Hostname: page-component-76fb5796d-zzh7m Total loading time: 0 Render date: 2024-04-26T03:16:27.180Z Has data issue: false hasContentIssue false

Endocrinology of Menopausal Transition and Its Brain Implications

Published online by Cambridge University Press:  07 November 2014

Abstract

The central nervous system is one of the main target tissues for sex steroid hormones, which act on both through genomic mechanisms, modulating synthesis, release, and metabolism of many neuropeptides and neurotransmitters, and through non-genomic mechanisms, influencing electrical excitability, synaptic function, morphological features, and neuron-glia interactions. During the climacteric period, sex steroid deficiency causes many neuroendocrine changes. At the hypothalamic level, estrogen withdrawal gives rise to vasomotor symptoms, to eating behavior disorders, and altered blood pressure control. On the other hand, at the limbic level, the changes in serotoninergic, noradrenergic, and opioidergic tones contribute to the modifications in mood, behavior, and nociception. Hormone replacement therapy (HRT) positively affects climateric depression throughout a direct effect on neural activity and on the modulation of adrenergic and serotoninergic tones and may modulate the decrease in cognitive efficiency observed in climaterium. The identification of the brain as a de novo source of neurosteroids, suggests that the modifications in mood and cognitive performances occurring in postmenopausal women may also be related to a change in the levels of neurosteroids. These findings open new perspectives in the study of the effects of sex steroids on the central nervous system and on the possible use of alternative and/or auxiliary HRT.

Type
Review Articles
Copyright
Copyright © Cambridge University Press 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Genazzani, AR, Petraglia, F, Purdy, RH, eds. The Brain: Source and Target for Sex Steroid Hormones. London, United Kingdom; The Parthenon Publishing Group; 1996.Google Scholar
2. Kruijver, FP, Zhou, JN, Pool, CW, et al. Male-to-female transsexuals have female neuron numbers in a limbic nucleus. J Clin Endocrinol Metab. 2000;85:20342041.Google Scholar
3. Cooke, B, Hegstrom, CD, Villeneuve, LS, et al. Sexual differentiation of the vertebrate brain: principles and mechanisms. Front Neuroendocrinol. 1998;19:323362.Google Scholar
4. Pfaff, DW. Estrogens and Brain Function. New York, NY: Springer-Verlag; 1980.Google Scholar
5. Fraser, IS, Jansen, RPS, Whitehead, MJ, eds. Effects of Estrogen and Progesterone on the Central System. Edinburgh, Scotland: Churchill Livingston; 1998.Google Scholar
6. Keefe, D, Garcia-Segura, LM, Naftolin, F. New insights into estrogen action on the brain. Neurobiol Aging. 1994;15:495497.CrossRefGoogle ScholarPubMed
7. Genazzani, AR, Gambacciani, M, Simoncini, T, Schneider, HP; International Menopause Society. “Controversial issues in climacteric medicine” series 3rd Pisa workshop “HRT in climacteric and aging brain”. Pisa, Italy, 15-18 March 2003. Maturitas. 2003:46:726.CrossRefGoogle ScholarPubMed
8. Gruber, CJ, Tschugguel, W, Schneeberger, C, et al. Production and actions of estrogens. N Engl J Med. 2002;346:340352.Google Scholar
9. Sherwin, BB. Estrogen effects on cognition in menopausal women. Neurology. 1997;48:S21S26.Google Scholar
10. Alonso-Soleis, R, Abreu, P, Leopez-Coviella, I, et al. Gonadal steroid modulation of neuroendocrine transduction: a transynaptic view. Cell Mol Neurobiol. 1996;3:357382.Google Scholar
11. Couse, JF, Lindzey, J, Grandien, K, Gustafsson, JA, Korach, KS. Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse. Endocrinology. 1997;138:46134621.Google Scholar
