Walter J. Meyer

Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7

ABSTRACT The Standards of Care (SOC) for the Health of Transsexual, Transgender, and Gender Nonconforming People is a publication of the World Professional Association for Transgender Health (WPATH). The overall goal of the SOC is to provide clinical guidance for health professionals to assist transsexual, transgender, and gender nonconforming people with safe and effective pathways to achieving lasting personal comfort with their gendered selves, in order to maximize their overall health, psychological well-being, and self-fulfillment. This assistance may include primary care, gynecologic and urologic care, reproductive options, voice and communication therapy, mental health services (e.g., assessment, counseling, psychotherapy), and hormonal and surgical treatments. The SOC are based on the best available science and expert professional consensus. Because most of the research and experience in this field comes from a North American and Western European perspective, adaptations of the SOC to other parts of the world are necessary. The SOC articulate standards of care while acknowledging the role of making informed choices and the value of harm reduction approaches. In addition, this version of the SOC recognizes that treatment for gender dysphoria i.e., discomfort or distress that is caused by a discrepancy between persons gender identity and that persons sex assigned at birth (and the associated gender role and/or primary and secondary sex characteristics) has become more individualized. Some individuals who present for care will have made significant self-directed progress towards gender role changes or other resolutions regarding their gender identity or gender dysphoria. Other individuals will require more intensive services. Health professionals can use the SOC to help patients consider the full range of health services open to them, in accordance with their clinical needs and goals for gender expression.

Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline

OBJECTIVE The aim was to formulate practice guidelines for endocrine treatment of transsexual persons. EVIDENCE This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence, which was low or very low. CONSENSUS PROCESS Committees and members of The Endocrine Society, European Society of Endocrinology, European Society for Paediatric Endocrinology, Lawson Wilkins Pediatric Endocrine Society, and World Professional Association for Transgender Health commented on preliminary drafts of these guidelines. CONCLUSIONS Transsexual persons seeking to develop the physical characteristics of the desired gender require a safe, effective hormone regimen that will 1) suppress endogenous hormone secretion determined by the persons genetic/biologic sex and 2) maintain sex hormone levels within the normal range for the persons desired gender. A mental health professional (MHP) must recommend endocrine treatment and participate in ongoing care throughout the endocrine transition and decision for surgical sex reassignment. The endocrinologist must confirm the diagnostic criteria the MHP used to make these recommendations. Because a diagnosis of transsexualism in a prepubertal child cannot be made with certainty, we do not recommend endocrine treatment of prepubertal children. We recommend treating transsexual adolescents (Tanner stage 2) by suppressing puberty with GnRH analogues until age 16 years old, after which cross-sex hormones may be given. We suggest suppressing endogenous sex hormones, maintaining physiologic levels of gender-appropriate sex hormones and monitoring for known risks in adult transsexual persons.

Trauma in the elderly: Intensive care unit resource use and outcome

BACKGROUND As the population ages, the elderly will constitute a prominent proportion of trauma patients. The elderly suffer more severe consequences from traumatic injuries compared with the young, presumably resulting in increased resource use. In this study, we sought to examine ICU resource use in trauma on the basis of age and injury severity. METHODS This study was a retrospective review of trauma registry data prospectively collected on 26,237 blunt trauma patients admitted to all trauma centers (n = 26) in one state over 24 months (January 1996-December 1997). Age-dependent and injury severity-dependent differences in mortality, ICU length of stay (LOS), and hospital LOS were evaluated by logistic regression analysis. RESULTS Elderly (age > or = 65 years, n = 7,117) patients had significantly higher mortality rates than younger (age < 65 years) trauma patients after stratification by Injury Severity Score (ISS), Revised Trauma Score, and other preexisting comorbidities. Age > 65 years was associated with a two- to threefold increased mortality risk in mild (ISS < 15, 3.2% vs. 0.4%; < 0.001), moderate (ISS 15-29, 19.7% vs. 5.4%; < 0.001), and severe traumatic injury (ISS > or = 30, 47.8% vs. 21.7%; < 0.001) compared with patients aged < 65 years. Logistic regression analysis confirmed that elderly patients had a nearly twofold increased mortality risk (odds ratio, 1.87; confidence interval, 1.60-2.18; < 0.001). Elderly patients also had significantly longer hospital LOS after stratifying for severity of injury by ISS (1.9 fewer days in the age 18-45 group, 0.89 fewer days in the age 46-64 group compared with the age > or = 65 group). Mortality rates were higher for men than for women only in the ISS < 15 (4.4% vs. 2.6%, < 0.001) and ISS 15 to 29 (21.7% vs. 17.6%, = 0.031) groups. ICU LOS was significantly decreased in elderly patients with ISS > or = 30. CONCLUSION Age is confirmed as an independent predictor of outcome (mortality) in trauma after stratification for injury severity in this largest study of elderly trauma patients to date. Elderly patients with severe injury (ISS > 30) have decreased ICU resource use secondary to associated increased mortality rates.

