Back to the Future: Is GnRHa Treatment in Transgender and Gender Diverse Adolescents Only an Extended Evaluation Phase?

CONTEXT: The role of body modifications induced by gonadal suppression in transgender and gender diverse adolescents on psychological functioning has not yet been evaluated. OBJECTIVE: The main aim of the present study was to explore several hormone, physical and psychological functioning changes during gonadotropin-releasing hormone analog (GnRHa) treatment in transgender and gender diverse adolescents (TGDAs). The potential relationship between the physical and hormone effects of GnRHa and psychological well-being, along with its magnitude, was assessed for the first time. METHODS: This prospective multidisciplinary study included 36 TGDA (22 assigned female at birth, and 14 assigned male at birth) who received psychological assessment followed by triptorelin prescription after referring to the Florence Gender Clinic. This study consisted of 3 time points: first referral (T0), psychological assessment (T1); and treatment with intramuscular injections of triptorelin for 3 up to 12 months (T2). Psychometric questionnaires were administered at each time point, and clinical and biochemical evaluations were performed at T1 and T2. RESULTS: The following results were found: (1) GnRHa showed efficacy in inhibiting puberty progression in TGDAs; (2) an increase in psychopathology was observed before starting GnRHa (T1) compared with baseline levels; (3) during GnRHa treatment (T2), a significant improvement in psychological functioning, as well as decrease in suicidality, body uneasiness, depression, and anxiety levels were observed; (4) hormone and physical changes (in terms of gonadotropin and sex steroid levels, height and body mass index percentiles, waist-hip ratio, and acne severity) observed during triptorelin treatment significantly correlated with a reduction in suicidal ideation, anxiety, and body image concerns. CONCLUSION: Psychological improvement in TGDA on GnRHa seems to be related to the objective body changes induced by a GnRHa. Therefore, the rationale for treatment with a GnRHa may not only be considered an extension of the evaluation phase, but also the start of a medical (even if reversible) gender-affirming path, especially in TGDAs whose puberty has already progressed.

Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies.

OBJECTIVE: To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs). DESIGN: Umbrella review. DATA SOURCES: PubMed, PsychInfo, Embase, up to 9 February 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted. RESULTS: 101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive). CONCLUSIONS: Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events. STUDY REGISTRATION: PROSPERO CRD42018093045. FUNDING: None.

Internalized transphobia predicts worse longitudinal trend of body uneasiness in transgender persons treated with gender affirming hormone therapy: a 1-year follow-up study.

BACKGROUND: Given the relationship between interiorized stigma and body image, it could be hypothesized that high levels of internalized transphobia (IT) might predict higher levels of body uneasiness in subjects with gender dysphoria (GD) and worse improvement of body image after gender affirming hormone therapy (GAHT). AIM: We sought to evaluate the relationship between IT and body uneasiness in subjects with GD and the role of IT in moderating the improvement of body image after GAHT. METHODS: In total, 200 individuals with GD performed the baseline assessment; 99 were re-evaluated 12 months after starting GAHT. At baseline participants were evaluated through a face-to-face interview and filled self-administered questionnaires to evaluate GD (Utrecht Gender Dysphoria Scale [UGDS]), IT attitudes (Attitudes Toward Transgendered Individuals [ATTI] Scale), body uneasiness (Body Uneasiness Test, part A [BUT-A]), and general psychopathology (Symptom Checklist 90-Revised [SCL 90-R]). The same questionnaires, except ATTI, were readministered at follow-ups. OUTCOMES: Outcomes were based on measures of the associations between IT and baseline characteristics of the sample, the longitudinal trends of GD, body uneasiness, and general psychopathology; and IT as a moderator of the longitudinal trend of body uneasiness. RESULTS: At baseline, IT correlated with lower level of education, higher GD, and more severe body uneasiness. Longitudinal analyses showed significant improvements in GD, body uneasiness, and general psychopathology during GAHT. Moderation analysis confirmed that participants with more transphobic attitudes showed less improvement after GAHT with regard to body uneasiness (bTime*ATTI = -.002, P = .040). The Johnson-Neyman technique revealed that no significant improvement in body uneasiness was found for participants with ATTI scores lower than 71.14. CLINICAL IMPLICATIONS: The presence of IT should be investigated in subjects with GD who require gender affirming treatments to provide specific interventions aimed at targeting this dimension. STRENGTHS AND LIMITATIONS: Strengths of this study include the mixed cross-sectional and longitudinal design and the dimensional evaluation of the investigated constructs. Limitations include the small sample size and the limited follow-up. Furthermore, the effects of gender affirming surgery were not evaluated. CONCLUSION: The association of IT with both baseline body uneasinessand the longitudinal course of this dimension highlighted the clinical significance of body uneasiness and the importance of making continuous efforts to improve education and information to fight societal stigmas.

