Association between psychosexual disorders and the risk of psychiatric disorders
The adjusted HR was 9.848 (95% CI= 7.298—13.291, p < 0.001) in the association between the psychosexual disorders and psychiatric disorders, and the female patients with psychosexual disorders had a 9.8-fold increase in the risk of psychiatric disorders, after the adjustment of age, monthly income, urbanization level, geographic region, and comorbidities. The Kaplan-Meier analysis demonstrated that the cohort with psychosexual disorders had a significantly higher 15-year psychiatric disorders cumulative incidence than the comparison cohort. To the best of our knowledge, this is the first study on the topic of an association between female patients with psychosexual disorders and the risk of psychiatric morbidity. This finding could serve as a reminder for the clinicians to pay much more attention to these patients because of the issues about psychiatric disorders.
Comparison of this study to previous literature
Previous studies have shown the association between psychosexual disorders and psychiatric disorders that included antidepressant-related sexual dysfunctions in patients with depressive or anxiety disorders [16, 45-47], female paraphilia focused and the personality disorders on the forensic psychiatric topics [14, 15], and the FTM gender disorders and depression, post-traumatic stress disorder, anxiety disorders and suicides [12, 13, 48]. However, these studies were mostly conducted in cross-section methods, and our study is unique for the retrospective cohort design, from a larger population-based database. Besides, male patients with psychosexual disorders have been associated with an increased risk of anxiety disorders, depressive disorders, bipolar disorders, sleep disorders, and psychotic disorders, respectively . There were several differences in the risk of different psychiatric disorders in these two studies. The underlying reasons for the difference of risk for psychiatric disorders, between female patients with psychosexual disorders, needs further studies.
Treatment prevalence of psychosexual disorders in this study
Previous studies revealed that the prevalence of female sexual dysfunctions was 30—60%, in different countries [49-52], but we found that there was 0.007% of sexual dysfunctions in this sample of 15-year of follow-up. In the present study, there were 70 paraphilia patients from the database, and the treatment prevalence of female paraphilias was around 0.004% in this LHID. The prevalence of the female paraphilias were 2% in exhibitionistic behaviors in previous studies [25, 53], 4% in voyeuristic behaviors [25, 53], 0.4% in transvestic fetishism , and 1% in sadomasochistic activity , from surveys in the population of Sweden [25, 53], and Australia . Previous reports have shown that there were 0.003% in Belgium ,, 0.82% in Japan , and 0.023%－0.058% in the United States veteran’s populations [12, 58] of FTM gender identity disorder. Furthermore, the present study found that the treatment prevalence of FTM gender identity disorder, was 0.017%, in the duration of the 15 years of follow-up. The discrepancy of the prevalence might be the difference of studies from a claims database or the survey. Cultural differences might also contribute to this difference: previous studies have shown that females have more difficulties in their help-seeking for sex-related problems in Asian countries [59, 60]. However, the present study is the first one for females with psychosexual disorders and the risk of psychiatric disorders in an Asian country.
Possible mechanisms for the increased risk of psychiatric disorders in patients with psychosexual disorders
In the present study, female patients with sexual dysfunctions were associated with psychiatric disorders. There are several neurodevelopmental, endocrine, and psychological factors related to the linkage between these two groups of disorders. The stress from the suffering of sexual dysfunction [61, 62], paraphilias [63, 64], and gender identity disorders [65-67], might well contribute to the association between these psychosexual disorders and the risk of psychiatric disorders, such as anxiety, depressive, or sleep disorders. One study has found that hyperprolactinemia seems to play a role in the pathogenesis of hypoactive sexual desire disorder, one of the female sexual dysfunctions , and hyperprolactinemia might induced psychiatric disorders, such as depression and anxiety [69-72].
Evidence suggests that female and male brains are different in the mean volumes of the hippocampus, amygdala, and thalamus , the concentration of estrogen or androgen receptors , and the total brain, cerebrum, and cerebellum volumes . Thus, the difference in the brain anatomy and neuronal signaling pathways are more closely aligned with a person's perceived gender identity, and individuals with discordant gonadal and brain developments might experience psychological challenges for the generalized dissatisfaction with their biological sex . Besides, paraphilias and depression might share a common dysregulation of this monoaminergic pathway in these patients [11, 77].
Psychological, social, and cultural factors might also contribute to both psychosexual disorders and psychiatric disorders. Previous studies have shown that patients with paraphilias might suffer emotional distress, social embarrassment , and stigma . For example, a study from Turkey has found that patients with vaginismus have higher levels of depression and anxiety . Phobic defense mechanisms , the rejection of the female role, and religious orthodoxy which regards sex as dirty or shameful  are the psychosocial factors that contribute to vaginismus, depression, and anxiety .
The present study has several limitations that warrant consideration. First, similar to previous studies using the NHIRD on psychosexual disorders [32, 81-83], we were unable to evaluate the severity, weakness severity, laboratory parameters, or psychological assessments in the patients with psychosexual disorders, since the data were not recorded in the NHIRD. Second, the genetic, psychosocial, and environmental factors, were not included in the dataset. Third, even though we have excluded the patients diagnosed with psychiatric disorders before 2000, or before their first visit for any psychosexual disorders, there is the possibility of the protopathic bias, in which some patients could have been introduced into this study by subjects who have an undiagnosed disease. Fourth, although paraphilias and gender dysphoria are distinct categories, there is some evidence for an overlap between paraphilias and gender dysphoria . The combination of distinct entities, in a single heterogeneous category of psychosexual disorders, is a limitation when discussing the results of the data analysis. Fifth, there is a possibility that the high prevalence of psychiatric disorders, among female patients with psychosexual disorders, is due to the high utilization of psychiatric services. However, as shown in Table S2, there were no significant differences in the times of psychiatric visits between the two cohorts.