2024, Number 1
<< Back Next >>
Salud Mental 2024; 47 (1)
Circulating sex hormones in women with severe anxiety during pregnancy
Leff-Gelman P, Camacho-Arroyo I, Camacho PRT, Coronel CFM, Gaspard CAV, Jiménez ALE, Solares-Bravo M, Flores-Ramos M
Language: English
References: 68
Page: 3-12
PDF size: 278.68 Kb.
ABSTRACT
Introduction. Anxiety, mood- and stress-related behaviors are regulated by sex hormones in pregnant and
non-pregnant women. Very scarce information exists about the role of sex steroids in pregnant women displaying
high levels of anxiety.
Objective. To determine sex hormones serum levels in pregnant women exhibiting
high levels of anxiety symptoms.
Method. The Hamilton Anxiety Rating Scale (HARS/ HAM-A) was used
to assess the intensity of anxiety symptoms in third-trimester pregnant women. Two groups were included in
the study, pregnant women exhibiting severe anxiety (ANX; HARS scores ≥ 25;
n = 101) and healthy control
subjects (CTRL;
n = 40) displaying lower scores for anxiety (HARS scores ≤ 7). Estradiol (E2), progesterone
(P4), and testosterone (T) serum levels were measured using a standard chemiluminescent immunoassay.
Bivariate and partial correlations were performed to detect significant associations between groups, clinical
measures, biochemical data, and HARS scores.
Results. The anxiety group (ANX) showed an increase in E2
and T serum levels (
p ‹ .001) compared to CTRL. Conversely, significantly lower P4 levels were found in the
symptomatic group (
p ‹ .001) as compared to the CTRL hormone values. The P4:E2 index was significantly
reduced in pregnant women with high levels of anxiety (
p ‹ .001). Negative correlations between anxiety
(HARS) scores, P4 serum levels (
p = .02), and P4:E2 ratio (
p = .04) were found in the symptomatic group.
Conversely, T serum levels displayed a positive association (
p = .001) with high levels of anxiety symptoms in
the same group, after adjusting our data by clinical
Discussion and conclusion. Serum levels
of sex-steroid hormones are altered in pregnant women exhibiting severe anxiety.
REFERENCES
Alipour, Z., Lamyian, M., & Hajizadeh, E. (2012). Anxiety and fear of childbirthas predictors of postnatal depression in nulliparous women. Women and Birth, 25(3), e37-e43. doi: 10.1016/j.wombi.2011.09.002
Altemus, M., Sarvaiya, N., & Epperson, C. N. (2014). Sex differences in anxiety anddepression clinical perspectives. Frontiers in Neuroendocrinology, 35(3), 320-330. doi: 10.1016/j.yfrne.2014.05.004
American Psychiatric Association, D. S. M. T. F., & American Psychiatric Association.(2013). Diagnostic and statistical manual of mental disorders: DSM-5 (Vol. 5,No. 5). Washington, DC: American Psychiatric Association.
