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Sex differences in ADHD


Sex differences in ADHD

ADHD is diagnosed significantly more often in boys than in girls. This difference levels out in adults.

While boys are 5 to 9 times more likely to be diagnosed with ADHD outside of clinics than girls, only 3 times as many boys are diagnosed as girls in inpatient clinical settings (likely due to the more detailed screening there).
In adults, the ADHD ratio is then balanced 1:1 in all environments.1

One large study found a sex ratio of 1.6 : 1 (boys to girls) in children with ADHD.2 While impulsivity was more common in boys and inattention in girls, hyperactivity was equally common.3

Whether the likelihood of occurrence of individual symptoms is gender-specific, such that females are more likely to develop the ADHD-I subtype and males are more likely to develop the ADHD-HI subtype, is now questioned. One study found that boys and girls do not differ in symptomatology of inattention and hyperactivity.4 Moreover, even in adults, the distribution of symptoms appears to be independent of gender.5

1. Sex hormones as drivers of gender-specific mental disorders

Sex hormones (gonadal hormones, sex hormones, gonadal hormones) are:

  • Androgens (C19 steroid hormones), including:
    • Testosterone
    • Androstenedione (biochemically reduced testosterone)
    • 5α- and 5β-dihyrotestosterone (DHT)
    • Dehydroepiandrosterone (DHEA).
  • Estrogens (C18 steroid hormones)
    Estrogens, like progestins, are female sex hormones. Estrogens are C-18 steroid hormones. They are synthesized in a cycle-dependent manner in the cells of the ovarian follicle.
    There are four natural estrogens:
    • Estradiol (17β-estradiol, estradiol; most bioactive estrogen)
    • Estrone (3/10 of the bioactivity of estradiol)
    • Estriol (1/10 of the bioactivity of estradiol)
    • Östetrol

Oral intake of natural estrogens is ineffective due to inactivation in the liver. Synthetic estrogens are therefore used as drugs and are primarily used to inhibit ovulation in hormonal contraception.

In addition, other hormones may also have a psychopathological influence (e.g., progestins (pregnancy hormones)).

Males are more prone to (externalizing) behavioral disorders in childhood (ADHD, ODD, CD, autism, learning disorders), whereas females are more prone to emotional (internalizing) disorders in adolescence (depression, anxiety disorders, dysthymia, eating disorders, PTSD). This could also be due to sex hormones.6789

In 2013, Martel et al discussed the contribution of sex hormones to this in more depth10
The following discussion is largely based on the work of Martel et al.

  • Testosterone might prenatally (“organizationally”) modulate dopaminergic circuits in the striatum, putting boys at greater risk for early development of inattention and disruptive behavior disorders.
    • An “extreme male brain” theory of autism views autism symptoms as exaggerations of typical sex differences and sees exposure to high prenatal testosterone levels as a risk factor for autism11
    • Testosterone appears to reduce pain responses in men6
    • Androstenedione correlated with behavioral problems only in boys12
    • Testosterone-estradiol-binding globulin correlated negatively with sad affect and acting out behavior.12
  • Estradiol might modulate circuits in puberty (“activating”), including in the amygdala (especially affecting serotonergic signaling pathways), such that girls are at higher risk for internalizing and affective disorders
    • In eating disorders, lower prenatal testosterone is considered a risk factor1314 , while rising estradiol levels during and after puberty reduce risk1516

Sex hormones have an important role in the organization and plasticity of the brain and behavioral systems.1718

  • “Organizational” effects
    • Exposure to androgens
      • Androgens
      • Between pregnancy and 4 months of life
      • permanent masculinizing effects on nervous system and behavior
    • “Activating” effect
      • Predominantly estrogens
      • During adolescence
        • Puberty as a phenotypic activating event
          • Testosterone level increases during puberty12
            • For men by a factor of 18
            • For women by 8 times
          • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) stimulate the production of androgens, estrogen and progesterone19
          • Estradiol and testosterone can regulate gene expression and neurotransmission , e.g. GABA20 and Serotonin21
          • Estradiol affects in puberty22
            • Orbital cortex
            • MPFC
            • Amygdala23
            • Hippocampus23
          • Estradiol interacts with the HPA axis24
          • Estradiol enhances stress response in the PFC in a sex-specific manner by means of serotonin, norepinephrine, and dopamine levels24
          • Estrogen might interact with the HPA axis
            • Increase in stress sensitivity of the HPA axis
            • Modulation of the HPA axis during puberty
              • Altered HPA activity may increase stress sensitivity and thereby susceptibility to depression24
            • Estrogen is a strong regulator of several serotonergic systems (e.g., the 5HT2a receptor)2526
            • Rapidly changing estrogen levels during puberty can directly affect transcription of serotonin genes. Consequence:
              • Abnormalities in the amygdala
              • Low serotonin levels
      • Transient effect on neuronal structure and behavior
      • Alteration and activation of previously organized neural circuits
      • Possibly also some organizational effects9

1.1. Genetic sex, gonadal sex, hormonal sex

Genetic sex leads to gonadal sex, which in turn is linked to hormonal sex.10
The genetic (i.e. chromosomal) sex is determined at conception. Subsequently, a gene on the Y chromosome causes the gonads to develop into testes. The testes release several androgenic steroid hormones (e.g., testosterone) that masculinize the body and brain during pregnancy development.
Ovaries release little or no hormone prenatally. The relative absence of androgens causes the development of a female body and brain .
Hormonal sex is the circulating estrogen to androgen ratio, which is higher in most females than in males. Sexual differentiation (this refers to the development of humans (and animals) into males and females) is closely linked to the organizational effects of sex hormones.

1.2. Sex-specific differentiation of neural circuitry and behavior

1.2.1. Theories

The following 3 theories are not mutually exclusive 2710 Classical theory
  • Androgens cause male development
  • lack of androgens causes female development
  • high testosterone levels (men) cause
    • “Upstream” effects
      • Increased cell proliferation
      • increased cell death in the right hemisphere of the brain
      • Slower prenatal development / slower brain development
        • thereby altered cerebral lateralization28
        • possible consequences in men:
          • more susceptible to environmental stresses
          • more variable behavioral results17
          • increased risk for learning disorders
          • increased risk for hyperactivity
          • prone to injury and structural abnormalities in the left hemisphere for prolonged periods of time
      • increased neuronal lateralization (= specialization of the brain hemispheres)
        • Consequence, among others: after a focal stroke, women regain speech more frequently than men29
      • Modulation of neurotransmission
      • Interaction with the genotype
    • “Downstream” effects
      • Influence on the selection of the environmental niche
      • Influence on the triggering of environmental reactions Active feminization

Ovarian hormones actively promote feminization of neural circuitry and behavior Gradient model

Influence hormones:

  • Behavioral differences between the sexes (e.g., in cognition, childhood play, and aggression)
  • Behavioral variations within the sexes
    • Females prenatally exposed to higher levels of androgens might exhibit more masculine characteristics (e.g., increased spatial abilities)

1.2.2. Sex hormones and dopamine

Pregnant rats placed under constraint stress had male offspring with decreased testosterone levels and with increased dopamine levels in the striatum.30 Further, testosterone levels may indirectly influence neuronal development through so-called “downstream” effects: via the organism’s selection of experiential niches and the triggering of environmental responses17

1.2.3. Sex hormones and sexually dimorphic brain structures, brain functions and behavior

Sex hormones influence the formation of brain structures and brain functions. This in turn influences behavior10

Larger for men:31

  • Total brain volume
  • White substance
  • CSF
  • Cerebellum
  • Pons
  • Amygdala
    • medial amygdala nucleus10
  • Hypothalamus
  • Frontomedial cortex
  • Corpus callosum (unclear)32

Larger for women:31

  • Gray substance
    • in posterior, temporal and inferior parietal brain regions
      • greater proportion
      • greater cortical thickness
  • Hippocampus
  • Frontoorbital cortex
  • Superior frontal and lingual gyrus
  • front commissure10
  • Caudate (unclear)
  • Corpus callosum (unclear)

Other differences:

  • lower lateralization (i.e., specialization) of cortical functions in females
    • lower prevalence of left-handedness
  • greater variation in extracellular striatal dopamine across the estrous cycle in women33
  • Estrogen and progesterone modulate dopamine in striatum and nucleus accumbens only in women34
  • significantly higher juvenile increases in dopamine receptor density in the striatum, nucleus accumbens, and prefrontal cortex in male rats (Andersen & Teicher, 2000).
  • global cerebral blood flow is higher in women31
  • Serotonin whole blood level is higher in women31
  • Men synthesize serotonin faster31
  • higher availability of dopamine transporters in women31
  • higher presynaptic dopamine synthesis in the striatum in women31
  • IQ correlates with gray matter volume35
    • in men in the frontal and parietal lobes
    • in women in the frontal lobe and Broca’s area

2. Theories about hormonal mechanisms of depression

2.1. Probability of depression increases in girls with puberty

Girls were twice as likely to be depressed as boys only from the age of 10 to 15 years. This 2:1 ratio was caused by altered estradiol and testosterone levels, but not by FSH and LH, was independent of Tanner stage, and persisted at later ages.3637
Higher levels of negative affect correlated with higher testosterone levels, higher cortisol, and lower adrenal hormones, but not with altered estradiol levels.38

2.2. Likelihood of depression and hormonal fluctuations in the menstrual cycle

Estradiol and progesterone levels are relatively low during menstrual bleeding. Estradiol levels increase during the follicular phase until the LH surge, at which time ovulation occurs. After ovulation, estradiol levels decrease while progesterone levels steadily increase. In the middle of the luteal phase, estradiol levels reach a second peak, but then both progesterone and estradiol decline throughout the premenstrual phase. At this time, menstrual bleeding begins and completes the cycle.39

Symptoms of depressed mood vary systematically across fluctuations in the menstrual cycle. In women, the likelihood of mood problems (i.e., depressed mood, apathy) is greatest during the mid-to-late luteal phase of the menstrual cycle. During this period, progesterone levels peak while estradiol levels decline. Negative affect is also cycle-dependent, occurring most strongly before or during the menstrual phase and less so during ovulatory or premenstrual phases10

Oral contraceptives altered the variability of mood over the course of the day. Triphasic preparations (oral contraceptives with three hormonal phases) caused increased affect variability.40 Depressed mood typically occurs during the premenstrual period when estradiol and progesterone decrease.41
In PMS, suppression of ovarian function with leuprolide improved symptoms. However, in a subset, these recurred after replacement with estradiol or progesterone, suggesting an abnormal response to hormonal changes as a cause of PMS mood problems.42 Indeed, women with premenstrual dysphoric mood showed an abnormal gonadotropin response to estradiol loading compared with other women:43

  • stronger negative feedback response to the nadir LH level
  • higher LH levels at the nadir
  • more LH surge-like reactions
  • 50 % higher LH-AUC
  • LH response was associated with VAS-rated symptoms
  • the negative increment (AOC) correlated with bloating in the luteal phase
  • AUC of LH correlated with irritability
  • Depressed mood correlated with
    • FSH base mirrors
    • AUC of FSH during the negative feedback phase

2.3. Depression likelihood and hormonal fluctuations after childbirth/at menopause

15% of women develop depression symptoms in the first six months postpartum, when sex hormones decline rapidly and dramatically.10 A sharp decline in estradiol and progesterone after childbirth correlated with depression in women with a history of postpartum depression44

The onset of menopause is associated with a decrease in estrogen levels and a 2-fold to 4.3-fold risk of irritability and depression,4546 47 while postmenopausal depression risk is decreased.
The risk of depression in women was4849

  • increased 2.5-fold during menopause
  • reduced after menopause
  • with a rapidly increasing profile of FSH reduces
  • with high level and increased variability of FSH increased
  • with high level and increased variability of LH increased
  • increased with rising estradiol levels and increased variability of estradiol increased

Estrogen administration during menopause significantly reduced depressed mood.3950
Low estrogen levels or dramatic changes in estrogen levels appear to increase depression risk.

Whether estradiol administration after childbirth / during perimenopause / during menopause correlates with a decrease in depression is inconsistent. There are quite a few studies for and against this.10
Estradiol administration may accelerate effect of antidepressants in menopausal nonresponders.51
Withdrawal of estradiol in rats exposed to high levels of estradiol and progesterone (to mimic levels during pregnancy) resulted in increased depressive symptoms.52 Estradiol administration increased mobility in rats, suggesting an antidepressant effect of estradiol administration.5354
It is possible that an inverted-U curve is at work here as well: optimal estradiol levels are protective, decreased as well as increased estradiol levels exacerbate depressive symptoms.
To examine the relationships between estradiol levels and affect over a 30- or 60-day period, daily measurements throughout the menstrual cycle are required.10

2.4. Estrogen appears to affect transcription and activity of serotonin genes

Estrogen modulates the central neurotransmitter systems involved in depression, particularly that of serotonin 55 46 5657

2.5. Estrogens influence HPA activity

2.5.1. Estradiol influences HPA stress response

Estrogens, particularly estradiol, appear to enhance the stress response (i.e., release of catecholamines) in the PFC.58 Estradiol does not appear to have antidepressant effects under stress conditions.59

Estrogen lowers the threshold for prefrontal cortical dysfunction resulting from stressful experiences.58
Estrogen, particularly estradiol, thus increases depression risk by altering thresholds for prefrontal activation in response to stress.

According to another view, estradiol should have moderating effects on depression via interaction with stressful life events and HPA axis. Estradiol moderates the function of the limbic-OPFC circuit and the HPA axis, which reduces the risk of depression.60 Estrogen significantly decreased the stress response of the HPA axis in postmenopausal women. Responses to ACTH, cortisol, and norepinephrine were attenuated.61

The antidepressant effects of estradiol may also depend on optimal corticoid levels, suggesting an interaction between estradiol effects and HPA axis tone62

2.5.2. Progesterone enhances HPA stress response

The progestin progesterone appears to enhance the stress response of the HPA axis in postmenopausal women. Responses to ACTH and cortisol were attenuated, and responses to norepinephrine were increased.61 Women with PMS did not show the normal increased HPA axis response to exercise during the luteal phase. Progesterone produced an increased HPA axis response to treadmill exercise testing in healthy controls. Estradiol did not cause an increased HPA response.63

3. Hormonal mechanisms of ADHD development and modulation

3.1. Sex hormones indirectly modulate development of dopaminergic circuits

Sex hormones may modulate the processes that control the development of dopaminergic circuits and influence corresponding deficits in cognitive control and reward processes in ADHD.

High testosterone levels may affect dopaminergic neuronal circuits by slowing overall neuronal development and rendering brain dopaminergic components vulnerable for a prolonged period during prenatal development. Thus, prenatal testosterone levels could moderate the relationship between prenatal risk factors (including genes, pollutants, low birth weight, maternal smoking) and developing ADHD-related neurobiology.17

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenemia, i.e. greatly increased androgen levels. PCOS in pregnancy increases the risk of ADHD by 95% in boys only.64
Women with PCOS were themselves at increased risk of ADHD, although no association was found between their testosterone levels and their ADHD symptoms66
See more at Prenatal stressors as ADHD environmental causes In the chapter Emergence,

Maternal smoking increases fetal testosterone levels.67 Prenatal smoking causes a 1.9-fold68 to 2.7-fold ADHD risk69 for the offspring. Other studies also found significantly increased risk scores.70717273
See more at Prenatal stressors as ADHD environmental causes In the chapter Emergence,

3.2. Sex hormones directly modulate development of dopaminergic circuits

Masculinizing effects of sex hormones directly affect prenatal development of dopaminergic neuronal circuits and dopamine function in

  • Nucleus accumbens
  • Striatum
  • PFC

thereby causing deficits in cognitive control and reward processes.
Androgen effects act on the striatum, including caudate nucleus and associated dopamine circuits.30

Animal studies based on prenatal hormone manipulation in relation to ADHD are not known so far. There are only experiments with early childhood hormone manipulation. The transferability of the ADHD animal model of SHR with respect to sex differences in ADHD is questionable because the animals do not show the sex differences in behavioral symptoms that are known in humans. Female SHR appear more impulsive than males, especially during diestrus.74
SHR (spontaneously hypertensive rat) and Wistar (WKY) control animals were exposed to testosterone during early development (postnatal day 10). At postnatal day 45, SHR animals showed:75

  • additional deficits in spatial memory in the water maze (but not WKY)
  • Evidence of a dysfunctional HPA axis:
    • high basal ACTH levels
    • low corticosterone levels
  • Suppression of tyrosine hydroxylase immunoreactivity in frontal cortex
    The authors see this as support for the hypothesis that in cases of genetic ADHD predisposition, early androgen exposure may contribute to increased expression of ADHD symptoms.