Uterine Fibroids, Perceived Stress, and Menstrual Distress: a Key Role of Heavy Menstrual Bleeding.

Uterine fibroids (UFs) are the most common benign tumors in women of reproductive age, frequently associated with pain symptoms and heavy menstrual bleeding (HMB), leading to impaired quality of life. Thus, the aim of the study was to evaluate the global perception of stress and the menstrual distress in patients with UFs. A cross-sectional observational study was conducted on a group (n = 69) of fertile age women with UFs compared to age-matched controls, by administering two questionnaires: the perceived stress scale (PSS) and the Menstrual Distress Questionnaire (MEDI-Q). The PSS, MEDI-Q Total Score and 3 subscales-menstrual symptoms (MS), menstrual symptoms distress (MSD), and menstrual specificity index (MESI)-were evaluated. Patients with UFs showed higher PSS than controls (18.5 ± 5.0 vs. 13.8 ± 5.0, p < 0.001) and PSS values were very high in those with HMB, severe dysmenorrhea, and impaired social and working life. Patients with UFs also showed significantly higher score for MEDI-Q Total Score (16.51 ± 12.99 vs. 10.86 ± 12.36) (p < 0.01) as well as for the subscales MSD (2.54 ± 1.07 vs. 1.57 ± 0.98) (p < 0.001) and MESI (0.76 ± 0.30 vs 0.60 ± 0.39) (p < 0.05). The menstrual distress was associated to being uncomfortable about uterine bleeding; in fact, MEDI-Q Total Score was significantly higher in women with HMB compared to those with moderate/normal bleeding. UF characteristics (number, type, and size) did not correlate with perceived stress or menstrual distress. In conclusion, women with UFs have significantly higher levels of perceived stress and menstrual distress than controls and HMB plays a major role in determining such conditions.

Rapid improvement of psychiatric stigmata after IFN-free treatment in HCV patients with and without cryoglobulinemic vasculitis.

OBJECTIVE: Hepatitis C virus (HCV) causes neuropsychiatric disorders and quality of life impairment, especially in patients with cryoglobulinemic vasculitis (CV). Direct acting antivirals (DAAs) are effective in most extrahepatic HCV diseases, but limited information exists regarding the outcome of psychiatric disorders in patients with and without CV, after therapy. We aimed to evaluate psychiatric outcomes, in HCV-patients with and without CV, before and after successful DAA therapy. METHODS: We prospectively studied DAA-treated HCV-patients, stratified into presence (CV) or absence of CV (NON-CV). Four psychometric scales were administered to assess depression (HAM-D and MADRS), anxiety (HAM-A), and mania (MRS). Short-Form-36 questionnaires evaluated quality of life. RESULTS: Seventy-six patients were recruited, and 47 CV and 29 NON-CV were treated with antivirals. At baseline, depression and anxiety, from mild to severe, were frequently shown, with the most advanced cases in thee CV group; no patients achieved the scores for mania. A significant improvement emerged for all the psychometric scales in the entire population and in the subgroups, after viral eradication even in the short-term outcome. The Short-Form-36 summary components showed benefits. CONCLUSIONS: After HCV eradication, the depression and anxiety scores significantly improved and severity grade generally lowered. DAA-positive effects on mental disorders should be considered part of the therapy outcome, being beneficial especially in CV patients who usually have worse baseline mental scores. Key Points • HCV frequently causes psychiatric disorders and an often-invalidating autoimmune/lymphoproliferative disease called cryoglobulinemic vasculitis. • The new direct acting antivirals (DAAs) are very effective and well tolerated by HCV-patients. • This study shows DAA-induced benefits on depression and anxiety in HCV-patients that are especially evident in CV patients who usually have worse baseline mental scores. • DAA-induced benefits are observed in the short-term post-therapy follow-up, in contrast with data previously obtained in HCV patients treated with IFN-based anti-HCV therapy.