Andréen, L., Nyberg, S., Turkmen, S., van Wingen, G., Fernández, G., & Bäckström, T.(2009). Sex steroid induced negative mood may be explained by the paradoxicaleffect mediated by GABAA modulators. Psychoneuroendocrinology, 34(8),1121-1132. doi: 10.1016/j.psyneuen.2009.02.003
Asselmann, E., Kische, H., Haring, R., Hertel, J., Schmidt, C. O., Nauck, M.,Beesdo-Baum, K., Hans-Jörgen, G., & Pané-Farré, C. A. (2019). Prospectiveassociations of androgens and sex hormone-binding globulin with 12-month,lifetime and incident anxiety and depressive disorders in men and womenfrom the general population. Journal of Affective Disorders, 245, 905-911. doi:10.1016/j.jad.2018.11.052
Baker, S., Chebli, M., Rees, S., LeMarec, N., Godbout, R., & Bielajew, C. (2008).Effects of gestational stress: 1. Evaluation of maternal and juvenile offspringbehavior. Brain Research, 1213, 98-110. doi: 10.1016/j.brainres.2008.03.035
Bali, A., & Jaggi, A. S. (2014). Multifunctional aspects of allopregnanolone in stressand related disorders. Progress in Neuro-Psychopharmacology and BiologicalPsychiatry, 48, 64-78. doi: 10.1016/j.pnpbp.2013.09.005
Barth, C., Villringer, A., & Sacher, J. (2015). Sex hormones affect neurotransmittersand shape the adult female brain during hormonal transition periods. Frontiersin Neuroscience, 9, 37. doi: 10.3389/fnins.2015.00037
Berga, S. L., & Loucks, T. L. (2006). Use of cognitive behavior therapy for functionalhypothalamic amenorrhea. Annals of the New York Academy of Sciences, 1092(1), 114-129. doi: 10.1196/annals.1365.010
Berglund, L. H., Prytz, H. S., Perski, A., & Svartberg, J. (2011). Testosterone levelsand psychological health status in men from a general population: the Tromsøstudy. The Aging Male, 14(1), 37-41. doi: 10.3109/13685538.2010.522276
Bernstein, L., Pike, M. C., Lobo, R. A., Depue, R. H., Ross, R. K., & Henderson, B. E.(1989). Cigarette smoking in pregnancy results in marked decrease in maternalhCG and oestradiol levels. British Journal of Obstetrics & Gynaecology, 96(1),92-96. doi: 10.1111/j.1471-0528.1989.tb01582.x
Chatuphonprasert, W., Jarukamjorn, K., & Ellinger, I. (2018). Physiology andpathophysiology of steroid biosynthesis, transport and metabolism in the humanplacenta. Frontiers in Pharmacology, 9, 1027. doi: 10.3389/fphar.2018.01027
Chinchilla-Ochoa, D., Barriguete-Chávez Peón, P., Farfán-Labonne, B. E., Garza-Morales, S., Leff-Gelman, P., & Flores-Ramos, M. (2019). Depressivesymptoms in pregnant women with high trait and state anxiety during pregnancyand postpartum. International Journal of Women’s Health, 11, 257-265. doi:10.2147/IJWH.S194021
Costa, M. A. (2016). The endocrine function of human placenta: an overview.Reproductive Biomedicine Online, 32(1), 14-43. doi: 10.1016/j.rbmo.2015.10.005
Cover, K. K., Maeng, L. Y., Lebrón-Milad, K., & Milad, M. (2014). Mechanisms ofestradiol in fear circuitry: implications for sex differences in psychopathology.Translational Psychiatry, 4(8), e422-e422. doi: 10.1038/tp.2014.67
Davis, E. P., Snidman, N., Wadhwa, P. D., Glynn, L. M., Schetter, C. D., & Sandman, C.A. (2004). Prenatal maternal anxiety and depression predict negative behavioralreactivity in infancy. Infancy, 6(3), 319-331. doi: 10.1207/s15327078in0603_1
