Инсулинорезистентность у пациенток с ожирением приводит к нарушению менструального цикла опосредованно через гиперинсулинемию и гиперлептинемию. При выборе оптимального гестагена с целью коррекции нарушений менструального цикла необходимо учитывать его метаболические характеристики, чтобы не усугублять уже имеющиеся нарушения жирового и углеводного обмена.
Insulin resistance in patients with obesity leads to indirect menstrual cycle disruption through hyperinsulinemia and hyperleptinemy. In order to correct menstrual disorders, the metabolic characteristics of the optimal progestin should be considered, so that the already existing disorders of fat and carbohydrate metabolism may not be aggravated even more.
1. De Pergola G, Tartagni M, d'Angelo F et al. Abdominal fat accumulation, and not insulin resistance, is associated to oligomenorrhea in non-hyperandrogenic overweight/obese women. J Endocrinol Invest 2009; 32 (2): 98–101.
2. Poretsky L, Cataldo NA, Rosenwaks Z, Giudice LC. The insulin-related ovarian regulatory system in health and disease. Endocrine Review 1999; 20: 535–82.
3. Pasquali R, Gambineri A. Metabolic effects of obesity on reproduction. Reproductive Biomedicine Online 2006; 12: 542–51.
4. Matthaei S, Stumvoll M, Kellerer M, Haring HU. Pathophysiology and pharmacological treatment of insulin resistance. Endocrine Reviews 2000; 21: 585–618.
5. Kiddy DS, Hamilton-Fairley D, Bush A et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol 1992; 36: 105–11.
6. Pettigrew R, Hamilton-Fairley D. Obesity and female reproductive function. Brit Med Bulletin 1997; 53: 341–58.
7. Butzow TL, Lehtovirta M, Siegberg R et al. The decrease in luteinizing hormone secretion in response to weight reduction is inversely related to the severity of insulin resistance in overweight women. J Clin Endocrinol Metab 2000; 85: 3271–5.
8. Clark AM, Thornley B, Tomlinson L et al. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998; 13: 1502–5.
9. Zhang Y, Proenca R, Maffei M et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425–32.
10. Licinio J, Mantzoros C, Negrao AB et al. Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nature Med 1997; 3: 575–9.
11. Jin L, Zhang S, Burguera BG et al. Leptin and leptin receptor expression in rat and mouse pituitary cells. Endocrinol 2000; 141 (1): 333–9.
12. Karlsson C, Lindell K, Svensson E et al. Expression of functional leptin receptors in the human ovary. J Clin Endocrinol Metab 1997; 82 (12): 4144–8.
13. Kitawaki J, Koshiba H, Ishihara H et al. Expression of leptin receptor in human endometrium and fluctuation during the menstrual cycle. J Clin Endocrinol Metab 2000; 85 (5): 1946–50.
14. Saad MF, Riad-Gabriel MG, Khan A et al. Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity. J Clin Endocrin Metab 1998; 83: 453–9.
15. Чубриева С.Ю., Глухов Н.В., Зайчик А.М. Жировая ткань как эндокринный регулятор. Вестн. Санкт-Петербургского ун-та. 2008. Вып 1; с. 32–43.
16. Norman RJ, Clark AM. Obesity and reproductive disorders: a review. Reprod Fertil Development 1998; 10: 55–63.
17. Messinis IE, Milingos SD. Leptin in human reproduction. Hum Reprod Update 1999; 5: 52–63.
18. Tamer Erel C, Senturk LM. The impact of body mass index on assisted reproduction. Cur Opin Obstet Gynecol 2009; 21: 228–35.
19. Brannian JD, Hansen KA. Leptin and ovarian folliculogenesis: implications for ovulation induction and ART outcomes. Seminars Reprod Med 2002; 20: 103–12.
20. Moschos S, Chan JL, Mantzoros CS. Leptin and reproduction: a review. Fertil Steril 2002; 77: 433–44.
21. Cioffi JA, Van Blerkom J, Antczak M et al. The expression of leptin and its receptors in pre-ovulatory human follicles. Mol Hum Reprod 1997; 3: 467–72.
22. Karlsson C, Lindell K, Svensson E et al. Expression of functional leptin receptors in the human ovary. J Clin Endocrinol Metab 1997; 82: 4144–8.
23. Agarwal SK, Vogel K, Weitsman SR, Magoffin DA. Leptin antagonizes the insulin-like growth factor-I augmentation of steroidogenesis in granulosa and theca cells of the human ovary. J Clin Endocrinol Metab 1999; 84: 1072–6.
24. Cervero A, Horcajadas JA, Dominguez F et al. Leptin system in embryo development and implantation: a protein in search of a function. Reprod Biomed Online 2005; 10: 217–23.
