A reduction in long-term spatial memory persists after discontinuation of peripubertal GnRH agonist treatment in sheep.

Chronic gonadotropin-releasing hormone agonist (GnRHa) administration is used where suppression of hypothalamic-pituitary-gonadal axis activity is beneficial, such as steroid-dependent cancers, early onset gender dysphoria, central precocious puberty and as a reversible contraceptive in veterinary medicine. GnRH receptors, however, are expressed outside the reproductive axis, e.g. brain areas such as the hippocampus which is crucial for learning and memory processes. Previous work, using an ovine model, has demonstrated that long-term spatial memory is reduced in adult rams (45 weeks of age), following peripubertal blockade of GnRH signaling (GnRHa: goserelin acetate), and this was independent of the associated loss of gonadal steroid signaling. The current study investigated whether this effect is reversed after discontinuation of GnRHa-treatment. The results demonstrate that peripubertal GnRHa-treatment suppressed reproductive function in rams, which was restored after cessation of GnRHa-treatment at 44 weeks of age, as indicated by similar testes size (relative to body weight) in both GnRHa-Recovery and Control rams at 81 weeks of age. Rams in which GnRHa-treatment was discontinued (GnRHa-Recovery) had comparable spatial maze traverse times to Controls, during spatial orientation and learning assessments at 85 and 99 weeks of age. Former GnRHa-treatment altered how quickly the rams progressed beyond a specific point in the spatial maze at 83 and 99 weeks of age, and the direction of this effect depended on gonadal steroid exposure, i.e. GnRHa-Recovery rams progressed quicker during breeding season and slower during non-breeding season, compared to Controls. The long-term spatial memory performance of GnRHa-Recovery rams remained reduced (P<0.05, 1.5-fold slower) after discontinuation of GnRHa, compared to Controls. This result suggests that the time at which puberty normally occurs may represent a critical period of hippocampal plasticity. Perturbing normal hippocampal formation in this peripubertal period may also have long lasting effects on other brain areas and aspects of cognitive function.

Spatial memory is impaired by peripubertal GnRH agonist treatment and testosterone replacement in sheep.

Chronic gonadotropin-releasing hormone agonist (GnRHa) is used therapeutically to block activity within the reproductive axis through down-regulation of GnRH receptors within the pituitary gland. GnRH receptors are also expressed in non-reproductive tissues, including areas of the brain such as the hippocampus and amygdala. The impact of long-term GnRHa-treatment on hippocampus-dependent cognitive functions, such as spatial orientation, learning and memory, is not well studied, particularly when treatment encompasses a critical window of development such as puberty. The current study used an ovine model to assess spatial maze performance and memory of rams that were untreated (Controls), had both GnRH and testosterone signaling blocked (GnRHa-treated), or specifically had GnRH signaling blocked (GnRHa-treated with testosterone replacement) during the peripubertal period (8, 27 and 41 weeks of age). The results demonstrate that emotional reactivity during spatial tasks was compromised by the blockade of gonadal steroid signaling, as seen by the restorative effects of testosterone replacement, while traverse times remained unchanged during assessment of spatial orientation and learning. The blockade of GnRH signaling alone was associated with impaired retention of long-term spatial memory and this effect was not restored with the replacement of testosterone signaling. These results indicate that GnRH signaling is involved in the retention and recollection of spatial information, potentially via alterations to spatial reference memory, and that therapeutic medical treatments using chronic GnRHa may have effects on this aspect of cognitive function.

A network analysis of body satisfaction of people with gender dysphoria.

In gender dysphoria (GD), much of the experienced distress results from body dissatisfaction. The current study analyzed the configuration of body satisfaction in trans men and women using network analysis. In total, 485 individuals diagnosed with GD from four European countries, applying for medical treatment, filled out the Body Image Scale for Transsexuals. A six-factor model reflecting different body areas was confirmed via confirmatory factor analysis. A further configuration of body satisfaction was modelled using correlation network analysis techniques in R. Genital dissatisfaction showed limited connection with other body areas in comparison to other subscales. Body characteristics influencing social gender recognition were most centrally involved in body (dis)satisfaction in both natal sexes. In trans women these characteristics were related mostly to voice and hair, whereas in trans men these characteristics were related to muscularity and posture. Focusing on these socially influential body characteristics may provide important targets for transgender healthcare.