Diotel, N., Charlier, T. D., Lefebvre d’Hellencourt, C., Couret, D., Trudeau, V. L.,Nicolau, J. C., Meilhac, O., Kah, O., & Pellegrini, E. (2018). Steroid Transport,Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis,Neuroprotection, and Sexual Behaviors. Frontiers in Neuroscience, 12, 84. doi:10.3389/fnins.2018.00084
Edey, L. F., Georgiou, H., O’Dea, K. P., Mesiano, S., Herbert, B. R., Lei, K., HuaR., Markovic, D., Waddington, S. N., MacIntyre, D., Bennett, P., Takata, M.,& Johnson, M. R. (2018). Progesterone, the maternal immune system and theonset of parturition in the mouse. Biology of Reproduction, 98(3), 376-395. doi:10.1093/biolre/iox146
Fiacco, S., Walther, A., & Ehlert, U. (2019). Steroid secretion in healthy aging.Psychoneuroendocrinology, 105, 64-78. doi: 10.1016/j.psyneuen.2018.09.035
Field, T. (2017). Prenatal anxiety effects: a review. Infant Behavior and Development,49, 120-128. doi: 10.1016/j.infbeh.2017.08.008
Frye, C. A., Petralia, S. M., & Rhodes, M. E. (2000). Estrous cycle and sex differencesin performance on anxiety tasks coincide with increases in hippocampalprogesterone and 3α, 5α-THP. Pharmacology Biochemistry and Behavior,67(3), 587-596. doi: 10.1016/s0091-3057(00)00392-0
Gelman, P. L., Flores-Ramos, M., López-Martínez, M., Cruz Fuentes, C., & ReyesGrajeda, J. P. (2015). Hypothalamic-pituitary-adrenal axis function duringperinatal depression. Neuroscience Bulletin, 31(3), 338-350. doi: 10.1007/s12264-014-1508-2
Genazzani, A. D., Ricchieri, F., Lanzoni, C., Strucchi, C., & Jasonni, V. M. (2006).Diagnostic and therapeutic approach to hypothalamic amenorrhea. Annals of theNew York Academy of Sciences, 1092(1), 103-113. doi: 10.1196/annals.1365.009
Genazzani, A. R., Petraglia, F., Bernardi, F., Casarosa, E., Salvestroni, C., Tonetti,A., Nappi, R. E., Luisi, S., Palumbo, M., Purdy, R. H., & Luisi, M. (1998).Circulating levels of allopregnanolone in humans: gender, age, and endocrineinfluences. The Journal of Clinical Endocrinology & Metabolism, 83(6), 2099-2103. doi: 10.1210/jcem.83.6.4905
Giltay, E. J., van der Mast, R. C., Lauwen, E., Heijboer, A. C., de Waal, M. W., &Comijs, H. C. (2017). Plasma testosterone and the course of major depressivedisorder in older men and women. The American Journal of GeriatricPsychiatry, 25(4), 425-437. doi: 10.1016/j.jagp.2016.12.014
Glowinska, A., Duleba, A. J., Zielona-Jenek, M., Siakowska, M., Pawelczyk, L., &Banaszewska, B. (2020). Disparate relationship of sexual satisfaction, selfesteem,anxiety, and depression with endocrine profiles of women with or withoutPCOS. Reproductive Sciences, 27(1), 432-442. doi: 10.1007/s43032-019-00061-0
Hall, K. S., Beauregard, J. L., Rentmeester, S. T., Livingston, M., & Harris, K.M. (2019). Adverse life experiences and risk of unintended pregnancyin adolescence and early adulthood: Implications for toxic stress andreproductive health. SSM-Population Health, 7, 100344. doi: 10.1016/j.ssmph.2018.100344
Hamilton, M. (1959). Hamilton anxiety rating scale. British Journal of MedicalPsychology, 32, 50-55.