High testosterone levels may increase the risk for ADHD symptoms through a maturational delay in the development of dopaminergic innervation and metabolism, as well as through increased lateralization of underlying dopaminergic neuronal circuits and increased reuptake of dopamine neurotransmission.76
Pavlovian conditioning of a visual stimulus paired with food was:77

  • weaker in female SHR than in male SHR
  • Wistar rats equal in both sexes
    Gonadectomy altered Pavlovian conditioning:78
  • in male and female SHR: enhanced conditioning
  • for female Wistar rats: unchanged
  • in male Wistar rats: reduced conditioning

SHR showed increased motor activity with early androgen administration. In contrast, Wistar showed no change.79

In male castrated SHR, testosterone increased the density of tyrosine hydroxylase immunoreactive fibers (an indicator of innervation by catecholamines) in the frontal cortex more than in WKY. The authors see this as a possible explanation for the fact that high testosterone levels in adulthood do not increase ADHD symptoms in either SHR or males .80

These results suggest that dopaminergic neuronal circuitry and cognition are hormonally affected in SHR10
This also seems to affect ADHD symptoms.

In contrast, girls and boys with ADHD showed equally weak cognitive control.818283 Boys with ADHD-I showed lower cognitive impairment than boys with ADHD-C and girls with ADHD-I or ADHD-C.84
To date, however, studies have always examined sex as a proxy, without examining the direct effect of hormones themselves on cognitive control and reinforcement learning.

3.3. ADHD and externalizing symptoms correlate positively with prenatal testosterone exposure

Overall, the research findings on finger length ratios suggest that prenatal testosterone exposure is positively associated with ADHD symptoms and possibly also with related traits such as externalizing problems and sensation seeking. However, contrary to the conclusion of Martel et al10, we cannot infer from the body of studies that this would be predominantly the case in boys.

Several studies investigated the finger length ratio (and thus indirectly prenatal testosterone exposure) in clinically diagnosed samples of children with ADHD. These studies thus indirectly addressed the hypothesis that higher prenatal testosterone exposure is associated with increased ADHD symptoms. The results are indifferent-at least with respect to sex.

Increased prenatal testosterone exposure is (indirectly) indexed by a decreased index finger to ring finger length ratio (index finger length divided by ring finger length, 2D:4D). A low 2D:4D ratio (i.e., high prenatal testosterone exposure) correlated with in several studies:

  • Hyperactivity
    • girls only (preschool age)85
    • only in girls (preschool age), also impulsivity86
    • only in women (student age) on the left hand (also impulsivity)87
    • only in boys (school enrollment age), also behavioral problems88
    • gender-independent89
  • social problems
    • only for boys (school enrollment age)88
  • Sensation seeking (at the same time high testosterone levels)90
    • Sensation seeking exhibits sex differences in favor of boys and is associated with externalizing disorders.919210
  • ADHD
    • only in boys, most markedly in ADHD-I.93
    • in boys and girls (from 7 to 15 years) with ADHD-I (smaller CEOAEs and smaller 2D:4D) than ADHD-C or controls94
    • in German men, but not in German women or Chinese men or women95
    • one study found no correlation between 2D:4D and ADHD symptoms or ADHD subtypes in children with ADHD.96
  • Inattention
    • gender-independent89
    • only in women, on the left hand (student age).87
    • Correlation low right 2D:4D / increased ADHD inattention symptomatology could be mediated by decreased conscientiousness.97

A high 2D:4D ratio (i.e., low prenatal testosterone exposure) correlated with

  • prosocial behavior
    • only for girls of school enrollment age88

Boys with autism/Asperger syndrome and ADHD/oppositional defiant disorder had lower finger length ratios than boys with anxiety disorders. Boys with autism spectrum disorders had lower finger length ratios than healthy controls98

A study using sibling sex distribution found circumstantial evidence of increased intrauterine testosterone exposure in ADHD and ASD and reading disability, which was significant only in reading disability.99

3.4. ADHD and decreased prenatal/postnatal estrogen

Decreased prenatal and postnatal estrogen levels also appear to correlate with ADHD symptoms.
Women with Turner syndrome or a single X chromosome have ovaries that produce decreased prenatal and postnatal estrogen levels.100 These women have at the same time a characteristic cognitive profile with well ADHD-like deficits in:

  • visual-motor integration
  • Pattern recognition
  • Face recognition
  • motor speed
  • Coordination
  • Attention
  • Planning (Test of Attention Variables, Familiar Figures Test, Tower of Hanoi)
  • for legal-lateral, spatially demanding executive tasks101

A study of the menstrual cycle of regularly cycling young women found that decreased estradiol levels associated with increased progesterone or testosterone levels correlated with higher ADHD symptoms the next day, particularly in women with high impulsivity. Phase analyses indicated an increase in ADHD symptoms in both the early follicular phase and the early luteal phase, or after ovulation.102

3.4.1. Estrogen reduces dopamine degradation in the PFC

The increased dopamine breakdown in the PFC caused by estrogen via COMT means that (mild) stress can have sex-specific differential effects.

Estrogen levels in women are low after menstruation (day 1 - 9), then rise steadily to their maximum by ovulation (day 10 - 15), fall to 1/3 of maximum with ovulation (day 16 / 17), then rise to 2/3 of maximum by day 24, and then fall by menstrual bleeding (day 27).103

In male humans and animals, the slight increase in dopamine levels in the PFC due to mild stress increases mental performance compared with the resting state. In contrast, in female humans and animals, the slight increase in dopamine in the PFC due to mild stress (on the overall average) leads to a deteriorated mental performance. This difference appears to be caused by estrogen. The deterioration of mental performance by mild stress occurs only in the estrogen-rich phase around menstruation. In the estrogen-depleted phase, mild stress raises mental performance in women just as it does in men.10410558106107108109

Estrogen reduces the activity of the dopamine-degrading enzyme COMT.110111112 Dopamine degradation in the PFC is therefore significantly increased before ovulation and noticeably reduced before menstruation
COMT is therefore 30% less active in women than in men.113114
Because COMT causes at least 60% of dopamine degradation in the PFC (and a maximum of 15% of dopamine degradation in the striatum115 ), women in the estrogen-rich menstrual phase have nearly 20% less dopamine degradation in the PFC.

It may follow that, with respect to PFC-mediated ADHD symptoms such as inattention, women may require lower doses of drugs (such as stimulants or atomoxetine) that act dopaminergically in the PFC during periods of high estrogen levels (3 - 4 days before ovulation as well as approximately one week after ovulation) than during periods of low estrogen levels.104
This could further explain increased sensitivity in women compared to men, as slightly elevated dopamine levels increase perceptual intensity.

Since the COMT Met-158-Met variant is also common in borderline, causing five times slower dopamine degradation in the PFC, and estrogen further slows COMT dopamine degradation by COMT, this association could potentially provide a clue to explain the clustering of borderline in women.116

3.4.2. Estrogen increases oxytocin levels

Since estrogen increases oxytocin levels, all effects of oxytocin are likely to be enhanced in women.


  • Decreases ACTH
  • Probably reduces CRH
  • Likely reduces stress symptoms mediated by the HPA axis
  • Increases the “tend and befriend” stress response
    • The combination of oxytocin and certain attachment patterns may be related to the female “tend and be friend” stress response117118

See more at Oxytocin

4. COMT gene variant influences stress perception in a gender-specific manner

Polymorphisms of the COMT gene primarily affect dopamine levels in the PFC and hardly affect dopamine levels in other brain regions. Similarly, norepinephrine levels in the PFC are not affected by COMT119

To be distinguished are:120

  • COMT-Val-158-Met (mixed Val/Met)
  • COMT-Val-158-Val (homozygous Val)
  • COMT-Met-158-Met (homozygous Met)

The COMT-Met-158-Met polymorphism causes dopamine degradation 4 times slower than the COMT-Val-158-Val variant.
COMT-Met-158-Met carriers are compared to COMT-Val-158-Val carriers121

  • Mentally more powerful (more efficient, not more intelligent)
  • Better executive functions of the PFC
  • More sensitive to stress (high dopamine levels (only) in the PFC already at rest, significant dopamine increase (only) in the PFC already at mild stress)122
    • Consequently, probably worse effect of amphetamine drugs (deterioration of working memory by AMP at high stress)123. We suspect that the result is likely to be transferable to MPH.
  • More anxious and
  • More sensitive to pain.

