**8. Clinical implications of sex differences in PTSD**

If males and females differ in their expression of PTSD symptomatology, it follows that they may respond differently to treatment. Even if there are no major differences in symptomatology, sex differences in the risk and protective factors associated with the development and maintenance of PTSD may still result in sex differences in treatment outcome. Finally, males and females may differ in how comfortable they feel in different treatment settings and with different treatment paradigms. It has been suggested that gender socialisation plays a role in the treatment of PTSD, and that males express less affect and are more cognitively oriented in therapy than females (Cason et al., 2002). It could be argued that such behaviour represents problem-focused coping and is consistent with activation of the fight-or-flight system.

Based on the idea that different pathways lead to PTSD in males and females, and that different risk factors may thus be important for the development of PTSD in the two sexes as illustrated in Figure 1, it might be expected that females will benefit more from therapy,

symptomatology to be expressed in males independently of the PTSD diagnosis. Although irritability and aggressive outbursts are not uncommon in people suffering from PTSD, particularly in males, the remaining symptoms are mostly internalising. It has been reported that females are more likely to suffer from internalising disorders such as anxiety disorders and depression, whereas males are more likely to suffer from externalising disorders, such as substance abuse or conduct disorder in the general population (Kessler et al., 1995) and following traumatic exposure (Pratchett et al., 2010). Similarly, although results have been mixed, increases in substance abuse have been registered primarily in male trauma survivors, whereas increases in somatisation, anxiety, and suicide attempts have been documented primarily in female trauma victims (Tolin & Foa, 2008). Furthermore, PTSD in females tends to be more chronic than in males, and females are more prone to develop complex PTSD. The concept of complex PTSD was specifically developed to capture posttraumatic symptoms other than the ones included in the PTSD diagnosis following prolonged and chronic trauma (Cloitre et al., 2002). Complex PTSD covers symptoms similar to those associated with borderline personality disorder (e.g. impulsivity, aggression, self-destructive behaviour, dissociation, and interpersonal problems) as well as

In sum, there appear to be some sex differences on measures of physiological arousal, state anger, dissociation, somatisation, and personality disorders. Such differences are likely to be caused by a combination of gender differences in how males and females express symptomatology and sex differences in how trauma affects brain development. However, it appears that even though females are at a higher risk of developing PTSD than males, once males do develop PTSD their overall symptomatology does not appear to differ much from that found in females. This suggests that although males and females appear to differ in their initial trauma response and may follow different pathways to PTSD, there is at present no support for the idea that the symptomatology of male and female trauma victims is best captured by more sex-specific syndromes. However, more research focusing on sex differences once PTSD has developed is needed in order to draw any conclusions in relation to this question, especially as both males and females also display some sex-specific symptomatology (e.g. complex PTSD, antisocial personality disorder), which is not fully

If males and females differ in their expression of PTSD symptomatology, it follows that they may respond differently to treatment. Even if there are no major differences in symptomatology, sex differences in the risk and protective factors associated with the development and maintenance of PTSD may still result in sex differences in treatment outcome. Finally, males and females may differ in how comfortable they feel in different treatment settings and with different treatment paradigms. It has been suggested that gender socialisation plays a role in the treatment of PTSD, and that males express less affect and are more cognitively oriented in therapy than females (Cason et al., 2002). It could be argued that such behaviour represents problem-focused coping and is consistent with

Based on the idea that different pathways lead to PTSD in males and females, and that different risk factors may thus be important for the development of PTSD in the two sexes as illustrated in Figure 1, it might be expected that females will benefit more from therapy,

feelings of alienation and trust issues (Cloitre et al., 2002).