Risk factors for eating disorders: an umbrella review of published meta-analyses

Objective: To grade the evidence about risk factors for eating disorders (anorexia nervosa, bulimia nervosa, and binge eating disorder) with an umbrella review approach. Methods: This was a systematic review of observational studies on risk factors for eating disorders published in PubMed/PsycInfo/Embase until December 11th, 2019. We recalculated random-effect meta-analyses, heterogeneity, small-study effect, excess significance bias and 95% prediction intervals, grading significant evidence (p < 0.05) from convincing to weak according to established criteria. Quality was assessed with the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool. Results: Of 2,197 meta-analyses, nine were included, providing evidence on 50 risk factors, 29,272 subjects with eating disorders, and 1,679,385 controls. Although no association was supported by convincing evidence, highly suggestive evidence supported the association between childhood sexual abuse and bulimia nervosa (k = 29, 1,103 cases with eating disorders, 8,496 controls, OR, 2.73, 95%CI 1.96-3.79, p = 2.1 x 10-9, AMSTAR-2 moderate quality) and between appearance-related teasing victimization and any eating disorder (k = 10, 1,341 cases with eating disorders, 3,295 controls, OR 2.91, 95%CI 2.05-4.12, p = 1.8x10-9, AMSTAR-2 moderate quality). Suggestive, weak, or no evidence supported 11, 29, and 8 associations, respectively. Conclusions: The most credible evidence indicates that early traumatic and stressful events are risk factors for eating disorders. Larger collaborative prospective cohort studies are needed to identify risk factors for eating disorders, particularly anorexia nervosa.

The non-aromatizable androgen dihydrotestosterone (DHT) facilitates sexual behavior in ovariectomized female rats primed with estradiol.

It is still unclear whether Testosterone (T) increases sexual desire through a stimulation of the androgen receptor in relevant brain regions or through its conversion to estrogens. The aim of this study was to clarify the mechanisms of T facilitation of female sexual desire by assessing the effect of a non-aromatizable androgen (Dihydrotestosterone, DHT) in a validated animal model. Ovariectomized (OVX) Long-Evans rats were treated with oil (O) + O, 10 mcg Estradiol Benzoate (EB) + O, 10 mcg EB + 500 mcg Progesterone (P), O + 500 mcg DHT or 10 mcg EB + 500 mcg DHT (n = 12 per group). EB was administered 48 h, while P and DHT 4 h, prior to 4 sexual behavioral testing sessions in bisected unilevel pacing chambers. Appetitive behaviors (the frequencies of hops/darts and solicitations) were considered as the main outcome measure. Sexual receptivity indexes [lordosis magnitude, expressed as lordosis rating (LR), and lordosis quotient (LQ)], rejection responses, as well as mounts, intromissions and ejaculations received from the male were also coded. The probability of transition among sexual behaviors was evaluated by Transition Matrices; T-Pattern analysis was performed to detect hidden repeated temporal behavioral sequences. Preliminary analyses found no statistically significant differences between the O + O and EB + O groups, therefore we excluded the EB + O group from further analyses. Rats treated with EB + DHT displayed significantly more appetitive behaviors compared to negative controls (O + O and O + DHT), whereas no difference was observed between EB + DHT rats and positive controls (EB + P); noteworthy, a higher number of appetitive behaviors was observed in the O + DHT group compared to the O + O group. Furthermore, rats treated with EB + DHT showed significantly higher receptivity measures (LR and LQ) and received more mounts, intromissions and ejaculations compared to negative controls (O + O and O + DHT), to levels equivalent to EB + P. No differences were detected in female-male mounts or rejection responses among the 4 groups. Under a qualitative perspective, full solicitation was found exclusively in T-patterns of the EB + DHT group, which was also the only one to display T-patterns of higher order encompassing appetitive behaviors-only events. In conclusion, the administration of DHT in EB-primed OVX Long-Evans rats enhances sexual behavior measures. Specifically, DHT seems to stimulate sequences of appetitive behaviors separated from copulative/reproductive measures. Our data support an independent role of androgens in the facilitation of female sexual desire.

