- Email: [email protected]
Metabolic and endocrine changes in climacteric women
International Congress Series 1229 (2002) 3 – 7
Metabolic and endocrine changes in climacteric women Andrzej Milewicz*, Marek Demissie Department of Endocrinology and Diabetology, Wroclaw Medical University, Wroclaw, Poland
Abstract The climacteric period is associated with gradual reduction of sex hormones secretion. Substantial evidence indicates that estrogen deficiency contributes to the long-term metabolic consequences. A range of age-related changes (e.g. a reduction in growth hormone (GH), dehydroepiandrosterone (DHEA), melatonin) may be involved in aggravation of described abnormalities. Our studies on plasma satiety and appetite-stimulating neuropeptides indicate that the modification of appetite preferences contributes to overconsumption of fat in postmenopausal women. It is known that 60% of postmenopausal women have central body obesity. This trend obviously favours insulin resistance, an atherogenic plasma lipid – lipoprotein profile, abnormal blood coagulation and the increase in prevalence of type 2 diabetes. This cluster of metabolic abnormalities may be described as menopausal metabolic syndrome. Importantly, the alterations that women suffer in the climacteric period are assumed to be a risk factor leading to a 26 – 30% increase in death due to coronary heart disease in the postmenopausal group. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Menopause; Aging; Obesity
The association between multiple hormonal changes in climacteric women and the sequence of metabolic disorders leading to increased cardiovascular risk becomes increasingly evident. With the progress of ageing, women experience not only a reduction in the levels of estrogens, but also DHEA and its sulphate (adrenopause), melatonin and growth hormone (somatopause) decline [1]. These endocrine alternations may result in
*
Corresponding author. ul. Pasteura 4, PL 50-367 Wroclaw, Poland. Tel./fax: +48-71-328-23-49. E-mail address: [email protected] (A. Milewicz).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 1 ) 0 0 4 7 8 - 2
4
A. Milewicz, M. Demissie / International Congress Series 1229 (2002) 3–7
visceral obesity, insulin resistance, lipid disorders, thrombotic risk and the increase in prevalence of type 2 diabetes. Thus, attention has focused on the possibility of the existence of a menopausal metabolic syndrome. Reduction in gonadal estrogen production is associated with an increase in the waist-tohip ratio and the development of a more android body habitus [2– 8]. Epidemiological studies confirmed that postmenopausal women tend to gain weight with a shift to visceral fat distribution [2 –8]. Some authors support that this change is associated with menopausal status [2,4], but other studies found a relationship between body weight gain and chronological age [5,6] or years since menopause [7]. Premenopausal women are protected against cardiovascular disease, yet after menopause, there is a dramatic increase in cardiovascular disease in women, which becomes equal to that of men at the age of 70 [9,10]. Estrogen, thanks to its favourable influence on lipid subfractions and its direct action on the arterial wall, contributes substantially to the cardiovascular-protective effect [11]. The negative changes associated with the menopausal estrogen deficiency result in an increase in total cholesterol and LDL cholesterol and a decrease in HDL cholesterol (especially subfraction 2). Traditionally, hormonal replacement therapy (HRT) has been thought to be valuable mainly because of its influence on lipid and lipoprotein metabolism [12 –14]. Even though benefits from replacement therapy had been challenged in the large randomised clinical trial — the Heart and Estrogen/Progestin Study (HERS)— they did not reduce the primary end point, the overall rate of coronary heart disease events. The common presence of insulin resistance in climacteric women may imply that estrogen deficiency is a separate risk factor of glucose intolerance. This can be well explained by estrogen’s effects on carbohydrate metabolism (reduced fasting glucose and insulin levels). However, several endocrine and metabolic factors underlie the development of diabetes in genetically susceptible, climacteric women. Estrogen decreases levels of fibrinogen, plasminogen, PAI-I, homocystein and antithrombin-III and also impairs platelet function. Taken together, estrogen deficiency is associated with abnormalities in the coagulation system that all appear to contribute to increased cardiovascular risk. Neuropeptides are factors that control