25. Strobel A, Issad T, Camoin L et al. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 1998; 18: 213–5.
26. Castellucci M, De Matteis R, Meisser A et al. Leptin modulates extracellular matrix molecules and metalloproteinases: possible implications for trophoblast invasion. Mol Hum Reprod 2000; 6: 951–8.
27. Gonzalez RR, Caballero-Campo P, Jasper M et al. Leptin and leptin receptor are expressed in the human endometrium and endometrial leptin secretion is regulated by the human blastocyst. J Clin Endocrinol Metab 2000; 85: 4883–8.
28. Kawamura K, Sato N, Fukuda J et al. The role of leptin during the development of mouse preimplantation embryos. Mol Cell Endocrinol 2003; 202: 185–9.
29. Maffei M, Halaas J, Ravussin E et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Med 1995; 1: 1155–61.
30. Stamets K, Taylor DS, Kunselman A et al. A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome. Fertil Steril 2004; 81: 630–7.
31. Gosman GG, Katcher HI, Legro RS. Obesity and the role of gut and adipose hormones in female reproduction. Hum Reprod Update 2006; 12: 585–601.
32. Considine RV, Sinha MK, Heiman ML et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New Engl J Med 1996; 334: 292–5.
33. Brzechffa PR, Jakimiuk AJ, Agarwal SK et al. Serum immunoreactive leptin concentrations in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1996; 81: 4166–9.
34. Vicennati V, Gambineri A, Calzoni F et al. Serum leptin in obese women with polycystic ovary syndrome is correlated with body weight and fat distribution but not with androgen and insulin levels. Metab 1998; 47: 988–92.
35. El Orabi H, Ghalia AA, Khalifa A et al. Serum leptin as an additional possible pathogenic factor in polycystic ovary syndrome. Clin Biochem 1999; 32: 71–5.
36. Baranowska B, Radzikowska M, Wasilewska-Dziubinska E et al. Leptin, galanin and insulin in women with polycystic ovary syndrome. Gynecol Endocrinol 1999; 13: 344–51.
37. Sir-Petermann T, Piwonka V, Perez F et al. Are circulating leptin and luteinizing hormone synchronized in patients with polycystic ovary syndrome? Hum Reprod 1999; 14: 1435–9.
38. Krassas GE, Kaltsas TT, Pontikides N et al. Leptin levels in women with polycystic ovary syndrome before and after treatment with diazoxide. Eur J Endocrinol 1998; 139: 184–9.
39. Morin-Papunen LC, Koivunen RM, Tomas C et al. Decreased serum leptin concentrations during metformin therapy in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998; 83: 2566–8.
40. Pasquali R, Gambineri A, Biscotti D et al. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab 2000; 85: 2767–74.
41. Kowalska I, Kinalski M, Straczkowski M et al. Insulin, leptin, IGF-I and insulin-dependent protein concentrations after insulin-sensitizing therapy in obese women with polycystic ovary syndrome. Eur J Endocrinol 2001; 144: 509–15.
42. Межевитинова Е.А., Довлетханова Э.Р. Возможности применения дидрогестерона у женщин с недостаточностью лютеиновой фазы менструального цикла. Гинекология. 2010; 12 (3): 5–28.
43. Крапивина Н.А. Оптимизация лечения ожирения у женщин репродуктивного возраста. Автореф. дис. … канд. мед. наук. Кемерово, 2005.
44. Тиканова В.В. Дифференцированное лечение больных с нарушениями менструального цикла на фоне ожирения. Автореф. дис. … канд. мед. наук. М., 2005.
45. Morin-Papunen LC, Koivunen RM, Tomas C et al. Decrease serum leptin concentration during metformin therapy in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998; 83 (7): 2566–8.
46. Руководство по контрацепции. Под ред. В.Н.Прилепской. М.: МЕДпресс-информ, 2006.
47. Глазкова О.Л., Топольская И.В., Подзолкова Н.М. Динамика метаболического синдрома у больных с железисто-кистозной гиперплазией эндометрия на фоне гормональной терапии. Актуальные вопросы акушерства и гинекологии. Сб. науч. матер. Под ред. В.И.Кулакова, В.Н.Серова. 2001–2002; 1 (1): 146–7.
48. Чернуха Г.Е. Аденоматозная и железистая гиперплазия эндометрия в репродуктивном возрасте (патогенез, клиника, лечение). Дис. … д-ра мед. наук. М., 1999.
49. Clark AM, Thornley B, Tomlinson L et al. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998; 13: 1502–5.
50. Hahn S, Haselhorst U, Quadbeck B et al. Decreased soluble leptin receptor levels in women with polycystic ovary syndrome. Eur J Endocrinol 2006; 154 (2): 287–94.
