Ulrike Kaufmann

Incidence of thrombophilia and venous thrombosis in transsexuals under cross-sex hormone therapy

OBJECTIVE To evaluate the incidence of venous thromboembolism (VTE) in transsexual patients and the value of screening for thrombophilia in this population. DESIGN Retrospective cohort study. SETTING Academic research institution. PATIENT(S) Two hundred fifty-one transsexuals (162 male-to-female [MtF] and 89 female-to-male [FtM] transsexuals). INTERVENTION(S) Screening for activated protein C (aPC) resistance, antithrombin III, free protein S antigen, and protein C deficiency. MAIN OUTCOME MEASURE(S) Incidence of thrombophilic defects and VTE during cross-sex hormone therapy. RESULT(S) Activated protein C resistance was detected in 18/251 patients (7.2%), and protein C deficiency was detected in one patient (0.4%). None of the patients developed VTE under cross-sex hormone therapy during a mean of 64.2 +/- 38.0 months. There was no difference in the incidence of thrombophilia comparing MtF and FtM transsexuals (8.0% [13/162] vs. 5.6% [5/89], respectively). CONCLUSION(S) VTE during cross-sex hormone therapy is rare. General screening for thrombophilic defects in transsexual patients is not recommended. Cross-sex hormone therapy is feasible in MtF as well as in FtM patients with aPC resistance.

Structural Connectivity Networks of Transgender People

Although previous investigations of transsexual people have focused on regional brain alterations, evaluations on a network level, especially those structural in nature, are largely missing. Therefore, we investigated the structural connectome of 23 female-to-male (FtM) and 21 male-to-female (MtF) transgender patients before hormone therapy as compared with 25 female and 25 male healthy controls. Graph theoretical analysis of whole-brain probabilistic tractography networks (adjusted for differences in intracranial volume) showed decreased hemispheric connectivity ratios of subcortical/limbic areas for both transgender groups. Subsequent analysis revealed that this finding was driven by increased interhemispheric lobar connectivity weights (LCWs) in MtF transsexuals and decreased intrahemispheric LCWs in FtM patients. This was further reflected on a regional level, where the MtF group showed mostly increased local efficiencies and FtM patients decreased values. Importantly, these parameters separated each patient group from the remaining subjects for the majority of significant findings. This work complements previously established regional alterations with important findings of structural connectivity. Specifically, our data suggest that network parameters may reflect unique characteristics of transgender patients, whereas local physiological aspects have been shown to represent the transition from the biological sex to the actual gender identity.

A Common Polymorphism of the SRD5A2 Gene and Transsexualism

The relation between genetic variation of the androgen metabolism and transsexualism is unknown. In a case-control study of 100 male-to-female (MtF) transsexuals, 47 female-to-male (FtM) transsexuals, and 1670 controls, the authors assess allele and genotype frequencies of the steroid 5-α reductase (SRD5A2) Val89Leu polymorphism using polymerase chain reaction. Allele and genotype frequencies are not significantly di ferent between MtF transsexuals and male controls (SRD5A2 V: 137/200 [69%] and SRD5A2 L: 63/200 [31%] vs 1065/1510 [71%] and 445/1510 [29%], respectively; P = .6; odds ratio [OR], 1.10; 95% confidence interval [CI], 0.76-1.58; SRD5A2 V/V+V/L: 92/100 [92%] and L/L 8/100 [8%] vs SRD5A2 683/755 [91%] and 72/755 [9%], respectively, P = .7; OR, 0.82; 95% CI, 0.24-2.84). Allele and genotype frequencies are also not significantly di ferent between FtM transsexuals and female controls (SRD5A2 V: 70/94 [74%] and SRD5A2 L: 24/94 [26%] vs 1253/1830 [69%] and 573/1830 [31%], respectively; P = .3; OR, 0.75; 95% CI, 0.45-1.26; SRD5A2 V/V+V/L: 44/47 [93%] and L/L 3/47 [7%] vs 823/915 [90%] and 92/915 [10%], respectively, P = .6; OR, 0.61; 95% CI, 0.11-3.32). Of note, there is no gender-specific genotype distribution among controls. The SRD5A2 Val89Leu SNP is not associated with transsexualism, refuting SRD5A2 as a candidate gene of transsexualism.

