Climacteric
ISSN: 1369-7137 (Print) 1473-0804 (Online) Journal homepage: http://www.tandfonline.com/loi/icmt20
Midlife ADHD in women: any relevance to
menopause?
A. Pines
To cite this article: A. Pines (2016): Midlife ADHD in women: any relevance to menopause?,
Climacteric, DOI: 10.3109/13697137.2016.1152536
To link to this article: http://dx.doi.org/10.3109/13697137.2016.1152536
Published online: 25 Feb 2016.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=icmt20
Download by: [University of California Santa Barbara]
Date: 26 February 2016, At: 18:26
CLIMACTERIC, 2016
http://dx.doi.org/10.3109/13697137.2016.1152536
SHORT COMMUNICATION
Midlife ADHD in women: any relevance to menopause?
A. Pines
Downloaded by [University of California Santa Barbara] at 18:26 26 February 2016
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
ABSTRACT
ARTICLE HISTORY
Recently, there has been a growing interest in better understanding of the adult-type attention deficit
hyperactive disorder (ADHD). It is now accepted that many children with ADHD continue to have symptoms later in life, although the characteristics of the disease may change substantially in adults. Data
are emerging on ADHD in midlife and old age and some studies analyze gender differences and comorbidities during the lifespan of ADHD patients. This short communication discusses the possible
resemblance of certain menopausal symptoms and those of adult ADHD and the potential contribution
of the female hormonal environment. Further, there might be a promising role for psychostimulants,
the mainstay of ADHD management, as treatment of impairment of some executive function domains
in menopausal women.
Received 30 October 2015
Revised 5 February 2016
Accepted 6 February 2016
Published online 25 February
2016
Some cognitive decline, particularly in the domains of executive functions, is common among menopausal women. A new
study examined the effect of the psychostimulant lisdexamfetamine (LDX) on subjective and objective cognitive function
among menopausal women who report new-onset executive
function complaints1. LDX is a very popular medication indicated for the treatment of attention deficit hyperactive disorder (ADHD). Thirty-two healthy perimenopausal and early
postmenopausal women experiencing mid-life-onset executive function difficulties, as measured using the Brown
Attention Deficit Disorder Scale (BADDS), were administered
LDX 40–60 mg/day for 4 weeks in this double-blind, placebocontrolled, cross-over study. Diagnosis of lifetime ADHD was
exclusionary. BADDS total and subscale scores and performance on verbal memory and working memory tasks were outcomes of interest. Analyses revealed a significant effect of
LDX treatment over placebo for total BADDS scores
(p ¼ 0.0001) and for four out of the five BADDS subscales (all
p < 0.004). LDX treatment also resulted in significant improvement in delayed paragraph recall (p ¼ 0.018), but there was
no significant effect of treatment on other cognitive measures. Systolic blood pressure (p ¼ 0.017) and heart rate
increased significantly (p ¼ 0.006) when women were on LDX
but remained, on average, within the normal range.
Treatment was well tolerated and improved the subjective
measures of executive function as well as objective measures
of delayed verbal recall in this sample of healthy menopausal
women. The above study results raise two questions:
(1) Could some of the classical adult ADHD symptoms be
related to reciprocal menopausal complaints?
(2) Should we use psychostimulants as a therapeutic mode
for certain menopausal ill outcomes, especially within the
cognitive domains?
CONTACT Professor A. Pines
apines@netvision.net.il
ß 2016 International Menopause Society
KEYWORDS
Attention deficit hyperactive
disorder; ADHD; menopause
Comment
ADHD is a neurobehavioral disease characterized by excessive
hyperactivity, inattention, and impulsiveness, which is wrongly
considered to occur in children and adolescents and to wane
or disappear in later years2,3. This relatively newly recognized
cluster of symptoms is now included in the DSM list of psychiatric illnesses, and its pathophysiology, clinical features,
outcomes, co-morbidities and treatment have been constantly
updated and better understood. In fact, originally thought to
be a childhood disorder, its clinical presentation may change
with age and become more conspicuous, yet it may actually
remain throughout life. Estimates of ADHD prevalence are
around 5–8% for children and adolescents. It is believed that
2–5% of the adult population has ADHD manifestations and
that about a half are diagnosed already in early childhood
and continue to have some of its features as adults4,5. While
addressing adult ADHD most of the studies and reviews bring
data on people younger than 30 years old. An exception was
the study of Faraone and colleagues, which included a group
of late-onset ADHD, and the oldest age recorded was 55
years6. Shaw’s extensive review included an adult group with
the highest age of 84 years, but no further age details were
disclosed7. The authors concluded that their analysis supports
the premise that, without treatment, people with ADHD often
experience poorer long-term outcomes and that treatment
may improve the long-term outcomes of ADHD for some individuals, but not necessarily to the degree of healthy controls.
