What causes hot flushes? The neuroendocrine origin of vasomotor symptoms in the menopause

References

• National Institutes of Health State-of-the-Science Conference statement. Management of Menopause-Related Symptoms. Ann Intern Med 2005; 142: 1003–1013
   PubMedGoogle Scholar
• Kuhl H. Klimakterium, Postmenopause und Hormonsubstitution, UNI-MED Verlag Bremen Kap. 3.2.(S. 50 ff.), 2. Auflage. 2001
   Google Scholar
• Kronenberg F. Hot flashes: epidemiology and physiology. Ann N Y Acad.Sci 1990; 592: 52–86
   PubMed Web of Science ®Google Scholar
• Woodward S, Freedman R R. The thermoregulatory effects of menopausal hot flashes on sleep. Sleep 1994; 17: 497–501
   PubMed Web of Science ®Google Scholar
• Joffe H, Hall J E, Soares C N, Hennen J, Reilly C J, Carlson K, Cohen L S. Vasomotor symptoms are associated with depression in perimenopausal women seeking primary care. Menopause 2002; 9: 392–398
   PubMed Web of Science ®Google Scholar
• Utian W H. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual Life Outcomes 2005; 3: 47
   PubMedGoogle Scholar
• Mom C H, Buijs C, Willemse P H, Mourits M J, de Vries E G. Hot flushes in breast cancer patients. Crit Rev.Oncol Hematol 2006; 57: 63–77
   PubMed Web of Science ®Google Scholar
• Ness J, Aronow W S, Beck G. Menopausal symptoms after cessation of hormone replacement therapy. Maturitas 2006; 53: 356–361
   PubMed Web of Science ®Google Scholar
• Baerug U, Winge T, Nordland G, Faber-Swensson E, Heldaas K, Norling B, Larsen S, Arce J C. Do combinations of 1 mg estradiol and low doses of NETA effectively control menopausal symptoms. Climacteric 1998; 1: 219–228
   PubMedGoogle Scholar
• Hendrix S L. Bilateral oophorectomy and premature menopause. Am J Med 2005; 118(Suppl 12B)131–135
   PubMedGoogle Scholar
• Randolph J F, Jr., Sowers M, Bondarenko I, Gold E B, Greendale G A, Bromberger J T, Brockwell S E, Matthews K A. The relationship of longitudinal change in reproductive hormones and vasomotor symptoms during the menopausal transition. J Clin Endocrinol Metab 2005; 90: 6106–6112
   PubMed Web of Science ®Google Scholar
• Overlie I, Moen M H, Holte A, Finset A. Androgens and estrogens in relation to hot flushes during the menopausal transition. Maturitas 2002; 41: 69–77
   PubMed Web of Science ®Google Scholar
• Berendsen H H. The role of serotonin in hot flushes. Maturitas 2000; 36: 155–164
   PubMed Web of Science ®Google Scholar
• Deecher D C. Physiology of thermoregulatory dysfunction and current approaches to the treatment of vasomotor symptoms. Expert Opin Investig Drugs 2005; 14: 435–448
   PubMed Web of Science ®Google Scholar
• Freedman R R. Physiology of hot flashes. Am J Hum Biol 2001; 13: 453–464
   PubMed Web of Science ®Google Scholar
• Rodstrom K, Bengtsson C, Lissner L, Milsom I, Sundh V, Bjorkelund C. A longitudinal study of the treatment of hot flushes: the population study of women in Gothenburg during a quarter of a century. Menopause 2002; 9: 156–161
   PubMed Web of Science ®Google Scholar
• Avis N E, Brockwell S, Colvin A. A universal menopausal syndrome?. Am J Med 2005; 118(Suppl 12B)37–46
   PubMedGoogle Scholar
• Guthrie J R, Dennerstein L, Taffe J R, Lehert P, Burger H G. The menopausal transition: a 9-year prospective population-based study. The Melbourne Women's Midlife Health Project. Climacteric 2004; 7: 375–389
   PubMed Web of Science ®Google Scholar
