Hormonal Contraception and the Brain: Examining Cognition and Psychiatric Disorders

Author(s): Stephanie Laird, Luke J. Ney, Kim L. Felmingham, Andrea Gogos*.

Journal Name: Current Psychiatry Research and Reviews
Formerly: Current Psychiatry Reviews

Volume 15 , Issue 2 , 2019

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Graphical Abstract:


Background: The combined oral contraceptive pill (OC), containing synthetic estrogens and progestins, is used by millions of women worldwide, yet little is known about its effects on cognition or on psychiatric disorders. The progestin component of OCs determines their androgenicity, i.e. whether the OC has androgen binding components with masculinising effects or antiandrogenic components with feminising effects.

Objective: The present review discusses the literature surrounding OC use and cognition in healthy women. Given the important role that sex hormones play in psychiatric disorders, we also consider the influence of OCs on symptoms of schizophrenia, post-traumatic stress disorder, depression, bipolar disorder, anxiety disorders and indirectly, sleep quality.

Results: Research has shown that while there are no differences between OC users and non-users, androgenic OCs enhance visuospatial ability and anti-androgenic OCs enhance verbal fluency. Little is known about OCs effects on other cognitive domains, such as memory and executive function. There is little research examining OC use in schizophrenia, post-traumatic stress disorder, bipolar disorder and anxiety disorders. There is some evidence that OC use is associated with depression, however the exact causality of this association remains to be verified.

Conclusion: We maintain that future studies need to address several methodological limitations, such as separating OCs based on androgenicity to avoid the masking effects that occur when various OCs are considered as one group. As this review highlights several significant effects of OC use on the brain, the implications of OC use needs to be considered in future research.

Keywords: Women, oral contraceptive pill, naturally-cycling, androgenicity, anxiety, depression, PTSD, schizophrenia.

de Bastos M, Stegeman BH, Rosendaal FR, et al. Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev 2014; (3): CD010813
Stegeman BH, de Bastos M, Rosendaal FR, et al. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ 2013; 347: f5298.
Iodice S, Barile M, Rotmensz N, et al. Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis. Eur J Can 2010; 46(12): 2275-84.
Smith JS, Green J, de Gonzalez BA, et al. Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet 2003; 361(9364): 1159-67.
Rapp SR, Espeland MA, Shumaker SA, et al. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 2003; 289(20): 2663-72.
Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. JAMA 1998; 279(9): 688-95.
Zec RF, Trivedi MA. The effects of estrogen replacement therapy on neuropsychological functioning in postmenopausal women with and without dementia: a critical and theoretical review. Neuropsychol Rev 2002; 12(2): 65-109.
Gordon HW, Lee PA. No difference in cognitive performance between phases of the menstrual cycle. Psychoneuroendocrinology 1993; 18(7): 521-31.
Hampson E. Variations in sex-related cognitive abilities across the menstrual cycle. Brain Cogn 1990; 14(1): 26-43.
Hausmann M, Slabbekoorn D, Van Goozen SH, Cohen-Kettenis PT, Güntürkün O. Sex hormones affect spatial abilities during the menstrual cycle. Behav Neurosci 2000; 114(6): 1245-50.
Maki PM, Rich JB, Rosenbaum RS. Implicit memory varies across the menstrual cycle: estrogen effects in young women. Neuropsychologia 2002; 40(5): 518-29.
Chadwick KD, Burkman RT, Tornesi BM, Mahadevan B. Fifty years of “the pill”: risk reduction and discovery of benefits beyond contraception, reflections, and forecast. Toxicol Sci 2012; 125(1): 2-9.
Pletzer BA, Kerschbaum HH. 50 years of hormonal contraception-time to find out, what it does to our brain. Front Neurosci 2014; 8: 256.
Stewart M, Black K. Choosing a combined oral contraceptive pill. Aust Prescr 2015; 38(1): 6-11.
Dragoman MV. The combined oral contraceptive pill - recent developments, risks and benefits. Best Pract Res Clin Obstet Gynaecol 2014; 28(6): 825-34.
Gogos A. Natural and synthetic sex hormones: effects on higher-order cognitive function and prepulse inhibition. Biol Psychol 2013; 93(1): 17-23.
Sun J, Walker AJ, Dean B, van den Buuse M, Gogos A. Progesterone: the neglected hormone in schizophrenia? A focus on progesterone-dopamine interactions. Psychoneuroendocrinology 2016; 74: 126-40.
Reed BG, Carr BR. The Normal Menstrual Cycle and the Control of Ovulation Endotext South Dartmouth (MA): MDTextcom, Inc 2018.
Miller L, Hughes JP. Continuous combination oral contraceptive pills to eliminate withdrawal bleeding: a randomized trial. Obstet Gynecol 2003; 101(4): 653-61.
Fleischman DS, Navarrete CD, Fessler DM. Oral contraceptives suppress ovarian hormone production. Psychol Sci 2010; 21(5): 750-2.
Elliott-Sale KJ, Smith S, Bacon J, et al. Examining the role of oral contraceptive users as an experimental and/or control group in athletic performance studies. Contraception 2013; 88(3): 408-12.