Holmes, A., Li, Q., Murphy, D. L., Gold, E., & Crawley, J. N. (2003). Abnormalanxiety‐related behavior in serotonin transporter null mutant mice: the influenceof genetic background. Genes, Brain and Behavior, 2(6), 365-380. doi:10.1046/j.1601-1848.2003.00050.x
Hu, M., Richard, J. E., Maliqueo, M., Kokosar, M., Fornes, R., Benrick, A., Jansson,T., Ohlsson, C., Wu, X., Skibicka, K. P., & Stener-Victorin, E. (2015). Maternaltestosterone exposure increases anxiety-like behavior and impacts the limbicsystem in the offspring. Proceedings of the National Academy of Sciences,112(46), 14348-14353. doi: 10.1073/pnas.1507514112
Kalin, N. H. (2020). Novel insights into pathological anxiety and anxiety-relateddisorders. American Journal of Psychiatry, 177(3), 187-189. doi: 10.1176/appi.ajp.2020.20010057
Kane, H. S., Schetter, C. D., Glynn, L. M., Hobel, C. J., & Sandman, C. A. (2014).Pregnancy anxiety and prenatal cortisol trajectories. Biological Psychology,100, 13-19. doi: 10.1016/j.biopsycho.2014.04.003
Kaspi, S. P., Otto, M. W., Pollack, M. H., Eppinger, S., & Rosenbaum, J. F. (1994).Premenstrual exacerbation of symptoms in women with panic disorder. Journalof Anxiety Disorders, 8(2), 131-138. doi: 10.1016/0887-6185(94)90011-6
Labad, J., Menchón, J. M., Alonso, P., Segalàs, C., Jimenez, S., & Vallejo, J. (2005).Female reproductive cycle and obsessive-compulsive disorder. Journal ofClinical Psychiatry, 66(4), 428-435. doi: 10.4088/jcp.v66n0404
Le Mellédo, J. M., & Baker, G. (2004). Role of progesterone and other neuroactivesteroids in anxiety disorders. Expert Review of Neurotherapeutics, 4(5), 851-860. doi: 10.1586/14737175.4.5.851
Lee, D. E., Lamb, S. V., & Reimers, T. J. (1991). Effects of hyperlipemia onradioimmunoassays for progesterone, testosterone, thyroxine, and cortisolin serum and plasma samples from dogs. American Journal of VeterinaryResearch, 52(9), 1489-1491.
Leff-Gelman, P., Flores-Ramos, M., Ávila Carrasco, A. E., López Martínez, M.,Sarabia Takashima, M. F., Cruz Coronel, F. M., Farfán Labonne, B., ZorrillaDosal, J. A., Barriguete Chávez-Peón P., Garza Morales, S., & Camacho-Arroyo, I. (2020). Cortisol and DHEA-S levels in pregnant women with severeanxiety. BMC Psychiatry, 20(1), 1-14. doi: 10.1186/s12888-020-02788-6
Li, S. H., & Graham, B. M. (2017). Why are women so vulnerable to anxiety, traumarelatedand stress-related disorders? The potential role of sex hormones. TheLancet Psychiatry, 4(1), 73-82. doi: 10.1016/S2215-0366(16)30358-3
Lobo, A., Chamorro, L., Luque, A., Dal-Ré, R., Badia, X., Baró, E., & Grupo deValidación en Español de Escalas Psicométricas [GVEEP]. (2002). Validaciónde las versiones en español de la Montgomery-Asberg Depression RatingScale y la Hamilton Anxiety Rating Scale para la evaluación de la depresióny de la ansiedad. Medicina Clínica, 118(13), 493-499. doi: 10.1016/s0025-7753(02)72429-9
Mahmoud, R., Wainwright, S. R., & Galea, L. A. (2016). Sex hormones andadult hippocampal neurogenesis: Regulation, implications, and potentialmechanisms. Frontiers in Neuroendocrinology, 41, 129-152. doi: 10.1016/j.yfrne.2016.03.002
Maier, W., Buller, R., Philipp, M., & Heuser, I. (1988). The Hamilton AnxietyScale: reliability, validity and sensitivity to change in anxiety and depressivedisorders. Journal of Affective Disorders, 14(1), 61-68. doi: 10.1016/0165-0327(88)90072-9
Mancuso, R. A., Schetter, C. D., Rini, C. M., Roesch, S. C., & Hobel, C. J. (2004).Maternal prenatal anxiety and corticotropin-releasing hormone associated withtiming of delivery. Psychosomatic Medicine, 66(5), 762-769. doi: 10.1097/01.psy.0000138284.70670.d5