• North American Menopause Society. Treatment of menopause-associated vasomotor symptoms: position statement of The North American Menopause Society. Menopause 2004; 11: 11–33
   PubMed Web of Science ®Google Scholar
• Charkoudian N. Skin blood flow in adult human thermoregulation: how it works, when it does not, and why. Mayo Clin Proc 2003; 78: 603–612
   PubMed Web of Science ®Google Scholar
• Cabanac M, Massonnet B. Thermoregulatory responses as a function of core temperature in humans. J Physiol 1977; 265: 587–596
   PubMed Web of Science ®Google Scholar
• Hensel H. Neural processes in thermoregulation. Physiol Rev 1973; 53: 948–1017
   PubMed Web of Science ®Google Scholar
• Boulant J A, Dean J B. Temperature receptors in the central nervous system. Annu Rev Physiol 1986; 48: 639–654
   PubMed Web of Science ®Google Scholar
• Romanovsky A A. Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system. Am J Physiol Regul Integr Comp Physiol 2007; 292: R37–R46
   PubMed Web of Science ®Google Scholar
• Simon E. The enigma of deep-body thermosensory specificity. Int J Biometeorol 2000; 44: 105–120
   PubMed Web of Science ®Google Scholar
• Frank S M, Raja S N, Bulcao C F, Goldstein D S. Relative contribution of core and cutaneous temperatures to thermal comfort and autonomic responses in humans. J Appl Physiol 1999; 86: 1588–1593
   PubMed Web of Science ®Google Scholar
• Crawshaw L, Grahn D, Wollmuth L, Simpson L. Central nervous regulation of body temperature in vertebrates: comparative aspects. Pharmacol Ther 1985; 30: 19–30
   PubMed Web of Science ®Google Scholar
• Boulant J A. Role of the preoptic-anterior hypothalamus in thermoregulation and fever. Clin Infect Dis 2000; 31(Suppl 5)S157–S161
   PubMed Web of Science ®Google Scholar
• Zhang Y H, Yamada K, Hosono T, Chen X M, Shiosaka S, Kanosue K. Efferent neuronal organization of thermoregulatory vasomotor control. Ann N Y Acad Sci 1997; 813: 117–122
   PubMed Web of Science ®Google Scholar
• Bruck K, Zeisberger E. Adaptive changes in thermoregulation and their neuropharmacological basis. Pharmacol Ther 1987; 35: 163–215
   PubMed Web of Science ®Google Scholar
• Gundlah C, Pecins-Thompson M, Schutzer W E, Bethea C L. Ovarian steroid effects on serotonin 1A, 2A and 2C receptor mRNA in macaque hypothalamus. Brain Res Mol Brain Res 1999; 63: 325–339
   PubMedGoogle Scholar
• Bethea C L, Lu N Z, Gundlah C, Streicher J M. Diverse actions of ovarian steroids in the serotonin neural system. Front Neuroendocrinol 2002; 23: 41–100
   PubMed Web of Science ®Google Scholar
• Karkanias G B, Ansonoff M A, Etgen A M. Estradiol regulation of alpha 1b-adrenoceptor mRNA in female rat hypothalamus-preoptic area. J Neuroendocrinol 1996; 8: 449–455
   PubMed Web of Science ®Google Scholar
• Karkanias G B, Li C S, Etgen A M. Estradiol reduction of alpha 2-adrenoceptor binding in female rat cortex is correlated with decreases in alpha 2A/D-adrenoceptor messenger RNA. Neuroscience 1997; 81: 593–597
   PubMed Web of Science ®Google Scholar
• Petitti N, Etgen A M. Alpha 1-adrenoceptor augmentation of beta-stimulated cAMP formation is enhanced by estrogen and reduced by progesterone in rat hypothalamic slices. J Neurosci 1990; 10: 2842–2849
   PubMed Web of Science ®Google Scholar
• Martin G R. Vascular receptors for 5-hydroxytryptamine: distribution, function and classification. Pharmacol Ther 1994; 62: 283–324