DiLiberti CE, O’Leary CM, Hendy CH, Waters DH, Margolis MB. Steady-state pharmacokinetics of an extended-regimen oral contraceptive with continuous estrogen. Contraception 2011; 83(1): 55-61.
Sitruk-Ware R, Nath A. Characteristics and metabolic effects of estrogen and progestins contained in oral contraceptive pills. Best Pract Res Clin Endocrinol Metab 2013; 27(1): 13-24.
Lawrie TA, Helmerhorst FM, Maitra NK, Kulier R, Bloemenkamp K, Gülmezoglu AM. Types of progestogens in combined oral contraception: effectiveness and side-effects. Cochrane Database Syst Rev 2011; (5): CD004861
Batur P, Elder J, Mayer M. Update on contraception: benefits and risks of the new formulations Cleve Clin J Med 2003; 70(8): 681- 2, 5-6, 68-90 passim.
Wharton W, Hirshman E, Merritt P, Doyle L, Paris S, Gleason C. Oral contraceptives and androgenicity: influences on visuospatial task performance in younger individuals. Exp Clin Psychopharmacol 2008; 16(2): 156-64.
Costello M, Shrestha B, Eden J, Sjoblom P, Johnson N. Insulin-sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome. Cochrane Database Syst Rev 2007; (1): CD005552
Ghosh S, Chaudhuri S, Jain VK, Aggarwal K. Profiling and hormonal therapy for acne in women. Indian J Dermatol 2014; 59(2): 107-15.
Kahn LS, Halbreich U. Oral contraceptives and mood. Expert Opin Pharmacother 2001; 2(9): 1367-82.
Gogos A, Wu YC, Williams AS, Byrne LK. The effects of ethinylestradiol and progestins (“the pill”) on cognitive function in pre-menopausal women. Neurochem Res 2014; 39(12): 2288-300.
Zacks JM. Neuroimaging studies of mental rotation: a meta-analysis and review. J Cogn Neurosci 2008; 20(1): 1-19.
Shepard RN, Metzler J. Mental rotation of three-dimensional objects. Science 1971; 171(3972): 701-3.
Vandenberg SG, Kuse AR. Mental rotations, a group test of three-dimensional spatial visualization. Percept Mot Skills 1978; 47(2): 599-604.
Beltz AM, Hampson E, Berenbaum SA. Oral contraceptives and cognition: A role for ethinyl estradiol. Horm Behav 2015; 74: 209-17.
Griksiene R, Monciunskaite R, Arnatkeviciute A, Ruksenas O. Does the use of hormonal contraceptives affect the mental rotation performance? Horm Behav 2018; 100: 29-38.
Voyer D. Effect of practice on laterality in a mental rotation task. Brain Cogn 1995; 29(3): 326-35.
Epting LK, Overman WH. Sex-sensitive tasks in men and women: a search for performance fluctuations across the menstrual cycle. Behav Neurosci 1998; 112(6): 1304-17.
Simić N, Santini M. Verbal and spatial functions during different phases of the menstrual cycle. Psychiatr Danub 2012; 24(1): 73-9.
Moody MS. Changes in scores on the mental rotations test during the menstrual cycle. Percept Mot Skills 1997; 84(3 Pt 1): 955-61.
Silverman I, Phillips K. Effects of estrogen changes during the menstrual cycle on spatial performance. Ethol Sociobiol 1993; 14(4): 257-69.
McCormick CM, Teillon SM. Menstrual cycle variation in spatial ability: relation to salivary cortisol levels. Horm Behav 2001; 39(1): 29-38.
Hampson E, Levy-Cooperman N, Korman JM. Estradiol and mental rotation: relation to dimensionality, difficulty, or angular disparity? Horm Behav 2014; 65(3): 238-48.
Griksiene R, Ruksenas O. Effects of hormonal contraceptives on mental rotation and verbal fluency. Psychoneuroendocrinology 2011; 36(8): 1239-48.
Lisofsky N, Riediger M, Gallinat J, Lindenberger U, Kühn S. Hormonal contraceptive use is associated with neural and affective changes in healthy young women. Neuroimage 2016; 134: 597-606.
Mordecai KL, Rubin LH, Maki PM. Effects of menstrual cycle phase and oral contraceptive use on verbal memory. Horm Behav 2008; 54(2): 286-93.
Rosenberg L, Park S. Verbal and spatial functions across the menstrual cycle in healthy young women. Psychoneuroendocrinology 2002; 27(7): 835-41.
Islam F, Sparkes C, Roodenrys S, Astheimer L. Short-term changes in endogenous estrogen levels and consumption of soy isoflavones affect working and verbal memory in young adult females. Nutr Neurosci 2008; 11(6): 251-62.
Solís-Ortiz S, Corsi-Cabrera M. Sustained attention is favored by progesterone during early luteal phase and visuo-spatial memory by estrogens during ovulatory phase in young women. Psychoneuroendocrinology 2008; 33(7): 989-98.
Anderson JR. Learning and memory: An integrated approach. New Jersey: John Wiley & Sons Inc. 2000.
