Патофизиология вегетативно-сосудистых пароксизмов (приливы) у женщин в период менопаузы и механизм действия β-аланина. Новая клинико-фармакологическая концепция

1. Freeman EW, Sherif K. Prevalence of hot flushes and night sweats around the world: a systematic review. Climacteric 2007; 10 (3): 197–214.
2. Shanafelt TD, Barton DL, Adjei AA, Loprinzi CL. Pathophysiology and treatment of hot flashes. Mayo Clin Proc 2002; 77 (11): 1207–18.
3. Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev 2004; 1052 (4): CD002978.
4. Rabin DS, Cipparrone N, Linn ES, Moen M. Why menopausal women do not want to take hormone replacement therapy. Menopause 1999; 6 (1): 61–7.
5. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, WHI Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Women's Health Initiative randomized controlled trial. JAMA 2002; 288 (3): 321–33.
6. Lacey JV, Mink PJ, Lubin JH et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA 2002; 288 (3): 334–41.
7. Coughlin SS, Giustozzi A, Smith SJ, Lee NC. A meta-analysis of estrogen replacement therapy and risk of epithelial ovarian cancer. J Clin Epidemiol 2000; 53 (4): 367–75.
8. Tanis BC, van den Bosch MA, Kemmeren JM et al. Oral contraceptives and the risk of myocardial infarction. N Engl J Med 2001; 345 (25): 1787–93.
9. Reynolds RF, Obermeyer CM, Walker AM et al. Side effects and sociobehavioral factors associated with the discontinuation of hormone therapy in a Massachusetts health maintenance organization. Menopause 2001; 8 (3): 189–99.
10. Nelson HD, Vesco KK, Haney E et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006; 295 (17): 2057–71.
11. Nachtigall LE, Baber RJ, Barentsen R et al. Complementary and hormonal therapy for vasomotor symptom relief: a conservative clinical approach. J Obstet Gyn Can 2006; 28 (4): 279–89.
12. Shen W, Stearns V. Treatment strategies for hot flushes. Expert Opin Pharmacother 2009; 10 (7): 1133–44.
13. Melis GB, Gambacciani M, Cagnacci A et al. Effects of the dopamine antagonist veralipride on hot flushes and luteinizing hormone secretion in postmenopausal women. Obstet Gyn 1988; 72 (5): 688–92.
14. Barton DL, Loprinzi CL, Quella SK et al. Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. J Clin Oncol 1998; 16 (2): 495–500.
15. Bourre JM. Dietary omega-3 fatty acids for women. Biomed Pharmacother 2007; 61 (2–3): 105–12.
16. Kurzer MS. Soy consumption for reduction of menopausal symptoms. Inflammopharmacology 2008; 16 (5): 227–9.
17. Williamson-Hughes PS, Flickinger BD, Messina MJ, Empie MW. Isoflavone supplements containing predominantly genistein reduce hot flash symptoms: a critical review of published studies. Menopause 2006; 13 (5): 831–9.
18. Carroll DG. Nonhormonal therapies for hot flashes in menopause. Am Fam Physician 2006; 73 (3): 457–64.
19. Toulis KA, Tzellos T, Kouvelas D, Goulis DG. Gabapentin for the treatment of hot flashes in women with natural or tamoxifen-induced menopause: a systematic review and meta-analysis. Clin Ther 2009; 31 (2): 221–35.
20. Hunter M, Rendall M. Bio-psycho-socio-cultural perspectives on menopause. Best Pract Res Clin Obstet Gyn 2007; 21 (2): 261–74.
21. Ланг Г.Ф. Учебник внутренних болезней. Т. I, ч. 1. Л.: Медгиз, 1938.
22. Chattha R, Nagarathna R, Padmalatha V, Nagendra HR. Effect of yoga on cognitive functions in climacteric syndrome: a randomised control study. BJOG 2008; 115 (8): 991–1000.
23. Сметник В.П. Приливы: загадка климактерия. Климактерий. 2009; 1.
24. Arendt M, Rosenberg R, Foldager L et al. Withdrawal symptoms do not predict relapse among subjects treated for cannabis dependence. Am J Addict 2007; 16 (6): 461–7.