body fat stores, energy and nutrient balance. Relationship between plasma satiety and appetite-stimulating peptides and menopausal obesity was apparent in our studies [15,16]. Our results suggest a possible influence of endo- and exogenous estrogens on serum cholecystokinin synergistically enhancing satiety sensation in climacteric women [16]. We also noted a significant increment in serum galanin values with decreased neuropeptide Y level in obese postmenopausal women compared to premenopausal group (both obese and non-obese) [15]. These changes in the neuropeptides regulating eating behaviour (neuropeptide Y stimulates carbohydrate and galanin fat intake in diet) may be the reason for modification of appetite preferences that contribute to overconsumption of fat observed in postmenopausal women and, in consequence, postmenopausal obesity development. There is limited evidence that decreased energy expenditure plays a role in the development of menopausal obesity. The basal metabolic rate (BMR) that is associated with weight decreases almost linearly with age [17]. This may be partly explained by a reduction in the quantity and metabolic activity of lean tissue in the elderly. Some
A. Milewicz, M. Demissie / International Congress Series 1229 (2002) 3–7
5
investigators reported an age-related decrease in sympathetic nervous system (SNS) activity that can also lead to obesity [18]. A primary mechanism of weight gain in postmenopausal women may relate to the association of estrogen receptor ER-alpha genotype with body mass index (BMI) and its interaction with age [19]. In recent years, dehydroepiandrosterone (DHEA) and its sulphated prohormone, dehydroepiandrosterone sulphate (DHEA-S) have been suggested to be antiobesitive, antidiabetic and antiarteriosclerotic factors [20,21]. Clinical studies have demonstrated that DHEA may play a major role in peripheral tissues acting through estrogen, androgen receptors and the cytokine system. DHEA production reaches its peak in the early 20s, gradually falling to 10% in eighth decade of life. Epidemiological studies reveal consistent decrement in DHEA secretion in aging men and women [22,23]. In humans, a positive influence of DHEA supplementation on metabolic parameters has been observed only in men [24,25]. No changes in body weight, body mass index or waistto-hip ratio have been seen in postmenopausal women after 12 months of DHEA therapy, despite a 10% reduction in subcutaneous fat [26]. In our study, we have observed that 3month treatment with DHEA in postmenopausal women led to increase in serum DHEA-S and estradiol without any changes in lipid and carbohydrate metabolic parameters [27]. Growth hormone (GH) levels and its circulating mediator insulin-like growth factor I (IGF I) have been reported to decrease with age both in women and men [28,29]. Premenopausal women show a two-fold less rapid decline than men in daily GH secretion with increasing age [30]. Estrogen deficiency in climacteric women weakens this tendency [31]. The age-related reduction in GH level may be involved in the aggravation of metabolic changes observed in climacteric women. GH deficiency in hypopituitary adults leads to reduced life expectancy, increased cardiovascular morbidity with premature atherosclerosis, adverse changes in cardiovascular risk factors and changes in body composition [32]. GH deficiency has profound effects on the amount and distribution of adipose tissue deficiency, resulting in an increased amount of adipose tissue and the abdominal deposit of adipose tissue. Remarkable changes in climacteric women’s hormonal milieu leading to cessation of reproduction dramatically impact long-term health. There is increasing evidence that menopause is often associated with visceral obesity, insulin resistance, alternations in glucose and lipid metabolism and high blood pressure, which have emerged as important components of a cluster of metabolic abnormalities strongly related to increased risk of coronary heart disease. References [1] S.W. Lamberts, A.W. van den Belt, A.J. van der Ley, The endocrinology of aging, Science 278 (1997) 419 – 424. [2] C.J. Ley, B. Lees, J.C. Stevenson, Sex- and menopause-associated changes in body fat distribution, Am. J. Clin. Nutr. 55 (1992) 950 – 954. [3] R. Pasquali, F. Casimirri, A. Labate, et al., Body weight, fat distribution and the menopausal status in women, Int. J. Obes. 18 (1994) 614 – 621. [4] F.A. Tremollieres, J.M. Poulles, C.A. Ribot, Relative influence of age and menopause on total and regional body composition changes in postmenopausal women, Am. J. Obstet. Gynecol. 175 (1996) 1594 – 1600.