Hussain D, Hanafi S, Konishi K, Brake WG, Bohbot VD. Modulation of spatial and response strategies by phase of the menstrual cycle in women tested in a virtual navigation task. Psychoneuroendocrinology 2016; 70: 108-17.
Phillips SM, Sherwin BB. Variations in memory function and sex steroid hormones across the menstrual cycle. Psychoneuroendocrinology 1992; 17(5): 497-506.
Hatta T, Nagaya K. Menstrual cycle phase effects on memory and Stroop task performance. Arch Sex Behav 2009; 38(5): 821-7.
Symonds CS, Gallagher P, Thompson JM, Young AH. Effects of the menstrual cycle on mood, neurocognitive and neuroendocrine function in healthy premenopausal women. Psychol Med 2004; 34(1): 93-102.
Nielsen SE, Ertman N, Lakhani YS, Cahill L. Hormonal contraception usage is associated with altered memory for an emotional story. Neurobiol Learn Mem 2011; 96(2): 378-84.
Man MS, MacMillan I, Scott J, Young AH. Mood, neuropsychological function and cognitions in premenstrual dysphoric disorder. Psychol Med 1999; 29(3): 727-33.
Kampen DL, Sherwin BB. Estradiol is related to visual memory in healthy young men. Behav Neurosci 1996; 110(3): 613-7.
Hampson E, Morley EE. Estradiol concentrations and working memory performance in women of reproductive age. Psychoneuroendocrinology 2013; 38(12): 2897-904.
Mihalik JP, Ondrak KS, Guskiewicz KM, McMurray RG. The effects of menstrual cycle phase on clinical measures of concussion in healthy college-aged females. J Sci Med Sport 2009; 12(3): 383-7.
Voyer D, Voyer SD, Saint-Aubin J. Sex differences in visual-spatial working memory: a meta-analysis. Psychon Bull Rev 2017; 24(2): 307-34.
Miyake A, Friedman NP, Emerson MJ, Witzki AH, Howerter A, Wager TD. The unity and diversity of executive functions and their contributions to complex “Frontal Lobe” tasks: a latent variable analysis. Cognit Psychol 2000; 41(1): 49-100.
Kohli A, Kaur M. Wisconsin card sorting test: normative data and experience. Indian J Psychiatry 2006; 48(3): 181-4.
Grigorova M, Sherwin BB, Tulandi T. Effects of treatment with leuprolide acetate depot on working memory and executive functions in young premenopausal women. Psychoneuroendocrinology 2006; 31(8): 935-47.
Grigorova M, Sherwin BB. No differences in performance on test of working memory and executive functioning between healthy elderly postmenopausal women using or not using hormone therapy. Climacteric 2006; 9(3): 181-94.
Henderson VW, Popat RA. Effects of endogenous and exogenous estrogen exposures in midlife and late-life women on episodic memory and executive functions. Neuroscience 2011; 191: 129-38.
Komnenich P, Lane DM, Dickey RP, Stone SC. Gonadal hormones and cognitive performance. Physiol Psychol 1978; 6(1): 115-20.
Wright KP Jr, Badia P. Effects of menstrual cycle phase and oral contraceptives on alertness, cognitive performance, and circadian rhythms during sleep deprivation. Behav Brain Res 1999; 103(2): 185-94.
Gogos A, Ney LJ, Seymour N, Van Rheenen T, Felmingam KL. Sex differences in schizophrenia, bipolar disorder and PTSD: are gonadal hormones the link? Br J Pharmacol 2019.
Pinares-Garcia P, Stratikopoulos M, Zagato A, Loke H, Lee J. Sex: a significant risk factor for neurodevelopmental and neurodegenerative disorders. Brain Sci 2018; 8(8)E154
Gogos A, Sbisa AM, Sun J, Gibbons A, Udawela M, Dean B. A role for estrogen in schizophrenia: clinical and preclinical findings Int J Endocrinol 2015; Article Id 2015615356: 16
Sbisa AM, Van den Buuse M, Gogos A. The effect of 17β-estradiol and its analogues on cognition in preclinical and clinical research: relevance to schizophreniapsychiatry and neuroscience update Vol II. Cham: Springer 2017.
Benitez A, Gunstad J. Poor sleep quality diminishes cognitive functioning independent of depression and anxiety in healthy young adults. Clin Neuropsychol 2012; 26(2): 214-23.
Bowie CR, Harvey PD. Cognitive deficits and functional outcome in schizophrenia. Neuropsychiatr Dis Treat 2006; 2(4): 531-6.
Green MF, Kern RS, Heaton RK. Longitudinal studies of cognition and functional outcome in schizophrenia: implications for matrics. Schizophr Res 2004; 72(1): 41-51.
Keefe RS. The longitudinal course of cognitive impairment in schizophrenia: an examination of data from premorbid through post-treatment phases of illness. J Clin Psychiatry 2014; 75(Suppl. 2): 8-13.
Forbes NF, Carrick LA, McIntosh AM, Lawrie SM. Working memory in schizophrenia: a meta-analysis. Psychol Med 2009; 39(6): 889-905.
Gogos A, Joshua N, Rossell SL. Use of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to investigate group and gender differences in schizophrenia and bipolar disorder. Aust N Z J Psychiatry 2010; 44(3): 220-9.