Comorbidity of gender dysphoria and other major psychiatric diagnoses.

Previous studies suggest that many transsexuals evidence an Axis I diagnosis according to the DSM-IV classification (e.g., psychoses, major affective disorder). The current study examined retrospectively the comorbidity between gender dysphoria and major psychopathology, evaluating the charts of 435 gender dysphoric individuals (318 male and 117 female). AH had undergone an extensive evaluation, addressing such areas as hormonal/surgical treatment, and histories of substance abuse, mental illness, genital mutilation, and suicide attempts. In addition, a subgroup of 137 individuals completed the MMPI. Findings revealed over two thirds were undergoing hormone reassignment, suggesting a commitment to the real-life cross-gender process. One quarter had had problems with substance abuse prior to entering treatment, but less than 10% evidenced problems associated with mental illness, genital mutilation, or suicide attempts. Those completing the MMPI (93 female and 44 male) demonstrated profiles that were notably free of psychopathology (e.g., Axis I or Axis II criteria). The one scale where significant differences were observed was the Mf scale, and this held true only for the male-to-female group. Psychological profiles as measured by the MMPI were more “normal” in the desired sex than the anatomic sex. Results support the view that transsexualism is usually an isolated diagnosis and not part of any general psychopathological disorder.

Virtual Reality as an Adjunctive Non-pharmacologic Analgesic for Acute Burn Pain During Medical Procedures

IntroductionExcessive pain during medical procedures is a widespread problem but is especially problematic during daily wound care of patients with severe burn injuries.MethodsBurn patients report 35–50% reductions in procedural pain while in a distracting immersive virtual reality, and fMRI brain scans show associated reductions in pain-related brain activity during VR. VR distraction appears to be most effective for patients with the highest pain intensity levels. VR is thought to reduce pain by directing patients’ attention into the virtual world, leaving less attention available to process incoming neural signals from pain receptors.ConclusionsWe review evidence from clinical and laboratory research studies exploring Virtual Reality analgesia, concentrating primarily on the work ongoing within our group. We briefly describe how VR pain distraction systems have been tailored to the unique needs of burn patients to date, and speculate about how VR systems could be tailored to the needs of other patient populations in the future.

Imipramine treatment in Pediatric burn patients with symptoms of acute stress disorder : A pilot study

OBJECTIVE Pediatric burn patients often exhibit acute stress disorder (ASD) symptoms. Information on psychopharmacological treatment of ASD symptoms in children is scarce. This pilot study used a prospective, randomized, double-blind design to test whether thermally injured children suffering ASD symptoms benefit from imipramine. METHOD Twenty-five children, aged 2 to 19 years, received either imipramine or chloral hydrate for 7 days. A structured interview (clinically useful, but validity and reliability not yet established) was used to assess the presence and frequency of ASD symptoms both before treatment and 3 times during the treatment period. RESULTS Eleven females and 14 males participated, with a mean total burn surface area of 45% (SD = 23%) and mean age of 8 years (SD = 6). Imipramine was more effective than chloral hydrate in treating ASD symptoms (chi 2 [1, N = 25] = 5.24, p < .02). Five of 13 were positive responders to chloral hydrate (38%). Ten of 12 were positive responders to low-dose imipramine (83%). CONCLUSIONS This pilot study suggests a place for cautious initial use of imipramine to reduce ASD symptoms in burned children. Care must be taken to minimize cardiovascular risks in an off-label application of imipramine in children, especially those receiving additional medications.