   PubMed Web of Science ®Google Scholar
• Abdelmawla A H, Langley R W, Szabadi E, Bradshaw C M. Comparison of the effects of venlafaxine, desipramine, and paroxetine on noradrenaline- and methoxamine-evoked constriction of the dorsal hand vein. Br J Clin Pharmacol 1999; 48: 345–354
   PubMed Web of Science ®Google Scholar
• Freedman R R. Hot flashes: behavioral treatments, mechanisms, and relation to sleep. Am J Med 2005; 118(Suppl 12B)124–130
   PubMed Web of Science ®Google Scholar
• Kurz A, Sessler D I, Tayefeh F, Goldberger R. Poikilothermia syndrome. J Intern Med 1998; 244: 431–436
   PubMed Web of Science ®Google Scholar
• Sullivan F, Hutchinson M, Bahandeka S, Moore R E. Chronic hypothermia in multiple sclerosis. J Neurol Neurosurg Psychiatry 1987; 50: 813–815
   PubMed Web of Science ®Google Scholar
• White K D, Scoones D J, Newman P K. Hypothermia in multiple sclerosis. J Neurol Neurosurg Psychiatry 1996; 61: 369–375
   PubMed Web of Science ®Google Scholar
• Edwards S, Lennox G, Robson K, Whiteley A. Hypothermia due to hypothalamic involvement in multiple sclerosis. J Neurol Neurosurg Psychiatry 1996; 61: 419–420
   PubMed Web of Science ®Google Scholar
• Crompton M R. Hypothalamic lesions following closed head injury. Brain 1971; 94: 165–172
   PubMed Web of Science ®Google Scholar
• Thompson H J, Tkacs N C, Saatman K E, Raghupathi R, McIntosh T K. Hyperthermia following traumatic brain injury: a critical evaluation. Neurobiol Dis 2003; 12: 163–173
   PubMed Web of Science ®Google Scholar
• Couzi R J, Helzlsouer K J, Fetting J H. Prevalence of menopausal symptoms among women with a history of breast cancer and attitudes toward estrogen replacement therapy. J Clin Oncol 1995; 13: 2737–2744
   PubMed Web of Science ®Google Scholar
• Fallowfield L, Fleissig A, Edwards R, West A, Powles T J, Howell A, Cuzick J. Tamoxifen for the prevention of breast cancer: psychosocial impact on women participating in two randomized controlled trials. J Clin Oncol 2001; 19: 1885–1892
   PubMed Web of Science ®Google Scholar
• Land S R, Wickerham D L, Costantino J P, Ritter M W, Vogel V G, Lee M, Pajon E R, Wade J L, III, Dakhil S, Lockhart J B, Jr, et al. Patient-reported symptoms and quality of life during treatment with tamoxifen or raloxifene for breast cancer prevention: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006; 295: 2742–2751
   PubMed Web of Science ®Google Scholar
• Jordan V C. SERMs: meeting the promise of multifunctional medicines. J Natl Cancer Inst 2007; 99: 350–356
   PubMed Web of Science ®Google Scholar
• Holzbeierlein J M, Castle E P, Thrasher J B. Complications of androgen-deprivation therapy for prostate cancer. Clin Prostate Cancer 2003; 2: 147–152
   PubMedGoogle Scholar
• Bachmann G A. Menopausal vasomotor symptoms: a review of causes, effects and evidence-based treatment options. J Reprod Med 2005; 50: 155–165
   PubMed Web of Science ®Google Scholar
• Santoro N. The menopausal transition. Am J Med 2005; 118(Suppl 12B)8–13
   PubMedGoogle Scholar
• Burger H G, Dudley E C, Robertson D M, Dennerstein L. Hormonal changes in the menopause transition. Recent Prog Horm Res 2002; 57: 257–275
   PubMedGoogle Scholar
• Santoro N, Brown J R, Adel T, Skurnick J H. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab 1996; 81: 1495–1501
   PubMed Web of Science ®Google Scholar