Couture SM, Penn DL, Roberts DL. The functional significance of social cognition in schizophrenia: a review Schizophr Bull 2006 32(suppl_1): S44-63.
Fett A-KJ, Viechtbauer W, Dominguez MD, Penn DL, van Os J, Krabbendam L. The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neurosci Biobehav Rev 2011; 35(3): 573-88.
McGregor C, Riordan A, Thornton J. Estrogens and the cognitive symptoms of schizophrenia: possible neuroprotective mechanisms. Front Neuroendocrinol 2017; 47: 19-33.
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 2005; 73(2-3): 357-66.
Huber TJ, Rollnik J, Wilhelms J, von zur Mühlen A, Emrich HM, Schneider U. Estradiol levels in psychotic disorders. Psychoneuroendocrinology 2001; 26(1): 27-35.
Zhang-Wong JH, Seeman MV. Antipsychotic drugs, menstrual regularity and osteoporosis risk. Arch Women Ment Health 2002; 5(3): 93-8.
Bergemann N, Parzer P, Nagl I, et al. Acute psychiatric admission and menstrual cycle phase in women with schizophrenia. Arch Women Ment Health 2002; 5(3): 119-26.
Riecher-Rössler A, Häfner H, Stumbaum M, Maurer K, Schmidt R. Can estradiol modulate schizophrenic symptomatology? Schizophr Bull 1994; 20(1): 203-14.
Rubin LH, Carter CS, Drogos L, Pournajafi-Nazarloo H, Sweeney JA, Maki PM. Peripheral oxytocin is associated with reduced symptom severity in schizophrenia. Schizophr Res 2010; 124(1-3): 13-21.
Bergemann N, Parzer P, Runnebaum B, Resch F, Mundt C. Estrogen, menstrual cycle phases, and psychopathology in women suffering from schizophrenia. Psychol Med 2007; 37(10): 1427-36.
Hallonquist JD, Seeman MV, Lang M, Rector NA. Variation in symptom severity over the menstrual cycle of schizophrenics. Biol Psychiatry 1993; 33(3): 207-9.
Huber TJ, Borsutzky M, Schneider U, Emrich HM. Psychotic disorders and gonadal function: evidence supporting the oestrogen hypothesis. Acta Psychiatr Scand 2004; 109(4): 269-74.
Ko YH, Joe SH, Cho W, et al. Estrogen, cognitive function and negative symptoms in female schizophrenia. Neuropsychobiology 2006; 53(4): 169-75.
Hoff AL, Kremen WS, Wieneke MH, et al. Association of estrogen levels with neuropsychological performance in women with schizophrenia. Am J Psychiatry 2001; 158(7): 1134-9.
Akhondzadeh S, Nejatisafa AA, Amini H, et al. Adjunctive estrogen treatment in women with chronic schizophrenia: a double-blind, randomized, and placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27(6): 1007-12.
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 1996; 20(3): 247-52.
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 2015; 20(6): 695-702.
Kulkarni J, de Castella A, Headey B, et al. Estrogens and men with schizophrenia: is there a case for adjunctive therapy? Schizophr Res 2011; 125(2-3): 278-83.
de Boer J, Prikken M, Lei WU, Begemann M, Sommer I. The effect of raloxifene augmentation in men and women with a schizophrenia spectrum disorder: a systematic review and meta-analysis. NPJ Schizophr 2018; 4(1): 1.
Huerta-Ramos E, Iniesta R, Ochoa S, et al. Effects of raloxifene on cognition in postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial. Eur Neuropsychopharmacol 2014; 24(2): 223-31.
Kianimehr G, Fatehi F, Hashempoor S, et al. Raloxifene adjunctive therapy for postmenopausal women suffering from chronic schizophrenia: a randomized double-blind and placebo controlled trial. Daru 2014; 22(1): 55.
Kulkarni J, Gavrilidis E, Gwini SM, et al. Effect of adjunctive raloxifene therapy on severity of refractory schizophrenia in women: a randomized clinical trial. JAMA Psychiatry 2016; 73(9): 947-54.
Kulkarni J, Gurvich C, Lee SJ, et al. Piloting the effective therapeutic dose of adjunctive selective estrogen receptor modulator treatment in postmenopausal women with schizophrenia. Psychoneuroendocrinology 2010; 35(8): 1142-7.
Raveendranathan D, Shivakumar V, Jayaram N, Rao N, Venkatasubramanian G. Beneficial effects of add-on raloxifene in schizophrenia. Arch Women Ment Health 2012; 15(2): 147-8.
Shivakumar V, Venkatasubramanian G. Successful use of adjuvant raloxifene treatment in clozapine-resistant schizophrenia. Indian J Psychiatry 2012; 54(4): 394.
Usall J, Huerta-Ramos E, Iniesta R, et al. Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry 2011; 72(11): 1552-7.
Usall J, Huerta-Ramos E, Labad J, et al. Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: A 24-Week double-blind, randomized, parallel, placebo-controlled trial. Schizophr Bull 2016; 42(2): 309-17.
