Correlating factors with depression and anxiety in endometriosis patients.
The role of endometriosis related pain and the association with depression and anxiety was the most commonly described factor. Facchin et al (2017) reported an increase of 9.6% in depression and 10.6% increase in anxiety symptoms in case of endometriosis-related predictors (hormonal treatment, surgical interventions, infertility, time from diagnosis, and pain severity) [36]. Four out of five studies comparing endometriosis patients with pain with pain-free endometriosis patients found significant higher rates of depression, up to 86% in the pain-group [28,35,47,62]. As-Sanie et al (2012) and Facchin et al (2015) also found significant differences for anxiety scores between these groups. However, Eriksen et al (2008) reported, except for slightly higher anxiety scores in the pain group, no significant correlation between the degree of pain and depression or anxiety scores [34]. There was no consensus on the association concerning the type of pain (CPP, dysmenorrhea, dyspareunia).
Infertility was the second most investigated factor that was hypothesized to contribute to depression or anxiety in endometriosis patients. However, comparison of infertile with fertile endometriosis patients [59] or with infertile patients without endometriosis [61,62] did not show any significant difference on depression or anxiety symptoms. In addition, Shaw et al, 1995 described that in women with endometriosis related pain, depression occurred more frequently (23.5%) compared with endometriosis patients with infertility (13%) [62].
Studies that investigated other factors than pain or infertility, reported that higher scores of depression or anxiety in endometriosis patients were correlated to poorer quality of sleep [27], fatigue [52], poorer quality of life [32,49,50,52], gastrointestinal symptoms [70], lower self-esteem [36], lower emotional self-efficacy [36], lower sexual functioning [32,51], dysfunction on social adjustment [54], pain imagery [42] and clinical signs of pain sensitization [68]. In addition, it was reported that patients who used positive coping strategies had less depression [33,34]. Furthermore, in the included studies, it was described that depression and anxiety occurred more frequently in patients with advanced age [38,63], lower cortisol levels [55], metabolic syndrome [31] and comorbid pain syndromes [65], and, the presence of depression and anxiety was independently associated with increased costs [45].
No correlation was found between depression or anxiety and endometriosis stage [30,63], being childless [37], experiencing no pain relief after surgery [41] or oral contraceptive therapy [72]. Correlations of anxiety and depression in endometriosis patients concerning time of diagnosis were described contradictorily [36,63,69].
Discussion Main Findings
The aim of this systematic review was to give an overview on the association between endometriosis and symptoms of depression and anxiety and the factors that are correlated to this association. A total of 47 articles comprising 1,933,846 subjects were reviewed. Data from 17 studies using validated outcome measures was pooled for a random effects meta-analysis comparing 677 endometriosis patients with 636 healthy controls and 407 CPP patients without endometriosis. Reviewed articles showed a prevalence ranging from 10-86% for depression and 10-79% for anxiety, whereas the global prevalence of depressive and anxiety disorders ranges from 4.5-7% and 5.5-6% respectively in women of reproductive age [19]. Derived from the pooled data, the standardized mean differences in anxiety and depression scores is significantly higher in studies of endometriosis patients compared with healthy controls but not in comparison to CPP patients. Hence, this elevated prevalence, seems to be not specific for endometriosis but is comparable to women with other conditions representing CPP. This systematic review included mostly studies with a cross-sectional design and does not allow for analysis of causal inference. Nevertheless, two studies with a longitudinal design showed an elevated likelihood of developing depression and anxiety disorders in endometriosis [31,39]. In addition, women with a previously diagnosed depression or anxiety disorder, were more likely to be later diagnosed with endometriosis [31,39]. Regrettably, the authors did not evaluate the impact of endometriosis related factors such as pain on the risk of mood disorders.
The majority of cross-sectional studies investigating pain as a dependent factor, reported a positive association between pain intensity and scores for depressive symptoms and anxiety. This is a well-known phenomenon in pain being part of functional psychosomatic syndromes [103]. In endometriosis studies however, there was no consensus on the relation between the type of pain (CPP, dysmenorrhea, dyspareunia) and affective symptoms. Facchin et al. (2015) was the first to test the ‘disease-focused hypothesis’ and the ‘pain-focused hypothesis’ in endometriosis by comparing asymptomatic endometriosis patients, endometriosis patients with pelvic pain and healthy pain-free controls. Their findings offered the conclusion that painless endometriosis does not necessarily involve psychological pain or discomfort. However, the researchers did not control for the effect of diagnostic and demographic factors. Other studies included in this review suggest that factors correlated to affective symptoms in endometriosis patients include age, quality of life, quality of sleep, fatigue, sexual function, gastrointestinal symptoms, comorbidity, self-esteem, emotional self-efficacy, coping style, social adjustment, pain imagery and pain sensitization. This indicates that other factors are involved in symptom burden and treatment refractoriness in women suffering from endometriosis. As in other complex patients, these aspects remain frequently undetected, which could lead to misdiagnosis and puzzled treatment pathways [104,105].