DNA Hybridization Test: Rapid Diagnostic Tool for Excluding Bacterial Vaginosis in Pregnant Women with Symptoms Suggestive of Infection

ABSTRACT This prospective comparative study evaluated a DNA hybridization test (Affirm VPIII) as an alternative to Gram stain for the diagnosis of bacterial vaginosis. We examined vaginal smears from 1,725 pregnant women between the 12th and 36th weeks of gestation with clinical signs of vaginal infection. The DNA hybridization test compared well with Gram stain and can be used as a rapid diagnostic tool to exclude bacterial vaginosis.

High-Dose Testosterone Treatment Increases Serotonin Transporter Binding in Transgender People

Background Women are two times more likely to be diagnosed with depression than men. Sex hormones modulating serotonergic transmission are proposed to partly underlie these epidemiologic findings. Here, we used the cross-sex steroid hormone treatment of transsexuals seeking sex reassignment as a model to investigate acute and chronic effects of testosterone and estradiol on serotonin reuptake transporter (SERT) binding in female-to-male and male-to-female transsexuals. Methods Thirty-three transsexuals underwent [11C]DASB positron emission tomography before start of treatment, a subset of which underwent a second scan 4 weeks and a third scan 4 months after treatment start. SERT nondisplaceable binding potential was quantified in 12 regions of interest. Treatment effects were analyzed using linear mixed models. Changes of hormone plasma levels were correlated with changes in regional SERT nondisplaceable binding potential. Results One and 4 months of androgen treatment in female-to-male transsexuals increased SERT binding in amygdala, caudate, putamen, and median raphe nucleus. SERT binding increases correlated with treatment-induced increases in testosterone levels, suggesting that testosterone increases SERT expression on the cell surface. Conversely, 4 months of antiandrogen and estrogen treatment in male-to-female transsexuals led to decreases in SERT binding in insula, anterior, and mid-cingulate cortex. Increases in estradiol levels correlated negatively with decreases in regional SERT binding, indicating a protective effect of estradiol against SERT loss. Conclusions Given the central role of the SERT in the treatment of depression and anxiety disorders, these findings may lead to new treatment modalities and expand our understanding of the mechanism of action of antidepressant treatment properties.

Combined Hysterectomy/Salpingo-Oophorectomy and Mastectomy is a Safe and Valuable Procedure for Female-to-Male Transsexuals

INTRODUCTION Sex reassignment surgery is an important step for transsexuals, since it is known to help the patients to live more easily in their gender role and to significantly increase quality of life. AIMS To critically evaluate our experience with the combined procedure of hysterectomy, bilateral salpingo-oophorectomy, and bilateral mastectomy for female-to-male (FtM) transsexual patients. METHODS Thirty-two FtM transsexuals who underwent hysterectomy, bilateral salpingo-oophorectomy, and bilateral mastectomy in one single operative setting. MAIN OUTCOME MEASURES Operating time and complications, both intra-and postoperatively. RESULTS Patients were 30.0 ± 5.8 years of age, with a body mass index of 24.8 ± 3.5 kg/m(2). The majority of patients underwent hysterectomy and bilateral salpingo-oophorectomy by laparoscopy (31/32, 96.9%). The median operating time was 222.5 minutes (inter-quartile range [IQR] 190-270 minutes). The median postoperative stay was eight days (IQR, 7-9 days). Postoperative adverse events were found in five patients (15.6%), including breast hematomas as the most frequent complication (4/32, 12.5%). In one patient (1/32; 3.1%), conversion from laparoscopy to laparotomy was necessary, which was considered an adverse event. None of our patients required reoperation or readmission to the hospital. CONCLUSION Combined hysterectomy/salpingo-oophorectomy, and bilateral mastectomy in a single operating session seems a safe, feasible, and valuable procedure for FtM transsexuals.

Gene expression signatures of breast tissue before and after cross-sex hormone therapy in female-to-male transsexuals.