12. Falkenstein, E, Wehling, M. Nongenomically initiated steroid actions. Eur J Clin Invest. 2000;30(suppl 3):5154.Google Scholar
13. Kuppers, E, Ivanova, T, Karolczak, M, et al. Classical and nonclassical estrogen action in the developing midbrain. Horm Behav. 2001;40:196202.Google Scholar
14. Brinton, RD. Cellular and molecular mechanisms of estrogen regulation of memory function and neuroprotection against Alzheimer's disease: recent insights and remaining challenges. Learn Memory. 2000;8:121133.Google Scholar
15. Kelly, MJ, Levin, ER. Rapid actions of plasma membrane estrogen receptors. Trends Endocrinol Metab. 2001;12:152156.Google Scholar
16. Kelly, MJ, Wagner, EJ. Estrogen modulation of G-protein-coupled receptors. Trends Endocrinol Metab. 1999;10:369374.Google Scholar
17. Panay, N, Sands, RH, Studd, JWW. Estrogen and behaviour. In: Genazzani, AR, Petraglia, F, Purdy, RH, eds. The Brain: Source and Target for Sex Steroid Hormones. London, United Kingdom; The Parthenon Publishing Group; 1996:257276.Google Scholar
18. Karla, SP. Gonadal steroid hormones promote interactive comunication. In: Genazzani, AR, Petraglia, F, Purdy, RH, eds. The Brain: Source and Target for Sex Steroid Hormones. London, United Kingdom; The Parthenon Publishing Group; 1996:153164.Google Scholar
19. Etgen, AM, Karkanias, GB Estrogen regulation of noradrenergic signaling in the hypothalamus. Psychonbeuroendocrinology. 1994;19:603610.Google Scholar
20. Ansonoff, MA, Etgen, AM. Evidence that oestradiol attenuates beta-adrenoceptor function in the hypothalamus of female rats by altering receptor phosphorylation and sequestration. J Neuroendocrinol. 2000;12:10601066.Google Scholar
21. Herbison, AE, Simonian, SX, Thanky, NR, Bicknell, RJ. Oestrogen modulation of noradrenaline neurotransmission. Novartis Found Symp. 2000;230:7485.CrossRefGoogle ScholarPubMed
22. Haywood, SA, Simonian, SX, van der Beek, EM, Bicknell, RJ, Herbison, AE. Fluctuating estrogen and progesterone receptor expression in brainstem norepinephrine neurons through the rat estrous cycle. Endocrinology. 1999;140:32553263.Google Scholar
23. Dickinson, SL, Curzon, G. 5-Hydroxytryptamine-mediated behavior in male and female rats. Neuropharmacology. 1986;25:771776.Google Scholar
24. Biegon, A, Bercovitz, H, Samuel, D. Serotonin receptor concentration during the estrous cycle of the rat. Brain Res. 1980;187:221225.Google Scholar
25. Mendelson, SD, McKittrick, CR, McEwen, BS. Autoradiographic analyses of the effects of estradiol benzoate on [3H]paroxetine binding in the cerebral cortex and dorsal hippocampus of gonadectomized male and female rats. Brain Res 1993;601:299301.Google Scholar
26. Luine, VN, McEwen, BS. Effect of oestradiol on turnover of type A monoamine oxidase in brain. J Neurochem. 1997;28:12211227.CrossRefGoogle Scholar
27. Bethea, CL, Lu, NZ, Gundlah, C, Streicher, JM. Diverse actions of ovarian steroids in the serotonin neural system. Front Neuroendocrinol. 2002;23:41100.Google Scholar
28. Sherwin, BB. Progestogens used in menopause. Side effects, mood and quality of life. J Reprod Med. 1999;44(2 suppl):227232.Google Scholar
29. Luine, VN, Rhodes, JC. Gonadal hormone regulation of MAO and other enzymes in hypothalamic areas. Neuroendocrinology. 1983;36:235241.Google Scholar
30. Studd, JW, Panay, N. Hormones and depression in women. Climateric. 2004;7:338346.Google Scholar
31. Decker, MW. The effects of aging on hippocampal and cortical projections of the forebrain cholinergic system. Brain Res Rev. 1987;12:423435.Google Scholar