6
A. Milewicz, M. Demissie / International Congress Series 1229 (2002) 3–7
[5] Q. Wang, C. Hassager, P. Ravn, et al., Total and regional body composition changes in early postmenopausal women: age related or menopause related? Am. J. Clin. Nutr. 60 (1994) 843 – 848. [6] J.F. Aloia, A. Vaswani, R. Ma, et al., Aging in women — the four-compartment model of body composition, Metabolism 45 (1996) 43 – 48. [7] O.L. Svendsen, C. Hassager, C. Christiansen, Age and menopause-associated variations in body composition and fat distribution in healthy women as measured by dual-energy X-ray absorptiometry, Metabolism 44 (1995) 369 – 373. [8] R.R. Wing, K.A. Matthews, L.H. Kuller, et al., Weight gain at the time of the menopause, Arch. Int. Med. 151 (1991) 97 – 102. [9] B. Ettinger, G.D. Friedman, T. Bush, C.P. Quesenberry Jr., Reduced mortality associated with long-term postmenopausal estrogen therapy, Obstet. Gynecol. 87 (1996) 6 – 12. [10] S.A. Samaan, M.H. Craward, Estrogen and cardiovascular function after menopause, J. Am. Coll. Cardiol. 26 (1995) 1403 – 1410. [11] D. Grady, S.M. Rubin, D.B. Pettiti, et al., Hormone therapy to prevent disease and prolong life in postmenopausal women, Ann. Intern. Med. 177 (1992) 1016 – 1037. [12] B.W. Walsh, I. Schiff, B. Rosner, et al., Effects of postmenopausal estrogen replacement on the concentrations and metabolism of lipoproteins, N. Engl. J. Med. 325 (1991) 1196 – 1204. [13] T.L. Bush, E. Barret-Connor, L.D. Cowan, et al., Cardiovascular mortality and noncontraceptive use of estrogen in women: results from Lipid Research Clinics Program Follow-up Study, Circulation 75 (1987) 1102 – 1109. [14] D. Crook, M.P. Cust, K.F. Gangar, et al., Comparison of transdermal and oral estrogen/progestin hormone replacement therapy: effect on serum lipids and lipoproteins, Am. J. Obstet. Gynecol. 166 (1992) 950 – 955. [15] A. Milewicz, B. Bidzin´ska, E. Mikulski, et al., Influence of obesity and menopausal status on serum leptin, cholecystokinin, galanin and neuropeptide Y levels, Gynecol. Endocrinol. 14 (2000) 196 – 203. [16] A. Milewicz, E. Mikulski, B. Bidzin´ska, Endogenous/exogenous estrogens and satiety + appetite stimulating peptides in women, in: T. Aso, T. Yanaihara, Y. Taketani, T. Suda, H. Tanaka, S. Maehara (Eds.), The 9th International Menopause Society World Congress on the Menopause, Yokohama (Japan), Monduzzi Editore, Bologna, 1999, pp. 147 – 151. [17] H. Shimokata, F. Kuzuya, Aging, basal metabolic rate, and nutrition, Nippon Ronen Igakkai Zasshi 30 (1993) 572 – 576. [18] S. Snitker, I. Macdonald, E. Ravussin, et al., The sympathetic nervous system and obesity: role in aetiology and treatment, Obes. Rev. 1 (2000) 5 – 15. [19] H.W. Deng, J. Li, J.L. Li, et al., Association of estrogen receptor-alpha genotypes with body mass index in normal healthy postmenopausal Caucasian women, J. Clin. Endocrinol. Metab. 85 (2000) 2748 – 2751. [20] M.P. Celary, The Role of DHEA in Obesity, Walter de Gruyter & Co., Berlin, 1990. [21] M.P. Celary, The antiobesity effect of dehydroepiandrosterone in rats, Proc. Soc. Exp. Biol. Med. 196 (1991) 8 – 16. [22] C. Berr, S. Lafont, B. Debuire, et al., Relationship of dehydroepiandrosterone sulphate in elderly with functional psychological and mental status and short term mortality: a French community-based study, Proc. Natl. Acad. Sci. 93 (1996) 13410 – 13415. [23] N. Orentreich, J.L. Brind, R.L. Rizer, et al., Age changes and sex differences in serum dehydroepiandrosterone sulphate content throughout adulthood, J. Clin. Endocrinol. Metab. 59 (1984) 551 – 555. [24] A.A. Lacroix, K. Yano, D.M. Reed, Dehydroepiandrosterone sulphate, incidence of myocardial infarction and extent of atherosclerosis in men, Circulation 86 (1992) 1529 – 1535. [25] J.E. Nestler, C.O. Barlascini, J.N. Clore, et al., Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat, but does not alter insulin sensitivity in normal men, J. Clin. Endocrinol. Metab. 66 (1988) 57 – 61. [26] P. Diamond, L. Cusan, J.L. Gomez, et al., Metabolic effects of 12-months precutaneous dehydroepiandrosterone replacement therapy in postmenopausal women, J. Endocrinol. 150 (1996) S43 – S50. [27] A. Milewicz, D. Je˛drzejuk, A. Bohdanowicz-Pawlak, et al., Metabolic and hormonal changes after DHEA treatment, in: T. Aso, T. Yanaihara, Y. Taketani, T. Suda, H. Tanaka, S. Maehara (Eds.), The 9th International
