title: Cognitive functions of regularly cycling women may differ throughout the month, depending on sex hormone status; a possible explanation to conflicting results of studies of ADHD in females.
abstract: Attention Deficit/Hyperactivity Disorder (ADHD) is considered as a model of neuro-developmental cognitive function. ADHD research previously studied mainly males. A major biological distinction between the genders is the presence of a menstrual cycle, which is associated with variations in sex steroid hormone levels. There is a growing body of literature showing that sex hormones have the ability to regulate intracellular signaling systems that are thought to be abnormal in ADHD. Thus, it is conceivable to believe that this functional interaction between sex hormones and molecules involved with synaptic plasticity and neurotransmitter systems may be associated with some of the clinical characteristics of women with ADHD. In spite of the impact of sex hormones on major neurotransmitter systems of the brain in a variety of clinical settings, the menstrual cycle is usually entered to statistical analyses as a nuisance or controlled for by only testing male samples. Evaluation of brain structure, function and chemistry over the course of the menstrual cycle as well as across the lifespan of women (premenarche, puberty, cycling period, premenopause, postmenopause) is critical to understanding sex differences in both normal and aberrant mental function and behavior. The studies of ADHD in females suggest confusing and non-consistent conclusions. None of these studies examined the possible relationship between phase of the menstrual cycle, sex hormones levels and ADHD symptoms. The menstrual cycle should therefore be taken into consideration in future studies in the neurocognitive field since it offers a unique opportunity to understand whether and how subtle fluctuations of sex hormones and specific combinations of sex hormones influence neuronal circuits implicated in the cognitive regulation of emotional processing. The investigation of biological models involving the role of estrogen, progesterone, and other sex steroids has the potential to generate new and improved diagnostic and treatment strategies that could change the course of cognitive-behavioral disorders such as ADHD.
authors.affiliation: Unit of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center Jerusalem, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Haimov-Kochman
authors.affiliation: The Neuro-Cognitive Center, Pediatric Wing, Hadassah Hebrew University Medical Center Jerusalem, Israel.
authors.forename: Itai
authors.initials: I
authors.lastname: Berger
keywords: attention deficit/hyperactivity disorder; cognitive functions; gender; menstrual cycle; sex hormones
references.citation: Clin EEG Neurosci. 2014 Oct;45(4):231-237
references.pmid: 24131620
references.citation: Arch Gen Psychiatry. 2002 Sep;59(9):851-8
references.pmid: 12215085
references.citation: Bipolar Disord. 2014 Feb;16(1):48-57
references.pmid: 24206266
references.citation: Behav Neurosci. 2005 Feb;119(1):104-17
references.pmid: 15727517
references.citation: JAMA. 2002 Oct 9;288(14):1740-8
references.pmid: 12365958
references.citation: BMC Psychiatry. 2013 Nov 09;13:298
references.pmid: 24206839
references.citation: Psychiatry Clin Neurosci. 2004 Dec;58(6):619-23
references.pmid: 15601386
references.citation: Am J Psychiatry. 1996 Aug;153(8):974-84
references.pmid: 8678193
references.citation: Neuroimage. 2006 Apr 1;30(2):529-38
references.pmid: 16260156
references.citation: Behav Pharmacol. 2010 Sep;21(5-6):465-72
references.pmid: 20661136
references.citation: J Neurosci. 2003 May 1;23(9):3790-5
references.pmid: 12736349
references.citation: N Engl J Med. 1998 Jan 22;338(4):209-16
references.pmid: 9435325
references.citation: Obstet Gynecol Clin North Am. 2011 Sep;38(3):609-25
references.pmid: 21961723
references.citation: Behav Brain Res. 2005 Mar 7;158(1):167-73
references.pmid: 15680204
references.citation: Neuron. 2010 Jan 14;65(1):7-19
references.pmid: 20152109
references.citation: Endocr Rev. 1999 Jun;20(3):279-307
references.pmid: 10368772
references.citation: Drug Alcohol Depend. 2006 Sep 1;84(1):1-13
references.pmid: 16413143
references.citation: Menopause Int. 2012 Jun;18(2):52-9
references.pmid: 22611222
