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Основные принципы диагностики и лечения синдрома гиперандрогении (обзор литературы)
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Аннотация
Синдром гиперандрогении (СГА) объединяет ряд заболеваний/состояний, ассоциированных с избыточной продукцией андрогенов в женском организме или повышением чувствительности к ним гормонозависимых органов. Нозологические варианты СГА распределяются от изолированных поражений кожи и ее придатков до системных заболеваний, сопровождающихся высоким риском метаболических расстройств, сердечно-сосудистой и онкологической патологии, бесплодия, гиперпластических процессов репродуктивной системы. Алгоритмы ведения таких больных отрабатываются в эндокринологии, гинекологии и дерматологии, но в реальной практике междисциплинарный подход к их ведению наблюдается редко. В большинстве случаев клиницистам не удается избежать полипрагмазии при планировании лечения, и число препаратов, способных оказать многоплановое действие, невелико. Это определяет необходимость продолжения поиска лекарственных, в том числе гормональных стратегий лечения больных СГА в зависимости от преимущественных проявлений эндокринопатии.
Ключевые слова: гиперандрогения, синдром поликистозных яичников, гирсутизм, акне, комбинированные оральные контрацептивы, хлормадинона ацетат.
Ключевые слова: гиперандрогения, синдром поликистозных яичников, гирсутизм, акне, комбинированные оральные контрацептивы, хлормадинона ацетат.
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The hyperandrogenism syndrome (HAS) brings together a number of diseases/conditions associated with excessive production of androgens in the female body, or increased sensitivity to them in hormone- dependent organs. Nosological SGA forms range from isolated lesions of the skin and its appendages to systemic diseases associated with a high risk of metabolic disorders, cardiovascular disease, infertility, hyperplastic processes of the reproductive system and cancer. Algorithms for management of these patients are processed in endocrinology, gynecology and dermatology, but in actual practice, a multidisciplinary approach to the management of patients is rare. In most cases, clinicians cannot avoid polypharmacy in treatment planning, and the number of medications that can have a multi-dimensional effect is small. This determines the need of continuing the search for drugs, including hormonal treatment strategies for patients with HAS, depending on the endocrinopathy primary display.
Key words: hyperandrogenism, polycystic ovary syndrome, hirsutism, acne, combined oral contraceptives, chlormadinone acetate.
Полный текст
Список литературы
1. Futterweit W, Nestler J, Reaven G. American Association of Clinical Endocrinologists. Position Statement on Metabolic and Cardiovascular Consequences of Polycystic Ovary Syndrome. Endocrine Practice 2005; 11 (2): 125–30.
2. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005; 352: 1223–36.
3. Escobar-Morreale HF. Polycystic ovary syndrome: treatment strategies and management. Expert Opin Pharmacother 2008; 9 (17): 2995–3008.
4. Azziz R, Carmina E, Dewailly D et al. The androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report. Task force on the phenotype of the polycystic ovary syndrome of the androgen excess and PCOS society. Fertil Steril 2009; 91: 456–88.
5. Azziz R, Sanchez LA, Knochenhauer ES et al. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab 2004; 89: 453–62.
6. Carmina E, Rosato F, Janni A et al. Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism. J Clin Endocrinol Metab 2006; 91: 2–6.
7. Kaltsas GA, Isidori AM, Kola BP et al. The value of the low-dose dexamethasone suppression test in the differential diagnosis of hyperandrogenism in women. J Clin Endocrinol Metab 2003; 88: 2634–43.
8. Escobar-Morreale HF, Sanchуn R, San Millon JL. A prospective study of the prevalence of nonclassical congenital adrenal hyperplasia among women presenting with hyperandrogenic symptoms and signs. J Clin Endocrinol Metab 2008; 93 (2): 527–33.
9. Schaefer I, Rustenbach SJ, Zimmer L et al. Prevalence of skin diseases in a cohort of 48,665 employees in Germany. Dermatology 2008; 217 (2): 169–72.
10. Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med 2005; 353: 2578–88.