• Nelson H D, Haney E, Humphrey L, Miller J, Nedrow A, Nicolaidis C, Vesco K, Walker M, Bougatsos C, Nygren P. Management of menopause-related symptoms. Evid Rep Technol Assess (Summ.) 2005; 1–6
   Google Scholar
• Cohen L S, Soares C N, Vitonis A F, Otto M W, Harlow B L. Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles. Arch Gen Psychiatry 2006; 63: 385–390
   PubMed Web of Science ®Google Scholar
• Freeman E W, Sammel M D, Lin H, Nelson D B. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry 2006; 63: 375–382
   PubMed Web of Science ®Google Scholar
• Dennerstein L, Smith A M, Morse C A, Burger H G. Sexuality and the menopause. J Psychosom Obstet Gynaecol 1994; 15: 59–66
   PubMed Web of Science ®Google Scholar
• Shaver J L, Paulsen V M. Sleep, psychological distress, and somatic symptoms in perimenopausal women. Fam Pract Res J 1993; 13: 373–384
   PubMedGoogle Scholar
• Rossmanith W G, Liu C H, Laughlin G A, Mortola J F, Suh B Y, Yen S S. Relative changes in LH pulsatility during the menstrual cycle: using data from hypogonadal women as a reference point. Clin Endocrinol (Oxf) 1990; 32: 647–660
   PubMed Web of Science ®Google Scholar
• Rossmanith W G, Ulrich U. Neuroendokrine Aspekte der Hormonregulation in Peri- und Postmenopause. Aktuelle Hormontherapie in der Gynäkologie (Kiesel L., Rabe T., Runnebaum B.) Hrsg. Zuckerschwerdt Verlag (103), München 1993
   Google Scholar
• Kuhl H, Taubert H D. Endokrine Veränderungen, Das Klimakterium, Stuttgart, New York Thieme Verlag (128) 1987
   Google Scholar
• Casper R F, Yen S S, Wilkes M M. Menopausal flushes: a neuroendocrine link with pulsatile luteninizing hormone secreation. Science 1979; 205: 823–825
   PubMed Web of Science ®Google Scholar
• Tataryn I V, Lomax P, Bajorek J G, Chesarek W, Meldrum D R, Judd H L. Postmenopausal hot flushes: a disorder of thermoregulation. Maturitas 1980; 2: 101–107
   PubMed Web of Science ®Google Scholar
• Freedman Robert R, Woodward S. Altered Shivering Threshold in Postmenopausal Women with Hot Flashes. Menopause: The Journal of the North American Menopause Society 1995; 2(3)163–168
   Web of Science ®Google Scholar
• Freedman R R, Norton D, Woodward S, Cornelissen G. Core body temperature and circadian rhythm of hot flashes in menopausal women. J Clin Endocrinol Metab 1995; 80: 2354–2358
   PubMed Web of Science ®Google Scholar
• Freedman R R, Woodward S. Core body temperature during menopausal hot flushes. Fertil Steril 1996; 65: 1141–1144
   PubMed Web of Science ®Google Scholar
• Freedman R R, Krell W. Reduced thermoregulatory null zone in postmenopausal women with hot flashes. Am J Obstet Gynecol 1999; 181: 66–70
   PubMed Web of Science ®Google Scholar
• Brooks E M, Morgan A L, Pierzga J M, Wladkowski S L, O'Gorman J T, Derr J A, Kenney W L. Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women. J Appl Physiol 1997; 83: 477–484
   PubMed Web of Science ®Google Scholar
• Joswig M, Hach-Wunderle V, Ziegler R, Nawroth P P. Postmenopausal hormone replacement therapy and the vascular wall: mechanisms of 17 beta-estradiol's effects on vascular biology. Exp Clin Endocrinol Diabetes 1999; 107: 477–487
   PubMed Web of Science ®Google Scholar
• Shanafelt T D, Barton D L, Adjei A A, Loprinzi C L. Pathophysiology and treatment of hot flashes. Mayo Clin Proc 2002; 77: 1207–1218
   PubMed Web of Science ®Google Scholar