32. Toran-Allerand, CD. The estrogen/neurotrophin connection during neuraldevelopment: is co-localization of estrogen receptors with the neurotrophins and their receptors biologically relevant? Dev Neurosci. 1996;18:3648.CrossRefGoogle Scholar
33. McMillan, PJ, Singer, CA, Dorsa, DM. The effects of ovariectomy andestrogen replacement on trkA and choline acetyltransferase mRNA expression in the basal forebrain of the adult female Sprague-Dawley rat. J Neurosci. 1996;16:18601865.CrossRefGoogle Scholar
34. Luine, V, Park, D, Joh, T, Reis, D, McEwen, B. Immunochemical demonstration of increased choline acetyltransferase concentration in rat preoptic area after estradiol administration. Brain Res. 1980;191:273277.Google Scholar
35. Kuhl, DE, Koeppe, RA, Minoshima, S, et al. In vivo mapping of cerebral cetylcholinesterase activity in aging and Alzheimer's disease. Neurology. 1999;52:691699.CrossRefGoogle Scholar
36. Baldereschi, M DiCarlo, A, Lepore, V, et al. Estrogen replacement therapy and Alzheimer's disease in the Italian Longitudinal Study on Aging. Neurology. 1998;50:9961002.Google Scholar
37. Birge, SJ. The role of estrogen in the treatment of Alzheimer's disease. Neurology. 1997;(5 suppl 7)48:S36S41.Google Scholar
38. Bluming, AZ. Hormone replacement therapy: the debate should continue. Geriatrics. 2004;59:30-31, 3537.Google ScholarPubMed
39. Kampen, DL, Sherwin, BB. Estrogen use and verbal memory in healthy postmenopausal women. Obstet Gynecol. 1994;83:979983.Google Scholar
40. Costa, MM, Reus, VI, Wolkowitz, OM, et al. Estrogen replacement therapy and cognitive decline in memory-impaired post-menopausal women. Biol Psychiatry. 1999;46:182188.CrossRefGoogle ScholarPubMed
41. Schneider, LS, Farlow, M. Combined tacrine and estrogen replacement therapy in patients with Alzheimer's disease. Ann N Y Acad Sci. 1997;826:317322.Google Scholar
42. Zanisi, M, Messi, E Sex steroid and the control of LHRH secretion. J Steroid Biochem Mol Biol. 1991;40:155163.Google Scholar
43. Zanisi, M, Galbiati, M, Messi, E. The multiple inputs to the LHRH neurons. In: Genazzani, AR, Petraglia, F, Nappi, G, Montemagno, U, eds. Neuroendocrinology of Female Reproductive Function. London, United Kingdom; The Parthenon Publishing Group; 1993:3341.Google Scholar
44. Stomati, M, Bernardi, F, Luisi, S, et al. Conjugated equine estrogens, estrone sulphate and estradiol valerate oral administration in ovariectomized rats: effects on central and peripheral allopregnanolone and beta-endorphin. Maturitas. 2002;43:195206.CrossRefGoogle ScholarPubMed
45. Bernardi, F, Stomati, M, Luisi, S, et al. Effects of the new generation selective estrogen receptor modulator EM-652 and oral administration of estradiol valerate on circulating, brain, and adrenal beta-endorphin and allopregnanolone levels in intact fertile and ovariectomized rats. Fertil Steril. 2002;77:10181027.Google Scholar
46. Genazzani, AR, Bernardi, F, Stomati, M, et al. Raloxifene analog LY 117018 effects on central and peripheral beta-endorphin. Gynecol Endocrinol. 1999;13:249258.Google Scholar
47. Genazzani, AR, Petraglia, F, Facchinetti, F, et al. Steroid replacement increase beta-endorphin and beta-lipotropin plasma levels in postmenopausal women. Gynecol Obstet Invest. 1988;26:153159.Google Scholar
48. Aleem, FA, McIntosh, T. Menopausal syndrome: plasma levels of b-endorphin in postmenopausal women measured by a specific radioimmunoassay. Maturitas. 1985;7:329334.CrossRefGoogle ScholarPubMed
49. Genazzani, AR, Petraglia, F, Facchinetti, F, et al. Increase of proopiomelanocortin-related peptides during subjective menopausal flushes. Am J Obstet Gynecol. 1984;149:775779.Google Scholar
50. Lightman, SL, Jacobs, HS, Maguire, AK, McGarrick, G, Jeffcoate, SL. Climateric flushing: clinical and endocrine response to infusion of naloxone. Br J Obstet Gynaecol. 1981;88:919924.Google Scholar