OBJECTIVE To evaluate gene expression signatures of breast tissue in female-to-male (FtM) transsexuals under cross-sex hormone therapy (HT). DESIGN Prospective cohort study. SETTING Academic research institution. PATIENT(S) Five hormone-naïve FtM transsexuals before and after HT. INTERVENTION(S) Breast tissue biopsy before and after 2 years of intramuscular testosterone undecanoate (1,000 mg every 12 wk) and oral lynestrenole (5 mg daily), and gene signature analysis by global gene expression array covering 28,869 genes. MAIN OUTCOME MEASURE(S) Differential regulation of specific genes and gene expression signatures. RESULT(S) We identified 2,250 differentially expressed probe sets. One hundred twenty probe sets showed >2-fold change, of which 77 (64.2%) were up-regulated and 43 (35.8%) down-regulated. Genes involved in transcription were most overrepresented, with 43 out of 97 (44.3%) annotated probes, e.g., the transcription factor complex activator protein 1, including all three Jun genes (c-Jun, JunB, and JunD), two Fos genes (c-Fos and FosB), and activating transcription factor 3. In a Database for Annotation, Visualization, and Integrated Discovery analysis of the 2,007 down-regulated probe sets, proteins of the ribosome pathway and of two pathways involved in protein degradation, i.e., proteasome- and ubiquitin-mediated proteolysis, were significantly down-regulated. We identified eight breast cancer-associated gene expression signatures significantly overlapping with differentially regulated probe sets after cross-sex HT. CONCLUSION(S) Cross-sex HT in FtM transsexuals leads to the up-regulation and down-regulation of 243 and 2,007 distinct genes, respectively, and is associated with breast cancer-related gene expression signatures.

Cerebral serotonin transporter asymmetry in females, males and male-to-female transsexuals measured by PET in vivo

The serotonergic system modulates brain functions that are considered to underlie affective states, emotion and cognition. Several lines of evidence point towards a strong lateralization of these mental processes, which indicates similar asymmetries in associated neurotransmitter systems. Here, our aim was to investigate a potential asymmetry of the serotonin transporter distribution using positron emission tomography and the radioligand [11C]DASB in vivo. As brain asymmetries may differ between sexes, we further aimed to compare serotonin transporter asymmetry between females, males and male-to-female (MtF) transsexuals whose brains are considered to be partly feminized. Voxel-wise analysis of serotonin transporter binding in all groups showed both strong left and rightward asymmetries in several cortical and subcortical structures including temporal and frontal cortices, anterior cingulate, hippocampus, caudate and thalamus. Further, male controls showed a rightward asymmetry in the midcingulate cortex, which was absent in females and MtF transsexuals. The present data support the notion of a lateralized serotonergic system, which is in line with previous findings of asymmetric serotonin-1A receptor distributions, extracellular serotonin concentrations, serotonin turnover and uptake. The absence of serotonin transporter asymmetry in the midcingulate in MtF transsexuals may be attributed to an absence of brain masculinization in this region.

Monthly itraconazole versus classic homeopathy for the treatment of recurrent vulvovaginal candidiasis: a randomised trial

Objective  Antimycotics effectively treat sporadic and recurrent vulvovaginal candidiasis (RVVC). Classic homeopathy (CH) is also used to treat this condition. We compared the efficacy of CH and itraconazole in reducing the frequency of RVVC episodes.

Effects of hormone replacement therapy on cerebral serotonin-1A receptor binding in postmenopausal women examined with [carbonyl-11C]WAY-100635

Preclinical research points to a strong modulatory influence of gonadal hormones on the serotonin system. However, human data corroborating this association remains scarce. The aim of this study was to examine the effects of hormone replacement therapy on 5-HT₁A receptor binding in postmenopausal women using positron emission tomography (PET) and the radioligand [carbonyl-(11)C]WAY-100635. In this randomized, double-blind, longitudinal study, 30 postmenopausal women underwent treatment with either a combination of oral 17β-estradiol valerate and micronized progesterone (group 1, n=10), oral 17β-estradiol valerate (group 2, n=10), or placebo (group 3, n=10). Two PET measurements were performed, one the day before treatment start and the second after at least eight weeks of treatment. Plasma levels of estradiol (E₂), progesterone (P₄), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were collected prior to PET measurements. As expected, hormone replacement therapy led to a significant increase in E₂ and P4 plasma levels in group 1 and to a significant increase in E₂ levels in group 2. The 5-HT₁A receptor binding did not change significantly after estrogen, combined estrogen/progesterone treatment or placebo in any of the investigated brain regions. There were no significant correlations between changes in E₂ or P4 values and changes in 5-HT₁A receptor binding. Although we were not able to confirm effects of gonadal hormone treatment on 5-HT₁A receptor binding, our data do not preclude associations between sex steroid levels and serotonin, the neurotransmitter implicated most strongly in the pathogenesis of affective and anxiety disorders. ClinicalTrials.gov Identifier: NCT00755963.