The Effect of Estrogens and Progestogens on the Occurrence of Major Mental Disorders
DOI:
https://doi.org/10.60988/pj.v35i4.21Keywords:
Estrogens, Progestogens, Depression, Bipolar Disorder, SchizophreniaAbstract
Estrogens seem to participate in various functions of the body, including the brain function, through estrogen receptors, affecting among others, the differentiation or the occurrence and promotion of serious or less serious mental disorders. Estrogens seem to be involved in depression, bipolar disorder and schizophrenia, with the fluctuation of their levels being aggravating or beneficial. In these mental disorders, progestogens appear to limit the beneficial effects of estrogens, which are nonetheless necessary in a variety of situations, including the reduction of the side effects of estrogens. These actions of hormones and their supplements seem to be exerted at the cellular level, through transcription and gene expression adjustment, but also regulation of mitochondrial function, while they seem to interfere with all the main signaling pathways, influencing the action of key excitatory and suppressive neurotransmitters. Furthermore, sex hormones seem to affect the regulation of eating habits, a factor that appears to change especially during many major mental disorders, but also due to the drug treatment of these diseases. It is therefore considered important the further study of these mechanisms, linking female hormones with mental disorders, as well as their possible treatment through hormonal therapy, possibly as adjunctive to the already prescribed for these diseases.
References
Osterlund M.K., Hurd Y.L. Estrogen receptors in the human forebrain and the relation to neuropsychiatric disorders. Prog. Neurobiol. 64,
-267, 2001.
Pearlstein T., Rosen K., Stone A.B. Mood disorders and menopause. Endocrinol. Metab. Clin. N. Am.
, 279–294, 1997.
Ostlund H., Keller E., Hurd Y.L. Estrogen receptor gene expression in relation to neuropsychiatric
disorders. Ann. N. Y. Acad. Sci. 1007, 54-63, 2003.
Studd J.W. A guide to the treatment of depression in women by estrogens. Climacteric. 14, 637-
, 2011.
Fornaro M., Perugi G. The impact of premenstrual dysphoric disorder among bipolar patients. Eur. Psychiatry. 8, 450–4, 2010.
Soares C.N., Zitek B. Reproductive hormone sensitivity and risk for depression across the female life cycle: a continuum of vulnerability? J.
PHARMAKEFTIKI, 35, IV, 2023 | 18-33
REVIEW ARTICLE
Psychiatry Neurosci. 33, 331–43, 2008.
Panay N., Studd J. Progestogen intolerance and compliance with hormone replacement therapy in menopausal women. Hum. Reprod. Update. 3,
– 71, 1997.
Rapkin A.J. Yaz in the treatment of premenstrual dysphoric disorder. J. Reprod. Med. 53, 729 – 41,
Yonkers K.A., O’ Brien P.M., Eriksson E.
Premenstrual syndrome. Lancet 371, 1200–10,
Studd J. Suppression of ovulation for the treatment of severe premenstrual depression. Menopause Int. 13, 182–4, 2007.
Herson M., Kulkarni J. Hormonal Agents for the Treatment of Depression Associated with the Menopause. Drugs Aging 39, 607-618, 2022.
Wium-Andersen M.K., Jørgensen T.S.H., Halvorsen A.H., Hartsteen B.H., Jørgensen M.B., Osler M. Association of Hormone Therapy With Depression During Menopause in a Cohort of Danish Women. JAMA Netw. Open. 5, e2239491,
Carroll D.G., Kelley K.W. Use of antidepressants for management of hot flushes. Pharmacotherapy
, 1357–66, 2009.
Dennerstein L., Lehert P., Burger H., Dudley E.
Mood and the menopausal transition. J. Nerv. Ment. Dis. 187, 685-91, 1999.
Soares C.N., Frey B.N. Challenges and opportunities to manage depression during the menopausal transition and beyond. Psychiat.r Clin. North Am. 33, 295-308, 2010.
Graziottin A., Serafini A. Depression and the menopause: why antidepressants are not enough? Menopause Int. 15, 76-81, 2009.
Kessing L.V. The prevalence of mixed episodes during the course of illness in bipolar disorder. Acta Psychiatr. Scand. 117, 216–24, 2008.
Baldassano C.F., Marangell L.B., Gyulai L., Ghaemi S.N., Joffe H., Kim D.R. et al. Gender differences in bipolar disorder: Retrospective data from the first 500 STEP-BD participants. Bipolar Disord. 7, 465–70, 2005.