51. Hollmann M, Runnebaum B, Gerhard I. Impact of waist-hip-ratio and body-mass-index on hormonal and metabolic parameters in young, obese women. Int J Obes Relat Metab Dis 1997; 21: 476–83.
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1. De Pergola G, Tartagni M, d'Angelo F et al. Abdominal fat accumulation, and not insulin resistance, is associated to oligomenorrhea in non-hyperandrogenic overweight/obese women. J Endocrinol Invest 2009; 32 (2): 98–101.
2. Poretsky L, Cataldo NA, Rosenwaks Z, Giudice LC. The insulin-related ovarian regulatory system in health and disease. Endocrine Review 1999; 20: 535–82.
3. Pasquali R, Gambineri A. Metabolic effects of obesity on reproduction. Reproductive Biomedicine Online 2006; 12: 542–51.
4. Matthaei S, Stumvoll M, Kellerer M, Haring HU. Pathophysiology and pharmacological treatment of insulin resistance. Endocrine Reviews 2000; 21: 585–618.
5. Kiddy DS, Hamilton-Fairley D, Bush A et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol 1992; 36: 105–11.
6. Pettigrew R, Hamilton-Fairley D. Obesity and female reproductive function. Brit Med Bulletin 1997; 53: 341–58.
7. Butzow TL, Lehtovirta M, Siegberg R et al. The decrease in luteinizing hormone secretion in response to weight reduction is inversely related to the severity of insulin resistance in overweight women. J Clin Endocrinol Metab 2000; 85: 3271–5.
8. Clark AM, Thornley B, Tomlinson L et al. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998; 13: 1502–5.
9. Zhang Y, Proenca R, Maffei M et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425–32.
10. Licinio J, Mantzoros C, Negrao AB et al. Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nature Med 1997; 3: 575–9.
11. Jin L, Zhang S, Burguera BG et al. Leptin and leptin receptor expression in rat and mouse pituitary cells. Endocrinol 2000; 141 (1): 333–9.
12. Karlsson C, Lindell K, Svensson E et al. Expression of functional leptin receptors in the human ovary. J Clin Endocrinol Metab 1997; 82 (12): 4144–8.
13. Kitawaki J, Koshiba H, Ishihara H et al. Expression of leptin receptor in human endometrium and fluctuation during the menstrual cycle. J Clin Endocrinol Metab 2000; 85 (5): 1946–50.
14. Saad MF, Riad-Gabriel MG, Khan A et al. Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity. J Clin Endocrin Metab 1998; 83: 453–9.
15. Чубриева С.Ю., Глухов Н.В., Зайчик А.М. Жировая ткань как эндокринный регулятор. Вестн. Санкт-Петербургского ун-та. 2008. Вып 1; с. 32–43.
16. Norman RJ, Clark AM. Obesity and reproductive disorders: a review. Reprod Fertil Development 1998; 10: 55–63.
17. Messinis IE, Milingos SD. Leptin in human reproduction. Hum Reprod Update 1999; 5: 52–63.
18. Tamer Erel C, Senturk LM. The impact of body mass index on assisted reproduction. Cur Opin Obstet Gynecol 2009; 21: 228–35.
19. Brannian JD, Hansen KA. Leptin and ovarian folliculogenesis: implications for ovulation induction and ART outcomes. Seminars Reprod Med 2002; 20: 103–12.
20. Moschos S, Chan JL, Mantzoros CS. Leptin and reproduction: a review. Fertil Steril 2002; 77: 433–44.
21. Cioffi JA, Van Blerkom J, Antczak M et al. The expression of leptin and its receptors in pre-ovulatory human follicles. Mol Hum Reprod 1997; 3: 467–72.
22. Karlsson C, Lindell K, Svensson E et al. Expression of functional leptin receptors in the human ovary. J Clin Endocrinol Metab 1997; 82: 4144–8.
23. Agarwal SK, Vogel K, Weitsman SR, Magoffin DA. Leptin antagonizes the insulin-like growth factor-I augmentation of steroidogenesis in granulosa and theca cells of the human ovary. J Clin Endocrinol Metab 1999; 84: 1072–6.
24. Cervero A, Horcajadas JA, Dominguez F et al. Leptin system in embryo development and implantation: a protein in search of a function. Reprod Biomed Online 2005; 10: 217–23.
25. Strobel A, Issad T, Camoin L et al. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 1998; 18: 213–5.
26. Castellucci M, De Matteis R, Meisser A et al. Leptin modulates extracellular matrix molecules and metalloproteinases: possible implications for trophoblast invasion. Mol Hum Reprod 2000; 6: 951–8.