Hormonal Treatment Effect on Sexual Distress in Transgender Persons: 2-Year Follow-Up Data.

INTRODUCTION: As far as we know, no studies to date have investigated the psychobiological correlates of sexual distress (SD) nor the impact of hormonal treatment (HT) on SD in transgender persons. AIM: To evaluate the psychobiological correlates of SD and assess the effects of HT on SD in transgender persons without gender-affirming surgery. METHODS: A consecutive series of 301 transgender persons (160 transwomen and 141 transmen) was considered for the cross-sectional study, and a subset of 72 subjects was studied in a 2-year follow-up. A physical examination was performed. Blood samples were drawn for determination of cortisol levels. Subjects completed psychometric measures. During 2 years of HT, the evaluation of SD was prospectively repeated. MAIN OUTCOME MEASURE: Psychobiological correlates of SD in transgender population. Changes in SD during gender affirming hormonal treatment. CLINICAL IMPLICATIONS: Knowing how hormonal treatment influence SD will help care providers when counseling transgender people. STRENGTHS & LIMITATIONS: To the authors' knowledge, this is the first study prospectively evaluating the impact of gender affirming hormonal treatment on sexual distress in transgender individuals. The main limitations are represented by the small size of the sample and the use of questionnaires validated only in the cisgender population. RESULTS: SD showed a positive correlation with body uneasiness (P < .0001) and with dissatisfaction toward gender-related body parts or shapes (all P < .05). In addition, SD correlated positively with general psychopathology (P < .0001), alexithymia, social anxiety, and humiliation scales (all P < .05). In transmen, SD was positively associated with autism levels (P < .005), as well as with cortisol levels (P < .02). A significant correlation between SD and perceived discrimination was observed in transwomen (P < .05). In transwomen, SD was positively associated with hair density and negatively with breast growth (both P < .05). Finally, in transmen, a negative correlation was found between SD and hair density (P < .05). When the impact of HT on SD was evaluated, a significant reduction of SD was observed across time in both transwomen and transmen (P = .001 and P = .01, respectively). CONCLUSIONS: The present results support the efficacy of HT in reducing SD in transgender persons. Ristori J, Cocchetti C, Castellini G, et al. Hormonal Treatment Effect on Sexual Distress in Transgender Persons: 2-Year Follow-Up Data. J Sex Med 2020;17:142-151.

The Role of Somatic Symptoms in Sexual Medicine: Somatization as Important Contextual Factor in Male Sexual Dysfunction.

INTRODUCTION: An important feature of somatic symptom disorder is the subjective perception of the physical symptoms and its maladaptive interpretation. Considering that psychological distress is often expressed through somatic symptoms, it is possible that they underlie at least a part of the symptoms in subjects complaining of sexual dysfunction. Nevertheless, studies on the impact of somatoform disorders in sexual dysfunction are scanty. AIM: To define the psychological, relational, and organic correlates of somatic symptoms in a large sample of patients complaining of sexual problems. METHODS: A consecutive series of 2833 men (mean age 50.2 ± 13.5 years) was retrospectively studied. MAIN OUTCOME MEASURES: Somatic symptoms were assessed using the "somatized anxiety symptoms" subscale of the Middlesex Hospital Questionnaire (MHQ-S). Several clinical, biochemical, psychological, and relational parameters were studied. Patients were interviewed with the previously validated Structured Interview on Erectile Dysfunction (SIEDY), and ANDROTEST (a structured interview for the screening of hypogonadism in patients with sexual dysfunction). RESULTS: Among the 2833 patients studied, subjects scoring higher on somatic symptoms were older, more obese, reporting unhealthy lifestyle (current smoking, alcohol consumption), and a lower education (all P < .05). Moreover, they reported a general impairment of their sexuality more often, including erectile problems (spontaneous or sexual-related), low sexual desire, decreased frequency of intercourse, and perceived reduction of ejaculate volume (all P < .005). Interestingly, we observed a significant association between MHQ-S scoring with a reduced testosterone level and hypogonadism symptoms (both P < .05). Finally, we found a significant association between somatic symptoms and both SIEDY Scales 1 (organic domain of ED) and 3 (intrapsychic domain of ED) (both P < .0001). CONCLUSION: The present study demonstrates that the presence of somatic symptoms can represent an important contextual factor in the determination of or in the exacerbation of male sexual dysfunction. High levels of somatic symptoms in subjects with sexual dysfunction can be related to the sexual symptom itself. The consequences of this pattern have great clinical relevance in a sexual medicine setting, considering their severe impact on sexuality.