A. Milewicz, M. Demissie / International Congress Series 1229 (2002) 3–7
[28]
[29] [30] [31]
[32]
7
Menopause Society World Congress on the Menopause, Yokohama (Japan), Monduzzi Editore, Bologna, 1999, pp. 215 – 220. A. Weltman, J.Y. Weltman, R.D. Abbott, et al., Relationship between age, percentage body fat, fitness and 24-hour growth hormone release in healthy young adults: effects of gender, J. Clin. Endocrinol. Metab. 78 (1994) 543 – 548. K. Tanaka, S. Inoue, J. Shiraki, et al., Age-related decrease in plasma growth hormone: response to growth hormone-releasing hormone, arginine, and L-dopa in obesity, Metabolism 40 (1991) 1257 – 1262. L. Wideman, J. Weltman, N. Shah, S. Story, J. Veldhuis, A. Weltman, Effects of gender on exercise-induced growth hormone release, J. Appl. Physiol. 87 (1999) 1154 – 1162. J. Veldhuis, W. Evans, N. Shah, S. Storey, M. Bray, S. Anderson, Proposed mechanisms of sex-steroid hormone neuromodulation of the human GH-IGF-I axis, in: J. Veldhuis, A. Giustina (Eds.), Sex Steroid Interactions With Growth Hormone, Springer-Verlag, New York, NY, 1999, pp. 93 – 121. R. Abs, B.A. Bengtsson, E. Hernberg-Stahl, et al., GH replacement in 1034 growth hormone deficient hypopituitary adults: demographic and clinical characteristics, dosing and safety, Clin. Endocrinol. 50 (1999) 703 – 713.
Metabolic and endocrine changes in climacteric women Andrzej Milewicz*, Marek Demissie Department of Endocrinology and Diabetology, Wroclaw Medical University, Wroclaw, Poland
Abstract The climacteric period is associated with gradual reduction of sex hormones secretion. Substantial evidence indicates that estrogen deficiency contributes to the long-term metabolic consequences. A range of age-related changes (e.g. a reduction in growth hormone (GH), dehydroepiandrosterone (DHEA), melatonin) may be involved in aggravation of described abnormalities. Our studies on plasma satiety and appetite-stimulating neuropeptides indicate that the modification of appetite preferences contributes to overconsumption of fat in postmenopausal women. It is known that 60% of postmenopausal women have central body obesity. This trend obviously favours insulin resistance, an atherogenic plasma lipid – lipoprotein profile, abnormal blood coagulation and the increase in prevalence of type 2 diabetes. This cluster of metabolic abnormalities may be described as menopausal metabolic syndrome. Importantly, the alterations that women suffer in the climacteric period are assumed to be a risk factor leading to a 26 – 30% increase in death due to coronary heart disease in the postmenopausal group. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Menopause; Aging; Obesity
The association between multiple hormonal changes in climacteric women and the sequence of metabolic disorders leading to increased cardiovascular risk becomes increasingly evident. With the progress of ageing, women experience not only a reduction in the levels of estrogens, but also DHEA and its sulphate (adrenopause), melatonin and growth hormone (somatopause) decline [1]. These endocrine alternations may result in
*
Corresponding author. ul. Pasteura 4, PL 50-367 Wroclaw, Poland. Tel./fax: +48-71-328-23-49. E-mail address: [email protected] (A. Milewicz).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 1 ) 0 0 4 7 8 - 2
4
A. Milewicz, M. Demissie / International Congress Series 1229 (2002) 3–7