11. Hahn S, Janssen OE, Tan S, Pleger K. Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome. Eur J Endocrinol 2005; 153: 853–60.
12. Himelein MJ, Thatcher SS. Polycystic ovary syndrome and mental health. A review. Obstet Gynecol Surv 2006; 61 (11): 723–32.
13. Ching HL, Burke V, Stuckey BGA. Quality of Life and Psychological Morbidity in Women with Polycystic Ovary Syndrome: Body Mass Index, Age and the Provision of Patient Information Are Significant Modifiers. Clin Endocrinol 2007; 66 (3): 373–9.
14. Elsenbruch S, Hahn S, Kowalsky D. Quality of life, psychosocial well-being, and sexual satisfaction in women with polycystic ovary syndrome.
J Clin Endocrinol Metab 2003; 88 (12): 5801–7.
15. Halvorsen JA, Dalgard F, Thoresen M. Is the association between acne and mental distress influenced by diet? Results from a crosssectional population study among 3775 late adolescents in Oslo, Norway. BMC Public Health 2009; 9: 340.
16. Azziz R, Woods KS, Reyna R et al. The prevalence and features of the polycystic ovary syndrome in unselected population. J Clin Endocrinol Metab 2004; 89: 2745–9.
17. Collier CN, Harper JC, Cafardi JA. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol 2008; 58 (1): 56–9.
18. Balen A, Laven J, Tan S. Ultrasound assessment of polycystic ovary: international consensus definitions. Human Reproduction Update 2003; 9 (6): 505–14.
19. Buggs C, Rosenfield RL. Polycystic ovary syndrome in adolescence. Endocrinol Metab Clin North Am 2005; 34: 677–705.
20. Martin KA, Chang RJ, Ehrmann DA et al. Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society Clinical Practice Guideline. J Clin Endocr Metab 2008; 93 (4): 1105–20.
21. Stener-Victorin E, ran Holm G, Labrie F et al. Are There Any Sensitive and Specific Sex Steroid Markers for Polycystic Ovary Syndrome? J Clin Endocrinol Metab 2010; 95: 810–9.
22. Souter I, Sanchez LA, Perez M et al. The prevalence of androgen excess among patients with minimal unwanted hair growth. Am J Obstet Gynecol 2004; 191: 1914–20.
23. Cho LW, Kilpatrick ES, Jayagopal V. Biological variation of total testosterone, free androgen index and bioavailable testosterone in polycystic ovarian syndrome: implications for identifying hyperandrogenaemia. Clin Endocrinol (Oxf) 2008; 68 (3): 390–4.
24. Practice Committee of the American Society for Reproductive Medicine. The evaluation and treatment of androgen excess. Fertil Steril 2006; 86: S241–7.
25. 2004 Revised 2003 consensus on diagnostic criteria and longterm health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19–25.
26. Townsend KA, Marlowe KF. Relative safety and efficacy of finasteride for treatment of hirsutism. Ann Pharmacother 2004; 38: 1070–3.
27. Inal MM, Yildirim Y, Taner CE. Comparison of the clinical efficacy of flutamide and spironolactone plus Diane 35 in the treatment of idiopathic hirsutism: a randomized controlled study. Fertil Steril 2005; 84: 1693–7.
28. Osculati A, Castiglioni C. Fatal liver complications with flutamide. Lancet 2006; 367: 1140–1.
29. Calaf J, Lopez E, Millet A et al. Long-term efficacy and tolerability of flutamide combined with oral contraception in moderate to severe hirsutism: a 12-month, double-blind, parallel clinical trial. J Clin Endocrinol Metab 2007; 92: 3446–52.
30. Tang T, Lord JM, Norman RJ. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database of Systematic Reviews 2010. Issue 1. Art. No.: CD003053. Doi: 10.1002/14651858. CD003053.pub4.
31. Доброхотова Ю.Э., Корсунская И.М., Джобава Э.М. Андрогензависимая дермопатия как проявление синдрома гиперандрогении: методы коррекции. Гинекология. 2006; 8 (5): 34–7.