Interactions Between Depression and Lower Urinary Tract Symptoms: The Role of Adverse Life Events and Inflammatory Mechanisms. Results From the European Male Ageing Study.

OBJECTIVES: Depression and lower urinary tract symptoms (LUTSs) have been found to co-occur among aging men. The present study attempted to clarify the nature of this relationship, considering adverse life events as potential moderators and the inflammation as an underlying biological mechanism. METHODS: The relationship between depression and LUTS was evaluated using data from the European Male Ageing Study, the largest multicenter population-based study of aging in European men. The sample included 3369 men who were assessed by means of several self-reported questionnaires, including the Beck Depression Inventory-II, the International Prostate Symptom Score, and the Adverse Life Events Scale. Participants were asked to provide information regarding general health and life-style, and medical comorbidities. Biological measures including prostate-specific antigen, testosterone, and C-reactive protein were measured. RESULTS: LUTS and depressive symptoms were correlated (R = 0.32, ß = .10, p < .001), even after adjusting for life-style, psychological, and medical variables. A history of adverse life events was associated with both higher LUTS and Beck Depression Inventory scores. Furthermore, adverse life events moderated the LUTS-depression association (F = 22.62, b = 0.061, p < .001), which increased as a function of the number of life events. C-reactive protein was found to mediate the LUTS-depression association. This mediation effect was moderated by number of adverse life events. CONCLUSIONS: Participants with a history of adverse life events represent a vulnerable population in whom the association between somatic and depressive symptoms is stronger. One of the biological mechanisms underlying this association could be an activation of the central inflammatory signaling pathways.

Psychological effects and outcome predictors of three bariatric surgery interventions: a 1-year follow-up study.

PURPOSE: Weight loss surgery efficacy has been demonstrated for morbid obesity. Different outcomes have been hypothesized, according to specific bariatric surgery interventions and psychological characteristics of obese patients. The present study compared three different surgery procedures, namely laparoscopic adjustable gastric band (LAGB), Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD), in terms of weight loss efficacy and psychological outcomes. METHODS: Eighty-three subjects seeking bariatric surgery have been evaluated before and 12 months after surgery intervention, by means of a clinical interview and different self-reported questionnaires, including Eating Disorder Examination Questionnaire, Emotional Eating Scale, Binge Eating Scale, Beck Depression Inventory, Symptom Checklist and State-Trait Anxiety Inventory. RESULTS: BPD group (26 subjects) showed the greatest weight loss, followed by RYGB (30 subjects), and LAGB group (27 subjects). All the treatments were associated with a significant improvement of anxiety, depression, and general psychopathology, and a similar pattern of reduction of binge eating symptomatology. BPD group reported a greater reduction of eating disorder psychopathology, compared to the other groups. Pre-treatment emotional eating severity was found to be a significant outcome modifier for the three treatment interventions. CONCLUSIONS: These results suggest that all the three types of bariatric surgery significantly improved psychopathology and eating disordered behaviors. They also support the importance of a pre-treatment careful psychological assessment in order to supervise the post-surgical outcome.

Psychopathological similarities and differences between obese patients seeking surgical and non-surgical overweight treatments.

PURPOSE: To compare the psychopathological characteristics of obese patients seeking bariatric surgery with those seeking a medical approach. METHODS: A total of 394 consecutive outpatients seeking bariatric surgery were compared with 683 outpatients seeking a medical treatment. All patients were referred to the same institution. RESULTS: Obesity surgery patients reported higher body mass index (BMI), objective/subjective binging and more severe general psychopathology, while obesity medical patients showed more eating and body shape concerns. Depression was associated with higher BMI among obesity surgery clinic patients, whereas eating-specific psychopathology was associated with higher BMI and objective binge-eating frequency among obesity medical clinic patients. CONCLUSIONS: Patients seeking bariatric surgery showed different psychopathological features compared with those seeking a non-surgical approach. This suggests the importance for clinicians to consider that patients could seek bariatric surgery on the basis of the severity of the psychological distress associated with their morbid obesity, rather than criteria only based on clinical indication.