25. Crawford SJ. Hot flushes and cold turkey. Br Med J 1977; 1 (6076): 1599.
26. Casper RF, Yen SS. Neuroendocrinology of menopausal flushes: an hypothesis of flush mechanism. Clin Endocrinol (Oxf) 1985; 22 (3): 293–312.
27. Andrikoula M, Prelevic G. Menopausal hot flushes revisited. Climacteric 2009; 12 (1): 3–15.
28. Freedman RR, Krell W. Reduced thermoregulatory null zone in postmenopausal women with hot flashes. Am J Obstet Gyn 1999; 181 (1): 66–70.
29. Rosenberg J, Larsen SH. Hypothesis: pathogenesis of postmenopausal hot flush. Med Hypotheses 1991; 35 (4): 349–50.
30. Freedman RR, Norton D, Woodward S, Cornelissen G. Core body temperature and circadian rhythm of hot flashes in menopausal women. J Clin Endocrinol Metab 1995; 80 (8): 2354–8.
31. Schurz B, Wimmer-Greinecker G, Metka M et al. Beta-endorphin levels during the climacteric period. Maturitas 1988; 10 (1): 45–50.
32. Gonzales GF, Carrillo C. Blood serotonin levels in postmenopausal women: effects of age and serum oestradiol levels. Maturitas 1993; 17 (1): 23–9.
33. Berendsen HH. The role of serotonin in hot flushes. Maturitas 2000; 36 (3): 155–64.
34. Yuri K., Kawata M. Estrogen receptor-immunoreactive neurons contain calcitonin gene-related peptide, methionine-enkephalin or tyrosine hydroxylase in the female rat preoptic area. Neurosci Res 1994; 21 (2): 135–41.
35. Yuri K, Kawata M. Estrogen affects calcitonin gene-related peptide- and methionine-enkephalin-immunoreactive neuron in the female rat preoptic area. Neurosci Lett 1994; 169 (1–2): 5–8.
36. Yuri K, Kawata M. Time-course analysis of changes in calcitonin gene-related peptide-and methionine-enkephalin-immunoreactivity in the female rat preoptic area after estrogen treatment. Neuroscience 1993; 55 (4): 1067–74.
37. Yuri K, Kawata M. Semi-quantitative analysis of the effects of estrogen on CGRP-immunoreactivity in the periventricular preoptic nucleus and the medial preoptic area of female rats. Brain Res 1992; 578 (1–2): 282–8.
38. Wyon Y, Frisk J, Lundeberg T et al. Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide. Maturitas 1998; 30 (3): 289–94.
39. Wyon YA, Spetz AC, Theodorsson GE, Hammar ML. Concentrations of calcitonin gene-related peptide and neuropeptide Y in plasma increase during flushes in postmenopausal women. Menopause 2000; 7 (1): 25–30.
40. Valentini A, Petraglia F, De Vita D et al. Changes of plasma calcitonin gene-related peptide levels in postmenopausal women. Am J Obstet Gyn 1996; 175 (3 Pt 1): 638–42.
41. Gupta P, Harte A, Sturdee DW et al. Effects of menopausal status on circulating calcitonin gene-related peptide and adipokines: implications for insulin resistance and cardiovascular risks. Climacteric 2008; 11 (5): 364–72.
42. Salem N, Dunbar JC. The insulin-mediated vascular and blood pressure responses are suppressed in CGRP-deficient normal and diabetic rats. Diabetes Metab Res Rev 2002; 18 (3): 238–44.
43. Pettersson M, Ahren B. Insulin and glucagon secretion in rats: effects of calcitonin gene-related peptide. Regul Pept 1988; 23 (1): 37–50.
44. Derave W, Ozdemir MS, Harris RC, Pottier A. beta-Alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters. J Appl Physiol 2007; 103 (5): 1736–43.
45. Hill CA, Harris RC, Kim HJ et al. Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids 2007; 32 (2): 225–33.
46. Zaloga GP, Roberts PR, Nelson TE. Carnosine: a novel peptide regulator of intracellular calcium and contractility in cardiac muscle. New Horiz 1996; 4 (1): 26–35.
47. Klebanov GI, Teselkin YuO, Babenkova IV et al. Effect of carnosine and its components on free-radical reactions. Membr Cell Biol 1998; 12 (1): 89–99.