32. Nader S, Aamanti-Kandarakis E. Polycystic ovary syndrome, oral contraceptives and metabolic issues: new perspectives and a unifying hypothesis. Hum Reprod 2007; 22 (2): 317–22.
33. Zouboulis CC, Chen WC, Thornton MJ et al. Sexual hormones in human skin. Horm Metab Res 2007; 39: 85–95.
34. Van der Spuy ZM, le Roux PA. Cyproterone acetate for hirsutism. Cochrane Database of Systematic Reviews 2003; 4: CD001125.
35. Batukan C, Muderris, II, Ozcelik B, Ozturk A. Comparison of two oral contraceptives containing either drospirenone or cyproterone acetate in the treatment of hirsutism. Gynecol Endocrinol 2007; 23: 38–44.
36. Raudrant D, Rabe T. Progestogens with antiandrogenic properties. Drugs 2003; 63: 463–92.
37. Schramm G, Steffens D. A 12-month evaluation of the CMA – containing oral contraceptive Belara: efficacy, tolerability and ANTI – androgenic properties. Contraception 2003; 67: 305–12.
38. Zahradnik HP. Belara – a reliable oral contraceptive with additional benefits for health and efficacy in dysmenorrhea. Eur J Contracept Reprod Health Care 2005; 10: 8–12.
39. Worret I, 2001 CMA 2mg/EE 0.03 mg (n=101) vs LNG 0.15mg/EE 0.03mg (n=98) for 12 cycles, phase III, single-blind, randomized CT.
2. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005; 352: 1223–36.
3. Escobar-Morreale HF. Polycystic ovary syndrome: treatment strategies and management. Expert Opin Pharmacother 2008; 9 (17): 2995–3008.
4. Azziz R, Carmina E, Dewailly D et al. The androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report. Task force on the phenotype of the polycystic ovary syndrome of the androgen excess and PCOS society. Fertil Steril 2009; 91: 456–88.
5. Azziz R, Sanchez LA, Knochenhauer ES et al. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab 2004; 89: 453–62.
6. Carmina E, Rosato F, Janni A et al. Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism. J Clin Endocrinol Metab 2006; 91: 2–6.
7. Kaltsas GA, Isidori AM, Kola BP et al. The value of the low-dose dexamethasone suppression test in the differential diagnosis of hyperandrogenism in women. J Clin Endocrinol Metab 2003; 88: 2634–43.
8. Escobar-Morreale HF, Sanchуn R, San Millon JL. A prospective study of the prevalence of nonclassical congenital adrenal hyperplasia among women presenting with hyperandrogenic symptoms and signs. J Clin Endocrinol Metab 2008; 93 (2): 527–33.
9. Schaefer I, Rustenbach SJ, Zimmer L et al. Prevalence of skin diseases in a cohort of 48,665 employees in Germany. Dermatology 2008; 217 (2): 169–72.
10. Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med 2005; 353: 2578–88.
11. Hahn S, Janssen OE, Tan S, Pleger K. Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome. Eur J Endocrinol 2005; 153: 853–60.
12. Himelein MJ, Thatcher SS. Polycystic ovary syndrome and mental health. A review. Obstet Gynecol Surv 2006; 61 (11): 723–32.
13. Ching HL, Burke V, Stuckey BGA. Quality of Life and Psychological Morbidity in Women with Polycystic Ovary Syndrome: Body Mass Index, Age and the Provision of Patient Information Are Significant Modifiers. Clin Endocrinol 2007; 66 (3): 373–9.
14. Elsenbruch S, Hahn S, Kowalsky D. Quality of life, psychosocial well-being, and sexual satisfaction in women with polycystic ovary syndrome.
J Clin Endocrinol Metab 2003; 88 (12): 5801–7.
15. Halvorsen JA, Dalgard F, Thoresen M. Is the association between acne and mental distress influenced by diet? Results from a crosssectional population study among 3775 late adolescents in Oslo, Norway. BMC Public Health 2009; 9: 340.