• Nelson H D, Vesco K K, Haney E. Clonidine, gabapentin, and some SSRIs effective for hot flashes. J Fam Pract 2006; 55: 662
   PubMed Web of Science ®Google Scholar
• Clayden J R. Effect of clonidine on menopausal flushing. Lancet 1972; 2: 1361
   PubMed Web of Science ®Google Scholar
• Williams C W. Clonidine in treatment of menopausal flushing. Lancet 1973; 1: 1388
   PubMed Web of Science ®Google Scholar
• Clayden J R, Bell J W, Pollard P. Menopausal flushing: double-blind trial of a non-hormonal medication. Br Med J 1974; 1: 409–412
   PubMed Web of Science ®Google Scholar
• Deecher D C, Alfinito P D, Leventhal L, Cosmi S, Johnston G H, Merchenthaler I, Winneker R. Alleviation of thermoregulatory dysfunction with the new serotonin and norepinephrine reuptake inhibitor desvenlafaxine succinate in ovariectomized rodent models. Endocrinology 2007; 148: 1376–1383
   PubMed Web of Science ®Google Scholar
• Nelson H D, Vesco K K, Haney E, Fu R, Nedrow A, Miller J, Nicolaidis C, Walker M, Humphrey L. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006; 295: 2057–2071
   PubMed Web of Science ®Google Scholar
• Loprinzi C L, Kugler J W, Sloan J A, Mailliard J A, LaVasseur B I, Barton D L, Novotny P J, Dakhil S R, Rodger K, Rummans T A, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet 2000; 356: 2059–2063
   PubMed Web of Science ®Google Scholar
• Stearns V, Slack R, Greep N, Henry-Tilman R, Osborne M, Bunnell C, Ullmer L, Gallagher A, Cullen J, Gehan E, et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol 2005; 23: 6919–6930
   PubMed Web of Science ®Google Scholar
• Gould E, Woolley C S, Frankfurt M, McEwen B S. Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J Neurosci 1990; 10: 1286–1291
   PubMed Web of Science ®Google Scholar
• McEwen B S, Alves S E. Estrogen actions in the central nervous system. Endocr Rev 1999; 20: 279–307
   PubMed Web of Science ®Google Scholar
• McEwen B S. Invited review: Estrogens effects on the brain: multiple sites and molecular mechanisms. J Appl Physiol 2001; 91: 2785–2801
   PubMed Web of Science ®Google Scholar
• Woolley C S, McEwen B S. Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol 1993; 336: 293–306
   PubMed Web of Science ®Google Scholar
• Genazzani A R, Pluchino N, Luisi S, Luisi M. Estrogen, cognition and female ageing. Hum Reprod Update 2007; 13: 175–187
   PubMed Web of Science ®Google Scholar
• Gibbs R B. Levels of trkA and BDNF mRNA, but not NGF mRNA, fluctuate across the estrous cycle and increase in response to acute hormone replacement. Brain Res 1998; 787: 259–268
   PubMed Web of Science ®Google Scholar
• Birge S J. Estrogen and the brain: implications for menopause management. Menopause: The State of the Art - in Research and Management 2002; 191–195
   Google Scholar
• McEwen B. Estrogen actions throughout the brain. Recent Prog Horm Res 2002; 57: 357–384
   PubMedGoogle Scholar
• Bethea C L, Gundlah C, Mirkes S J. Ovarian steroid action in the serotonin neural system of macaques. Novartis Found Symp 2000; 230: 112–130
   PubMedGoogle Scholar
• Gundlah C, Kohama S G, Mirkes S J, Garyfallou V T, Urbanski H F, Bethea C L. Distribution of estrogen receptor beta (ERbeta) mRNA in hypothalamus, midbrain and temporal lobe of spayed macaque: continued expression with hormone replacement. Brain Res Mol Brain Res 2000; 76: 191–204
   PubMedGoogle Scholar