Kawa I., Carter J.D., Joyce P.R., Doughty
C.J., Frampton C.M., Wells J.E. et al. Gender differences in bipolar disorder: Age of onset, course, comorbidity, and symptom resentation. Bipolar Disord. 7, 119–25, 2005.
Meinhard N., Kessing L.V., Vinberg M. The role of estrogen in bipolar disorder, a review. Nord. J. Psychiatry. 68, 81-87, 2014.
Payne J.L. The role of estrogen in mood disorders in women. Int. Rev. Psychiatry 15, 280–90, 2003.
Douma S.L., Husband C., O’ Donnell M.E., Barwin B.N., Woodend A.K. Estrogen-related mood disorders: Reproductive life cycle factors. ANS Adv. Nurs. Sci. 28, 364–75, 2005.
Theodosis-Nobelos P., Asimakopoulou E., Madianos M. Pathophysiological mechanisms of major mental disorders related to cardiovascular disease. Psychiatriki. 10, 113-123, 2022.
Wieck A., Davies R.A., Hirst A.D., Brown N., Papadopoulos A., Marks M.N. et al. Menstrual cycle effects on hypothalamic dopamine receptor function in women with a history of puerperal bipolar disorder. J. Psychopharmacol. 17, 204-9,
Baker J.M., Al-Nakkash L., Herbst-Kralovetz M.M.
Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas. 103, 45-53,
TriantisC.,Theodosis-Nobelos P.,Asimakopoulou E., Spathis A. The gut microbiome and its association with mental disorders. Pharmakeftiki
, 72-87, 2021.
Yildiz A., Guleryuz S., Ankerst D.P., Ongur D., Renshaw P.F. Protein kinase C inhibition in the treatment of mania: A double-blind, placebo- controlled trial of tamoxifen. Arch.Gen.Psychiatry
, 255-63, 2008.
Zarate C.A. Jr, Singh J.B., Carlson P., Quiroz J., Jolkovsky L., Luckenbaugh D.A. et al. Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: A pilot study. Bipolar Disord. 9, 561–70, 2007.
Amrollahi Z., Rezaei F., Salehi B., Modabbernia A.H., Maroufi A., Esfandiari G.R. et al. Double- blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen
Theodosis-Nobelos P. et al., Pharmakeftiki, 35, IV, 2023 | 18-33
adjunctive to lithium in acute bipolar mania. J. Affect. Disord. 129, 327–31, 2011.
Cohen I., Figer A., Tepper R., Shapira J., Altaras M.M., Yigael D. et al. Ovarian overstimulation and cystic formation in premenopausal tamoxifen exposure: Comparison between tamoxifen- treated and nontreated breast cancer patients. Gyneco.l Oncol. 72, 202-7, 1999.
Eranti S.V., MacCabe J.H., Bundy H., Murray R.M. Gender difference in age at onset of schizophrenia: a meta-analysis. Psychol. Med. 43,
–167, 2013.
Häfner H., Riecher-Rössler A., an Der Heiden W., Maurer K., Fatkenheuer B., Loffler W. Generating and testing a causal explanation of the gender difference in age at first onset of schizophrenia. Psychol. Med.23(4), 925–940, 1993.
Aleman A., Kahn R.S., Selten J.-P. Sex differences in the risk of schizophrenia: evidence from meta- analysis. Arch. Gen. Psychiatry. 60, 565–571,
McGrath J., Saha S., Welham J., El Saadi O., MacCauley C., Chant D. A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Medicine.
, 13, 2004.
Begemann M.J.H., Dekker C.F., van Lunenburg M., Sommer I.E. Estrogen augmentation in schizophrenia: a quantitative review of current evidence. Schizophr. Res. 141, 179–184, 2012.
Ochoa S., Usall J., Cobo J., Labad X., Kulkarni J.
Gender differences in schizophrenia and first- episode psychosis: a comprehensive literature review. Schizophr. Res. Treatment. 2012, 916198,
Narr K.L., Thompson P.M., Sharma T. et al. Three- dimensional mapping of temporo-limbic regions and the lateral ventricles in schizophrenia: gender effects. Biol.Psychiatry. 50, 84–97, 2001.
Nopoulos P., Flaum M., Andreasen N.C. Sex differencesinbrainmorphologyinschizophrenia. Am. J. Psychiatry. 154, 1648–1654, 1997.