16. Azziz R, Woods KS, Reyna R et al. The prevalence and features of the polycystic ovary syndrome in unselected population. J Clin Endocrinol Metab 2004; 89: 2745–9.
17. Collier CN, Harper JC, Cafardi JA. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol 2008; 58 (1): 56–9.
18. Balen A, Laven J, Tan S. Ultrasound assessment of polycystic ovary: international consensus definitions. Human Reproduction Update 2003; 9 (6): 505–14.
19. Buggs C, Rosenfield RL. Polycystic ovary syndrome in adolescence. Endocrinol Metab Clin North Am 2005; 34: 677–705.
20. Martin KA, Chang RJ, Ehrmann DA et al. Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society Clinical Practice Guideline. J Clin Endocr Metab 2008; 93 (4): 1105–20.
21. Stener-Victorin E, ran Holm G, Labrie F et al. Are There Any Sensitive and Specific Sex Steroid Markers for Polycystic Ovary Syndrome? J Clin Endocrinol Metab 2010; 95: 810–9.
22. Souter I, Sanchez LA, Perez M et al. The prevalence of androgen excess among patients with minimal unwanted hair growth. Am J Obstet Gynecol 2004; 191: 1914–20.
23. Cho LW, Kilpatrick ES, Jayagopal V. Biological variation of total testosterone, free androgen index and bioavailable testosterone in polycystic ovarian syndrome: implications for identifying hyperandrogenaemia. Clin Endocrinol (Oxf) 2008; 68 (3): 390–4.
24. Practice Committee of the American Society for Reproductive Medicine. The evaluation and treatment of androgen excess. Fertil Steril 2006; 86: S241–7.
25. 2004 Revised 2003 consensus on diagnostic criteria and longterm health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19–25.
26. Townsend KA, Marlowe KF. Relative safety and efficacy of finasteride for treatment of hirsutism. Ann Pharmacother 2004; 38: 1070–3.
27. Inal MM, Yildirim Y, Taner CE. Comparison of the clinical efficacy of flutamide and spironolactone plus Diane 35 in the treatment of idiopathic hirsutism: a randomized controlled study. Fertil Steril 2005; 84: 1693–7.
28. Osculati A, Castiglioni C. Fatal liver complications with flutamide. Lancet 2006; 367: 1140–1.
29. Calaf J, Lopez E, Millet A et al. Long-term efficacy and tolerability of flutamide combined with oral contraception in moderate to severe hirsutism: a 12-month, double-blind, parallel clinical trial. J Clin Endocrinol Metab 2007; 92: 3446–52.
30. Tang T, Lord JM, Norman RJ. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database of Systematic Reviews 2010. Issue 1. Art. No.: CD003053. Doi: 10.1002/14651858. CD003053.pub4.
31. Доброхотова Ю.Э., Корсунская И.М., Джобава Э.М. Андрогензависимая дермопатия как проявление синдрома гиперандрогении: методы коррекции. Гинекология. 2006; 8 (5): 34–7.
32. Nader S, Aamanti-Kandarakis E. Polycystic ovary syndrome, oral contraceptives and metabolic issues: new perspectives and a unifying hypothesis. Hum Reprod 2007; 22 (2): 317–22.
33. Zouboulis CC, Chen WC, Thornton MJ et al. Sexual hormones in human skin. Horm Metab Res 2007; 39: 85–95.
34. Van der Spuy ZM, le Roux PA. Cyproterone acetate for hirsutism. Cochrane Database of Systematic Reviews 2003; 4: CD001125.
35. Batukan C, Muderris, II, Ozcelik B, Ozturk A. Comparison of two oral contraceptives containing either drospirenone or cyproterone acetate in the treatment of hirsutism. Gynecol Endocrinol 2007; 23: 38–44.
36. Raudrant D, Rabe T. Progestogens with antiandrogenic properties. Drugs 2003; 63: 463–92.
37. Schramm G, Steffens D. A 12-month evaluation of the CMA – containing oral contraceptive Belara: efficacy, tolerability and ANTI – androgenic properties. Contraception 2003; 67: 305–12.