48. Babizhayev MA, Seguin MC, Gueyne J et al. L-carnosine act as natural antioxidants. Biochem J 1994; 304 (Pt 2) (8): 509–16.
49. Nagai K, Suda T. Realization of spontaneous healing function by carnosine. Methods Find Exp Clin Pharmacol 1988; 10 (8): 497–507.
50. Voet D, Voet JG, Pratt CW. Fundamentals of Biochemistry: Life at the Molecular Level, 2nd ed. Hoboken, 2006 NJ: John Wiley & Sons, Inc.
51. Naruta E, Buko V. Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose. Exp Toxicol Pathol 2001; 53 (5): 393–8.
52. Peskov AB, Maevskii EI, Uchitel' ML et al. Succinate-based preparation alleviates manifestations of the climacteric syndrome in women. Bull Exp Biol Med; 2005 Sep; 140(3):312-4.
53. Dormire S, Howharn C. The effect of dietary intake on hot flashes in menopausal women. J Obstet Gynecol Neonatal Nurs 2007; 36 (3): 255–62.
54. Dormire SL, Reame NK. Menopausal hot flash frequency changes in response to experimental manipulation of blood glucose. Nurs Res 2003; 52 (5): 338–43.
55. Ratka A. Menopausal hot flashes and development of cognitive impairment. Ann N Y Acad Sci 2005; 1052 (3): 11–26.
56. Henley JM. Encyclopedia of Life Sciences Amino Acid Neurotransmitters. 2001 John Wiley & Sons, Ltd.
57. Harris RC, Tallon MJ, Dunnett M et al. The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids 2006; 30 (3): 279–89.
58. Malacara JM, Perez-Luque EL, Martinez-Garza S, Sanchez-Marin FJ. The relationship of estrogen receptor-alpha polymorphism with symptoms and other characteristics in post-menopausal women. Maturitas 2004; 49 (2): 163–9.

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1. Freeman EW, Sherif K. Prevalence of hot flushes and night sweats around the world: a systematic review. Climacteric 2007; 10 (3): 197–214.
2. Shanafelt TD, Barton DL, Adjei AA, Loprinzi CL. Pathophysiology and treatment of hot flashes. Mayo Clin Proc 2002; 77 (11): 1207–18.
3. Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev 2004; 1052 (4): CD002978.
4. Rabin DS, Cipparrone N, Linn ES, Moen M. Why menopausal women do not want to take hormone replacement therapy. Menopause 1999; 6 (1): 61–7.
5. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, WHI Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Women's Health Initiative randomized controlled trial. JAMA 2002; 288 (3): 321–33.
6. Lacey JV, Mink PJ, Lubin JH et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA 2002; 288 (3): 334–41.
7. Coughlin SS, Giustozzi A, Smith SJ, Lee NC. A meta-analysis of estrogen replacement therapy and risk of epithelial ovarian cancer. J Clin Epidemiol 2000; 53 (4): 367–75.
8. Tanis BC, van den Bosch MA, Kemmeren JM et al. Oral contraceptives and the risk of myocardial infarction. N Engl J Med 2001; 345 (25): 1787–93.
9. Reynolds RF, Obermeyer CM, Walker AM et al. Side effects and sociobehavioral factors associated with the discontinuation of hormone therapy in a Massachusetts health maintenance organization. Menopause 2001; 8 (3): 189–99.
10. Nelson HD, Vesco KK, Haney E et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006; 295 (17): 2057–71.
11. Nachtigall LE, Baber RJ, Barentsen R et al. Complementary and hormonal therapy for vasomotor symptom relief: a conservative clinical approach. J Obstet Gyn Can 2006; 28 (4): 279–89.
12. Shen W, Stearns V. Treatment strategies for hot flushes. Expert Opin Pharmacother 2009; 10 (7): 1133–44.
13. Melis GB, Gambacciani M, Cagnacci A et al. Effects of the dopamine antagonist veralipride on hot flushes and luteinizing hormone secretion in postmenopausal women. Obstet Gyn 1988; 72 (5): 688–92.
14. Barton DL, Loprinzi CL, Quella SK et al. Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. J Clin Oncol 1998; 16 (2): 495–500.