COMT is influenced by estrogen. In females, the COMT-Val-158-Val polymorphism leads to better executive functions and mental performance during periods of high estrogen levels compared to the COMT-Met-158-Met polymorphism.124

5. Thyroid hormones in women as a masking factor of ADHD?

The updated 2018 European Consensus on the Treatment and Diagnosis of ADHD in Adults1 notes the special role of thyroid hormones in the etiology of ADHD in women and girls.

Healthy 4-year-old children with thyroid-stimulating hormone levels in the upper normal range have a higher risk of ADHD than children with low free thyroxine levels. Thyroid disorders are more common in females than males. Since ADHD is further associated with thyroid hormone receptor insensitivity, a role of thyroid hormones in the development and manifestation of ADHD in women and girls should be further investigated.125

6. Creatine, choline, glutamate/glutamine in ACC and cerebellum

One study found significant sex- and age-specific differences in creatine, choline, and glutamate/glutamine in the ACC, and significant age-specific differences in choline and glutamate/glutamine in the cerebellum.126

7. Anxiety symptoms more common in girls with ADHD than in boys

ADHD-affected girls are far more likely to have anxiety symptoms than ADHD-affected boys.127

8. Temporal symptom development by gender

While girls typically develop a large spurt of increased symptoms in early adolescence, boys have increased symptom expression from childhood onward. For both sexes, early adolescence is associated with the risk of significant symptom increase.128

9. Higher symptom intensity in diagnosed girls and women?

Girls with autism who also had ADHD showed significantly more severe symptoms of ADHD, learning disabilities, and ODD than boys with ASD and ADHD in a large study.129

This is reminiscent of the increased symptom intensity of women diagnosed with ADHD as adults.

10. Higher divorce rate among women with ADHD

Women (in Japan) with ADHD appear to have even higher divorce rates than men with ADHD.130

11. More comorbidities in women with ADHD

Females (in Japan) with ADHD appear to have a higher rate of comorbidity than males with ADHD.130

12. No gender differences in ADHD and ASD social behavior

A meta-study failed to find gender differences in social behavior and communication behaviors in ADHD and ASD.131

  1. Kooij, Bijlenga, Salerno, Jaeschke, Bitter, Balázs, Thome, Dom, Kasper, Filipe, Stes, Mohr, Leppämäki, Brugué, Bobes, Mccarthy, Richarte, Philipsen, Pehlivanidis, Niemela, Styr, Semerci, Bolea-Alamanac, Edvinsson, Baeyens, Wynchank, Sobanski, Philipsen, McNicholas, Caci, Mihailescu, Manor, Dobrescu, Krause, Fayyad, Ramos-Quiroga, Foeken, Rad, Adamou, Ohlmeier, Fitzgerald, Gill, Lensing, Mukaddes, Brudkiewicz, Gustafsson, Tania, Oswald, Carpentier, De Rossi, Delorme, Simoska, Pallanti, Young, Bejerot, Lehtonen, Kustow, Müller-Sedgwick, Hirvikoski, Pironti, Ginsberg, Félegeházy, Garcia-Portilla, Asherson (2018): Updated European Consensus Statement on diagnosis and treatment of adult ADHD, European Psychiatrie, European Psychiatry 56 (2019) 14–34,, Seite 17

  2. Fayyad, Sampson, Hwang, Adamowski, Aguilar-Gaxiola, Al-Hamzawi, Andrade, Borges, de Girolamo, Florescu, Gureje, Haro, Hu, Karam, Lee, Navarro-Mateu, O’Neill, Pennell, Piazza, Posada-Villa, Ten Have, Torres, Xavier, Zaslavsky, Kessler; WHO World Mental Health Survey Collaborators (2017): The descriptive epidemiology of DSM-IV Adult ADHD in the World Health Organization World Mental Health Surveys. Atten Defic Hyperact Disord. 2017 Mar;9(1):47-65. doi: 10.1007/s12402-016-0208-3.

  3. Slobodin, Davidovitch (2019): Gender Differences in Objective and Subjective Measures of ADHD Among Clinic-Referred Children. Front Hum Neurosci. 2019 Dec 13;13:441. doi: 10.3389/fnhum.2019.00441. eCollection 2019.

  4. Appelbaum, Lefering, Wolff, Tomasik, Ostermann (2019): Differential Item Functioning for Boys and Girls in a Screening Instrument for Attention Deficit Hyperactivity Disorder. Stud Health Technol Inform. 2019 Sep 3;267:3-8. doi: 10.3233/SHTI190797. n = 1449

  5. Biederman, Faraone, Monuteaux, Bober, Cadogen (2004): Gender effects on attention-deficit/hyperactivity disorder in adults, revisited. Biol Psychiatry. 2004 Apr 1;55(7):692-700.

  6. Holden C (2005): Sex and the suffering brain. Science. 2005 Jun 10;308(5728):1574. doi: 10.1126/science.308.5728.1574. PMID: 15947170.

  7. Arnold LE (1996): Sex differences in ADHD: conference summary. J Abnorm Child Psychol. 1996 Oct;24(5):555-69. doi: 10.1007/BF01670100. PMID: 8956084. REVIEW

  8. Miller, G. (2005): Sex and the Suffering Brain. Science, 308(5728), 1574–1577.

  9. Sisk CL, Zehr J (2005):. Pubertal hormones organize the adolescent brain and behavior. Front Neuroendocrinol. 2005 Oct-Dec;26(3-4):163-74. doi: 10.1016/j.yfrne.2005.10.003. PMID: 16309736.

  10. Martel MM, Klump K, Nigg JT, Breedlove SM, Sisk CL (2009): Potential hormonal mechanisms of attention-deficit/hyperactivity disorder and major depressive disorder: a new perspective. Horm Behav. 2009 Apr;55(4):465-79. doi: 10.1016/j.yhbeh.2009.02.004. PMID: 19265696; PMCID: PMC3616481.

  11. Knickmeyer RC, Baron-Cohen S (2006): Fetal testosterone and sex differences in typical social development and in autism. J Child Neurol. 2006 Oct;21(10):825-45. doi: 10.1177/08830738060210101601. PMID: 17005117. REVIEW

  12. Susman EJ, Inoff-Germain G, Nottelmann ED, Loriaux DL, Cutler GB Jr, Chrousos GP (1987): Hormones, emotional dispositions, and aggressive attributes in young adolescents. Child Dev. 1987 Aug;58(4):1114-34. PMID: 3608660.

  13. Culbert KM, Breedlove SM, Burt SA, Klump KL (2008): Prenatal hormone exposure and risk for eating disorders: a comparison of opposite-sex and same-sex twins. Arch Gen Psychiatry. 2008 Mar;65(3):329-36. doi: 10.1001/archgenpsychiatry.2007.47. PMID: 18316679; PMCID: PMC2883912.

  14. Klump KL, Gobrogge KL, Perkins PS, Thorne D, Sisk CL, Breedlove SM (2005): Preliminary evidence that gonadal hormones organize and activate disordered eating. Psychol Med. 2006 Apr;36(4):539-46. doi: 10.1017/S0033291705006653. PMID: 16336745.

  15. Klump KL, Perkins PS, Alexandra Burt S, McGue M, Iacono WG (2007): Puberty moderates genetic influences on disordered eating. Psychol Med. 2007 May;37(5):627-34. doi: 10.1017/S0033291707000189. PMID: 17335640.

  16. Klump KL, Keel PK, Culbert KM, Edler C (2008): Ovarian hormones and binge eating: exploring associations in community samples. Psychol Med. 2008 Dec;38(12):1749-57. doi: 10.1017/S0033291708002997. PMID: 18307829; PMCID: PMC2885896.

  17. Morris JA, Jordan CL, Breedlove SM (2004): Sexual differentiation of the vertebrate nervous system. Nat Neurosci. 2004 Oct;7(10):1034-9. doi: 10.1038/nn1325. PMID: 15452574.

  18. Phoenix CH, Goy RW, Gerall AA, Young WC (1959): Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology. 1959 Sep;65:369-82. doi: 10.1210/endo-65-3-369. PMID: 14432658.