Weickert TW, Weickert CS. Raloxifene improves cognition in schizophrenia: spurious result or valid effect? Front Psychiatry 2017; 8: 202.
Weickert TW, Weinberg D, Lenroot R, et al. Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia. Mol Psychiatry 2015; 20(6): 685-94.
Bergemann N, Mundt C, Parzer P, et al. Estrogen as an adjuvant therapy to antipsychotics does not prevent relapse in women suffering from schizophrenia: results of a placebo-controlled double-blind study. Schizophr Res 2005; 74(2-3): 125-34.
Bergemann N, Parzer P, Kaiser D, Maier-Braunleder S, Mundt C, Klier C. Testosterone and gonadotropins but not estrogen associated with spatial ability in women suffering from schizophrenia: a double-blind, placebo-controlled study. Psychoneuroendocrinology 2008; 33(4): 507-16.
Bergemann N, Parzer P, Jaggy S, Auler B, Mundt C, Maier-Braunleder S. Estrogen and comprehension of metaphoric speech in women suffering from schizophrenia: results of a double-blind, placebo-controlled trial. Schizophr Bull 2008; 34(6): 1172-81.
Lindamer LA, Buse DC, Lohr JB, Jeste DV. Hormone replacement therapy in postmenopausal women with schizophrenia: positive effect on negative symptoms? Biol Psychiatry 2001; 49(1): 47-51.
Pitman RK, Rasmusson AM, Koenen KC, et al. Biological studies of post-traumatic stress disorder. Nat Rev Neurosci 2012; 13(11): 769-87.
Glover EM, Jovanovic T, Norrholm SD. Estrogen and extinction of fear memories: implications for posttraumatic stress disorder treatment. Biol Psychiatry 2015; 78(3): 178-85.
Ney LJ, Matthews A, Bruno R, Felmingam KL. Modulation of the endocannabinoid system by sex hormones: Implications for post-traumatic stress disorder. Neurosci Biobehav Rev 2018; 94: 302-20.
Li SH, Graham BM. Why are women so vulnerable to anxiety, trauma-related and stress-related disorders? The potential role of sex hormones. Lancet Psychiatry 2017; 4(1): 73-82.
Rasmusson AM, Marx CE, Pineles SL, et al. Neuroactive steroids and PTSD treatment. Neurosci Lett 2017; 649: 156-63.
Lebron-Milad K, Graham BM, Milad MR. Low estradiol levels: A vulnerability factor for the development of post-traumatic stress disorder biological psychiatry. Biol Psychiatry 2012; 72: 6-7.
Nillni YI, Pineles SL, Patton SC, Rouse MH, Sawyer AT, Rasmusson AM. Menstrual cycle effects on psychological symptoms in women with PTSD. J Trauma Stress 2015; 28(1): 1-7.
Lonsdorf TB, Menz MM, Andreatta M, et al. Don’t fear ‘fear conditioning’: methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear. Neurosci Biobehav Rev 2017; 77: 247-85.
Merz CJ, Tabbert K, Schweckendiek J, et al. Oral contraceptive usage alters the effects of cortisol on implicit fear learning. Horm Behav 2012; 62(4): 531-8.
Graham BM, Milad MR. Blockade of estrogen by hormonal contraceptives impairs fear extinction in female rats and women. Biol Psychiatry 2013; 73(4): 371-8.
White EC, Graham BM. Estradiol levels in women predict skin conductance response but not valence and expectancy ratings in conditioned fear extinction Neurobiol Learn Mem 2016; 134 Pt B: 339-48
Lonsdorf TB, Haaker J, Schümann D, et al. Sex differences in conditioned stimulus discrimination during context-dependent fear learning and its retrieval in humans: the role of biological sex, contraceptives and menstrual cycle phases. J Psychiatry Neurosci 2015; 40(6): 368-75.
Aleknaviciute J, Tulen JHM, De Rijke YB, et al. The levonorgestrel-releasing intrauterine device potentiates stress reactivity. Psychoneuroendocrinology 2017; 80: 39-45.
Hertel J, König J, Homuth G, et al. Evidence for stress-like alterations in the HPA-Axis in women taking oral contraceptives. Sci Rep 2017; 7(1): 14111.
Nielsen SE, Segal SK, Worden IV, Yim IS, Cahill L. Hormonal contraception use alters stress responses and emotional memory. Biol Psychol 2013; 92(2): 257-66.
Kirschbaum C, Kudielka BM, Gaab J, Schommer NC, Hellhammer DH. Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosom Med 1999; 61(2): 154-62.
Nielsen SE, Ahmed I, Cahill L. Postlearning stress differentially affects memory for emotional gist and detail in naturally cycling women and women on hormonal contraceptives. Behav Neurosci 2014; 128(4): 482-93.
Miedl SF, Wegerer M, Kerschbaum H, Blechert J, Wilhelm FH. Neural activity during traumatic film viewing is linked to endogenous estradiol and hormonal contraception. Psychoneuroendocrinology 2018; 87: 20-6.
Studd J, Panay N. Hormones and depression in women Climacteric: the journal of the International Menopause Society 2004; 7(4): 338-46
Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen H-U. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res 2012; 21(3): 169-84.