27. Gonzalez RR, Caballero-Campo P, Jasper M et al. Leptin and leptin receptor are expressed in the human endometrium and endometrial leptin secretion is regulated by the human blastocyst. J Clin Endocrinol Metab 2000; 85: 4883–8.
28. Kawamura K, Sato N, Fukuda J et al. The role of leptin during the development of mouse preimplantation embryos. Mol Cell Endocrinol 2003; 202: 185–9.
29. Maffei M, Halaas J, Ravussin E et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Med 1995; 1: 1155–61.
30. Stamets K, Taylor DS, Kunselman A et al. A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome. Fertil Steril 2004; 81: 630–7.
31. Gosman GG, Katcher HI, Legro RS. Obesity and the role of gut and adipose hormones in female reproduction. Hum Reprod Update 2006; 12: 585–601.
32. Considine RV, Sinha MK, Heiman ML et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New Engl J Med 1996; 334: 292–5.
33. Brzechffa PR, Jakimiuk AJ, Agarwal SK et al. Serum immunoreactive leptin concentrations in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1996; 81: 4166–9.
34. Vicennati V, Gambineri A, Calzoni F et al. Serum leptin in obese women with polycystic ovary syndrome is correlated with body weight and fat distribution but not with androgen and insulin levels. Metab 1998; 47: 988–92.
35. El Orabi H, Ghalia AA, Khalifa A et al. Serum leptin as an additional possible pathogenic factor in polycystic ovary syndrome. Clin Biochem 1999; 32: 71–5.
36. Baranowska B, Radzikowska M, Wasilewska-Dziubinska E et al. Leptin, galanin and insulin in women with polycystic ovary syndrome. Gynecol Endocrinol 1999; 13: 344–51.
37. Sir-Petermann T, Piwonka V, Perez F et al. Are circulating leptin and luteinizing hormone synchronized in patients with polycystic ovary syndrome? Hum Reprod 1999; 14: 1435–9.
38. Krassas GE, Kaltsas TT, Pontikides N et al. Leptin levels in women with polycystic ovary syndrome before and after treatment with diazoxide. Eur J Endocrinol 1998; 139: 184–9.
39. Morin-Papunen LC, Koivunen RM, Tomas C et al. Decreased serum leptin concentrations during metformin therapy in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998; 83: 2566–8.
40. Pasquali R, Gambineri A, Biscotti D et al. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab 2000; 85: 2767–74.
41. Kowalska I, Kinalski M, Straczkowski M et al. Insulin, leptin, IGF-I and insulin-dependent protein concentrations after insulin-sensitizing therapy in obese women with polycystic ovary syndrome. Eur J Endocrinol 2001; 144: 509–15.
42. Межевитинова Е.А., Довлетханова Э.Р. Возможности применения дидрогестерона у женщин с недостаточностью лютеиновой фазы менструального цикла. Гинекология. 2010; 12 (3): 5–28.
43. Крапивина Н.А. Оптимизация лечения ожирения у женщин репродуктивного возраста. Автореф. дис. … канд. мед. наук. Кемерово, 2005.
44. Тиканова В.В. Дифференцированное лечение больных с нарушениями менструального цикла на фоне ожирения. Автореф. дис. … канд. мед. наук. М., 2005.
45. Morin-Papunen LC, Koivunen RM, Tomas C et al. Decrease serum leptin concentration during metformin therapy in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998; 83 (7): 2566–8.
46. Руководство по контрацепции. Под ред. В.Н.Прилепской. М.: МЕДпресс-информ, 2006.
47. Глазкова О.Л., Топольская И.В., Подзолкова Н.М. Динамика метаболического синдрома у больных с железисто-кистозной гиперплазией эндометрия на фоне гормональной терапии. Актуальные вопросы акушерства и гинекологии. Сб. науч. матер. Под ред. В.И.Кулакова, В.Н.Серова. 2001–2002; 1 (1): 146–7.
48. Чернуха Г.Е. Аденоматозная и железистая гиперплазия эндометрия в репродуктивном возрасте (патогенез, клиника, лечение). Дис. … д-ра мед. наук. М., 1999.
49. Clark AM, Thornley B, Tomlinson L et al. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998; 13: 1502–5.
50. Hahn S, Haselhorst U, Quadbeck B et al. Decreased soluble leptin receptor levels in women with polycystic ovary syndrome. Eur J Endocrinol 2006; 154 (2): 287–94.
51. Hollmann M, Runnebaum B, Gerhard I. Impact of waist-hip-ratio and body-mass-index on hormonal and metabolic parameters in young, obese women. Int J Obes Relat Metab Dis 1997; 21: 476–83.