**8. Clinical implications of sex differences in PTSD** 

captured by the PTSD diagnosis.

activation of the fight-or-flight system.

which aims to reduce levels of dissociation and increase levels of social support. In contrast, a therapeutic approach, which aims to reduce physiological arousal and dampen anxiety may be more beneficial to males. In accordance with these ideas, a recent pilot study has indicated that propranolol, a beta-blocker known to reduce heart rate and blood pressure, may decrease PTSD severity in males but increase PTSD severity in females (Nugent et al., 2010). Whereas there is some support for the hypothesis that emotion-focused coping is more beneficial in females than in males, it is possible that males as well as females will benefit more from a therapeutic approach, which aims to strengthen the coping strategies, which they do not automatically use. The idea is, that once PTSD has developed, it appears that the preferred coping strategies have proved ineffective. Some support has been reported for this idea in grief counselling, as problem-focused counselling was found to be more effective in females compared to males, whereas an emotion-focused intervention form appeared to be more effective in males compared to females 11 months postbereavement. However, such sex differences may not be transferable to less chronic populations or to PTSD treatment.

Finally, an important implication of the influence of multiple factors on HPA reactivity is the possibility that the disturbed HPA reactivity found in patients with PTSD can be treated through either pharmacological, psychotherapeutic, or social interventions. The efficacy of different treatment strategies may therefore not be dependent on what caused the HPA disturbances in the first place. Unfortunately, sex differences in treatment outcome are grossly understudied. Many PTSD treatment effect studies are based on sex-specific trauma samples, such as war veterans and sexual assault victims. Furthermore, of the few studies, which do include both-sex samples, few examine the impact of sex on treatment efficacy. As a result, little is known about whether the same treatments are equally effective (or noneffective) in males and females. Blain, Galovski, and Robinson (2010) reviewed the literature on sex differences in response to treatment and found only nine randomised controlled trials, which assessed sex differences in primary PTSD treatment outcome. Most of these studies were based on samples, which were too small to detect minor sex differences. Furthermore, 6/9 studies were based on samples exposed to a variety of trauma types, and not a single study examined sex differences in treatment outcome following interpersonal violence. Results from randomised as well as non-randomised clinical trials were mixed regarding the impact of sex on treatment outcome. The majority of studies reported no sex differences, but others found that females may respond better to trauma focused therapy than males, and that males may be more likely to drop out of treatment. However, more than anything this review highlights the need for more research in the area.

#### **9. Future research on sex differences in PTSD**

As stated earlier, we believe that the research on sex differences in PTSD is still in its childhood. Consistent sex differences still remain to be documented following certain types of trauma (e.g. sexual assault, combat exposure). Furthermore, the degree to which sex differences in risk factors associated with PTSD may account for the increased vulnerability of PTSD in females is still unknown and deserves more attention. However, future research should move beyond simply focusing on establishing and explaining sex differences in exposure and PTSD.

Sex differences have been reported in the initial response to threat, but the degree to which the tend-and-befriend response is dominant in females in response to specifically traumatic

Finally, although sex is generally thought of as a relatively simple concept, different levels of the sex hormones (including oxytocin and AVP) included in the model presented in this chapter vary within each sex as well as between males and females. Thus, one last question for future research to answer, is how much sex differences in PTSD are affected by intra-sex variations in levels of testosterone, oestrogen, AVP, and oxytocin. In particular, the female menstrual cycle as well as the use of oral contraceptives have been reported to affect secretion of free cortisol levels in response to stressors (Biondi & Picardi, 1999; Kirschbaum et al., 1999). In fact, it has been suggested that prolonged use of oral contraceptives may alter the reaction of the HPA axis to psychological stress (Biondi & Picardi, 1999). We suggest that the impact of such intra-sex variations on the development of PTSD should be more closely