A recent review addressed ADHD in the > 50-year-old population and argues whether there might be a related lower life
expectancy due to greater rates of accidents, substance
abuse, mood disorders, and other health issues8. To note that
ADHD prevalence and rate of symptom persistence over time
seem to be highly affected by methodological characteristics
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Downloaded by [University of California Santa Barbara] at 18:26 26 February 2016
2
A. PINES
of the studies and the rating scales used. Typical features of
adult ADHD include constant mental activity, feelings of restlessness and difficulty engaging in sedentary activities, boredom, inability to concentrate, disorganization, mood lability
and sensitivity to stress4. Additionally, tasks are not completed, problem-solving is lacking in strategy and time management is particularly poor. Impulsivity continues and leads
to problems in teamwork, abrupt initiation and termination of
relationships, and a tendency to make rapid and facile decisions without full analysis of the situation9. As a matter of
fact, the wide variability of potential features of ADHD may
actually weaken its special distinction from other cognitive
and psychiatric disorders which share similar characteristics.
There is a gender difference in the incidence and expression of ADHD10–12. Boys outnumber girls at least 2 : 1 in preponderance, and the co-morbidity profile shows that females
tend to have more physiological components of anxiety.
Some therapists claim that ADHD symptomatology ameliorates during pregnancy. Genetic and hormonal factors were
suggested as potential causes of these gender variances, and
the intriguing question is whether the change in ADHD symptomatology in adults has any relevance to these gender discrepancies. Needless to say, that the first assumption that
comes into the mind while investigating a situation that
occurs much more, or much less frequently in women, as
compared to men, is that there could be an association with
sex hormones. It is well established that estrogen and progesterone have various brain effects which are linked to affect,
emotions, behavior and cognitive function. Fluctuations of sex
hormone levels during the menstrual cycle clearly impact the
above parameters in many women, whereas the menopauserelated estrogen deficiency state creates another expression
of such interactions. ADHD with its male preponderance and
neurobehavioral characteristics, which resemble those related
to the impact of changes in the sex hormone milieu in
women, raises intriguing questions that need to be
addressed. Sex hormones have the ability to regulate intracellular signaling systems that are thought to be abnormal also
in ADHD. Could the interplay between estrogen and brain
dopamine or serotonin or other neurotransmitters (glutamine,
acetylcholine) be among the underlying mechanisms in
ADHD?
Interestingly, as found in a Canadian survey, there were
more midlife females then males who self-reported a diagnosis of ADHD sometime during their life13. Assessment of mental disorders by standard instruments showed that the ADHD
group had a higher prevalence of psychiatric diagnoses then
the control group, whereas women had more lifetime or current depressive and anxiety disorders than men. The occurrence of ADHD in midlife women brings forward the question
whether menopause per se or the related estrogen deficiency
have any potential effect or interaction with ADHD symptomatology. Favorable outcomes of off-label therapies indicated
for ADHD tested in menopausal women with cognitive
impairments provide a possible indirect link for such an
assumption1,14. Thus LDX improved the domains of executive
function and delayed verbal recall1, whereas atomoxetine
given to perimenopausal and postmenopausal women presenting with midlife-onset subjective cognitive difficulties
resulted in improvement in memory and attention/concentration14. One may argue and should be cautious with interpretation of such data, since ADHD therapies are actually based
on psychostimulants that have certain brain effects at any
age, regardless of menopause. Nevertheless, the findings suggest that some women report a syndrome of cognitive difficulties emerging in midlife that bear strong resemblance to
cognitive impairments commonly reported by adults with
ADHD. Perhaps a link to estrogen might be the missing piece
in that puzzle. The effects of sex hormones on brain function
and cognitive performance are very well documented, and so
are the outcomes of the menopause-related hormone deficiency in these respects12. It seems logical that the hormonal
milieu, whether derived from endogenic sources or from
medications, is involved and interacts with neurotransmitters
and various brain pathways, and can lead to cognitive, emotional and mood changes which resemble those found in
adult female ADHD patients. However, despite favorable
effects on certain menopausal symptoms of medications identified with ADHD treatment, relevant data are still insufficient
for establishing a clear link. Perhaps the right phrasing for
future research should be: can cognitive complaints in midlife
or menopausal women be treated successfully with
psychostimulants?