• Bethea C L, Brown N A, Kohama S G. Steroid regulation of estrogen and progestin receptor messenger ribonucleic acid in monkey hypothalamus and pituitary. Endocrinology 1996; 137: 4372–4383
   PubMed Web of Science ®Google Scholar
• Osterlund M K, Gustafsson J A, Keller E, Hurd Y L. Estrogen receptor beta (ERbeta) messenger ribonucleic acid (mRNA) expression within the human forebrain: distinct distribution pattern to ERalpha mRNA. J Clin Endocrinol Metab 2000; 85: 3840–3846
   PubMed Web of Science ®Google Scholar
• Temel S, Lin W, Lakhlani S, Jennes L. Expression of estrogen receptor-alpha and cFos in norepinephrine and epinephrine neurons of young and middle-aged rats during the steroid-induced luteinizing hormone surge. Endocrinology 2002; 143: 3974–3983
   PubMed Web of Science ®Google Scholar
• Lu H, Ozawa H, Nishi M, Ito T, Kawata M. Serotonergic neurones in the dorsal raphe nucleus that project into the medial preoptic area contain oestrogen receptor beta. J Neuroendocrinol 2001; 13: 839–845
   PubMed Web of Science ®Google Scholar
• Kallo I, Liposits Z, Flerko B, Coen C W. Immunocytochemical characterization of afferents to estrogen receptor-containing neurons in the medial preoptic area of the rat. Neuroscience 1992; 50: 299–308
   PubMed Web of Science ®Google Scholar
• Maswood N, Cosmi S, Alfinito P D, Leventhal L, Deecher D C. The role of the selective serotonin reuptake inhibitor fluoxetine in temperature regulation in ovariectomized rat models. Neuroendocrinology 2006; 84: 330–338
   PubMed Web of Science ®Google Scholar
• Bethea C L, Pecins-Thompson M, Schutzer W E, Gundlah C, Lu Z N. Ovarian steroids and serotonin neural function. Mol Neurobiol 1998; 18: 87–123
   PubMed Web of Science ®Google Scholar
• Amin Z, Canli T, Epperson C N. Effect of estrogen-serotonin interactions on mood and cognition. Behav Cogn Neurosci Rev 2005; 4: 43–58
   PubMedGoogle Scholar
• Herbison A E, Simonian S X, Thanky N R, Bicknell R J. Oestrogen modulation of noradrenaline neurotransmission. Novartis Found Symp 2000; 230: 74–85
   PubMedGoogle Scholar
• Etgen A M, Ansonoff M A, Quesada A. Mechanisms of ovarian steroid regulation of norepinephrine receptor-mediated signal transduction in the hypothalamus: implications for female reproductive physiology. Horm Behav 2001; 40: 169–177
   PubMed Web of Science ®Google Scholar
• Genazzani A R, Lucchesi A, Stomati M, Catarsi S, Genazzani A D, Criscuolo M, Petraglia F. Effects of sex steroid hormones on the neuroendocrine system. Eur J Contracept Reprod Health Care 1997; 2: 63–69
   PubMedGoogle Scholar
• Pecins-Thompson M, Brown N A, Kohama S G, Bethea C L. Ovarian steroid regulation of tryptophan hydroxylase mRNA expression in rhesus macaques. J Neurosci 1996; 16: 7021–7029
   PubMed Web of Science ®Google Scholar
• Gundlah C, Alves S E, Clark J A, Pai L Y, Schaeffer J M, Rohrer S P. Estrogen receptor-beta regulates tryptophan hydroxylase-1 expression in the murine midbrain raphe. Biol Psychiatry 2005; 57: 938–942
   PubMed Web of Science ®Google Scholar
• Sanchez R L, Reddy A P, Centeno M L, Henderson J A, Bethea C L. A second tryptophan hydroxylase isoform, TPH-2 mRNA, is increased by ovarian steroids in the raphe region of macaques. Brain Res Mol Brain Res 2005; 135: 194–203
   PubMedGoogle Scholar