Kendell R.E., Chalmers J.C., Platz C. Epidemiology of puerperal psychoses. Br. J. Psychiatry 150,
–673, 1987.
Bergemann N., Mundt C., Parzer P. et al. Plasma concentrations of estradiol in women suffering from schizophrenia treated with conventional versus atypical antipsychotics. Schizophr. Res.
, 357–366, 2005.
Bergemann N., Riecher-Rössler A. (2005).
Estrogen Effects in Psychiatric Disorders, New
York, Springer.
Gogos A., Sbisa A.M., Sun J., Gibbons A., Udawela M., Dean B. A Role for Estrogen in Schizophrenia: ClinicalandPreclinicalFindings. Int.J.Endocrinol.
, 615356, 2015.
Zhang-Wong J.H., Seeman M.V. Antipsychotic drugs, menstrual regularity and osteoporosis risk. Arch. Womens Ment. Health. 5, 93–98, 2002.
Montgomery J., Winterbottom E., Jessani M. et al. Prevalence of hyperprolactinemia in schizophrenia: association with typical and atypical antipsychotic treatment. J. Clin. Psychiatry. 65, 1491–1498, 2004.
González-Rodríguez A., Guàrdia A., Monreal J.A. Peri- and Post-Menopausal Women with Schizophrenia and Related Disorders Are a Population with Specific Needs: A Narrative Review of Current Theories. J. Pers. Med. 11, 849,
Akhondzadeh S., Nejatisafa A.A., Amini H. et al. Adjunctive estrogen treatment in women with chronic schizophrenia: a double-blind, randomized, and placebo-controlled trial. Prog. Neuropsychopharmacol. Biol. Psychiatry.27,
–1012, 2003.
Kulkarni J., Gavrilidis E., Wang W. et al. Estradiol for treatment-resistant schizophrenia: a large- scale randomized-controlled trial in women of child-bearing age. Mol. Psychiatry. 20, 695–702,
Kulkarni J., de Castella A., Smith D., Taffe J., Keks N., Copolov D. A clinical trial of the effects of estrogen in acutely psychotic women. Schizophr. Res. 20, 247–252, 1996.
Lindamer L.A., Buse D.C., Lohr J.B., Jeste D.V. Hormone replacement therapy in postmenopausal women with schizophrenia:
PHARMAKEFTIKI, 35, IV, 2023 | 18-33
REVIEW ARTICLE
positive effect on negative symptoms? Biol. Psychiatry. 49, 47–51, 2001.
Kulkarni J., de Castella A., Headey B. et al.
Estrogens and men with schizophrenia: is there a case for adjunctive therapy? Schizophr. Res.
, 278–283, 2011.
Tandon R., Keshavan M.S., Nasrallah H.A.
Schizophrenia, ‘Just the Facts’: what we know in 2008. Part 1: overview. Schizophr. Res. 100,
–19, 2008.
Manatt M., Chandra S.B. The effects of mitochondrial dysfunction in schizophrenia. J.Med. Genet. Genomics 3, 84–94, 2011.
Ko Y.H., Joe S.H., Cho W., Park J.H., Lee J.J., Jung I.K. et al. Estrogen, cognitive function and negative symptoms in female schizophrenia. Neuropsychobiology. 53, 169-75, 2006.
Sánchez M.G., Bourque M., Morissette M., Di Paolo T. Steroids-dopamine interactions in the pathophysiology and treatment of cns disorders. CNS Neurosci. Ther. 16, e43–e71, 2010.
Leranth C., Roth R.H., Elswoth J.D., Naftolin F., Horvath T.L., Redmond D.E. Estrogen is essential for maintaining nigrostriatal dopamine neurons in primates: implications for Parkinson’s disease and memory. J. Neurosci. 20, 8604–8609, 2000.
Chavez C., Hollaus M., Scarr E., Pavey G., Gogos A., van den Buuse M. The effect of estrogen on dopamine and serotonin receptor and transporter levels in the brain: an autoradiography study. Brain Research. 1321,
–59, 2010.
Emamian ES. AKT/GSK3 signaling pathway and schizophrenia. Front. Mol. Neurosci. 5, 33, 2012.
Madularu D., Shams W.M., Brake W.G. Estrogen potentiates the behavioral and nucleus accumbens dopamine response to continuous haloperidol treatment in female rats. Eur. J. Neurosci. 39, 257–265, 2014.