Cross-sex hormonal treatment and body uneasiness in individuals with gender dysphoria.

INTRODUCTION: Cross-sex hormonal treatment (CHT) used for gender dysphoria (GD) could by itself affect well-being without the use of genital surgery; however, to date, there is a paucity of studies investigating the effects of CHT alone. AIMS: This study aimed to assess differences in body uneasiness and psychiatric symptoms between GD clients taking CHT and those not taking hormones (no CHT). A second aim was to assess whether length of CHT treatment and daily dose provided an explanation for levels of body uneasiness and psychiatric symptoms. METHODS: A consecutive series of 125 subjects meeting the criteria for GD who not had genital reassignment surgery were considered. MAIN OUTCOME MEASURES: Subjects were asked to complete the Body Uneasiness Test (BUT) to explore different areas of body-related psychopathology and the Symptom Checklist-90 Revised (SCL-90-R) to measure psychological state. In addition, data on daily hormone dose and length of hormonal treatment (androgens, estrogens, and/or antiandrogens) were collected through an analysis of medical records. RESULTS: Among the male-to-female (MtF) individuals, those using CHT reported less body uneasiness compared with individuals in the no-CHT group. No significant differences were observed between CHT and no-CHT groups in the female-to-male (FtM) sample. Also, no significant differences in SCL score were observed with regard to gender (MtF vs. FtM), hormone treatment (CHT vs. no-CHT), or the interaction of these two variables. Moreover, a two-step hierarchical regression showed that cumulative dose of estradiol (daily dose of estradiol times days of treatment) and cumulative dose of androgen blockers (daily dose of androgen blockers times days of treatment) predicted BUT score even after controlling for age, gender role, cosmetic surgery, and BMI. CONCLUSIONS: The differences observed between MtF and FtM individuals suggest that body-related uneasiness associated with GD may be effectively diminished with the administration of CHT even without the use of genital surgery for MtF clients. A discussion is provided on the importance of controlling both length and daily dose of treatment for the most effective impact on body uneasiness.

Gender identity disorder and eating disorders: similarities and differences in terms of body uneasiness.

INTRODUCTION: Subjects with gender identity disorder (GID) have been reported to be highly dissatisfied with their body, and it has been suggested that the body is their primary source of suffering. AIMS.: To evaluate quality and intensity of body uneasiness in GID subjects, comparing them with a sample of eating disorder patients and a control group. To detect similarities and differences between subgroups of GID subjects, on the basis of genotypic sex and transitional stage. METHODS: Fifty male-to-female (MtF) GID (25 without and 25 with genital reassignment surgery performed), 50 female-to-male (FtM) GID (28 without and 22 with genital reassignment surgery performed), 88 eating disorder subjects (26 anorexia nervosa, 26 bulimia nervosa, and 36 binge eating disorder), and 107 healthy subjects were evaluated. MAIN OUTCOME MEASURES: Subjects were studied by means of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the Symptom Checklist (SCL-90), and the Body Uneasiness Test (BUT). RESULTS: GID and controls reported lower psychiatric comorbidity and lower SCL-90 General Severity Index (GSI) scores than eating disorder subjects. GID MtF without genital reassignment surgery showed the highest BUT values, whereas GID FtM without genital reassignment surgery and eating disorder subjects showed higher values compared with both GID MtF and FtM who underwent genital reassignment surgery and controls. Considering BUT subscales, a different pattern of body uneasiness was observed in GID and eating disorder subjects. GID MtF and FtM without genital reassignment surgery showed the highest BUT GSI/SCL-90 GSI ratio compared with all the eating disorder groups. CONCLUSIONS: GID and eating disorders are characterized by a severe body uneasiness, which represents the core of distress in both conditions. Different dimensions of body uneasiness seem to be involved in GID subsamples, depending on reassignment stage and genotypic sex. In eating disorder subjects body uneasiness is primarily linked to general psychopathology, whereas in GID such a relationship is lacking.