• Hiroi R, McDevitt R A, Neumaier J F. Estrogen selectively increases tryptophan hydroxylase-2 mRNA expression in distinct subregions of rat midbrain raphe nucleus: association between gene expression and anxiety behavior in the open field. Biol Psychiatry 2006; 60: 288–295
   PubMed Web of Science ®Google Scholar
• Bethea C L, Mirkes S J, Shively C A, Adams M R. Steroid regulation of tryptophan hydroxylase protein in the dorsal raphe of macaques. Biol Psychiatry 2000; 47: 562–576
   PubMed Web of Science ®Google Scholar
• Gundlah C, Lu N Z, Bethea C L. Ovarian steroid regulation of monoamine oxidase-A and -B mRNAs in the macaque dorsal raphe and hypothalamic nuclei. Psychopharmacology (Berl) 2002; 160: 271–282
   PubMed Web of Science ®Google Scholar
• Le Saux M, Di P T. Changes in 5-HT1A receptor binding and G-protein activation in the rat brain after estrogen treatment: comparison with tamoxifen and raloxifene. J Psychiatry Neurosci 2005; 30: 110–117
   PubMed Web of Science ®Google Scholar
• Lu N Z, Bethea C L. Ovarian steroid regulation of 5-HT1A receptor binding and G protein activation in female monkeys. Neuropsychopharmacology 2002; 27: 12–24
   PubMed Web of Science ®Google Scholar
• Serova L, Rivkin M, Nakashima A, Sabban E L. Estradiol stimulates gene expression of norepinephrine biosynthetic enzymes in rat locus coeruleus. Neuroendocrinology 2002; 75: 193–200
   PubMed Web of Science ®Google Scholar
• Serova L I, Maharjan S, Huang A, Sun D, Kaley G, Sabban E L. Response of tyrosine hydroxylase and GTP cyclohydrolase I gene expression to estrogen in brain catecholaminergic regions varies with mode of administration. Brain Res 2004; 1015: 1–8
   PubMed Web of Science ®Google Scholar
• Karkanias G B, Etgen A M. Estradiol reduction of the agonist high affinity form of the alpha 2-adrenoceptor in the hypothalamus of female rats: identification as the alpha 2D subtype. Mol Pharmacol 1994; 45: 509–516
   PubMed Web of Science ®Google Scholar
• Burger H G. The endocrinology of the menopause. Maturitas 1996; 23: 129–136
   PubMed Web of Science ®Google Scholar
• Haimov-Kochman R, Barak-Glantz E, Arbel R, Leefsma M, Brzezinski A, Milwidsky A, Hochner-Celnikier D. Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: a randomized prospective study. Menopause 2006; 13: 370–376
   PubMed Web of Science ®Google Scholar
• Farquhar C M, Marjoribanks J, Lethaby A, Lamberts Q, Suckling J A. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2005; CD004143
   PubMed Web of Science ®Google Scholar
• Johnson S R, Ettinger B, Macer J L, Ensrud K E, Quan J, Grady D. Uterine and vaginal effects of unopposed ultralow-dose transdermal estradiol. Obstet Gynecol 2005; 105: 779–787
   PubMed Web of Science ®Google Scholar
• Lacey J V, Jr., Brinton L A, Leitzmann M F, Mouw T, Hollenbeck A, Schatzkin A, Hartge P. Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort. J Natl Cancer Inst 2006; 98: 1397–1405
   PubMed Web of Science ®Google Scholar
• North American Menopause Society. Recommendations for estrogen and progestogen use in peri-and postmenopausal women: October 2004 position statement of The North American Menopause Society. Menopause 2004; 11: 589–600
   PubMed Web of Science ®Google Scholar
• DGGG (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe). Leitlinien der Hormontherapie in der Peri- und Postmenopause. Vorbereitung. DGGG. 2009
   Google Scholar