Maron, E., Kuikka, J. T., Shlik, J., Vasar, V., Vanninen, E., & Tiihonen, J. (2004).Reduced brain serotonin transporter binding in patients with panic disorder.Psychiatry Research: Neuroimaging, 132(2), 173-181. doi: 10.1016/j.pscychresns.2003.10.004
Marrocco, J., & McEwen, B. S. (2016). Sex in the brain: hormones and sexdifferences. Dialogues in Clinical Neuroscience, 18(4), 373-383. doi: 10.31887/DCNS.2016.18.4/jmarrocco
Martínez-Paredes, J. F., & Jácome-Pérez, N. (2019). Depression in pregnancy. RevistaColombiana de Psiquiatría, 48(1), 58-65. doi: 10.1016/j.rcp.2017.07.003
Matsuzaka, H., Maeshima, H., Kida, S., Kurita, H., Shimano, T., Nakano, Y., Baba,H., Suzuki, T., & Arai, H. (2013). Gender differences in serum testosterone andcortisol in patients with major depressive disorder compared with controls. TheInternational Journal of Psychiatry in Medicine, 46(2), 203-221. doi: 10.2190/PM.46.2.g
Monk, C., Myers, M. M., Sloan, R. P., Ellman, L. M., & Fifer, W. P. (2003). Effectsof women’s stress-elicited physiological activity and chronic anxiety on fetalheart rate. Journal of Developmental & Behavioral Pediatrics, 24(1), 32-38.doi: 10.1097/00004703-200302000-00008
Murrough, J. W., Huang, Y., Hu, J., Henry, S., Williams, W., Gallezot, J. D., Bailey,C. R., Krystal, J. H., Carson, R. E., & Neumeister, A. (2011). Reduced amygdalaserotonin transporter binding in posttraumatic stress disorder. BiologicalPsychiatry, 70(11), 1033-1038. doi: 10.1016/j.biopsych.2011.07.003
Napso, T., Yong, H. E., Lopez-Tello, J., & Sferruzzi-Perri, A. N. (2018). The roleof placental hormones in mediating maternal adaptations to support pregnancyand lactation. Frontiers in Physiology, 9, 1091. doi: 10.3389/fphys.2018.01091
Pillerová, M., Borbélyová, V., Hodosy, J., Riljak, V., Renczés, E., Frick, K. M., &Tóthová, Ľ. (2021). On the role of sex steroids in biological functions by classicaland non-classical pathways. An update. Frontiers in Neuroendocrinology, 62,100926. doi: 10.1016/j.yfrne.2021.100926
Radoš, S. N., Tadinac, M., & Herman, R. (2018). Anxiety during pregnancy andpostpartum: course, predictors and comorbidity with postpartum depression.Acta Clinica Croatica, 57(1), 39-51. doi: 10.20471/acc.2018.57.01.05
Risal, S., Manti, M., Lu, H., Fornes, R., Larsson, H., Benrick, A., Deng, Q., Cesta,C. E., Rosenqvist, M. A., & Stener-Victorin, E. (2021). Prenatal androgenexposure causes a sexually dimorphic transgenerational increase in offspringsusceptibility to anxiety disorders. Translational Psychiatry, 11(1), 1-12. doi:10.1038/s41398-020-01183-9
Rubinow, D. R., Schmidt, P. J., & Roca, C. A. (1998). Estrogen–serotonin interactions:implications for affective regulation. Biological Psychiatry, 44(9), 839-850. doi:10.1016/s0006-3223(98)00162-0
Santoro, N., Torrens, J., Crawford, S., Allsworth, J. E., Finkelstein, J. S., Gold, E.B., Korenman, S., Lasley, W. L., Luborsky, J. L., McConnell, D., Sowers,M. F., & Weiss, G. (2005). Correlates of circulating androgens in mid-lifewomen: the study of women’s health across the nation. The Journal of ClinicalEndocrinology & Metabolism, 90(8), 4836-4845. doi: 10.1210/jc.2004-2063
Schiller, C. E., Johnson, S. L., Abate, A. C., Schmidt, P. J., & Rubinow, D. R.(2016). Reproductive steroid regulation of mood and behavior. ComprehensivePhysiology, 6(3), 1135-1160. doi: 10.1002/cphy.c150014
Schüle, C., Nothdurfter, C., & Rupprecht, R. (2014). The role of allopregnanolone indepression and anxiety. Progress in Neurobiology, 113, 79-87. doi: 10.1016/j.pneurobio.2013.09.003
Soma-Pillay, P., Nelson-Piercy, C., Tolppanen, H., & Mebazaa, A. (2016).Physiological changes in pregnancy: review articles. Cardiovascular Journalof Africa, 27(2), 89-94.