A European network for the investigation of gender incongruence: the ENIGI initiative.

Studies on diagnostic subtypes of gender identity disorder (GID) or gender incongruence (GI), comorbidity and treatment outcome show considerable variability in results. Clinic/country specific factors may account for the contradictory results, but these factors have never been studied. This article is the first of a series reporting on a unique collaborative study of four European gender identity clinics (the European network for the investigation of gender incongruence [ENIGI]). Here, we present the diagnostic procedures of the four clinics (Amsterdam, Ghent, Hamburg, and Oslo), the standard battery of instruments, and the first results regarding applicants with GI who seek treatment. Applicants in the four clinics did not differ in living situation, employment status, sexual orientation, and age of onset of GI feelings. However, the Amsterdam and Ghent clinic were visited by a majority of natal males, whereas Hamburg and Oslo see more natal females. Male applicants were older than female applicants within each country, but female applicants in one country were sometimes older than male applicants in another country. Also, educational level differed between applicants of the four clinics. These data indicate that certain sociodemographic and/or cultural characteristics of applicants have to be taken into account in future studies.

Cross-sex pattern of bone mineral density in early onset gender identity disorder.

Hormonally controlled differences in bone mineral density (BMD) between males and females are well studied. The effects of cross-sex hormones on bone metabolism in patients with early onset gender identity disorder (EO-GID), however, are unclear. We examined BMD, total body fat (TBF) and total lean body mass (TLBM) in patients prior to initiation of sex hormone treatment and during treatment at months 3 and 12. The study included 33 EO-GID patients who were approved for sex reassignment and a control group of 122 healthy Norwegians (males, n=77; females, n=45). Male patients (n=12) received an oral dose of 50 mug ethinylestradiol daily for the first 3 months and 100 mug daily thereafter. Female patients (n=21) received 250 mg testosterone enantate intramuscularly every third week. BMD, TBF and TLBM were estimated using dual energy X-ray absorptiometry (DXA). In male patients, the DXA measurements except TBF were significantly lower compared to their same-sex control group at baseline and did not change during treatment. In female patients, the DXA measurements were slightly higher than in same-sex controls at baseline and also remained unchanged during treatment. In conclusion, this study reports that body composition and bone density of EO-GID patients show less pronounced sex differences compared to controls and that bone density was unaffected by cross-sex hormone treatment.

Sex-sensitive cognitive performance in untreated patients with early onset gender identity disorder.

BACKGROUND: We explored whether the cognitive performance of gender identity disorder patients (GID) was comparable to that of their biological sex or skewed towards that of their gender identity. METHOD: We tested four potentially sex-sensitive cognitive factors (rotation, visualization, perception, and verbalization) as well as two neutral factors (logic and arithmetic) in GID patients from Norway (GID-N, n = 33) or the USA (GID-US, n = 19) and in a control group (C, n = 29). The testing was undertaken prior to cross sex hormone treatment. Four-way ANOVA was applied in the final analysis of the cognitive performance and its dependency on different predictors (age, biological sex, education, group). RESULTS: In both GID groups as well as in the control group (C) males excelled in visualization and rotation, also when controlling for potential confounders (biological sex, group, age and education). No female advantage was detected. Furthermore, no interaction between biological sex and group assignment was revealed in the samples. CONCLUSION: In this study the cognitive pattern of GID patients is consistent with that of their biological sex and not that of their gender identity.

Symptom profiles of gender dysphoric patients of transsexual type compared to patients with personality disorders and healthy adults.

OBJECTIVE: Gender dysphoric patients of transsexual type (TS) have been considered to have severe psychopathology. However, these notions have a weak empirical documentation. METHOD: TS patients (n = 86), patients with personality disorder (PD, n = 98) and adult healthy controls (HC, n = 1068) were compared by means of the Symptom Checklist 90 (SCL-90). All patients were diagnosed by structured interviews (Axis I, II and V of DSM-III-R/IV). PD patients were further characterized according to the LEAD-standard. RESULTS: TS patients scored significantly lower than PD patients on the Global Symptom Index and all SCL-90 subscales. Although the TS group generally scored slightly higher than the HC group, all scores were within the normal range. CONCLUSION: TS patients selected for sex reassignment showed a relatively low level of self-rated psychopathology before and after treatment. This finding casts doubt on the view that transsexualism is a severe mental disorder.