visceral obesity, insulin resistance, lipid disorders, thrombotic risk and the increase in prevalence of type 2 diabetes. Thus, attention has focused on the possibility of the existence of a menopausal metabolic syndrome. Reduction in gonadal estrogen production is associated with an increase in the waist-tohip ratio and the development of a more android body habitus [2– 8]. Epidemiological studies confirmed that postmenopausal women tend to gain weight with a shift to visceral fat distribution [2 –8]. Some authors support that this change is associated with menopausal status [2,4], but other studies found a relationship between body weight gain and chronological age [5,6] or years since menopause [7]. Premenopausal women are protected against cardiovascular disease, yet after menopause, there is a dramatic increase in cardiovascular disease in women, which becomes equal to that of men at the age of 70 [9,10]. Estrogen, thanks to its favourable influence on lipid subfractions and its direct action on the arterial wall, contributes substantially to the cardiovascular-protective effect [11]. The negative changes associated with the menopausal estrogen deficiency result in an increase in total cholesterol and LDL cholesterol and a decrease in HDL cholesterol (especially subfraction 2). Traditionally, hormonal replacement therapy (HRT) has been thought to be valuable mainly because of its influence on lipid and lipoprotein metabolism [12 –14]. Even though benefits from replacement therapy had been challenged in the large randomised clinical trial — the Heart and Estrogen/Progestin Study (HERS)— they did not reduce the primary end point, the overall rate of coronary heart disease events. The common presence of insulin resistance in climacteric women may imply that estrogen deficiency is a separate risk factor of glucose intolerance. This can be well explained by estrogen’s effects on carbohydrate metabolism (reduced fasting glucose and insulin levels). However, several endocrine and metabolic factors underlie the development of diabetes in genetically susceptible, climacteric women. Estrogen decreases levels of fibrinogen, plasminogen, PAI-I, homocystein and antithrombin-III and also impairs platelet function. Taken together, estrogen deficiency is associated with abnormalities in the coagulation system that all appear to contribute to increased cardiovascular risk. Neuropeptides are factors that control body fat stores, energy and nutrient balance. Relationship between plasma satiety and appetite-stimulating peptides and menopausal obesity was apparent in our studies [15,16]. Our results suggest a possible influence of endo- and exogenous estrogens on serum cholecystokinin synergistically enhancing satiety sensation in climacteric women [16]. We also noted a significant increment in serum galanin values with decreased neuropeptide Y level in obese postmenopausal women compared to premenopausal group (both obese and non-obese) [15]. These changes in the neuropeptides regulating eating behaviour (neuropeptide Y stimulates carbohydrate and galanin fat intake in diet) may be the reason for modification of appetite preferences that contribute to overconsumption of fat observed in postmenopausal women and, in consequence, postmenopausal obesity development. There is limited evidence that decreased energy expenditure plays a role in the development of menopausal obesity. The basal metabolic rate (BMR) that is associated with weight decreases almost linearly with age [17]. This may be partly explained by a reduction in the quantity and metabolic activity of lean tissue in the elderly. Some
A. Milewicz, M. Demissie / International Congress Series 1229 (2002) 3–7
5
investigators reported an age-related decrease in sympathetic nervous system (SNS) activity that can also lead to obesity [18]. A primary mechanism of weight gain in postmenopausal women may relate to the association of estrogen receptor ER-alpha genotype with body mass index (BMI) and its interaction with age [19]. In recent years, dehydroepiandrosterone (DHEA) and its sulphated prohormone, dehydroepiandrosterone sulphate (DHEA-S) have been suggested to be antiobesitive, antidiabetic and antiarteriosclerotic factors [20,21]. Clinical studies have demonstrated that DHEA may play a major role in peripheral tissues acting through estrogen, androgen receptors and the cytokine system. DHEA production reaches its peak in the early 20s, gradually falling to 10% in eighth decade of life. Epidemiological studies reveal consistent decrement in