51. Adler, MW. Opioid peptides. Life Sci. 1980;26:497510.CrossRefGoogle ScholarPubMed
52. Zarate, A, Fonseca, E, Ochoa, R, Basurto, L, Hernandez, M. Low-dose conjugated equine estrogens elevate circulating neurotransmitters and improve the psychological well-being of menopausal women. Fertil Steril. 2002;77:952955.CrossRefGoogle ScholarPubMed
53. Stomati, M, Bersi, C, Bernardi, F, et al. Beta-endorphin response to oral glucose tolerance test in obese and non-obese pre- and postmenopausal women. Gynecol Endocrinol. 1998;12:3540.Google Scholar
54. Donouhe, TL, Dorse, DM. The opiomelanotropinergic neuronal and endocrine system. Peptides. 1982;3:383395.Google Scholar
55. Genazzani, AR, Petraglia, F, Cleva, M, et al. Norgestimate increases pituitary and hypothalamic concentrations of immunoreactive beta-endorphin. Contraception. 1989;5:605613.Google Scholar
56. Genazzani, AR, Petraglia, F, Mercuri, N, et al. Effect of steroid hormones and anti-hormones on hypothalamic beta-endorphin concentrations in intact and castrated female rats. J Endocrinol Invest. 1990;13:9196.CrossRefGoogle Scholar
57. Stomati, M, Bersi, C, Rubino, S, et al. Neuroendocrine effects of different estradiol-progestin regimens in postmenopausal women. Maturitas. 1997;28:127135.Google Scholar
58. Petraglia, F, Comitini, G, Genazzani, AR, et al. B-Endorphin in human reproduction. In: Herz, A. Opioids II. Berlin, Germany: Springer-Verlag; 1993:763780.Google Scholar
59. Florio, P, Quirici, B, Casarosa, E, et al. Neuroendocrine effects of raloxifene hydrochloride in postmenopausal women. Gynecol Endocrinol. 2001;15:359366.CrossRefGoogle ScholarPubMed
60. Stomati, M, Monteleone, P, Casarosa, E, et al. Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause. Gynecol Endocrinol. 2000;14:342363.Google Scholar
61. Zarjevski, N, Cusin, I, Vettor, R, et al. Intracerebroventricular administration of neuropeptide Y to normal rats has divergent effects on glucose utilization by adipose tissue and skeletal muscle. Diabetes. 1994;43:764769.Google Scholar
62. Milewicz, A, Bidzinska, B, Mikulski, E, Demissie, M, Tworowska, U. Influence of obesity and menopausal status on serum leptin, cholecystokinin, galanin and neuropeptide Y levels. Gynecol Endocrinol. 2000;14:196203.Google Scholar
63. Milewicz, A, Mikulski, E, Bidzinska, B. Plasma insulin, cholecystokinin, galanin, neuropeptide Y and leptin levels in obese women with and without type 2 diabetes mellitus. Int J Obes Relat Metab Disord. 2000;24(suppl 2):S152S153.CrossRefGoogle ScholarPubMed
64. Baranowska, B, Radzikowska, M, Wasilewska-Dziubinska, E, Roguski, K, Polonowski, A. Relationship among leptin, neuropeptide Y, and galanin in young women and in postmenopausal women. Menopause. 2000;7:149155.CrossRefGoogle ScholarPubMed
65. Kaplan, LM, Gabriel, SM, Koenig, JL, et al. Galanin is an estrogen inducible secretory product of the rat anterior pituitary. Proc Natl Acad Sci U S A. 1988;85:74087412.Google Scholar
66. Meczekalski, B, Slopien, R, Warenik-Szymankiewicz, A. Estimation of hormone replacement therapy influence on serum galanin level in postmenopausal women. Climacteric. 2001;4:215218.CrossRefGoogle ScholarPubMed
67. Reiter, RJ. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev. 1991;12:151180.Google Scholar
68. Reiter, RJ. Oxidative damage in the central nervous system: protection by melatonin. Prog Neurobiol. 1998;56:359384.CrossRefGoogle ScholarPubMed
69. Morioka, N, Okatani, Y, Wakatsuki, A. Melatonin protect against age-related DNA damage in the brains of female senescence-accelerated mice. J Pineal Res. 1999;27:202209.Google Scholar