Douma SL, Husband C, O’Donnell ME, Barwin BN, Woodend AK. Estrogen-related mood disorders: reproductive life cycle factors. ANS Adv Nurs Sci 2005; 28(4): 364-75.
Wise DD, Felker A, Stahl SM. Tailoring treatment of depression for women across the reproductive lifecycle: the importance of pregnancy, vasomotor symptoms, and other estrogen-related events in psychopharmacology. CNS Spectr 2008; 13(8): 647-62.
Harlow BL, Wise LA, Otto MW, Soares CN, Cohen LS. Depression and its influence on reproductive endocrine and menstrual cycle markers associated with perimenopause: the Harvard Study of Moods and Cycles. Arch Gen Psychiatry 2003; 60(1): 29-36.
Soares CN, Almeida OP, Joffe H, Cohen LS. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 2001; 58(6): 529-34.
Kulkarni J. Depression as a side effect of the contraceptive pill. Expert Opin Drug Saf 2007; 6(4): 371-4.
Shahnazi M, Farshbaf Khalili A, Ranjbar Kochaksaraei F, et al. A comparison of second and third generations combined oral contraceptive pills’ effect on mood. Iran Red Crescent Med J 2014; 16(8)e13628
Skovlund CW, Mørch LS, Kessing LV, Lidegaard O. Association of hormonal contraception with depression. JAMA Psychiatry 2016; 73(11): 1154-62.
Skovlund CW, Mørch LS, Kessing LV, Lange T, Lidegaard O. Association of hormonal contraception with suicide attempts and suicides. Am J Psychiatry 2018; 175(4): 336-42.
Toffol E, Heikinheimo O, Koponen P, Luoto R, Partonen T. Hormonal contraception and mental health: results of a population-based study. Hum Reprod 2011; 26(11): 3085-93.
Keyes KM, Cheslack-Postava K, Westhoff C, et al. Association of hormonal contraceptive use with reduced levels of depressive symptoms: a national study of sexually active women in the United States. Am J Epidemiol 2013; 178(9): 1378-88.
Pagano HP, Zapata LB, Berry-Bibee EN, Nanda K, Curtis KM. Safety of hormonal contraception and intrauterine devices among women with depressive and bipolar disorders: a systematic review. Contraception 2016; 94(6): 641-9.
Young EA, Kornstein SG, Harvey AT, et al. Influences of hormone-based contraception on depressive symptoms in premenopausal women with major depression. Psychoneuroendocrinology 2007; 32(7): 843-53.
Duke JM, Sibbritt DW, Young AF. Is there an association between the use of oral contraception and depressive symptoms in young Australian women? Contraception 2007; 75(1): 27-31.
Brent D. Contraceptive conundrum: use of hormonal contraceptives is associated with an increased risk of suicide attempt and suicide. Am J Psychiatry 2018; 175(4): 300-2.
Hamstra DA, de Kloet ER, de Rover M, Van der Does W. Oral contraceptives positively affect mood in healthy PMS-free women: a longitudinal study. J Psychosom Res 2017; 103: 119-26.
Worly BL, Gur TL, Schaffir J. The relationship between progestin hormonal contraception and depression: a systematic review. Contraception 2018; 97(6): 478-89.
Nyberg S. Mood and physical symptoms improve in women with severe cyclical changes by taking an oral contraceptive containing 250-mcg norgestimate and 35-mcg ethinyl estradiol. Contraception 2013; 87(6): 773-81.
Gingnell M, Engman J, Frick A, et al. Oral contraceptive use changes brain activity and mood in women with previous negative affect on the pill--a double-blinded, placebo-controlled randomized trial of a levonorgestrel-containing combined oral contraceptive. Psychoneuroendocrinology 2013; 38(7): 1133-44.
Meier TB, Drevets WC, Teague TK, et al. Kynurenic acid is reduced in females and oral contraceptive users: implications for depression. Brain Behav Immun 2018; 67: 59-64.
Roberts TA, Hansen S. Association of Hormonal Contraception with depression in the postpartum period. Contraception 2017; 96(6): 446-52.
Svendal G, Berk M, Pasco JA, Jacka FN, Lund A, Williams LJ. The use of hormonal contraceptive agents and mood disorders in women. J Affect Disord 2012; 140(1): 92-6.
Wiréhn AB, Foldemo A, Josefsson A, Lindberg M. Use of hormonal contraceptives in relation to antidepressant therapy: a nationwide population-based study. Eur J Contracept Reprod Health Care 2010; 15(1): 41-7.
Berenson AB, Asem H, Tan A, Wilkinson GS. Continuation rates and complications of intrauterine contraception in women diagnosed with bipolar disorder. Obstet Gynecol 2011; 118(6): 1331-6.
Rasgon N, Bauer M, Glenn T, Elman S, Whybrow PC. Menstrual cycle related mood changes in women with bipolar disorder. Bipolar Disord 2003; 5(1): 48-52.
Nguyen T-V, Low NCP. Hormonal treatments for bipolar disorder: a review of the literature. J Behavioral Brain Sci 2012; 02(01): 4.