38. Zahradnik HP. Belara – a reliable oral contraceptive with additional benefits for health and efficacy in dysmenorrhea. Eur J Contracept Reprod Health Care 2005; 10: 8–12.
39. Worret I, 2001 CMA 2mg/EE 0.03 mg (n=101) vs LNG 0.15mg/EE 0.03mg (n=98) for 12 cycles, phase III, single-blind, randomized CT.
________________________________________________
1. Futterweit W, Nestler J, Reaven G. American Association of Clinical Endocrinologists. Position Statement on Metabolic and Cardiovascular Consequences of Polycystic Ovary Syndrome. Endocrine Practice 2005; 11 (2): 125–30.
2. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005; 352: 1223–36.
3. Escobar-Morreale HF. Polycystic ovary syndrome: treatment strategies and management. Expert Opin Pharmacother 2008; 9 (17): 2995–3008.
4. Azziz R, Carmina E, Dewailly D et al. The androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report. Task force on the phenotype of the polycystic ovary syndrome of the androgen excess and PCOS society. Fertil Steril 2009; 91: 456–88.
5. Azziz R, Sanchez LA, Knochenhauer ES et al. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab 2004; 89: 453–62.
6. Carmina E, Rosato F, Janni A et al. Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism. J Clin Endocrinol Metab 2006; 91: 2–6.
7. Kaltsas GA, Isidori AM, Kola BP et al. The value of the low-dose dexamethasone suppression test in the differential diagnosis of hyperandrogenism in women. J Clin Endocrinol Metab 2003; 88: 2634–43.
8. Escobar-Morreale HF, Sanchуn R, San Millon JL. A prospective study of the prevalence of nonclassical congenital adrenal hyperplasia among women presenting with hyperandrogenic symptoms and signs. J Clin Endocrinol Metab 2008; 93 (2): 527–33.
9. Schaefer I, Rustenbach SJ, Zimmer L et al. Prevalence of skin diseases in a cohort of 48,665 employees in Germany. Dermatology 2008; 217 (2): 169–72.
10. Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med 2005; 353: 2578–88.
11. Hahn S, Janssen OE, Tan S, Pleger K. Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome. Eur J Endocrinol 2005; 153: 853–60.
12. Himelein MJ, Thatcher SS. Polycystic ovary syndrome and mental health. A review. Obstet Gynecol Surv 2006; 61 (11): 723–32.
13. Ching HL, Burke V, Stuckey BGA. Quality of Life and Psychological Morbidity in Women with Polycystic Ovary Syndrome: Body Mass Index, Age and the Provision of Patient Information Are Significant Modifiers. Clin Endocrinol 2007; 66 (3): 373–9.
14. Elsenbruch S, Hahn S, Kowalsky D. Quality of life, psychosocial well-being, and sexual satisfaction in women with polycystic ovary syndrome.
J Clin Endocrinol Metab 2003; 88 (12): 5801–7.
15. Halvorsen JA, Dalgard F, Thoresen M. Is the association between acne and mental distress influenced by diet? Results from a crosssectional population study among 3775 late adolescents in Oslo, Norway. BMC Public Health 2009; 9: 340.
16. Azziz R, Woods KS, Reyna R et al. The prevalence and features of the polycystic ovary syndrome in unselected population. J Clin Endocrinol Metab 2004; 89: 2745–9.
17. Collier CN, Harper JC, Cafardi JA. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol 2008; 58 (1): 56–9.
18. Balen A, Laven J, Tan S. Ultrasound assessment of polycystic ovary: international consensus definitions. Human Reproduction Update 2003; 9 (6): 505–14.
19. Buggs C, Rosenfield RL. Polycystic ovary syndrome in adolescence. Endocrinol Metab Clin North Am 2005; 34: 677–705.
20. Martin KA, Chang RJ, Ehrmann DA et al. Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society Clinical Practice Guideline. J Clin Endocr Metab 2008; 93 (4): 1105–20.