  19. Sisk CL, Foster DL (2004): The neural basis of puberty and adolescence. Nat Neurosci. 2004 Oct;7(10):1040-7. doi: 10.1038/nn1326. PMID: 15452575. REVIEW

  20. Amin Z, Mason GF, Cavus I, Krystal JH, Rothman DL, Epperson CN (2006): The interaction of neuroactive steroids and GABA in the development of neuropsychiatric disorders in women. Pharmacol Biochem Behav. 2006 Aug;84(4):635-43. doi: 10.1016/j.pbb.2006.06.007. PMID: 16860856. REVIEW

  21. Rubinow DR, Schmidt PJ, Roca CA (1998): Estrogen-serotonin interactions: implications for affective regulation. Biol Psychiatry. 1998 Nov 1;44(9):839-50. doi: 10.1016/s0006-3223(98)00162-0. PMID: 9807639. REVIEW

  22. McEwen BS (2001): Invited review: Estrogens effects on the brain: multiple sites and molecular mechanisms. J Appl Physiol (1985). 2001 Dec;91(6):2785-801. doi: 10.1152/jappl.2001.91.6.2785. PMID: 11717247. REVIEW

  23. Walf AA, Frye CA (2006): A review and update of mechanisms of estrogen in the hippocampus and amygdala for anxiety and depression behavior. Neuropsychopharmacology. 2006 Jun;31(6):1097-111. doi: 10.1038/sj.npp.1301067. PMID: 16554740; PMCID: PMC3624621. REVIEW

  24. Shansky RM, Glavis-Bloom C, Lerman D, McRae P, Benson C, Miller K, Cosand L, Horvath TL, Arnsten AF (2004): Estrogen mediates sex differences in stress-induced prefrontal cortex dysfunction. Mol Psychiatry. 2004 May;9(5):531-8. doi: 10.1038/ PMID: 14569273.

  25. Andrade TG, Nakamuta JS, Avanzi V, Graeff FG (2005): Anxiolytic effect of estradiol in the median raphe nucleus mediated by 5-HT1A receptors. Behav Brain Res. 2005 Aug 30;163(1):18-25. doi: 10.1016/j.bbr.2005.04.015. PMID: 15951031.

  26. Birzniece V, Bäckström T, Johansson IM, Lindblad C, Lundgren P, Löfgren M, Olsson T, Ragagnin G, Taube M, Turkmen S, Wahlström G, Wang MD, Wihlbäck AC, Zhu D (2005): Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems. Brain Res Rev. 2006 Aug;51(2):212-39. doi: 10.1016/j.brainresrev.2005.11.001. PMID: 16368148. REVIEW

  27. Collaer ML, Hines M (1995): Human behavioral sex differences: a role for gonadal hormones during early development? Psychol Bull. 1995 Jul;118(1):55-107. doi: 10.1037/0033-2909.118.1.55. PMID: 7644606.

  28. McManus IC, Bryden MP (1991): Geschwind’s theory of cerebral lateralization: developing a formal, causal model. Psychol Bull. 1991 Sep;110(2):237-53. doi: 10.1037/0033-2909.110.2.237. PMID: 1946868.

  29. Yager JY, Wright S, Armstrong EA, Jahraus CM, Saucier DM (2005): A new model for determining the influence of age and sex on functional recovery following hypoxic-ischemic brain damage. Dev Neurosci. 2005 Mar-Aug;27(2-4):112-20. doi: 10.1159/000085982. PMID: 16046844.

  30. Gerardin DC, Pereira OC, Kempinas WG, Florio JC, Moreira EG, Bernardi MM. Sexual behavior, neuroendocrine, and neurochemical aspects in male rats exposed prenatally to stress. Physiol Behav. 2005 Jan 31;84(1):97-104. doi: 10.1016/j.physbeh.2004.10.014. PMID: 15642612.

  31. Cosgrove KP, Mazure CM, Staley JK (2007): Evolving knowledge of sex differences in brain structure, function, and chemistry. Biol Psychiatry. 2007 Oct 15;62(8):847-55. doi: 10.1016/j.biopsych.2007.03.001. PMID: 17544382; PMCID: PMC2711771. REVIEW

  32. Allen JS, Damasio H, Grabowski TJ (2002): Normal neuroanatomical variation in the human brain: an MRI-volumetric study. Am J Phys Anthropol. 2002 Aug;118(4):341-58. doi: 10.1002/ajpa.10092. PMID: 12124914.

  33. Becker JB (1999): Gender differences in dopaminergic function in striatum and nucleus accumbens. Pharmacol Biochem Behav. 1999 Dec;64(4):803-12. doi: 10.1016/s0091-3057(99)00168-9. PMID: 10593204. REVIEW

  34. Xiao L, Becker JB (1994): Quantitative microdialysis determination of extracellular striatal dopamine concentration in male and female rats: effects of estrous cycle and gonadectomy. Neurosci Lett. 1994 Oct 24;180(2):155-8. doi: 10.1016/0304-3940(94)90510-x. PMID: 7700570.

  35. Haier RJ, Jung RE, Yeo RA, Head K, Alkire MT (2005): The neuroanatomy of general intelligence: sex matters. Neuroimage. 2005 Mar;25(1):320-7. doi: 10.1016/j.neuroimage.2004.11.019. PMID: 15734366.

  36. Angold A, Costello EJ, Worthman CM (1998): Puberty and depression: the roles of age, pubertal status and pubertal timing. Psychol Med. 1998 Jan;28(1):51-61. doi: 10.1017/s003329179700593x. PMID: 9483683. n = 800

  37. Angold A, Costello EJ, Erkanli A, Worthman CM (1999): Pubertal changes in hormone levels and depression in girls. Psychol Med. 1999 Sep;29(5):1043-53. doi: 10.1017/s0033291799008946. PMID: 10576297. n = 800

  38. Susman EJ, Dorn LD, Chrousos GP (1991): Negative affect and hormone levels in young adolescents: Concurrent and predictive perspectives. J Youth Adolesc. 1991 Apr;20(2):167-90. doi: 10.1007/BF01537607. PMID: 24265005. n = 108

  39. Rosenfield RL (1991): Puberty and its disorders in girls. Endocrinol Metab Clin North Am. 1991 Mar;20(1):15-42. PMID: 2029884. REVIEW

  40. Oinonen KA, Mazmanian D (2001): Effects of oral contraceptives on daily self-ratings of positive and negative affect. J Psychosom Res. 2001 Nov;51(5):647-58. doi: 10.1016/s0022-3999(01)00240-9. PMID: 11728505. n = 96

  41. Sundström Poromaa I, Smith S, Gulinello M (2003): GABA receptors, progesterone and premenstrual dysphoric disorder. Arch Womens Ment Health. 2003 Feb;6(1):23-41. doi: 10.1007/s00737-002-0147-1. PMID: 12715262. REVIEW

  42. Schmidt PJ, Nieman LK, Danaceau MA, Adams LF, Rubinow DR (1998): Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. N Engl J Med. 1998 Jan 22;338(4):209-16. doi: 10.1056/NEJM199801223380401. PMID: 9435325. n = 35

  43. Eriksson O, Bäckström T, Stridsberg M, Hammarlund-Udenaes M, Naessén T (2006): Differential response to estrogen challenge test in women with and without premenstrual dysphoria. Psychoneuroendocrinology. 2006 May;31(4):415-27. doi: 10.1016/j.psyneuen.2005.10.004. PMID: 16359822. n = 25

  44. Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR (2000): Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry. 2000 Jun;157(6):924-30. doi: 10.1176/appi.ajp.157.6.924. PMID: 10831472. n = 16

  45. Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL (2006): Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles. Arch Gen Psychiatry. 2006 Apr;63(4):385-90. doi: 10.1001/archpsyc.63.4.385. PMID: 16585467. n = 460

  46. Buchanan CM, Eccles JS, Becker JB (1992): Are adolescents the victims of raging hormones: evidence for activational effects of hormones on moods and behavior at adolescence. Psychol Bull. 1992 Jan;111(1):62-107. doi: 10.1037/0033-2909.111.1.62. PMID: 1539089. REVIEW

  47. Freeman EW, Sammel MD, Lin H, Nelson DB (2006): Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006 Apr;63(4):375-82. doi: 10.1001/archpsyc.63.4.375. PMID: 16585466.