Abnormal Insulin Sensitivity Persists up to Three Years in Pediatric Patients Post-Burn

CONTEXT The acute hypermetabolic response post-burn is associated with insulin resistance and hyperglycemia, significantly contributing to adverse outcome of these patients. OBJECTIVE The aim of the study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree of insulin resistance in severely burned children for up to 3 yr after the burn injury. DESIGN, SETTING AND PATIENTS A total of 194 severely burned pediatric patients, admitted to our institute between 2002 and 2007, were enrolled in this prospective study and compared to a cohort of 95 nonburned, noninjured children. MAIN OUTCOME MEASURES Urinary cortisol, epinephrine, and norepinephrine, serum cytokines, and resting energy requirements were determined at admission and 1, 2, 6, 9, 12, 18, 24, and 36 months post-burn. A 75-g oral glucose tolerance test was performed at similar time points; serum glucose, insulin, and C-peptide were measured; and insulin sensitivity indices, such as ISI Matsuda, homeostasis model assessment, quantitative insulin sensitivity check index, and ISI Cederholm, were calculated. Statistical analysis was performed by ANOVA with Bonferroni correction with significance accepted at P < 0.05. RESULTS Urinary cortisol and catecholamines, serum IL-7, IL-10, IL-12, macrophage inflammatory protein-1b, monocyte chemoattractant protein-1, and resting energy requirements were significantly increased for up to 36 months post-burn (P < 0.05). Glucose values were significantly augmented for 6 months post-burn (P < 0.05), associated with significant increases in serum C-peptide and insulin that remained significantly increased for 36 months compared to nonburned children (P < 0.05). Insulin sensitivity indices, ISI Matsuda, ISI quantitative insulin sensitivity check index, and homeostasis model assessment were abnormal throughout the whole study period, indicating peripheral and whole body insulin resistance. The insulinogenic index displayed physiological values, indicating normal pancreatic beta-cell function. CONCLUSIONS A severe burn is associated with stress-induced insulin resistance that persists not only during the acute phase but also for up to 3 yr post-burn.

Mineralocorticoid binding in cultured smooth muscle cells and fibroblasts from rat aorta

Based on changes in electrolyte content, the direct action of adrenal steroids on blood vessel wall has been postulated for many years. High affinity corticosteroid binding sites have been found in both smooth muscle and fibroblast cultures from aortic explants of Sprague-Dawley rats. [3H]-aldosterone and [3H]-corticosterone bind to the same two distinct classes of sites: (a) corticoid receptor I with a Kd ranging from 0.11 to 1.31 × 10−9 M and a Bmax ranging from 22 to 282 mol × 10−18/μg DNA (measured by either steroid); (b) corticoid receptor II with a Kd ranging from 2.09 to 20.83 × 10−9 M and a Binmax ranging from 97 to 1410 mol × 10−18/μg DNA (measured by [3H]-aldostcronc) or a Bmax ranging from 1336 to 5520 mol × 10−18/μg DNA (measured by [3H]-corticosterone or [3H]-dexamethasone). Corticoid receptor I is easily detected by [3H]-aldostcrone in the presence of 40 nM dexamethasone and is not detected by [3H]-dexamethasone alone. Displacement experiments with corticoid receptor I labeled with [3H]-aldoslerone indicate the following hierarchy of binding: corticosterone ⩾ desoxycorticosterone ⩾ aldosterone > cortisol ⩾ dexamethasone > 17β-estradiol = 5α-dihydrotestosterone. Displacement experiments with corticoid receptor II labeled with [3H]-dexamethasone indicate the following binding hierarchy: corticosterone = desoxycorticosterone = cortisol = dexamethasone > aldosterone > 17β-estradiol = 5α-dihydrotestosterone. The steroid specificity of corticoid receptor I is unique and distinguishes these sites from classical mineralocorticoid or glucocorticoid receptors. These sites may mediate new physiological effects of corticosterone, desoxycorticosterone and/or aldosterone in vascular tissue.