DHEA secretion in aging men and women [22,23]. In humans, a positive influence of DHEA supplementation on metabolic parameters has been observed only in men [24,25]. No changes in body weight, body mass index or waistto-hip ratio have been seen in postmenopausal women after 12 months of DHEA therapy, despite a 10% reduction in subcutaneous fat [26]. In our study, we have observed that 3month treatment with DHEA in postmenopausal women led to increase in serum DHEA-S and estradiol without any changes in lipid and carbohydrate metabolic parameters [27]. Growth hormone (GH) levels and its circulating mediator insulin-like growth factor I (IGF I) have been reported to decrease with age both in women and men [28,29]. Premenopausal women show a two-fold less rapid decline than men in daily GH secretion with increasing age [30]. Estrogen deficiency in climacteric women weakens this tendency [31]. The age-related reduction in GH level may be involved in the aggravation of metabolic changes observed in climacteric women. GH deficiency in hypopituitary adults leads to reduced life expectancy, increased cardiovascular morbidity with premature atherosclerosis, adverse changes in cardiovascular risk factors and changes in body composition [32]. GH deficiency has profound effects on the amount and distribution of adipose tissue deficiency, resulting in an increased amount of adipose tissue and the abdominal deposit of adipose tissue. Remarkable changes in climacteric women’s hormonal milieu leading to cessation of reproduction dramatically impact long-term health. There is increasing evidence that menopause is often associated with visceral obesity, insulin resistance, alternations in glucose and lipid metabolism and high blood pressure, which have emerged as important components of a cluster of metabolic abnormalities strongly related to increased risk of coronary heart disease. References [1] S.W. Lamberts, A.W. van den Belt, A.J. van der Ley, The endocrinology of aging, Science 278 (1997) 419 – 424. [2] C.J. Ley, B. Lees, J.C. Stevenson, Sex- and menopause-associated changes in body fat distribution, Am. J. Clin. Nutr. 55 (1992) 950 – 954. [3] R. Pasquali, F. Casimirri, A. Labate, et al., Body weight, fat distribution and the menopausal status in women, Int. J. Obes. 18 (1994) 614 – 621. [4] F.A. Tremollieres, J.M. Poulles, C.A. Ribot, Relative influence of age and menopause on total and regional body composition changes in postmenopausal women, Am. J. Obstet. Gynecol. 175 (1996) 1594 – 1600.
6
A. Milewicz, M. Demissie / International Congress Series 1229 (2002) 3–7
[5] Q. Wang, C. Hassager, P. Ravn, et al., Total and regional body composition changes in early postmenopausal women: age related or menopause related? Am. J. Clin. Nutr. 60 (1994) 843 – 848. [6] J.F. Aloia, A. Vaswani, R. Ma, et al., Aging in women — the four-compartment model of body composition, Metabolism 45 (1996) 43 – 48. [7] O.L. Svendsen, C. Hassager, C. Christiansen, Age and menopause-associated variations in body composition and fat distribution in healthy women as measured by dual-energy X-ray absorptiometry, Metabolism 44 (1995) 369 – 373. [8] R.R. Wing, K.A. Matthews, L.H. Kuller, et al., Weight gain at the time of the menopause, Arch. Int. Med. 151 (1991) 97 – 102. [9] B. Ettinger, G.D. Friedman, T. Bush, C.P. Quesenberry Jr., Reduced mortality associated with long-term postmenopausal estrogen therapy, Obstet. Gynecol. 87 (1996) 6 – 12. [10] S.A. Samaan, M.H. Craward, Estrogen and cardiovascular function after menopause, J. Am. Coll. Cardiol. 26 (1995) 1403 – 1410. [11] D. Grady, S.M. Rubin, D.B. Pettiti, et al., Hormone therapy to prevent disease and prolong life in postmenopausal women, Ann. Intern. Med. 177 (1992) 1016 – 1037. [12] B.W. Walsh, I. Schiff, B. Rosner, et al., Effects of postmenopausal estrogen replacement on the concentrations and metabolism of lipoproteins, N. Engl. J. Med. 325 (1991) 1196 – 1204. [13] T.L. Bush, E. Barret-Connor, L.D. Cowan, et al., Cardiovascular mortality and noncontraceptive use of estrogen in women: results from Lipid Research Clinics Program Follow-up Study, Circulation 75 (1987) 1102 – 1109. [14] D. Crook, M.P. Cust, K.F. Gangar, et al., Comparison of transdermal and oral estrogen/progestin hormone replacement therapy: effect on serum lipids and lipoproteins, Am. J. Obstet. Gynecol. 