Bebchuk JM, Arfken CL, Dolan-Manji S, Murphy J, Hasanat K, Manji HK. A preliminary investigation of a protein kinase C inhibitor in the treatment of acute mania. Arch Gen Psychiatry 2000; 57(1): 95-7.
Fallah E, Arman S, Najafi M, Shayegh B. Effect of tamoxifen and lithium on treatment of acute mania symptoms in children and adolescents. Iran J Child Neurol 2016; 10(2): 16-25.
Kulkarni J, Garland KA, Scaffidi A, et al. A pilot study of hormone modulation as a new treatment for mania in women with bipolar affective disorder. Psychoneuroendocrinology 2006; 31(4): 543-7.
Yildiz A, Guleryuz S, Ankerst DP, Ongür D, Renshaw PF. Protein kinase C inhibition in the treatment of mania: a double-blind, placebo-controlled trial of tamoxifen. Arch Gen Psychiatry 2008; 65(3): 255-63.
Zarate CA Jr, Singh JB, Carlson PJ, et al. Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study. Bipolar Disord 2007; 9(6): 561-70.
Freeman MP, Smith KW, Freeman SA, et al. The impact of reproductive events on the course of bipolar disorder in women. J Clin Psychiatry 2002; 63(4): 284-7.
Chouinard G, Steinberg S, Steiner W. Estrogen-progesterone combination: another mood stabilizer? Am J Psychiatry 1987; 144(6): 826.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association 2013.
Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci 2015; 17(3): 327-35.
McLean CP, Asnaani A, Litz BT, Hofmann SG. Gender differences in anxiety disorders: prevalence, course of illness, comorbidity and burden of illness. J Psychiatr Res 2011; 45(8): 1027-35.
Pineles SL, Nillni YI, Pinna G, et al. PTSD in women is associated with a block in conversion of progesterone to the GABAergic neurosteroids allopregnanolone and pregnanolone measured in plasma. Psychoneuroendocrinology 2018; 93: 133-41.
Graham BM, Li SH, Black MJ, Öst LG. The association between estradiol levels, hormonal contraceptive use, and responsiveness to one-session-treatment for spider phobia in women. Psychoneuroendocrinology 2018; 90: 134-40.
Ushiroyama T, Okamoto Y, Toyoda K, Sugimoto O. A case of panic disorder induced by oral contraceptive. Acta Obstet Gynecol Scand 1992; 71(1): 78-80.
Deci PA, Lydiard RB, Santos AB, Arana GW. Oral contraceptives and panic disorder. J Clin Psychiatry 1992; 53(5): 163-5.
Cheslack-Postava K, Keyes KM, Lowe SR, Koenen KC. Oral contraceptive use and psychiatric disorders in a nationally representative sample of women. Arch Women Ment Health 2015; 18(1): 103-11.
Buckhalt JA, El-Sheikh M, Keller P. Children’s sleep and cognitive functioning: race and socioeconomic status as moderators of effects. Child Dev 2007; 78(1): 213-31.
Buyesse DJ, Halligan EM, Houck PR, Nebes RD, Monk TH. Self-reported sleep quality predicts poor cognitive performance in healthy older adults. J Gerontol B Psychol Sci Soc Sci 2009; 64B(2): 180-7.
Dewald JF, Meijer AM, Oort FJ, Kerkhof GA, Bögels SM. The influence of sleep quality, sleep duration and sleepiness on school performance in children and adolescents: A meta-analytic review. Sleep Med Rev 2010; 14(3): 179-89.
Gildner TE, Liebert MA, Kowal P, Chatterji S, Snodgrass JJ. Associations between sleep duration, sleep quality, and cognitive test performance among older adults from six middle income countries: results from the Study on Global Ageing and Adult Health (SAGE). J Clin Sleep Med 2014; 10(6): 613-21.
Paavonen EJ, Räikkönen K, Pesonen A-K, et al. Sleep quality and cognitive performance in 8-year-old children. Sleep Med 2010; 11(4): 386-92.
Buysse DJ, Hall ML, Strollo PJ, et al. Relationships between the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and clinical/polysomnographic measures in a community sample. J Clin Sleep Med 2008; 4(6): 563-71.
Germain A. Sleep disturbances as the hallmark of PTSD: where are we now? Am J Psychiatry 2013; 170(4): 372-82.
Olson LG, Cole MF, Ambrogetti A. Correlations among Epworth Sleepiness Scale scores, multiple sleep latency tests and psychological symptoms. J Sleep Res 1998; 7(4): 248-53.
Selvi Y, Aydin A, Boysan M, Atli A, Agargun MY, Besiroglu L. Associations between chronotype, sleep quality, suicidality, and depressive symptoms in patients with major depression and healthy controls. Chronobiol Int 2010; 27(9-10): 1813-28.
Hachul H, Andersen ML, Bittencourt L, Santos-Silva R, Tufik S. A population-based survey on the influence of the menstrual cycle and the use of hormonal contraceptives on sleep patterns in São Paulo, Brazil. Int J Gynaecol Obstet 2013; 120(2): 137-40.
Hachul H, Andersen ML, Bittencourt LR, Santos-Silva R, Conway SG, Tufik S. Does the reproductive cycle influence sleep patterns in women with sleep complaints? Climacteric 2010; 13(6): 594-603.