15. Bourre JM. Dietary omega-3 fatty acids for women. Biomed Pharmacother 2007; 61 (2–3): 105–12.
16. Kurzer MS. Soy consumption for reduction of menopausal symptoms. Inflammopharmacology 2008; 16 (5): 227–9.
17. Williamson-Hughes PS, Flickinger BD, Messina MJ, Empie MW. Isoflavone supplements containing predominantly genistein reduce hot flash symptoms: a critical review of published studies. Menopause 2006; 13 (5): 831–9.
18. Carroll DG. Nonhormonal therapies for hot flashes in menopause. Am Fam Physician 2006; 73 (3): 457–64.
19. Toulis KA, Tzellos T, Kouvelas D, Goulis DG. Gabapentin for the treatment of hot flashes in women with natural or tamoxifen-induced menopause: a systematic review and meta-analysis. Clin Ther 2009; 31 (2): 221–35.
20. Hunter M, Rendall M. Bio-psycho-socio-cultural perspectives on menopause. Best Pract Res Clin Obstet Gyn 2007; 21 (2): 261–74.
21. Ланг Г.Ф. Учебник внутренних болезней. Т. I, ч. 1. Л.: Медгиз, 1938.
22. Chattha R, Nagarathna R, Padmalatha V, Nagendra HR. Effect of yoga on cognitive functions in climacteric syndrome: a randomised control study. BJOG 2008; 115 (8): 991–1000.
23. Сметник В.П. Приливы: загадка климактерия. Климактерий. 2009; 1.
24. Arendt M, Rosenberg R, Foldager L et al. Withdrawal symptoms do not predict relapse among subjects treated for cannabis dependence. Am J Addict 2007; 16 (6): 461–7.
25. Crawford SJ. Hot flushes and cold turkey. Br Med J 1977; 1 (6076): 1599.
26. Casper RF, Yen SS. Neuroendocrinology of menopausal flushes: an hypothesis of flush mechanism. Clin Endocrinol (Oxf) 1985; 22 (3): 293–312.
27. Andrikoula M, Prelevic G. Menopausal hot flushes revisited. Climacteric 2009; 12 (1): 3–15.
28. Freedman RR, Krell W. Reduced thermoregulatory null zone in postmenopausal women with hot flashes. Am J Obstet Gyn 1999; 181 (1): 66–70.
29. Rosenberg J, Larsen SH. Hypothesis: pathogenesis of postmenopausal hot flush. Med Hypotheses 1991; 35 (4): 349–50.
30. Freedman RR, Norton D, Woodward S, Cornelissen G. Core body temperature and circadian rhythm of hot flashes in menopausal women. J Clin Endocrinol Metab 1995; 80 (8): 2354–8.
31. Schurz B, Wimmer-Greinecker G, Metka M et al. Beta-endorphin levels during the climacteric period. Maturitas 1988; 10 (1): 45–50.
32. Gonzales GF, Carrillo C. Blood serotonin levels in postmenopausal women: effects of age and serum oestradiol levels. Maturitas 1993; 17 (1): 23–9.
33. Berendsen HH. The role of serotonin in hot flushes. Maturitas 2000; 36 (3): 155–64.
34. Yuri K., Kawata M. Estrogen receptor-immunoreactive neurons contain calcitonin gene-related peptide, methionine-enkephalin or tyrosine hydroxylase in the female rat preoptic area. Neurosci Res 1994; 21 (2): 135–41.
35. Yuri K, Kawata M. Estrogen affects calcitonin gene-related peptide- and methionine-enkephalin-immunoreactive neuron in the female rat preoptic area. Neurosci Lett 1994; 169 (1–2): 5–8.
36. Yuri K, Kawata M. Time-course analysis of changes in calcitonin gene-related peptide-and methionine-enkephalin-immunoreactivity in the female rat preoptic area after estrogen treatment. Neuroscience 1993; 55 (4): 1067–74.
37. Yuri K, Kawata M. Semi-quantitative analysis of the effects of estrogen on CGRP-immunoreactivity in the periventricular preoptic nucleus and the medial preoptic area of female rats. Brain Res 1992; 578 (1–2): 282–8.