• Pines A, Sturdee D W, Birkhauser M H, Schneider H P, Gambacciani M, Panay N. IMS updated recommendations on postmenopausal hormone therapy. Climacteric 2007; 10: 181–194
   PubMed Web of Science ®Google Scholar
• Stearns V, Beebe K L, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA 2003; 289: 2827–2834
   PubMed Web of Science ®Google Scholar
• Loprinzi C L, Sloan J A, Perez E A, Quella S K, Stella P J, Mailliard J A, Halyard M Y, Pruthi S, Novotny P J, Rummans T A. Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol 2002; 20: 1578–1583
   PubMed Web of Science ®Google Scholar
• Nappi R E, Malavasi B, Brundu B, Facchinetti F. Efficacy of Cimicifuga racemosa on climacteric complaints: a randomized study versus low-dose transdermal estradiol. Gynecol Endocrinol 2005; 20: 30–35
   PubMed Web of Science ®Google Scholar
• Ma J, Drieling R, Stafford R S. US women desire greater professional guidance on hormone and alternative therapies for menopause symptom management. Menopause 2006; 13: 506–516
   PubMed Web of Science ®Google Scholar
• Caserta L, Caserta R, Torella M, Nappo C, De L D, Panariello S. [The effects of phytoestrogen therapy on the endometrium in postmenopausal women]. Minerva Ginecol 2005; 57: 551–555
   PubMedGoogle Scholar
• Alfinito P D, Huselton C, Chen X, Deecher D C. Pharmacokinetic and pharmacodynamic profiles of the novel serotonin and norepinephrine reuptake inhibitor desvenlafaxine succinate in ovariectomized Sprague-Dawley rats. Brain Res 2006; 1098: 71–78
   PubMed Web of Science ®Google Scholar
• Deecher D C, Beyer C E, Johnston G, Bray J, Shah S, Abou-Gharbia M, Andree T H. Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther 2006; 318: 657–665
   PubMed Web of Science ®Google Scholar
• Archer David F, DuPont Caroline M, Pickar James H, Olivier Sophie, Constantine Ginger D. Desvenlafaxine Succinate is Effective in the Treatment of Menopausal Vasomotor Symptoms. 55th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists, San Diego, California (Posterpräsentation), 2007
   Google Scholar
• Gass Margery, Olivier Sophie, Constantine Ginger D. Efficacy and Safety of Desvenlafaxine Succinate for treatment of Menopausal Vasomotor Symptoms. 55th Annual Meeting of the American College of Obstetricians and Gynecologists (ACOG) San Diego, , California, 2007
   Google Scholar
• Loprinzi C L, Barton D L, Rhodes D. Management of hot flashes in breast-cancer survivors. Lancet Oncol 2001; 2: 199–204
   PubMed Web of Science ®Google Scholar
• Loibl S, Schwedler K, von M G, Strohmeier R, Mehta K M, Kaufmann M. Venlafaxine is superior to clonidine as treatment of hot flashes in breast cancer patients – a double-blind, randomized study. Ann Oncol 2007; 18: 689–693
   PubMed Web of Science ®Google Scholar
• Pandya K J, Morrow G R, Roscoe J A, Zhao H, Hickok J T, Pajon E, Sweeney T J, Banerjee T K, Flynn P J. Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial. Lancet 2005; 366: 818–824
   PubMed Web of Science ®Google Scholar
• Goldberg R M, Loprinzi C L, O'Fallon J R, Veeder M H, Miser A W, Mailliard J A, Michalak J C, Dose A M, Rowland K M, Jr., Burnham N L. Transdermal clonidine for ameliorating tamoxifen-induced hot flashes. J Clin Oncol 1994; 12: 155–158
   PubMed Web of Science ®Google Scholar
• Guyton A C, Hall J E. Body temperature, temperature regulation, and fever. Textbook of Medical Physiology11th ed. Elsevier Saunders, Philadelphia, PA 2006; 889–901
   Google Scholar