Burdick RS, Hoffmann R, Armitage R. Short note: oral contraceptives and sleep in depressed and healthy women. Sleep 2002; 25(3): 347-9.
Baker F, Mitchell D, Driver H. Oral contraceptives alter sleep and raise body temperature in young women. Pflugers Arch 2001; 442(5): 729-37.
Baker FC, Waner JI, Vieira EF, Taylor SR, Driver HS, Mitchell D. Sleep and 24 hour body temperatures: a comparison in young men, naturally cycling women and women taking hormonal contraceptives. J Physiol 2001; 530(Pt 3): 565-74.
Bezerra AG, Andersen ML, Pires GN, Tufik S, Hachul H. Effects of hormonal contraceptives on sleep - A possible treatment for insomnia in premenopausal women. Sleep Sci 2018; 11(3): 129-36.
Caufriez A, Leproult R, L’Hermite-Balériaux M, Kerkhofs M, Copinschi G. Progesterone prevents sleep disturbances and modulates GH, TSH, and melatonin secretion in postmenopausal women. J Clin Endocrinol Metab 2011; 96(4): E614-23.
Hachul H, Bittencourt LR, Andersen ML, Haidar MA, Baracat EC, Tufik S. Effects of hormone therapy with estrogen and/or progesterone on sleep pattern in postmenopausal women. Int J Gynaecol Obstet 2008; 103(3): 207-12.
Leeangkoonsathian E, Pantasri T, Chaovisitseree S, Morakot N. The effect of different progestogens on sleep in postmenopausal women: a randomized trial. Gynecol Endocrinol 2017; 33(12): 933-6.
Montplaisir J, Lorrain J, Denesle R, Petit D. Sleep in menopause: differential effects of two forms of hormone replacement therapy. Menopause 2001; 8(1): 10-6.
Schüssler P, Kluge M, Yassouridis A, et al. Progesterone reduces wakefulness in sleep EEG and has no effect on cognition in healthy postmenopausal women. Psychoneuroendocrinology 2008; 33(8): 1124-31.
Kalleinen N, Polo O, Himanen SL, Joutsen A, Polo-Kantola P. The effect of estrogen plus progestin treatment on sleep: a randomized, placebo-controlled, double-blind trial in premenopausal and late postmenopausal women. Climacteric 2008; 11(3): 233-43.
Rettenbacher MA, Mechtcheriakov S, Bergant A, Brugger A, Fleischhacker WW. Improvement of psychosis during treatment with estrogen and progesterone in a patient with hypoestrogenemia. J Clin Psychiatry 2004; 65(2): 275-7.
Gahr M, Freudenmann RW, Connemann BJ, Kolle MA, Schonfeldt-Lecuona C. Rapid relapse in depression following initialization of oral contraception with ethinyl estradiol and chlormadinone acetate Gen Hosp Psychiatry 2014; 36(2): 230 e1-2
Oinonen KA, Mazmanian D. To what extent do oral contraceptives influence mood and affect? J Affect Disord 2002; 70(3): 229-40.
Lundin C, Danielsson KG, Bixo M, et al. Combined oral contraceptive use is associated with both improvement and worsening of mood in the different phases of the treatment cycle-A double-blind, placebo-controlled randomized trial. Psychoneuroendocrinology 2017; 76: 135-43.
Bengtsdotter H, Lundin C, Gemzell Danielsson K, et al. Ongoing or previous mental disorders predispose to adverse mood reporting during combined oral contraceptive use. Eur J Contracept Reprod Health Care 2018; 23(1): 45-51.
Beltz AM, Loviska AM, Kelly D. No personality differences between oral contraceptive users and naturally cycling women: Implications for research on sex hormones. Psychoneuroendocrinology 2019; 100: 127-30.
Davison SL, Bell RJ, Gavrilescu M, et al. Testosterone improves verbal learning and memory in postmenopausal women: results from a pilot study. Maturitas 2011; 70(3): 307-11.
Davis SR, Davison SL, Gavrilescu M, et al. Effects of testosterone on visuospatial function and verbal fluency in postmenopausal women: results from a functional magnetic resonance imaging pilot study. Menopause 2014; 21(4): 410-4.
Pletzer B, Kronbichler M, Kerschbaum H. Differential effects of androgenic and anti-androgenic progestins on fusiform and frontal gray matter volume and face recognition performance. Brain Res 2015; 1596: 108-15.
Blue SW, Winchell AJ, Kaucher AV, et al. Simultaneous quantitation of multiple contraceptive hormones in human serum by LC-MS/MS. Contraception 2018; 97(4): 363-9.
Montoya ER, Bos PA. How oral contraceptives impact social-emotional behavior and brain function. Trends Cogn Sci 2017; 21(2): 125-36.
Brötzner CP, Klimesch W, Kerschbaum HH. Progesterone-associated increase in ERP amplitude correlates with an improvement in performance in a spatial attention paradigm. Brain Res 2015; 1595: 74-83.

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Year: 2019
Page: [116 - 131]
Pages: 16
DOI: 10.2174/1573400515666190521113841

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