Sociodemographic and clinical features of gender identity disorder: an Italian multicentric evaluation.

INTRODUCTION: Male to female (MtFs) and female to male (FtMs) subjects with gender identity disorder (GID) seem to differ with regard to some sociodemographic and clinical features. Currently, no descriptive studies focusing on MtFs and FtMs attending an Italian clinic are available. AIM: To describe the sociodemographic characteristics of a GID population seeking assistance for gender transition and to assess possible differences in those features between MtFs and FtMs. METHODS: A consecutive series of 198 patients was evaluated for gender dysphoria from July 2008 to May 2011 in four dedicated centers. A total of 140 subjects (mean age 32.6 ± 9.0 years old) meeting the criteria for GID, with their informed consent and without genital reassignment surgery having already been performed, were considered (92 MtFs and 48 FtMs). Diagnosis was based on formal psychiatric classification criteria. MAIN OUTCOME MEASURES: Medical history and sociodemographic characteristics were investigated. Subjects were asked to complete the Body Uneasiness Test (a self-rating scale exploring different areas of body-related psychopathology), Symptom Checklist-90 Revised (a self-rating scale to measure psychological state), and the Bem Sex Role Inventory (a self-rating scale to evaluate gender role). The presence of psychiatric comorbidities was evaluated using the Structured Clinical Interviews for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) (SCID I and SCID II). RESULTS: Several significant differences were found between MtFs and FtMs regarding lifestyle and sociodemographic factors and in psychometric test scores. No differences were found in terms of psychiatric comorbidity. CONCLUSIONS: This is the first large study reporting the sociodemographic characteristics of a GID sample referring to Italian clinics, and it provides different profiles for MtFs and FtMs. In particular, FtMs display significantly better social functioning.

SIEDY scale 3, a new instrument to detect psychological component in subjects with erectile dysfunction.

INTRODUCTION: We previously developed and validated a structured interview (SIEDY) dealing with the organic (Scale 1), relational (Scale 2), and psychological (Scale 3) components of erectile dysfunction (ED). AIM: To identify a pathological threshold for SIEDY Scale 3 and to analyze Scale 3 score with biological and psychological correlates in subjects with sexual dysfunction. METHOD: A pathological threshold of SIEDY Scale 3 score in predicting subjects with a medical history of psychopathology and using psychiatric drugs was identified through receiver operating characteristic (ROC) curve analysis in a sample of 484 patients (Sample A). MAIN OUTCOME MEASURE: Sensitivity and specificity, along with possible interactions with biological and psychological (Middlesex Hospital Questionnaire, MHQ-score) correlates were verified in a further sample of 1,275 patients (Sample B). RESULTS: In sample A, 39 (8%) and 60 (12.4%) subjects reported a positive medical history for psychiatric disturbances or for the use of psychotropic medication, respectively. The association with both conditions was present in 28 (5.8%) subjects. ROC curve showed that SIEDY Scale 3 score predicts psychopathology with an accuracy of 69.5 ± 5.9% (P<0.002), when a threshold of 3 was chosen. When the same threshold was applied in Sample B, it identified a higher ranking in MHQ-A (free-floating anxiety), MHQ-S (somatized anxiety) and MHQ-D (depressive symptoms) subscales, even after adjustment for age and Σ-MHQ (a broader index of general psychopathology). In the same sample, we also confirmed that pathological Scale 3 score was related to a higher risk of psychopathology at medical history or to the use of psychotropic drugs as well as with risky lifestyle behaviors, including smoking and alcohol abuse, and elevated BMI. CONCLUSIONS: SIEDY represents an easy tool for the identification of patients with a relevant intra-psychic component who should be considered for psychological/psychiatric treatment.

Generalized anxiety disorder: is there any specific symptom?