70. Harrod, CG, Bendok, BR, Hunt Batjer, H. Interactions between melatonin and estrogen may regulate cerebrovascular function in women: clinical implications for the effective use of HRT during menopause and aging. Med Hypotheses. 2005;64:725735.Google Scholar
71. Lewy, AJ, Sack, RL. Exogenous melatonin's phase-shifting effects on the endogenous melatonin profile in sighted humans: a brief review and critique of the literature. J Biol Rhythms. 1997;12:588594.Google Scholar
72. Zhdanova, IV, Wurtman, RJ. Efficacy of melatonin as a sleep-promoting agent. J Pineal Res. 1997;12:644650.Google Scholar
73. Cagnacci, A. Melatonin in relation to physiology in adult humans. J Pineal Res. 1996;21:200213.Google Scholar
74. Birau, N, Peterssen, U, Meyer, C. Hypotensive effect of melatonin in essential hypertension. IRSC. Med Sci. 1981;9:901906.Google Scholar
75. Cagnacci, A, Arangino, S, Angiolucci, M, et al. Influences of melatonin administration on the circulation of women. Am J Physiol. 1998;274(2 pt 2):335338.Google Scholar
76. Cagnacci, A, Arangino, S, Angiolucci, M, et al. Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy. Clin Endocrinol (Oxf). 2001;54:261266.Google Scholar
77. Viswanathan, M, Laitinen, JT, Saavedra, JM. Differential expression of melatonin receptors in spontaneously hypertensive rats. Neuroendocrinology. 1992;56:864870.Google Scholar
78. Arendt, J, Laud, CA, Symons, AM, Pryde, SJ. Plasma melatonin in ewes after ovariectomy. J Reprod Fertil. 1983;68:213218.Google Scholar
79. Okatani, Y, Morioka, N, Wakatsuki, A. Changes in nocturnal melatonin secretion in perimenopausal women: Correlation with endogenous estrogen concentrations. J Pineal Res. 2000;28:111118.CrossRefGoogle ScholarPubMed
80. Cagnacci, A, Soldani, R, Yen, SS. Melatonin enhances cortisol levels in aged women: reversible by estrogens. J Pineal Res. 1997;22:8185.Google Scholar
81. Akwa, Y, Baulieu, EE. Neurosteroids: behavioral aspects and physiological implications [French]. J Soc Biol. 1999;193:293298.CrossRefGoogle ScholarPubMed
82. Mellon, SH. Neurosteroids: biochemistry, modes of action, and clinical relevance. J Clin Endocrinol Metab. 1994;78:10031008.Google Scholar
83. Majewska, MD. Neurosteroids: endogenous bimodal modulators of the GABAA receptors. Mechanism of action and physiological significance. Prog Neurobiol. 1992;38:379395.Google Scholar
84. Wolf, OT, Neumenm, O, Helhammer, DH, et al. Effects of a two-week physiological dehydroepiandrosterone substitution on cognitive performance and well-being in healthy elderly women and men. J Clin Endocrinol Metab. 1997;82:23632367.Google Scholar
85. Monteleone, P, Luisi, S, Tonetti, A, et al. Allopregnanolone concentrations and premenstrual syndrome. Eur J Endocrinol. 2000;142:269273.Google Scholar
86. Palumbo, MA, Salvestroni, C, Gallo, R, et al. Allopregnanolone concentrations in hippocampus of prepubertal rats and female rats throughout estrous cycle. J Endocrinol Invest. 1995;18:853856.Google Scholar
87. Schumacher, M, Coirini, H, McEwen, BS. Regulation of high affinity GABAA receptors in the dorsal hippocampus by estradiol and progesteron. Brain Res. 1989;487:178184.CrossRefGoogle Scholar
88. Serra, M, Pisu, MG, Littera, M, et al. Social isolation-induced decreases in both the abundance of neuroactive steroids and GABA(A) receptor function in rat brain. J Neurochem. 2000;75:732740.CrossRefGoogle ScholarPubMed
89. Genazzani, AR, Bernardi, F, Stomati, M, et al. Effects of estradiol and raloxifene analog on brain, adrenal and serum allopregnanolone content in fertile and ovariectomized female rats. Neuroendocrinology. 2000;72:162170.CrossRefGoogle ScholarPubMed