Insulin resistance with acanthosis nigricans: The roles of obesity and androgen excess☆

The roles of hyperandrogenemia and obesity in the syndrome of severe insulin resistance with acanthosis nigricans were evaluated in studies of 11 females with this condition. Our results in these subjects were compared to evaluations of control subjects matched for degree of androgen excess or obesity. Fasting insulin levels were 3-, 5-, and 15-fold higher in the obese (OB), hyperandrogenemic (HO), and acanthosis nigricans (AN) groups, respectively, when compared to normal females. Responsiveness to a standard bolus of exogenous insulin was 78% of normal in the OB group, 40% of normal in the HO group, and 30% of normal in the AN group. Insulin binding to monocytes from both the OB group, and the HO group was modestly diminished primarily due to decreased receptor number. As a group, AN subjects when compared to either normal or weight-matched controls, demonstrated a significant decrease in monocyte insulin binding predominantly due to a decrease in receptor number. However, two patients in the AN group had normal insulin binding suggesting a postreceptor mechanism for the insulin resistance in at least some of these subjects. In vivo glucose utilization insulin dose response curves were determined in 3 acanthotic subjects using the euglycemic clamp technique. All 3 of these subjects had a right shift of the curve and diminished maximal utilization, consistent with combined receptor and postreceptor defects in insulin action. In evaluating the relationship between hyperandrogenemia, insulin resistance, and acanthosis nigricans, significant correlations among basal levels of plasma insulin, and both testosterone and androstenedione were demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen receptor in human skin fibroblasts characterization of a specific 17β-hydroxy-5α-androstan-3-one-protein complex in cell sonicates and nuclei☆

Cultured human skin fibroblasts were shown to contain an androgen binding activity (receptor) which was heat-labile and destroyed by trypsin. Specific binding was seen after incubations of these cells with 1,2-3-H-testosterone, 1,2-3-H17beta-hydroxy-5alpha-androstan-3-one (dihydrotestosterone, DHT) and 1,2-3-H-5alpha-androstane-3alpha, 17beta-diol. This receptor had a high affinity (Kd=0,2-1.6 nM) and a high degree of specificity for DHT. It was measured as a 3-H-DHT-protein complex by gel filtration chromatography using a method which distinguishes specific from nonspecific binding. Receptor activity was distributed about equally between nuclear and extranuclear components at all times studied and was present in both compartments when cell incubations were carried out at 4 degrees and 37 degrees. Saturation analysis indicated that there were 1250-18,600 binding sites per whole cell. By sucrose gradient centrifugation the receptor had a sedimentation coefficient (S20,w) of about 4. Cells grown for 8 days without serum in the medium maintained the same levels of 3-H-DHT binding. Within 15 hours puromycin (20 mug/ml) in serum-free medium caused a 40-60 percent decrease in binding for the same cell lines. Although the highest levels of 3-H-DHT binding were observed in fibroblasts from newborn foreskin, appreciable cytosol and nuclear binding were seen in cells from forearm, neck and abdominal skin. Receptor activity was stable during prolonged culture. Fibroblasts from several skin sites from patients with the androgen insensitivity syndrome (testicular feminization) had no detectable specific DHT binding. In this study it was demonstrated that skin fibroblasts can rapidly convert testosterone to its active form, DHT, bind DHT to a specific receptor protein and transport this complex to their nuclei. Therefore this may prove to be a convenient system for studying androgen action in vitro.