In conclusion, although numerous studies have been published on sex or gender differences in PTSD, most have focused on establishing and explaining sex differences in PTSD prevalence. There is general consensus that females are approximately twice as likely as males to be diagnosed with PTSD following a wide range of trauma types, although sex differences in the prevalence of PTSD following some trauma types (e.g. rape, CSA, combat) have not been fully established. Sex differences in the types of trauma that males and females are exposed to and in the risk factors associated with PTSD appear to account for at least some of the increased PTSD prevalence in females compared to males. However, more research is needed to establish the degree to which sex differences in PTSD prevalence and severity is mediated by trauma type and risk factors, which are more prevalent in females. In this chapter we have gone beyond simply focusing on sex differences in the prevalence of PTSD and have examined how sex differences in the acute response to trauma may cause males and females to follow different pathways to PTSD. There is some evidence that whereas males tend to react to trauma with the well-known fight-or-flight response, females may be more prone to react with a tend-and-befriend response. These two distinct responses to stress are associated with marked physiological differences in SNS, PNS, and HPA activity. Dysregulation of these systems may lead to sensitisation of the fight-or-flight response in males and the tend-and-befriend response in females. This may result in males and females following separate pathways to PTSD. There is some support for the existence of such pathways, as preliminary findings suggest that sex may serve as a moderator on the relationship between certain risk factors and PTSD. In this chapter we have reviewed some support for the hypothesis that physiological arousal and possibly anxiety may be more closely associated with the development of PTSD in males compared to females. In contrast, some studies have found that social support and dissociation are more closely linked to the development of PTSD in females. Sex differences in the relationship between coping and

Despite sex differences in the initial response to trauma and risk factors associated with PTSD, there do not appear to be major differences in the core symptomatology of PTSD in treatment seeking males and females. However, there is some evidence that males may experience more physiological arousal and anger, whereas females report more dissociation and somatisation. Although the combined impact of multiple variables on the reactivity of the HPA axis makes it theoretically possible for males and females to primarily follow different pathways to PTSD, the end result appears to be similar, although sex differences in

examined in future studies.

PTSD may exist but are less well documented.

**10. Conclusion** 

stressors remains to be documented across trauma types. One study of sex differences in the stress response of young children reported that sex differences were only significant under high levels of stress (David & Lyons-Ruth, 2005). This suggests that sex differences may exist in response to traumatic incidents and in the development of PTSD, which may not necessarily be detectable under lower levels of stress. Therefore, research on sex differences in PTSD and in the initial response to trauma should rely less on studies of non-traumatic stressors, such as the ones set up in laboratories, and instead focus more on the male and female response to actual trauma, both in the peritraumatic and post-traumatic phases.

While there is some support for the existence of different pathways to PTSD in children, such pathways remain to be confirmed in adults. Particularly, it is up to future research to establish how many pathways may exist, and whether males and females tend to follow different pathways to PTSD. Different pathways are likely to stem from different physiological and behavioural reactions in the acute trauma phase and to be mediated by different risk factors. Thus, the degree to which physiological systems, which are activated in the face of trauma, are sensitised in trauma victims with and without PTSD remains to be examined.

Although research has identified numerous risk factors associated with PTSD in both sexes, there are some indications that such risk factors may not predict PTSD equally well in males and females, and more studies need to focus on sex as a possible moderator of the impact of risk factors on PTSD development. The model proposed in the present chapter suggests that moderation effects may be particularly likely to be found for emotional support, physiological arousal, anxiety, dissociation, and coping. However, research should by no means be limited to these risk factors, as there may exist numerous pathways to PTSD, all of which may be moderated by sex. Haines, Beggs, and Hurlbert (2008) argued that even if sex only has a small moderating effect on the relationship between different risk factors and PTSD, such effects are still important to identify. Even small sex differences may point to different mechanisms involved in the development of PTSD in males and females, and such different mechanisms may call for different intervention strategies. Finally, as stated earlier, it appears that we have identified more of the risk factors involved in the development and maintenance of PTSD in females than in males. This suggests, that important risk factors related to the development of PTSD in males remain to be identified. It is our belief that by routinely including peritraumatic physiological arousal as a risk factor of PTSD, more variance in the symptomatology of males can be accounted for.

Furthermore, sex differences in symptomatology once PTSD has developed need to be examined. In particular, males and females with PTSD could be expected to differ on levels of dissociation and physiological arousal, and these two variables should be included in future studies on posttraumatic symptomatology in males and females. Research on sex differences in PTSD should include differences in symptomatology not covered by the PTSD diagnosis, in order to help us understand how the symptomatology of male and female trauma victims is best categorised, assessed, and treated.