Jamu I.M., Okamoto H. Recent advances in understanding adverse effects associated with drugs targeting the serotonin receptor, 5-HT GPCR. Front. Glob. Womens Health.3, 1012463,
Inagaki T., Gautreaux C., Luine V. Acute estrogen treatment facilitates recognition memory consolidation and alters monoamine levels in memory-related brain areas. Horm. Behav. 58,
–426, 2010.
Adams M.M., Fink S.E., Janssen W.G.M., Shah R.A., Morrison J.H. Estrogen modulates synaptic N-methyl-D-aspartate receptor subunit distribution in the aged hippocampus. J. Comp. Neurol. 474, 419–426, 2004.
Phillis J.W., Song D., O’Regan M.H. Tamoxifen, a chloride channel blocker, reduces glutamate and aspartate release from the ischemic cerebral cortex. Brain Research. 780, 352–355, 1998.
Karki P., Webb A., Zerguine A., Choi J., Son D.- S., Lee E. Mechanism of raloxifene-induced upregulation of glutamate transporters in rat primary astrocytes. Glia. 62, 1270–1283, 2014.
Herbison AE, Simonian SX, Thanky NR, Bicknell RJ. Oestrogen modulation of noradrenaline neurotransmission. Novartis Found Symp. 230,
-85, 2000.
Henriksson, M.M., Aro H.M., Marttunen M J. et al. Mental disorders and comorbidity in suicide. Am. J. Psychiatry 150, 935–940, 1993.
Timby E., Balgård M., Nyberg S., Spigset O., Andersson A., Porankiewicz-Asplund J. et al. Pharmacokinetic and behavioral effects of allopregnanolone in healthy women. Psychopharmacology (Berl). 186, 414-24, 2006.
Nyberg S., Backstrom T., Zingmark E., Purdy R.H., Sundstrom-Poromaa I.S. Allopregnanolone decrease with symptom improvement during placebo and gonadotropin-releasing hormone agonist treatment in women with severe premenstrual syndrome. Gynecol. Endocrinol. 5,
-266, 2007.
Andréen L., Nyberg S., Turkmen S., van Wingen G., Fernández G., Bäckström T. Sex steroid induced negative mood may be explained by the paradoxical effect mediated by GABA-A modulators. Psychoneuroendocrinology. 34,
-1132, 2009.
Chan A.F., Mortola J.F., Wood S.H., Yen S.S.
Theodosis-Nobelos P. et al., Pharmakeftiki, 35, IV, 2023 | 18-33
Persistence of premenstrual syndrome during low-dose administration of the progesterone antagonist RU 486. Obstet. Gynecol. 6, 1001-
, 1994.
Sundstrom, I., Backstrom, T. Citalopram increases pregnanolone sensitivity in patients with premenstrual syndrome: an open trial. Psychoneuroendocrinology 1, 73-88, 1998.
Bjorn I., Sundstrom-Poromaa I., Bixo M., Nyberg, S., Backstrom G., Backstrom T. Increase of estrogen dose deteriorates mood during progestin phase in sequential hormonal therapy. J.Clin. Endocrinol. Metab. 5, 2026-2030,
Klump K.L., Keel P.K., Racine S.E., Burt S.A., Neale M., Sisk C.L. et al. The interactive effects of estrogen and progesterone on changes in emotional eating across the menstrual cycle. J. Abnorm. Psychol. 122, 131-7, 2013.
Asarian L., Geary N. Modulation of appetite
by gonadal steroid hormones. Philosophical Transactions of the Royal Society of London. Series B. Biol. Sci. 361, 1251–1263, 2006.
Klump K.L., Suisman J.L., Culbert K.M., Kashy D.A., Keel P.K., Sisk C.L. The effects of ovariectomy on binge eating proneness in adult female rats. Horm. Beh. 59, 585–593, 2011.
Edler C., Lipson S.F., Keel P.K. Ovarian hormones and binge eating in bulimia nervosa. Psychol. Med. 37, 131–141, 2007.
Van Vugt D.A. Brain imaging study of appetite in the context of obesity and the menstrual cycle. Hum. Reprod. Update. 16, 276–292, 2010.
Eckel, L.A. Estradiol: a rhythmic, inhibitory, indirect control of meal size. Physiol. Behav. 82,
-41, 2004.
Eckel L.A., Geary N. Endogenous cholecystokinin’s satiating action increases during estrus in female rats. Peptides 20, 451-
, 1999.