166 (1992) 950 – 955. [15] A. Milewicz, B. Bidzin´ska, E. Mikulski, et al., Influence of obesity and menopausal status on serum leptin, cholecystokinin, galanin and neuropeptide Y levels, Gynecol. Endocrinol. 14 (2000) 196 – 203. [16] A. Milewicz, E. Mikulski, B. Bidzin´ska, Endogenous/exogenous estrogens and satiety + appetite stimulating peptides in women, in: T. Aso, T. Yanaihara, Y. Taketani, T. Suda, H. Tanaka, S. Maehara (Eds.), The 9th International Menopause Society World Congress on the Menopause, Yokohama (Japan), Monduzzi Editore, Bologna, 1999, pp. 147 – 151. [17] H. Shimokata, F. Kuzuya, Aging, basal metabolic rate, and nutrition, Nippon Ronen Igakkai Zasshi 30 (1993) 572 – 576. [18] S. Snitker, I. Macdonald, E. Ravussin, et al., The sympathetic nervous system and obesity: role in aetiology and treatment, Obes. Rev. 1 (2000) 5 – 15. [19] H.W. Deng, J. Li, J.L. Li, et al., Association of estrogen receptor-alpha genotypes with body mass index in normal healthy postmenopausal Caucasian women, J. Clin. Endocrinol. Metab. 85 (2000) 2748 – 2751. [20] M.P. Celary, The Role of DHEA in Obesity, Walter de Gruyter & Co., Berlin, 1990. [21] M.P. Celary, The antiobesity effect of dehydroepiandrosterone in rats, Proc. Soc. Exp. Biol. Med. 196 (1991) 8 – 16. [22] C. Berr, S. Lafont, B. Debuire, et al., Relationship of dehydroepiandrosterone sulphate in elderly with functional psychological and mental status and short term mortality: a French community-based study, Proc. Natl. Acad. Sci. 93 (1996) 13410 – 13415. [23] N. Orentreich, J.L. Brind, R.L. Rizer, et al., Age changes and sex differences in serum dehydroepiandrosterone sulphate content throughout adulthood, J. Clin. Endocrinol. Metab. 59 (1984) 551 – 555. [24] A.A. Lacroix, K. Yano, D.M. Reed, Dehydroepiandrosterone sulphate, incidence of myocardial infarction and extent of atherosclerosis in men, Circulation 86 (1992) 1529 – 1535. [25] J.E. Nestler, C.O. Barlascini, J.N. Clore, et al., Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat, but does not alter insulin sensitivity in normal men, J. Clin. Endocrinol. Metab. 66 (1988) 57 – 61. [26] P. Diamond, L. Cusan, J.L. Gomez, et al., Metabolic effects of 12-months precutaneous dehydroepiandrosterone replacement therapy in postmenopausal women, J. Endocrinol. 150 (1996) S43 – S50. [27] A. Milewicz, D. Je˛drzejuk, A. Bohdanowicz-Pawlak, et al., Metabolic and hormonal changes after DHEA treatment, in: T. Aso, T. Yanaihara, Y. Taketani, T. Suda, H. Tanaka, S. Maehara (Eds.), The 9th International
A. Milewicz, M. Demissie / International Congress Series 1229 (2002) 3–7
[28]
[29] [30] [31]
[32]
7
Menopause Society World Congress on the Menopause, Yokohama (Japan), Monduzzi Editore, Bologna, 1999, pp. 215 – 220. A. Weltman, J.Y. Weltman, R.D. Abbott, et al., Relationship between age, percentage body fat, fitness and 24-hour growth hormone release in healthy young adults: effects of gender, J. Clin. Endocrinol. Metab. 78 (1994) 543 – 548. K. Tanaka, S. Inoue, J. Shiraki, et al., Age-related decrease in plasma growth hormone: response to growth hormone-releasing hormone, arginine, and L-dopa in obesity, Metabolism 40 (1991) 1257 – 1262. L. Wideman, J. Weltman, N. Shah, S. Story, J. Veldhuis, A. Weltman, Effects of gender on exercise-induced growth hormone release, J. Appl. Physiol. 87 (1999) 1154 – 1162. J. Veldhuis, W. Evans, N. Shah, S. Storey, M. Bray, S. Anderson, Proposed mechanisms of sex-steroid hormone neuromodulation of the human GH-IGF-I axis, in: J. Veldhuis, A. Giustina (Eds.), Sex Steroid Interactions With Growth Hormone, Springer-Verlag, New York, NY, 1999, pp. 93 – 121. R. Abs, B.A. Bengtsson, E. Hernberg-Stahl, et al., GH replacement in 1034 growth hormone deficient hypopituitary adults: demographic and clinical characteristics, dosing and safety, Clin. Endocrinol. 50 (1999) 703 – 713.