38. Wyon Y, Frisk J, Lundeberg T et al. Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide. Maturitas 1998; 30 (3): 289–94.
39. Wyon YA, Spetz AC, Theodorsson GE, Hammar ML. Concentrations of calcitonin gene-related peptide and neuropeptide Y in plasma increase during flushes in postmenopausal women. Menopause 2000; 7 (1): 25–30.
40. Valentini A, Petraglia F, De Vita D et al. Changes of plasma calcitonin gene-related peptide levels in postmenopausal women. Am J Obstet Gyn 1996; 175 (3 Pt 1): 638–42.
41. Gupta P, Harte A, Sturdee DW et al. Effects of menopausal status on circulating calcitonin gene-related peptide and adipokines: implications for insulin resistance and cardiovascular risks. Climacteric 2008; 11 (5): 364–72.
42. Salem N, Dunbar JC. The insulin-mediated vascular and blood pressure responses are suppressed in CGRP-deficient normal and diabetic rats. Diabetes Metab Res Rev 2002; 18 (3): 238–44.
43. Pettersson M, Ahren B. Insulin and glucagon secretion in rats: effects of calcitonin gene-related peptide. Regul Pept 1988; 23 (1): 37–50.
44. Derave W, Ozdemir MS, Harris RC, Pottier A. beta-Alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters. J Appl Physiol 2007; 103 (5): 1736–43.
45. Hill CA, Harris RC, Kim HJ et al. Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids 2007; 32 (2): 225–33.
46. Zaloga GP, Roberts PR, Nelson TE. Carnosine: a novel peptide regulator of intracellular calcium and contractility in cardiac muscle. New Horiz 1996; 4 (1): 26–35.
47. Klebanov GI, Teselkin YuO, Babenkova IV et al. Effect of carnosine and its components on free-radical reactions. Membr Cell Biol 1998; 12 (1): 89–99.
48. Babizhayev MA, Seguin MC, Gueyne J et al. L-carnosine act as natural antioxidants. Biochem J 1994; 304 (Pt 2) (8): 509–16.
49. Nagai K, Suda T. Realization of spontaneous healing function by carnosine. Methods Find Exp Clin Pharmacol 1988; 10 (8): 497–507.
50. Voet D, Voet JG, Pratt CW. Fundamentals of Biochemistry: Life at the Molecular Level, 2nd ed. Hoboken, 2006 NJ: John Wiley & Sons, Inc.
51. Naruta E, Buko V. Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose. Exp Toxicol Pathol 2001; 53 (5): 393–8.
52. Peskov AB, Maevskii EI, Uchitel' ML et al. Succinate-based preparation alleviates manifestations of the climacteric syndrome in women. Bull Exp Biol Med; 2005 Sep; 140(3):312-4.
53. Dormire S, Howharn C. The effect of dietary intake on hot flashes in menopausal women. J Obstet Gynecol Neonatal Nurs 2007; 36 (3): 255–62.
54. Dormire SL, Reame NK. Menopausal hot flash frequency changes in response to experimental manipulation of blood glucose. Nurs Res 2003; 52 (5): 338–43.
55. Ratka A. Menopausal hot flashes and development of cognitive impairment. Ann N Y Acad Sci 2005; 1052 (3): 11–26.
56. Henley JM. Encyclopedia of Life Sciences Amino Acid Neurotransmitters. 2001 John Wiley & Sons, Ltd.
57. Harris RC, Tallon MJ, Dunnett M et al. The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids 2006; 30 (3): 279–89.
58. Malacara JM, Perez-Luque EL, Martinez-Garza S, Sanchez-Marin FJ. The relationship of estrogen receptor-alpha polymorphism with symptoms and other characteristics in post-menopausal women. Maturitas 2004; 49 (2): 163–9.

О.А.Громова1, 2, И.Ю.Торшин1, 2, О.А.Лиманова1, 2, А.А.Никонов1, 3

1. Российский сотрудничающий центр «Нейробиология» Международного института микроэлементов ЮНЕСКО,
2. ГОУ ВПО Ивановская государственная медицинская академия РФ (ректор – акад. РАЕН Р.Р.Шиляев),
3. ГОУ ВПО Российский государственный медицинский университет РФ (ректор – акад. РАМН Н.Н.Володин)