OBJECTIVE: The main aim of the present research was to evaluate the coherence of generalized anxiety disorder (GAD) psychopathological pattern, the robustness of its diagnostic criteria, and the clinical utility of considering this disorder as a discrete condition rather than assigning it a dimensional value. METHOD: The study was designed in a purely naturalistic setting and carried out using a community sample; data from the Sesto Fiorentino Study were reanalyzed. RESULTS: Of the 105 subjects who satisfied the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for the diagnosis of GAD, only 18 (17.1%) had no other comorbid DSM-IV disorder. The most frequent comorbid condition was major depressive disorder (70.4 %). Only 2 of the GAD diagnostic symptoms (excessive worry and muscle tension) showed a specific association with the diagnosis itself, whereas the others, such as feeling wound up, tense, or restless, concentration problems, and fatigue, were found to be more prevalent in major depressive disorder than in GAD. CONCLUSION: Our study demonstrates that GAD, as defined by DSM-IV criteria, shows a substantial overlap with other DSM-IV diagnoses (especially with mood disorders) in the general population. Furthermore, GAD symptoms are frequent in all other disorders included in the mood/anxiety spectrum. Finally, none of the GAD symptoms, apart from muscle tension, distinguished GAD from patients without GAD.

Role of the neurotrophin network in eating disorders' subphenotypes: body mass index and age at onset of the disease.

Eating disorders (ED) are severe psychiatric diseases that most likely result from, and are sustained by socio-cultural, psychological and biological factors. We explored whether members of the neurotrophin family are disease-modifying factors of quantitative traits, potentially contributing to the outcome or prognosis of the disease. We studied lifetime minimum and maximum body mass index (minBMI and maxBMI) and age at onset of the disease in a sample of 991 ED patients from France, Germany, Italy and Spain and analysed 183 genetic variants located in 10 candidate genes encoding different neurotrophins and their receptors. We used a hierarchical model approach to include prior genetic knowledge of the specific and found that variants in CNTF, in its receptor CNTFR, and in NTRK2 were significantly associated with a lower age at onset of the ED. In addition, one variant in NTRK1 was associated with a higher minBMI. The results suggest that for these two subphenotypes, CNTF, CNTFR, NTRK1 and NTRK2 might act as disease-modifying factors and add preliminary evidence to the global hypothesis that EDs are the result of complex interactions and reciprocal controls between the immune, endocrine and central nervous systems.

Hypoprolactinemia: a new clinical syndrome in patients with sexual dysfunction.

INTRODUCTION: The physiological role of prolactin (PRL) in male sexual behavior is poorly understood. Conversely, the association between PRL pathological elevation in both reproductive and sexual behavior is well defined. AIM: The aim of the present study is to assess the correlates of normal PRL (PRL < 735 mU/L or 35 ng/mL), in male subjects consulting for sexual dysfunction. METHODS: A consecutive series of 2,531 (mean age 52.0 +/- 12.9 years) subjects was investigated. Patients were interviewed using the structured interview on erectile dysfunction (SIEDY), a 13-item tool for the assessment of erectile dysfunction (ED)-related morbidities. Middlesex Hospital Questionnaire was used for the evaluation of psychological symptoms. MAIN OUTCOME MEASURES: Several hormonal (testosterone, thyroid stimulation hormone, and PRL) and biochemical parameters (glycemia and lipid profile) were studied, along with penile Doppler ultrasound (PDU) and SIEDY items. RESULTS: After adjustment for confounders anxiety symptoms decreased across PRL quartiles (I: <113 mU/L or 5 ng/mL; II: 113-156 mU/L or 5.1-7 ng/mL; III: 157-229 mU/L or 7.1-11 ng/mL; IV: 229-734 mU/L or 11.1-34.9 ng/mL). Patients in the lowest PRL quartile showed a higher risk of metabolic syndrome (MetS; odds ratio [OR] = 1.74 [1.01-2.99], P < 0.05), arteriogenic ED (peak systolic velocity at PDU < 35 cm/sec; OR = 1.43 [1.01-2.03], P < 0.05), and premature ejaculation (PE; OR = 1.38 [1.02-1.85]; P < 0.05). Conversely, comparing subjects with PRL-secreting pituitary adenomas (N = 13) with matched controls, no significant difference was observed, except for a higher prevalence of hypoactive sexual desire in hyperprolactinemia. CONCLUSIONS: Our findings demonstrate that, in subjects consulting for sexual dysfunction, PRL in the lowest quartile levels are associated with MetS and arteriogenic ED, as well as with PE and anxiety symptoms. Further studies are advisable in order to confirm our preliminary results in different populations.