90. Bernardi, F, Casarosa, E, Pluchino, N, et al. Effect of dehydroepiandrosteron on central and peripheral levels of allopregnanolone and β-endorphin. Fertil Steril. 2005;83(suppl 4):11611168.Google Scholar
91. Genazzani, AR, Petraglia, F, Bernardi, F, et al. Circulating levels of allopregnanolone in humans: gender, age and endocrine influences. J Clin Endocrinol Metab. 1998;83:20992103.Google Scholar
92. Wilson, MA. Influences of gender, gonadectomy and estrous cycle on GABA/BZ receptors and benzodiazepine responses in rats. Brain Res Bull. 1992;29:165172.CrossRefGoogle ScholarPubMed
93. Schumacher, M, Coirini, H, Robert, F, et al. Genomic and membrane actions of progesterone: implications for reproductive physiology and behavior. Behav Brain Res. 1999;105:3752.Google Scholar
94. Yamaji, T, Ibayashi, H. Serum deydroepiandrosterone sulphate in normal and pathological conditions. J Clin Endocrinol Metab. 1969;29:273278.Google Scholar
95. Parker, LN, Odell, WD. Control of adrenal androgen secretion. Endocr Rev. 1980;4:392410.Google Scholar
96. Corpechot, C, Robert, P, Axelson, M, Sjovall, J, Baulieu, EE. Characterization and measurement of dehydroepiandrosterone sulfate in the rat brain. Proc Natl Acad Sci U S A. 1981;78:47044707.Google Scholar
97. Davis, SR, Burger, HG. Androgens and the postmenopausal woman J Clin Endocrinol Metab. 1996;81:27592763.Google Scholar
98. Utian, WH. The true clinical features of postmenopausal oophorectomy and their response to estrogens replacement therapy. S Afr Med J. 1972;46:732737.Google Scholar
99. Majewska, MD, Demirgoren, S, Spivak, CE, et al. The neurosteroid DHEA is an allosteric antagonist of the GABA A receptor. Brain Res. 1990;526:143146.CrossRefGoogle Scholar
100. Baulieu, EE. Dehydroepiandrosterone: a fountain of youth? J Clin Endocrinol Metab. 1996;81:31473151.Google Scholar
101. Thijssen, JH, Nieuwenhuyse, H. DHEA: A Comprehensive Review. London, United Kingdom; The Parthenon Publishing Group; 1999.Google Scholar
102. Rubino, S, Stomati, M, Bersi, C, et al. Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal women. Maturitas. 1998;28:251257.Google Scholar
103. Taelman, P, Kayman, JM, Janssens, X, et al. Persistence of increased bone-resumption and possible role of dehydroepiandrosterone as a bone metabolism determinant in osteoporotic women in late menopause. Maturitas. 1989;11:6573.CrossRefGoogle Scholar
104. Nordin, BEC, Robertson, A, Seamark, RF. The relation between calcium absorption, serum DHEA and vertebral mineral density in postmenopausal women. J Clin Endocrinol Metab. 1985;60:651657.Google Scholar
105. Wolkowitz, OM, Reus, VI, Roberts, E, et al. Dehydroepiandrosterone (DHEA) treatment of depression. Biol Psychiatry. 1997;41:311318.CrossRefGoogle ScholarPubMed
106. Genazzani, AD, Stomati, M, Bernardi, F, et al. Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids. Fertil Steril. 2003;80:14951501.Google Scholar
107. Ginzburg, J, Hardiman, P. Adrenergic agonist for menopausal complaints. In: Genazzani, AR, Montemagno, U, Nappi, C, et al, ed. The Brain and Female Reproductive Function. London, United Kingdom; Parthenon Publishing Group; 1987:623625.Google Scholar
108. Melis, G, Cagnacci, A, Gambacciani, M. Restoration of luteinizing hormone response to naloxone in postmenopausal women by chronic administration of the antidopaminergic drug veralipride. J Clin Endocrinol Metab. 1988;66:964969.Google Scholar
109. Bernardi, F, Pieri, M, Stomati, M, Luisi, S, et al. Effect of different hormonal replacement therapies on circulating allopregnanolone and dehydroepiandrosterone levels in postmenopausal women. Gynecol Endocrinol. 2003;17:6577.Google Scholar