As mentioned in the beginning of this chapter, most studies claiming to study gender have in fact studied sex. The extent to which gender roles, masculinity and femininity, sexuality, and other gender related concepts play a role in the development and maintenance of PTSD remains to be studied. Such variables may be relevant in relation to PTSD prevalence, initial stress response, different pathways to PTSD, symptomatology, and treatment efficacy. Any moderation effects which sex may have on the relationship between other risk factors and PTSD are likely to be affected by gender.

stressors remains to be documented across trauma types. One study of sex differences in the stress response of young children reported that sex differences were only significant under high levels of stress (David & Lyons-Ruth, 2005). This suggests that sex differences may exist in response to traumatic incidents and in the development of PTSD, which may not necessarily be detectable under lower levels of stress. Therefore, research on sex differences in PTSD and in the initial response to trauma should rely less on studies of non-traumatic stressors, such as the ones set up in laboratories, and instead focus more on the male and female response to actual trauma, both in the peritraumatic and post-traumatic phases. While there is some support for the existence of different pathways to PTSD in children, such pathways remain to be confirmed in adults. Particularly, it is up to future research to establish how many pathways may exist, and whether males and females tend to follow different pathways to PTSD. Different pathways are likely to stem from different physiological and behavioural reactions in the acute trauma phase and to be mediated by different risk factors. Thus, the degree to which physiological systems, which are activated in the face of trauma, are sensitised in trauma victims with and without PTSD remains to be

Although research has identified numerous risk factors associated with PTSD in both sexes, there are some indications that such risk factors may not predict PTSD equally well in males and females, and more studies need to focus on sex as a possible moderator of the impact of risk factors on PTSD development. The model proposed in the present chapter suggests that moderation effects may be particularly likely to be found for emotional support, physiological arousal, anxiety, dissociation, and coping. However, research should by no means be limited to these risk factors, as there may exist numerous pathways to PTSD, all of which may be moderated by sex. Haines, Beggs, and Hurlbert (2008) argued that even if sex only has a small moderating effect on the relationship between different risk factors and PTSD, such effects are still important to identify. Even small sex differences may point to different mechanisms involved in the development of PTSD in males and females, and such different mechanisms may call for different intervention strategies. Finally, as stated earlier, it appears that we have identified more of the risk factors involved in the development and maintenance of PTSD in females than in males. This suggests, that important risk factors related to the development of PTSD in males remain to be identified. It is our belief that by routinely including peritraumatic physiological arousal as a risk factor of PTSD, more

Furthermore, sex differences in symptomatology once PTSD has developed need to be examined. In particular, males and females with PTSD could be expected to differ on levels of dissociation and physiological arousal, and these two variables should be included in future studies on posttraumatic symptomatology in males and females. Research on sex differences in PTSD should include differences in symptomatology not covered by the PTSD diagnosis, in order to help us understand how the symptomatology of male and female

As mentioned in the beginning of this chapter, most studies claiming to study gender have in fact studied sex. The extent to which gender roles, masculinity and femininity, sexuality, and other gender related concepts play a role in the development and maintenance of PTSD remains to be studied. Such variables may be relevant in relation to PTSD prevalence, initial stress response, different pathways to PTSD, symptomatology, and treatment efficacy. Any moderation effects which sex may have on the relationship between other risk factors and

variance in the symptomatology of males can be accounted for.

trauma victims is best categorised, assessed, and treated.

PTSD are likely to be affected by gender.

examined.

Finally, although sex is generally thought of as a relatively simple concept, different levels of the sex hormones (including oxytocin and AVP) included in the model presented in this chapter vary within each sex as well as between males and females. Thus, one last question for future research to answer, is how much sex differences in PTSD are affected by intra-sex variations in levels of testosterone, oestrogen, AVP, and oxytocin. In particular, the female menstrual cycle as well as the use of oral contraceptives have been reported to affect secretion of free cortisol levels in response to stressors (Biondi & Picardi, 1999; Kirschbaum et al., 1999). In fact, it has been suggested that prolonged use of oral contraceptives may alter the reaction of the HPA axis to psychological stress (Biondi & Picardi, 1999). We suggest that

the impact of such intra-sex variations on the development of PTSD should be more closely
