.

Hirobe, S., He, W.W., Gustafson, M.L., et al. “Mullerian inhibiting substance gene expression in the cycling rat ovary correlates with recruited or graafian follicle selection.” Biol Reprod 50 (2007): 1238–43.

Homocysteine Lowering Trialists’ Collaboration. “Dose-dependent effects of folic acid and blood concentrations of homocysteine: a meta-analysis of the randomized trials.” Am Y Clin Nutr 82 (2005): 806–12.

Kazerooni, T., Asadi, N., Dehbashi, S., Zalghadriy, Y. “Effect of folic acid in woman with and without insulin resistance who have hyperhomocysteinemic polycystic ovary syndrome.” Int Y Gynecol Obstet 101.2 (2008): 156–60.

Klentzeris, L.D. “The role of endometrium in implantation.“ Hum Reprod 7.12 (2007): 1170–5.

Knochenhauer, E.S., Key, T.J., Kahsar-Miller, M. “Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study.” J Clin Endocrinol Metab 83 (2008): 3078–82.

Larher, G. ”D-chiro-inositol: its functional role in insulin action and its deficit in insulin resistance.” Int J Exp Diab Res 402 (2012): 1716–21.

Lee, M.M., Donahoe, P.K. “Mullerian Inhibiting Substance: a gonadal hormone with multiple functions.” Endocr Rew 14.1 (2009): 152–64.

Leopoldini, M., et al. “On the inhibitor effects of bergamot juice flavonoids bilding to the 3-hydroxy-3-methylglutaryl- CoA reductase (HMGR) enzyme.” Y Agric Dood Chem 55 (2010): 618–23.

Li, Y., et al. “A meta-analysis of red yeast rice: on effective and relatively safe alternative approach for dyslipidemia.” PLOS One (2004): 277–311.

Liu, G. ”Chinese red yeast rice (Monascus purpurens) for primary hyper with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placontrolled-lipidemia: a meta-analysis of randomized controlled trials.” Chin Med 89 (2006): 53–61.

Matsuda, M., DeFronzo, R.A. “Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the еuglycemic insulin clamp.” Diab Care 22 (1999): 1462–70.

Mattews, D.R., Hоsker, J.P., Rudenski, A.S., et al. “Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentratіon in man.” Diabetologia 28 (1985): 412–9.

Mollace, V., et al. “Hipolipemic and hypoglycaemic activity of bergamot polyphenols: from animale models to human studies.” Fitoterapia (2010): 216–27.

Oehler, M.K., Rees, M.C., Bicknell, R. “Steroids and the endometrium.” Curr Med Chem 7.5 (2010): 543–60.

Rotterdam ESHRE/ASRM Sposored PCOS Consensus Workshop Group. “Revised 2003 consensus on diagnostic criteria and longterm health risks related to polycystic ovary syndrome.” Fertil Steril 81 (2004): 19–25.

Seifer, D.B., MacLaughlin, D.T., Christian, B.P., et al. “Early follicular serum mullerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles.” Fertil Steril 77 (2009): 468–71.

Seltzer, H.S., Allen, W., Herron, A.L., Brennan, M.T. “Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus.” J Clin Invest 46 (1967): 323–34.

Silfen, M.E., Denburg, M.R., Manibo, A.M., et al. “Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese adolescents.” J Clin Endocrinol Metab 88.10 (2009): 4682–8.

Sivan, E., Boden, G. “Free fatty acids, insulin resistance, and pregnancy.” Curr Diab Rep 3 (2008): 319–22.

Solomon, C.G., Hu, F.B., Dunaif, A., et al. “Long or highly irregular menstrual cycles as a marker for risk of type 2 diabetes mellitus.” JAMA 286 (2010): 2421–6.

Stumvoll, M., Mitrakov, A., Pimenta W., et al. “Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity.” Diab Care 23 (2000): 295–301.

Willems, F.F., et al. “Pharmacokinetic study on the utilization of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease.” Pharmacol 195 (2004): 815–21.


GOST Style Citations


1. Семенина, Г.Б. Акушерські та перинатальні ускладнення у третьому триместрі вагітності в жінок із яєчниковою та наднирковою формою гіперандрогенії / Г.Б. Семенина // Практична медицина. – 2011. – Т. XVII, № 3 . – С. 3–8.

2. Asada, H., Yamagata, Y., Taketani, T., et al.

“Potential link between estrogen receptor-alpha gene hypomethylation and uterine fibroid formation.” Mol Hum Reprod 14 (2008): 539–45.

3. Asuncion, M., Calvo, R.M., San Millan, J.L. “A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain.” J Clin Endocrinol Metab 105 (2010): 4434–38.

4. Azziz, R., Woods, K.S., Reyna, R. “The prevalence and feautures of the polycystic ovary syndrome in an unselected population.” J Clin Endocrinol Metab 89.6 (2007): 2745–9.

5. Balen, A.H., Conway, G.S., Kaltsas, G. “Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients.” Hum Reprod 10.8 (2009): 2107–11.

6. Belosi, C., Guiliani, M., Suriano, R., et al. “Diagnosis of polycystic ovary syndrome.” Minerva Ginecol 56.1 (2009): 7–13.

7. Carmina, E. “Diagnosis of polycystic ovary syndrome: from NIH criteria to ESHRE-ASRM guidelines.” Minerva Ginecol 56.1 (2011): 1–6.

8. Cederhоlm, J., Wibell, L. “Insulin release and peripheral sensitivity at the oral glucose tolerance test.” Diab Res Clin Pract 10 (1990): 167–75.

9. Cate, R.L., Mattaliano, R.J., Hession, C., et al. “Isolation of the bovine and human genes for Mullerian inhibiting substance and expression of the human gene in animal cells.“ Cell 45 (1986): 685–98.