  48. Freeman EW, Sammel MD, Liu L, Gracia CR, Nelson DB, Hollander L (2004): Hormones and menopausal status as predictors of depression in women in transition to menopause. Arch Gen Psychiatry. 2004 Jan;61(1):62-70. doi: 10.1001/archpsyc.61.1.62. PMID: 14706945. n = 436

  49. [Freeman EW, Sammel MD, Lin H, Nelson DB (2006): Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006 Apr;63(4):375-82. doi: 10.1001/archpsyc.63.4.375. PMID: 16585466.](

  50. Zweifel JE, O’Brien WH (1997) A meta-analysis of the effect of hormone replacement therapy upon depressed mood. Psychoneuroendocrinology. 1997 Apr;22(3):189-212. doi: 10.1016/s0306-4530(96)00034-0. Erratum in: Psychoneuroendocrinology 1997 Nov;22(8):655. PMID: 9203229. METASTUDY

  51. Rasgon NL, Dunkin J, Fairbanks L, Altshuler LL, Troung C, Elman S, Wroolie TE, Brunhuber MV, Rapkin A (2007): Estrogen and response to sertraline in postmenopausal women with major depressive disorder: a pilot study. J Psychiatr Res. 2007 Apr-Jun;41(3-4):338-43. doi: 10.1016/j.jpsychires.2006.03.009. PMID: 16697413.

  52. Galea LA, Wide JK, Barr AM (2001): Estradiol alleviates depressive-like symptoms in a novel animal model of post-partum depression. Behav Brain Res. 2001 Jul;122(1):1-9. doi: 10.1016/s0166-4328(01)00170-x. PMID: 11287071.

  53. Estrada-Camarena E, Fernández-Guasti A, López-Rubalcava C (2003): Antidepressant-like effect of different estrogenic compounds in the forced swimming test. Neuropsychopharmacology. 2003 May;28(5):830-8. doi: 10.1038/sj.npp.1300097. PMID: 12637949.

  54. Bekku N, Yoshimura H (2005): Animal model of menopausal depressive-like state in female mice: prolongation of immobility time in the forced swimming test following ovariectomy. Psychopharmacology (Berl). 2005 Dec;183(3):300-7. doi: 10.1007/s00213-005-0179-0. PMID: 16228195.

  55. Bertrand PP, Paranavitane UT, Chavez C, Gogos A, Jones M, van den Buuse M (2005): The effect of low estrogen state on serotonin transporter function in mouse hippocampus: a behavioral and electrochemical study. Brain Res. 2005 Dec 7;1064(1-2):10-20. doi: 10.1016/j.brainres.2005.10.018. PMID: 16298349.

  56. Cameron JL (2004): Interrelationships between hormones, behavior, and affect during adolescence: understanding hormonal, physical, and brain changes occurring in association with pubertal activation of the reproductive axis. Introduction to part III. Ann N Y Acad Sci. 2004 Jun;1021:110-23. doi: 10.1196/annals.1308.012. PMID: 15251880. REVIEW

  57. Cameron JL (2004): Interrelationships between hormones, behavior, and affect during adolescence: complex relationships exist between reproductive hormones, stress-related hormones, and the activity of neural systems that regulate behavioral affect. Comments on part III. Ann N Y Acad Sci. 2004 Jun;1021:134-42. doi: 10.1196/annals.1308.015. PMID: 15251882. REVIEW

  58. Shansky, Glavis-Bloom, Lerman, McRae, Benson, Miller, Cosand, Horvath, Arnsten (2004): Estrogen mediates sex differences in stress-induced prefrontal cortex dysfunction. Mol Psychiatry. 2004 May;9(5):531-8.

  59. Frye CA, Wawrzycki J (2003): Effect of prenatal stress and gonadal hormone condition on depressive behaviors of female and male rats. Horm Behav. 2003 Nov;44(4):319-26. doi: 10.1016/s0018-506x(03)00159-4. PMID: 14613726.

  60. Goldstein JM, Jerram M, Poldrack R, Ahern T, Kennedy DN, Seidman LJ, Makris N (2005): Hormonal cycle modulates arousal circuitry in women using functional magnetic resonance imaging. J Neurosci. 2005 Oct 5;25(40):9309-16. doi: 10.1523/JNEUROSCI.2239-05.2005. PMID: 16207891; PMCID: PMC6725775.

  61. Lindheim SR, Legro RS, Morris RS, Wong IL, Tran DQ, Vijod MA, Stanczyk FZ, Lobo RA (1994): The effect of progestins on behavioral stress responses in postmenopausal women. J Soc Gynecol Investig. 1994 Jan-Mar;1(1):79-83. doi: 10.1177/107155769400100116. PMID: 9419752. n = 14

  62. Walf AA, Frye CA (2005): Antianxiety and antidepressive behavior produced by physiological estradiol regimen may be modulated by hypothalamic-pituitary-adrenal axis activity. Neuropsychopharmacology. 2005 Jul;30(7):1288-301. doi: 10.1038/sj.npp.1300708. PMID: 15756306.

  63. Roca CA, Schmidt PJ, Altemus M, Deuster P, Danaceau MA, Putnam K, Rubinow DR (2003): Differential menstrual cycle regulation of hypothalamic-pituitary-adrenal axis in women with premenstrual syndrome and controls. J Clin Endocrinol Metab. 2003 Jul;88(7):3057-63. doi: 10.1210/jc.2002-021570. PMID: 12843143.

  64. Maleki, Bashirian, Soltanian, Jenabi, Farhadinasab (2021): Association between polycystic ovary syndrome and risk of attention-deficit/hyperactivity disorder in offspring: a meta-analysis. Clin Exp Pediatr. 2021 Apr 15. doi: 10.3345/cep.2021.00178. PMID: 33872487. METASTUDY

  65. Dalgaard, Andersen, Jensen, Larsen, Find, Boye, Jensen, Bilenberg, Glintborg (2021): Maternal polycystic ovary syndrome and attention deficit hyperactivity disorder in offspring at 3 years of age: Odense Child Cohort. Acta Obstet Gynecol Scand. 2021 Sep 6. doi: 10.1111/aogs.14259. PMID: 34490610. n = 1.776 Mütter

  66. Hergüner S, Harmancı H, Toy H. Attention deficit-hyperactivity disorder symptoms in women with polycystic ovary syndrome. Int J Psychiatry Med. 2015;50(3):317-25. doi: 10.1177/0091217415610311. PMID: 26449924. n = 80

  67. Rizwan S, Manning JT, Brabin BJ (2007): Maternal smoking during pregnancy and possible effects of in utero testosterone: evidence from the 2D:4D finger length ratio. Early Hum Dev. 2007 Feb;83(2):87-90. doi: 10.1016/j.earlhumdev.2006.05.005. PMID: 16814493.


  69. Banerjee TD, Middleton F, Faraone SV: Environmental risk factors for attention-deficit hyperactivity disorder. Acta Pædiatrica 2007;96, 1269–74. Zitiert nach Philipsen, Heßlinger, Tebartz van Elst: AufmerksamkeitsdefizitHyperaktivitätsstörung im Erwachsenenalter – Diagnostik, Ätiologie und Therapie (ÜBERSICHTSARBEIT), Deutsches Ärzteblatt, Jg. 105, Heft 17, 25. April 2008, Seite 311 – 317, 313

  70. Schwenke, Fasching, Faschingbauer, Pretscher, Kehl, Peretz, Keller, Häberle, Eichler, Irlbauer-Müller, Dammer, Beckmann, Schneider (2018): Predicting attention deficit hyperactivity disorder using pregnancy and birth characteristics. Arch Gynecol Obstet. 2018 Sep 8. doi: 10.1007/s00404-018-4888-0.

  71. Wang, Hu, Chen, Xue, Du (2019): Prenatal Tobacco Exposure Modulated the Association of Genetic variants with Diagnosed ADHD and its symptom domain in children: A Community Based Case-Control Study. Sci Rep. 2019 Mar 12;9(1):4274. doi: 10.1038/s41598-019-40850-w.

  72. Zambrano-Sánchez, Martínez-Cortés, Poblano, Dehesa-Moreno, Vázquez-Urbano, Del Río-Carlos (2019): Maternal smoking during pregnancy and physiological anxiety in children with attention deficit hyperactivity disorder. Appl Neuropsychol Child. 2019 Jul 3:1-8. doi: 10.1080/21622965.2019.1632708.

  73. McCarthy, Zhang, Wilkes, Vaillancourt, Biederman, Bhide (2022): Nicotine and the developing brain: Insights from preclinical models. Pharmacol Biochem Behav. 2022 Feb 14:173355. doi: 10.1016/j.pbb.2022.173355. PMID: 35176350.

