Indeed, the body of research suggesting that girls with ADHD may be at increased risk for SUD is growing [29,32,34,61,62,63,64]. Two studies, by Biederman et al. (2002) [65] and Biederman and Faraone (2004) [66], indicated that ADHD in girls was a greater risk factor for SUD than ADHD in boys, noting that girls with the disorder were at particular risk in early adolescence. Along the same lines, Ottosen et al. (2019) [67] confirmed that girls with ADHD were at an increased risk of SUD, indicating that delayed diagnosis and the late initiation of treatment was a risk factor for the development of SUD. In contrast, other studies emphasized that the association between ADHD and SUD is greater in adolescent boys [51] and considered male sex to be a risk factor for this comorbidity [33,60,66].

Yildiz et al. (2020) [60] found that alcohol consumption in adolescents with ADHD was associated with a SUD comorbidity in boys and with hyperactivity–impulsivity in girls [45], with girls presenting greater SUD [55]. However, the two studies with participants with severe childhood ADHD, found no sex differences: both sexes started drinking alcohol earlier, and the consumption was more frequent than in individuals without the disorder [45,59]. This could be because the severity of ADHD in childhood is related to the risk of consumption or because sex does not modulate this relationship. This finding suggests that it is important to consider the severity of ADHD when evaluating sex differences.

Nevertheless, the results of the study by Madsen and Dalsgaard (2013) [53] were opposite to all the other work in the field, showing that the boys in the control group had a pattern of more intense and frequent alcohol consumption than those who followed pharmacological treatments for ADHD. However, the latter consumed more tobacco than the control group of boys. Moreover, they found no difference in alcohol and tobacco use between adolescent girls with and without ADHD. These results could be justified, on the one hand, precisely by the fact that diagnosis and pharmacological intervention tends to be earlier in boys than in girls, thus facilitating improvement of the symptoms of the disorder in boys rather than girls. On the other hand, published studies addressing drug therapy indicate that people with ADHD who receive prompt treatment show the same rates of SUD as age-matched community controls [16,68]. In other words, when started early, medication lowers the risk of substance use [69], and this lower risk is sustained in the long term among men [70]. This seems to indicate the importance of early diagnosis and treatment, especially in girls.

This would lead to an earlier diagnosis in boys than in girls [41,50,54], who are usually diagnosed later and have a significantly lower probability of receiving pharmacotherapy than boys [40,49]. Previous studies have already indicated that ADHD seems to affect more men than women, with the exact proportion differing between clinical and general population samples [37,71,72,73,74,75]. The lack of externalizing symptoms in girls and women with ADHD hampers both their referral and earlier diagnosis [75]. Furthermore, the inattentive-type ADHD, which usually involves less disruptive behaviors, is more often diagnosed in women, both in childhood and in adulthood [19]. This could perhaps contribute to the explanation of why girls with ADHD tend to be underdiagnosed [76,77], probably due to sex differences in the presentation of the symptoms and comorbidities of the disorder [65,72].

Indeed, the study of ADHD has long focused primarily on boys [78] despite the still relatively high percentage of girls with the disorder [79]. The samples in most published work comprised mainly men with only a few female participants. This situation has caused many girls to receive a late diagnosis, and even more worryingly, these patients often do not receive appropriate pharmacological treatment after their diagnosis [80,81]. Follow-up studies have further suggested that women with ADHD may have more serious problems than their male counterparts [67]. For example, they have a higher risk of substance use, admission to inpatient psychiatric units, and higher mortality rates than men [32,76,80]. These results support the idea that the current diagnostic criteria may not adequately detect girls with ADHD [82,83]. Most of these criteria refer to behaviors that are more easily manifested and observed in boys. Therefore, the DSM-5 continues to present a considerable limitation in this sense because the symptoms it lists for ADHD are not modulated by sex differences. This situation causes a significant obstacle when it comes to recognizing and diagnosing girls with ADHD, thus producing erroneous or late diagnoses, which can lead to a worsening of symptoms in this population over time [77].

Adolescent girls had higher levels of cognitive impulsiveness and motor impulsivity [47]; made more errors of omission (deficits in attentional control); had more deficits in design memory, general visual memory, verbal arithmetic skills, and working memory skills [56]; and had higher processing and encoding speed scores, greater inhibitory control, and lower vocabulary scores than adolescent boys with ADHD [57]. These findings are consistent with those obtained in two meta-analyses. The first, conducted by Hasson and Fine (2012) [84], found that boys with ADHD made more commission errors (inhibitory control) in the Conners’ Performance Test (CPT) than girls who, in turn, made more omission errors (attentional control). The second meta-analysis was carried out by Loyer Carbonneau et al. (2021) [78] and found significant differences between both sexes regarding inhibition capacity (motor response inhibition and interference control) and cognitive flexibility such that boys with ADHD presented more hyperactive behaviors and greater inhibition problems than girls with ADHD. Previous research has shown that girls with ADHD were more likely to have the inattentive subtype [19] and because of these problems in attentional control showed more difficulties in design memory, visual memory, perceptual and visuospatial reasoning, and working memory [56,65,72,85]. Consequently, it seems that neuropsychological functions are more affected in girls with ADHD compared to boys with the same disorder [58]. This finding coincides with previous studies indicating that ADHD affects neuropsychological functioning differently depending on sex [78,86,87]. The more deteriorated neuropsychological profile in girls might be related to the fact that girls tend to receive a later diagnosis and less frequently receive therapeutic interventions. In addition, cognitive and motor impulsiveness and deficits in cognitive and executive functioning may be related to the higher risk of substance use in girls. In turn, consumption could worsen these deficits and impulsiveness. Therefore, in the future, early diagnosis and intervention in girls with this disorder is of vital importance to help improve the symptoms of ADHD and prevent other problems associated with it (such as substance use) among women. However, a review conducted in children showed that ADHD was frequently associated with poorer academic performance and that they were more likely to need to repeat a grade or even drop out of school [88]. In a similar vein, other studies have indicated that one of the factors that increases the risk of SUD in ADHD is academic failure [89]. That is, ADHD associated with a negative academic trajectory can lead to early substance use [90]. This points to the importance of specific programs to prevent school failure as well as substance use in adolescents with ADHD regardless of sex.