Acknowledgements
To Pauline Maki (Department of Psychiatry, University of Illinois at
Chicago, USA) and Michael Craig (Human Cognitive Neuroscience,
Department of Psychology, The University of Edinburgh, UK), for their
valuable comments.
Conflict of interest The author reports no conflict of interest. The
author alone is responsible for the content and writing of this paper.
Source of funding Nil.
References
1.
2.
3.
4.
5.
6.
7.
Epperson CN, Shanmugan S, Kim DR, et al. New onset executive
function difficulties at menopause: a possible role for lisdexamfetamine. Psychopharmacology (Berl) 2015;232:3091–100
NIH Consensus Statement. Diagnosis and treatment of attention
deficit hyperactivity disorder (ADHD). NIH Consensus Statement
1998;16:1–37
Lange KW, Reichl S, Lange KM, Tucha L, Tucha O. The history of
attention deficit hyperactivity disorder. Atten Defic Hyperact Disord
2010;2:241–55
Kooij SJ, Bejerot S, Blackwell A, et al. European consensus statement on diagnosis and treatment of adult ADHD: The European
Network Adult ADHD. BMC Psychiatry 2010;10:67
Polanczyk G, Rohde LA. Epidemiology of attention-deficit/
hyperactivity disorder across the lifespan. Curr Opin Psychiatry
2007;20:386–92
Faraone SV, Biederman J, Spencer T, et al. Diagnosing adult attention deficit hyperactivity disorder: are late onset and subthreshold
diagnoses valid? Am J Psychiatry 2006;163:1720–9
Shaw M, Hodgkins P, Caci H, et al. A systematic review and analysis
of long-term outcomes in attention deficit hyperactivity disorder:
effects of treatment and non-treatment. BMC Med 2012;10:99
CLIMACTERIC
8.
9.
10.
Downloaded by [University of California Santa Barbara] at 18:26 26 February 2016
11.
Torgersen T, Gjervan B, Lensing MB, Rasmussen K. Optimal management of ADHD in older adults. Neuropsychiatr Dis Treat
2016;12:79–87
Asherson P, Chen W, Craddock B, Taylor E. Adult attention-deficit
hyperactivity disorder: recognition and treatment in general adult
psychiatry. Br J Psychiatry 2007;190:4–5
Skogli EW, Teicher MH, Andersen PN, Hovik KT, Øie M. ADHD in
girls and boys – gender differences in co-existing symptoms and
executive function measures. BMC Psychiatry 2013;13:298
Haimov-Kochman R, Berger I. Cognitive functions of regularly
cycling women may differ throughout the month, depending
on sex hormone status; a possible explanation to conflicting
12.
13.
14.
3
results of studies of ADHD in females. Front Hum Neurosci
2014;8:191
Lipnicki DM, Sachdev PS, Crawford J, et al. Sex differences could
reflect discrepancies in the presence or extent of various risk and
protective factors and/or prevalence of outcomes. PLoS One
2013;8:e65841
Hesson J, Fowler K. Prevalence and correlates of self-reported ADD/
ADHD in a large national sample of Canadian adults. J Atten Disord
2015 Mar 6; Epub ahead of print
Epperson CN, Pittman B, Czarkowski KA, et al. Impact of atomoxetine on subjective attention and memory difficulties in perimenopausal and postmenopausal women. Menopause 2011;18:542–8