  74. Berger DF, Sagvolden T (1998): Sex differences in operant discrimination behaviour in an animal model of attention-deficit hyperactivity disorder. Behav Brain Res. 1998 Jul;94(1):73-82. doi: 10.1016/s0166-4328(97)00171-x. PMID: 9708841.

  75. King JA, Barkley RA, Delville Y, Ferris CF (2000): Early androgen treatment decreases cognitive function and catecholamine innervation in an animal model of ADHD. Behav Brain Res. 2000 Jan;107(1-2):35-43. doi: 10.1016/s0166-4328(99)00113-8. PMID: 10628728.

  76. Andersen SL, Teicher MH (2000): Sex differences in dopamine receptors and their relevance to ADHD. Neurosci Biobehav Rev. 2000 Jan;24(1):137-41. doi: 10.1016/s0149-7634(99)00044-5. PMID: 10654670.

  77. Bucci DJ, Hopkins ME, Keene CS, Sharma M, Orr LE (2008): Sex differences in learning and inhibition in spontaneously hypertensive rats. Behav Brain Res. 2008 Feb 11;187(1):27-32. doi: 10.1016/j.bbr.2007.08.022. PMID: 17904233; PMCID: PMC2213537.

  78. Bucci DJ, Hopkins ME, Nunez AA, Breedlove SM, Sisk CL, Nigg JT (2008): Effects of sex hormones on associative learning in spontaneously hypertensive rats. Physiol Behav. 2008 Feb 27;93(3):651-7. doi: 10.1016/j.physbeh.2007.11.005. PMID: 18054054; PMCID: PMC2323907.

  79. Li JS, Huang YC (2006): Early androgen treatment influences the pattern and amount of locomotion activity differently and sexually differentially in an animal model of ADHD. Behav Brain Res. 2006 Nov 25;175(1):176-82. doi: 10.1016/j.bbr.2006.08.020. PMID: 16979765.

  80. King JA, Kelly TA, Delville Y (2000): Adult levels of testosterone alter catecholamine innervation in an animal model of attention-deficit hyperactivity disorder. Neuropsychobiology. 2000;42(4):163-8. doi: 10.1159/000026687. PMID: 11096329.

  81. Seidman LJ, Biederman J, Monuteaux MC, Valera E, Doyle AE, Faraone SV (2005): Impact of gender and age on executive functioning: do girls and boys with and without attention deficit hyperactivity disorder differ neuropsychologically in preteen and teenage years? Dev Neuropsychol. 2005;27(1):79-105. doi: 10.1207/s15326942dn2701_4. PMID: 15737943.

  82. Castellanos FX, Marvasti FF, Ducharme JL, Walter JM, Israel ME, Krain A, Pavlovsky C, Hommer DW (2000): Executive function oculomotor tasks in girls with ADHD. J Am Acad Child Adolesc Psychiatry. 2000 May;39(5):644-50. doi: 10.1097/00004583-200005000-00019. PMID: 10802983.

  83. Rucklidge JJ, Tannock R (2002): Neuropsychological profiles of adolescents with ADHD: effects of reading difficulties and gender. J Child Psychol Psychiatry. 2002 Nov;43(8):988-1003. doi: 10.1111/1469-7610.00227. PMID: 12455921.

  84. Nigg JT, Blaskey LG, Huang-Pollock CL, Rappley MD (2002): Neuropsychological executive functions and DSM-IV ADHD subtypes. J Am Acad Child Adolesc Psychiatry. 2002 Jan;41(1):59-66. doi: 10.1097/00004583-200201000-00012. PMID: 11800208.

  85. Williams JH, Greenhalgh KD, Manning JT (2003): Second to fourth finger ratio and possible precursors of developmental psychopathology in preschool children. Early Hum Dev. 2003 May;72(1):57-65. doi: 10.1016/s0378-3782(03)00012-4. PMID: 12706312.

  86. Roberts BA, Martel MM (2013):. Prenatal Testosterone and Preschool Disruptive Behavior Disorders. Pers Individ Dif. 2013 Nov;55(8):962-966. doi: 10.1016/j.paid.2013.08.002. PMID: 25598567; PMCID: PMC4295489. n = 109

  87. Stevenson JC, Everson PM, Williams DC, Hipskind G, Grimes M, Mahoney ER (2007): Attention deficit/hyperactivity disorder (ADHD) symptoms and digit ratios in a college sample. Am J Hum Biol. 2007 Jan-Feb;19(1):41-50. doi: 10.1002/ajhb.20571. PMID: 17160985. n = 187

  88. Fink B, Manning J, Williams J, Podmore-Nappin C (2007): The 2nd to 4th digit ratio and developmental psychopathology in school-aged children. Personality and Individual Differences, Volume 42, Issue 2, January 2007, Pages 369-379. n = 58

  89. Bitsko RH, Holbrook JR, O’Masta B, Maher B, Cerles A, Saadeh K, Mahmooth Z, MacMillan LM, Rush M, Kaminski JW (2022): A Systematic Review and Meta-analysis of Prenatal, Birth, and Postnatal Factors Associated with Attention-Deficit/Hyperactivity Disorder in Children. Prev Sci. 2022 Mar 18:10.1007/s11121-022-01359-3. doi: 10.1007/s11121-022-01359-3. PMID: 35303250; PMCID: PMC9482663. REVIEW und METASTUDY

  90. Fink B, Neave N, Laughton K, Manning J (2006): Second to fourth digit ratio and sensation seeking. Personality and Individual Differences, Volume 41, Issue 7, November 2006, Pages 1253-1262

  91. Aluja A, Torrubia R ( 2004): Hostility-aggressiveness, sensation seeking, and sex hormones in men: re-exploring their relationship. Neuropsychobiology. 2004;50(1):102-7. doi: 10.1159/000077947. PMID: 15179027.

  92. Rosenblitt JC, Soler H, Johnson SE, Quadagno DM (2001): Sensation seeking and hormones in men and women: exploring the link. Horm Behav. 2001 Nov;40(3):396-402. doi: 10.1006/hbeh.2001.1704. PMID: 11673912.

  93. Martel MM, Gobrogge KL, Breedlove SM, Nigg JT (2008): Masculinized finger-length ratios of boys, but not girls, are associated with attention-deficit/hyperactivity disorder. Behav Neurosci. 2008 Apr;122(2):273-81. doi: 10.1037/0735-7044.122.2.273. PMID: 18410167; PMCID: PMC2902868., n = 58

  94. McFadden D, Westhafer G, Pasanen E, Carlson C, Tucker D (2005): Physiological evidence of hypermasculinization in boys with the inattentive type of attention-deficit/hyperactivity disorder (ADHD), Clinical Neuroscience Research, Volume 5, Issues 5–6, 2005, Pages 233-245, ISSN 1566-2772, n = 79

  95. Wernicke J, Zabel JT, Zhang Y, Becker B, Montag C (2020): Association between tendencies for attention-deficit/hyperactivity disorder (ADHD) and the 2D:4D digit ratio: a cross-cultural replication in Germany and China. Early Hum Dev. 2020 Apr;143:104943. doi: 10.1016/j.earlhumdev.2019.104943. PMID: 32126477. REVIEW, n = 192

  96. Lemiere J, Boets B (2010): Danckaerts M. No association between the 2D:4D fetal testosterone marker and multidimensional attentional abilities in children with ADHD. Dev Med Child Neurol. 2010 Sep;52(9):e202-8. doi: 10.1111/j.1469-8749.2010.03684.x. PMID: 20491856. N = 110

  97. Martel MM (2009): Conscientiousness as a mediator of the association between masculinized finger-length ratios and attention-deficit/hyperactivity disorder (ADHD). J Child Psychol Psychiatry. 2009 Jul;50(7):790-8. doi: 10.1111/j.1469-7610.2009.02065.x. PMID: 19298468; PMCID: PMC4311552. n = 312

  98. de Bruin EI, Verheij F, Wiegman T, Ferdinand RF (2006): Differences in finger length ratio between males with autism, pervasive developmental disorder-not otherwise specified, ADHD, and anxiety disorders. Dev Med Child Neurol. 2006 Dec;48(12):962-5. doi: 10.1017/S0012162206002118. PMID: 17109783. n = 240

  99. James WH (2008) Further evidence that some male-based neurodevelopmental disorders are associated with high intrauterine testosterone concentrations. Dev Med Child Neurol. 2008 Jan;50(1):15-8. doi: 10.1111/j.1469-8749.2007.02001.x. PMID: 18173623. METASTUDY

  100. Ross JL, Stefanatos GA, Kushner H, Zinn A, Bondy C, Roeltgen D (2002): Persistent cognitive deficits in adult women with Turner syndrome. Neurology. 2002 Jan 22;58(2):218-25. doi: 10.1212/wnl.58.2.218. PMID: 11805247. n = 121

  101. Liben LS, Susman EJ, Finkelstein JW, Chinchilli VM, Kunselman S, Schwab J, Dubas JS, Demers LM, Lookingbill G, Darcangelo MR, Krogh HR, Kulin HE (2002): The effects of sex steroids on spatial performance: a review and an experimental clinical investigation. Dev Psychol. 2002 Mar;38(2):236-53. PMID: 11881759.