Steiner, M., Dunn, E., & Born, L. (2003). Hormones and mood: from menarcheto menopause and beyond. Journal of Affective Disorders, 74(1), 67-83. doi:10.1016/s0165-0327(02)00432-9
Trifu, S., Vladuti, A., & Popescu, A. (2019). The neuroendocrinological aspectsof pregnancy and postpartum depression. Acta Endocrinologica (Bucharest),15(3), 410-415. doi: 10.4183/aeb.2019.410
Van den Bergh, B. R., Mulder, E. J., Mennes, M., & Glover, V. (2005). Antenatalmaternal anxiety and stress and the neurobehavioural development of thefetus and child: links and possible mechanisms. A review. Neuroscience &Biobehavioral Reviews, 29(2), 237-258. doi: 10.1016/j.neubiorev.2004.10.007
van Veen, J. F., Jonker, B. W., van Vliet, I. M., & Zitman, F. G. (2009). The effectsof female reproductive hormones in generalized social anxiety disorder. TheInternational Journal of Psychiatry in Medicine, 39(3), 283-295. doi: 10.2190/PM.39.3.e
Walther, A., Breidenstein, J., & Miller, R. (2019b). Association of testosteronetreatment with alleviation of depressive symptoms in men: a systematicreview and meta-analysis. JAMA Psychiatry, 76(1), 31-40. doi: 10.1001/jamapsychiatry.2018.2734
Walther, A., Tsao, C., Pande, R., Kirschbaum, C., Field, E., & Berkman, L. (2019a).Do dehydroepiandrosterone, progesterone, and testosterone influence women’sdepression and anxiety levels? Evidence from hair-based hormonal measuresof 2105 rural Indian women. Psychoneuroendocrinology, 109, 104382. doi:10.1016/j.psyneuen.2019.104382
Walther, A., Wasielewska, J. M., & Leiter, O. (2019c). The antidepressant effect oftestosterone: An effect of neuroplasticity?. Neurology, Psychiatry and BrainResearch, 32, 104-110. doi: 10.1016/j.npbr.2019.05.004
Weber, B., Lewicka, S., Deuschle, M., Colla, M., & Heuser, I. (2000). Testosterone,androstenedione and dihydrotestosterone concentrations are elevated in femalepatients with major depression. Psychoneuroendocrinology, 25(8), 765-771.doi: 10.1016/s0306-4530(00)00023-8
World Health Organization [WHO]. (2017). Depression and other common mentaldisorders: global health estimates (No. WHO/MSD/MER/2017.2). WorldHealth Organization.
Wuu, J., Hellerstein, S., Lipworth, L., Wide, L., Xu, B., Yu, G.-P., Kuper, H., Lagiou,P., Hankinson, S. E., Ekbom, A., Carlström, K., Trichopoulos, D., Adami, H-O.,& Hsieh, C.-C. (2002). Correlates of pregnancy oestrogen, progesterone and sexhormone-binding globulin in the USA and China. European Journal of CancerPrevention, 11(3), 283-293. doi: 10.1097/00008469-200206000-00012
Zou, Y., Fan, F., Ma, A., Yue, Y., Mao, W., & Ma, X. (2009). Hormonal changes andsomatopsychologic manifestations in the first trimester of pregnancy and postpartum. International Journal of Gynecology & Obstetrics, 105(1), 46-49. doi:10.1016/j.ijgo.2008.12.001