references.citation: J Dev Behav Pediatr. 1998 Apr;19(2):77-83
references.pmid: 9584935
references.citation: Psychiatr Genet. 2012 Jun;22(3):115-22
references.pmid: 22336992
references.citation: Menopause. 2010 Jul;17(4):823-7
references.pmid: 20531231
references.citation: Neurobiol Aging. 2000 Mar-Apr;21(2):373-83
references.pmid: 10867223
references.citation: J Neurosci. 2009 Oct 14;29(41):12815-23
references.pmid: 19828794
references.citation: Biol Psychiatry. 2002 Oct 1;52(7):759-63
references.pmid: 12372667
references.citation: Hum Reprod. 1996 Dec;11(12):2799-805
references.pmid: 9021395
references.citation: J Endocrinol. 2005 Mar;184(3):447-53
references.pmid: 15749804
references.citation: J Consult Clin Psychol. 2006 Feb;74(1):179-85
references.pmid: 16551155
references.citation: Front Neuroendocrinol. 2006 Jul;27(2):210-6
references.pmid: 16650465
references.citation: J Psychiatry Neurosci. 2008 Jul;33(4):331-43
references.pmid: 18592034
references.citation: Maturitas. 2008 Jan 20;59(1):72-82
references.pmid: 18060706
references.citation: Schizophr Res. 2012 Nov;141(2-3):179-84
references.pmid: 22998932
references.citation: Behav Genet. 1993 Jul;23(4):337-41
references.pmid: 8240213
references.citation: Psychol Bull. 1995 Jul;118(1):55-107
references.pmid: 7644606
references.citation: Am J Psychiatry. 2001 Sep;158(9):1492-9
references.pmid: 11532737
references.citation: Eur J Nucl Med. 2000 Jul;27(7):867-9
references.pmid: 10952500
references.citation: Brain Res. 2011 Oct 28;1420:37-47
references.pmid: 21955726
references.citation: Recent Prog Horm Res. 2002;57:357-84
references.pmid: 12017552
references.citation: J Steroid Biochem Mol Biol. 2000 Nov 30;74(5):365-73
references.pmid: 11162946
references.citation: Behav Neurosci. 2012 Feb;126(1):4-16
references.pmid: 22289042
references.citation: J Am Acad Child Adolesc Psychiatry. 1999 Aug;38(8):966-75
references.pmid: 10434488
references.citation: Am J Psychiatry. 2000 Jun;157(6):924-30
references.pmid: 10831472
references.citation: PLoS One. 2011;6(7):e22343
references.pmid: 21818311
references.citation: Dev Med Child Neurol. 2006 Nov;48(11):901-5
references.pmid: 17044958
references.citation: Front Hum Neurosci. 2013 Jul 24;7:374
references.pmid: 23898247
references.citation: Neuroreport. 2006 Mar 20;17(4):417-21
references.pmid: 16514369
references.citation: J Clin Psychol. 2009 Dec;65(12):1258-69
references.pmid: 19827112
references.citation: Ann N Y Acad Sci. 1988;515:203-14
references.pmid: 2966605
references.citation: J Clin Child Adolesc Psychol. 2004 Mar;33(1):125-37
references.pmid: 15028547
references.citation: Clin Exp Pharmacol Physiol. 1998 Oct;25(10):764-75
references.pmid: 9784914
references.citation: Br J Obstet Gynaecol. 1992 May;99(5):422-9
references.pmid: 1622917
references.citation: Biol Psychol. 2011 Apr;87(1):106-12
references.pmid: 21356267
references.citation: Neuroimage. 2005 Mar;25(1):320-7
references.pmid: 15734366
references.citation: Ann Nucl Med. 2000 Apr;14(2):97-101
references.pmid: 10830526
references.citation: Neuropsychologia. 2007 Nov 5;45(14):3203-14
references.pmid: 17689571
references.citation: Horm Behav. 1998 Oct;34(2):171-82
references.pmid: 9799627
references.citation: Dev Med Child Neurol. 2010 Sep;52(9):e202-8
references.pmid: 20491856
references.citation: Biol Psychiatry. 2000 Oct 15;48(8):854-60
references.pmid: 11063980
references.citation: Synapse. 2001 Sep 15;41(4):275-84
references.pmid: 11494398
references.citation: Cognition. 2006 Sep;101(2):385-413
references.pmid: 16844106
references.citation: Schizophr Res. 2013 Oct;150(1):114-20
references.pmid: 23938177
references.citation: J Appl Physiol (1985). 2001 Dec;91(6):2785-801
references.pmid: 11717247
references.citation: J Atten Disord. 2002 Jan;5(3):143-54
references.pmid: 11911007
references.citation: Arch Gen Psychiatry. 1999 Nov;56(11):1043-7
references.pmid: 10565505
references.citation: Am J Psychiatry. 2001 Feb;158(2):308-11
references.pmid: 11156817
references.citation: Dev Med Child Neurol. 2010 Sep;52(9):790-1
references.pmid: 20497456
references.citation: Major Probl Obstet Gynecol. 1977;7:1-193
references.pmid: 836520
references.citation: Nat Neurosci. 2004 Oct;7(10):1034-9
references.pmid: 15452574
references.citation: Trends Cogn Sci. 2010 Oct;14(10):448-56
references.pmid: 20724210