  102. Roberts B, Eisenlohr-Moul T, Martel MM (2018): Reproductive steroids and ADHD symptoms across the menstrual cycle. Psychoneuroendocrinology. 2018 Feb;88:105-114. doi: 10.1016/j.psyneuen.2017.11.015. PMID: 29197795; PMCID: PMC5803442.


  104. Diamond (2014): Biologische und soziale Einflüsse auf kognitive Kontrollprozesse, die vom präfrontalen Kortex abhängen; In: Kubesch (Herausgeberin): Exekutive Funktionen und Selbstregulation – Neurowissenschaftliche Grundlagen und Transfer in die pädagogische Praxis; Huber, Seite 31

  105. Wood, Beylin, Shors (2001): The contribution of adrenal and reproductive hormones to the opposing effects of stress on trace conditioning in males versus females. Behav Neurosci. 2001 Feb;115(1):175-87.

  106. Shors, Leuner (2003): Estrogen-mediated effects on depression and memory formation in females. J Affect Disord. 2003 Mar;74(1):85-96.

  107. Arnsten, Cai, Murphy, Goldman-Rakic (1994): Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys. Psychopharmacology (Berl). 1994 Oct;116(2):143-51.

  108. Shors (2001): Acute stress rapidly and persistently enhances memory formation in the male rat. Neurobiol Learn Mem. 2001 Jan;75(1):10-29.

  109. Wood, Shors (1998): Stress facilitates classical conditioning in males, but impairs classical conditioning in females through activational effects of ovarian hormones; Proc Natl Acad Sci U S A. 1998 Mar 31; 95(7): 4066–4071. PMCID: PMC19964

  110. Ho, P., Garner, Ho, J., Leung, Chu, Kwok, Kung, Burka, Ramsden, Ho, S. (2008): Estrogenic Phenol and Catechol Metabolites of PCBs Modulate Catechol-Omethyltransferase Expression Via the Estrogen Receptor: Potential Contribution to Cancer Risk; Current Drug Metabolism, Volume 9, Number 4, May 2008, pp. 304-309(6); DOI:

  111. Lamb, McKay, Singh, Waldie, Kirk (2003): Catechol-O-methyltransferase val158met Polymorphism Interacts with Sex to Affect Face Recognition Ability; Front Psychol. 2016; 7: 965. doi: 10.3389/fpsyg.2016.00965; PMCID: PMC4921451

  112. Xie, Ho, Ramsden (1999): Characterization and implications of estrogenic down-regulation of human catechol-O-methyltransferase gene transcription. Mol Pharmacol. 1999 Jul;56(1):31-8.

  113. Boudíková, Szumlanski, Maidak, Weinshilboum (1990): Human liver catechol-O-methyltransferase pharmacogenetics. Clin Pharmacol Ther. 1990 Oct;48(4):381-9.

  114. Chen, Lipska, Halim, Ma, Matsumoto, Melhem, Kolachana, Hyde, Herman, Apud, Egan, Kleinman, Weinberger (2004): Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet. 2004 Nov;75(5):807-21.

  115. Karoum, Chrapusta, Egan (1994): 3-Methoxytyramine Is the Major Metabolite of Released Dopamine in the Rat Frontal Cortex: Reassessment of the Effects of Antipsychotics on the Dynamics of Dopamine Release and Metabolism in the Frontal Cortex, Nucleus Accumbens, and Striatum by a Simple Two Pool Model. Journal of Neurochemistry, 63: 972–979. doi:10.1046/j.1471-4159.1994.63030972.x


  117. Tops, Van Peer, Korf, Wijers, Tucker (2007): Anxiety, cortisol, and attachment predict plasma oxytocin. Psychophysiology, 44: 444-449. doi:10.1111/j.1469-8986.2007.00510.x

  118. Klein, Corwin (2002): Seeing the unexpected: how sex differences in stress responses may provide a new perspective on the manifestation of psychiatric disorders. Curr Psychiatry Rep. 2002 Dec;4(6):441-8.

  119. Papaleo, Crawley, Song, Lipska, Pickel, Weinberger, Chen (2008): Genetic dissection of the role of catechol-O-methyltransferase in cognition and stress reactivity in mice. J Neurosci. 2008 Aug 27;28(35):8709-23. doi: 10.1523/JNEUROSCI.2077-08.2008.

  120. Nackley, Shabalina, Tchivileva, Satterfield, Korchynskyi, Makarov, Maixner, Diatchenko (2006): Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science. 2006 Dec 22;314(5807):1930-3.

  121. Diamond (2014): Biologische und soziale Einflüsse auf kognitive Kontrollprozesse, die vom präfrontalen Kortex abhängen; In: Kubesch (Herausgeberin): Exekutive Funktionen und Selbstregulation – Neurowissenschaftliche Grundlagen und Transfer in die pädagogische Praxis; Huber, Seite 28

  122. Egan, Goldberg, Kolachana, Callicott, Mazzanti, Straub, Goldman, Weinberger (20019): Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6917-22.

  123. Mattay, Goldberg, Fera, Hariri, Tessitore, Egan, Kolachana, Callicott, Weinberger (2003): Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6186-91.

  124. Evans, Fossella, Hampson, Kirschbaum, Diamond (2009): Gender Differences in the Cognitive Functions Sensitive to the Level of Dopamine in Prefrontal Cortex. n = 30

  125. Quinn, Madhoo (2014): A Review of Attention-Deficit/Hyperactivity Disorder in Women and Girls: Uncovering This Hidden Diagnosis; Prim Care Companion CNS Disord. 2014; 16(3): PCC.13r01596. PMCID: PMC4195638; PMID: 25317366

  126. Endres, Tebartz van Elst, Maier, Feige, Goll, Meyer, Matthies, Domschke, Lange, Sobanski, Philipsen, Nickel, Perlov (2019): Neurochemical sex differences in adult ADHD patients: an MRS study. Biol Sex Differ. 2019 Oct 29;10(1):50. doi: 10.1186/s13293-019-0264-4.

  127. Skogli, Teicher, Andersen, Hovik, Merete (2013): ADHD in girls and boys – gender differences in co-existing symptoms and executive function measures; BMC Psychiatry 2013, 13:298;

  128. Murray, Booth, Eisner, Auyeung, Murray, Ribeaud (2018): Sex differences in ADHD trajectories across childhood and adolescence. Dev Sci. 2018 Aug 29:e12721. doi: 10.1111/desc.12721.

  129. Lundström, Mårland, Kuja-Halkola, Anckarsäter, Lichtenstein, Gillberg, Nilsson (2019): Assessing autism in females: The importance of a sex-specific comparison. Psychiatry Res. 2019 Sep 13:112566. doi: 10.1016/j.psychres.2019.112566. n = 30,392

  130. Hayashi, Suzuki, Saga, Arai, Igarashi, Tokumasu, Ota, Yamada, Takashio, Iwanami (2019): Clinical Characteristics of Women with ADHD in Japan. Neuropsychiatr Dis Treat. 2019 Dec 4;15:3367-3374. doi: 10.2147/NDT.S232565. eCollection 2019.

  131. Mahendiran, Brian, Dupuis, Muhe, Wong, Iaboni, Anagnostou (2019): Meta-Analysis of Sex Differences in Social and Communication Function in Children With Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. Front Psychiatry. 2019 Nov 4;10:804. doi: 10.3389/fpsyt.2019.00804. eCollection 2019.

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