10. Diamanti-Kandarakis, E., Kouli, C.R., Bergiele, A.T., et al. “A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile.” J Clin Endocrinol Metab 104 (2009): 4006–11.

11. Draveska, I., Lazurova, I., Kraus, V. “Obesity in the major factor determining an insulin sensitivity and androgen production in women with anovulatory cycles.” Bratisl Lek Listy 104.12 (2009): 393–9.

12. Drivsholm, T., Hansen, T., Urhammer, S.A., et al. “Assessment of insulin-sensitivity and beta-cell function from an oral glucose tolerance test.” Diabetologia 42.1 (1999): 185.

13. Dunaif, A. Diabetes mullitus and PCOS. Blackwell Sci Publ (2002): 238–347.

14. Durlinger, A.L, Visser, J.A. Themmen, A.P. “Regulation of ovarian function: the role of anti-Mullerian hormone.” Reprod 124 (2008): 601–9.

15. Geleijnse, Y.M., et al. ”Dietary intake of menaquinones is associated with a reduced risk of coronary heart disease.” Nutr Metab Cardiovas Dis 190 (2009): 1195–207.

16. Goverde, A.J., van Koert, A.J., Eijkemans, M.J., et al. “Indicators for metabolic disturbances in anovulatory women with polycystic ovary syndrome diagnosed according to the Rotterdam consensus criteria.“ Hum Reprod 24.3 (2009): 710–7.

17. Hirobe, S., He, W.W., Gustafson, M.L., et al. “Mullerian inhibiting substance gene expression in the cycling rat ovary correlates with recruited or graafian follicle selection.” Biol Reprod 50 (2007): 1238–43.

18. Homocysteine Lowering Trialists’ Collaboration. “Dose-dependent effects of folic acid and blood concentrations of homocysteine: a meta-analysis of the randomized trials.” Am Y Clin Nutr 82 (2005): 806–12.

19. Kazerooni, T., Asadi, N., Dehbashi, S., Zalghadriy, Y. “Effect of folic acid in woman with and without insulin resistance who have hyperhomocysteinemic polycystic ovary syndrome.” Int Y Gynecol Obstet 101.2 (2008): 156–60.

20. Klentzeris, L.D. “The role of endometrium in implantation.“ Hum Reprod 7.12 (2007): 1170–5.

21. Knochenhauer, E.S., Key, T.J., Kahsar-Miller, M. “Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study.” J Clin Endocrinol Metab 83 (2008): 3078–82.

22. Larher, G. ”D-chiro-inositol: its functional role in insulin action and its deficit in insulin resistance.” Int J Exp Diab Res 402 (2012): 1716–21.

23. Lee, M.M., Donahoe, P.K. “Mullerian Inhibiting Substance: a gonadal hormone with multiple functions.” Endocr Rew 14.1 (2009): 152–64.

24. Leopoldini, M., et al. “On the inhibitor effects of bergamot juice flavonoids bilding to the 3-hydroxy-3-methylglutaryl- CoA reductase (HMGR) enzyme.” Y Agric Dood Chem 55 (2010): 618–23.

25. Li, Y., et al. “A meta-analysis of red yeast rice: on effective and relatively safe alternative approach for dyslipidemia.” PLOS One (2004): 277–311.

26. Liu, G. ”Chinese red yeast rice (Monascus purpurens) for primary hyper with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placontrolled-lipidemia: a meta-analysis of randomized controlled trials.” Chin Med 89 (2006): 53–61.

27. Matsuda, M., DeFronzo, R.A. “Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the еuglycemic insulin clamp.” Diab Care 22 (1999): 1462–70.

28. Mattews, D.R., Hоsker, J.P., Rudenski, A.S., et al. “Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentratіon in man.” Diabetologia 28 (1985): 412–9.

29. Mollace, V., et al. “Hipolipemic and hypoglycaemic activity of bergamot polyphenols: from animale models to human studies.” Fitoterapia (2010): 216–27.

30. Oehler, M.K., Rees, M.C., Bicknell, R. “Steroids and the endometrium.” Curr Med Chem 7.5 (2010): 543–60.

31. Rotterdam ESHRE/ASRM Sposored PCOS Consensus Workshop Group. “Revised 2003 consensus on diagnostic criteria and longterm health risks related to polycystic ovary syndrome.” Fertil Steril 81 (2004): 19–25.

32. Seifer, D.B., MacLaughlin, D.T., Christian, B.P., et al. “Early follicular serum mullerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles.” Fertil Steril 77 (2009): 468–71.

33. Seltzer, H.S., Allen, W., Herron, A.L., Brennan, M.T. “Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus.” J Clin Invest 46 (1967): 323–34.

34. Silfen, M.E., Denburg, M.R., Manibo, A.M., et al. “Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese adolescents.” J Clin Endocrinol Metab 88.10 (2009): 4682–8.

35. Sivan, E., Boden, G. “Free fatty acids, insulin resistance, and pregnancy.” Curr Diab Rep 3 (2008): 319–22.

36. Solomon, C.G., Hu, F.B., Dunaif, A., et al. “Long or highly irregular menstrual cycles as a marker for risk of type 2 diabetes mellitus.” JAMA 286 (2010): 2421–6.

37. Stumvoll, M., Mitrakov, A., Pimenta W., et al. “Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity.” Diab Care 23 (2000): 295–301.

38. Willems, F.F., et al. “Pharmacokinetic study on the utilization of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease.” Pharmacol 195 (2004): 815–21.





DOI: http://dx.doi.org/10.18370/2309-4117.2016.32.69-76

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