21. Stener-Victorin E, ran Holm G, Labrie F et al. Are There Any Sensitive and Specific Sex Steroid Markers for Polycystic Ovary Syndrome? J Clin Endocrinol Metab 2010; 95: 810–9.
22. Souter I, Sanchez LA, Perez M et al. The prevalence of androgen excess among patients with minimal unwanted hair growth. Am J Obstet Gynecol 2004; 191: 1914–20.
23. Cho LW, Kilpatrick ES, Jayagopal V. Biological variation of total testosterone, free androgen index and bioavailable testosterone in polycystic ovarian syndrome: implications for identifying hyperandrogenaemia. Clin Endocrinol (Oxf) 2008; 68 (3): 390–4.
24. Practice Committee of the American Society for Reproductive Medicine. The evaluation and treatment of androgen excess. Fertil Steril 2006; 86: S241–7.
25. 2004 Revised 2003 consensus on diagnostic criteria and longterm health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19–25.
26. Townsend KA, Marlowe KF. Relative safety and efficacy of finasteride for treatment of hirsutism. Ann Pharmacother 2004; 38: 1070–3.
27. Inal MM, Yildirim Y, Taner CE. Comparison of the clinical efficacy of flutamide and spironolactone plus Diane 35 in the treatment of idiopathic hirsutism: a randomized controlled study. Fertil Steril 2005; 84: 1693–7.
28. Osculati A, Castiglioni C. Fatal liver complications with flutamide. Lancet 2006; 367: 1140–1.
29. Calaf J, Lopez E, Millet A et al. Long-term efficacy and tolerability of flutamide combined with oral contraception in moderate to severe hirsutism: a 12-month, double-blind, parallel clinical trial. J Clin Endocrinol Metab 2007; 92: 3446–52.
30. Tang T, Lord JM, Norman RJ. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database of Systematic Reviews 2010. Issue 1. Art. No.: CD003053. Doi: 10.1002/14651858. CD003053.pub4.
31. Доброхотова Ю.Э., Корсунская И.М., Джобава Э.М. Андрогензависимая дермопатия как проявление синдрома гиперандрогении: методы коррекции. Гинекология. 2006; 8 (5): 34–7.
32. Nader S, Aamanti-Kandarakis E. Polycystic ovary syndrome, oral contraceptives and metabolic issues: new perspectives and a unifying hypothesis. Hum Reprod 2007; 22 (2): 317–22.
33. Zouboulis CC, Chen WC, Thornton MJ et al. Sexual hormones in human skin. Horm Metab Res 2007; 39: 85–95.
34. Van der Spuy ZM, le Roux PA. Cyproterone acetate for hirsutism. Cochrane Database of Systematic Reviews 2003; 4: CD001125.
35. Batukan C, Muderris, II, Ozcelik B, Ozturk A. Comparison of two oral contraceptives containing either drospirenone or cyproterone acetate in the treatment of hirsutism. Gynecol Endocrinol 2007; 23: 38–44.
36. Raudrant D, Rabe T. Progestogens with antiandrogenic properties. Drugs 2003; 63: 463–92.
37. Schramm G, Steffens D. A 12-month evaluation of the CMA – containing oral contraceptive Belara: efficacy, tolerability and ANTI – androgenic properties. Contraception 2003; 67: 305–12.
38. Zahradnik HP. Belara – a reliable oral contraceptive with additional benefits for health and efficacy in dysmenorrhea. Eur J Contracept Reprod Health Care 2005; 10: 8–12.
39. Worret I, 2001 CMA 2mg/EE 0.03 mg (n=101) vs LNG 0.15mg/EE 0.03mg (n=98) for 12 cycles, phase III, single-blind, randomized CT.
Авторы
И.В.Кузнецова, П.А.Набиева
ГБОУ ВПО Первый Московский государственный медицинский университет им. И.М.Сеченова Минздрава РФ
ГБОУ ВПО Первый Московский государственный медицинский университет им. И.М.Сеченова Минздрава РФ
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I.V.Kuznetsova, P.A.Nabiyeva
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