A Simple Intervention Raised Resident-Physician Willingness to Assist Transgender Patients Seeking Hormone Therapy

Objective: Lack of physician knowledge about transgender medicine is a barrier to care. An intervention with medical students changed attitudes about providing transgender medical care, but it is unknown whether at the level of postgraduate education an intervention could have a similar effect. We conducted such an intervention with resident-physicians.Methods: An intervention on transgender medicine covering the durability of gender identity and hormonal treatment regimens was added to the curriculum for residents. An anonymous survey assessed the residents' knowledge and willingness to assist with hormonal therapy before and after the lecture.Results: The percent of residents who agreed that they felt sufficiently knowledgeable to assist with hormonal therapy for a female-to-male patient increased significantly, from 5% before to 76% following the lecture (χ², 24.7; degrees of freedom, 1; P<.001). The percent of residents who reported that they felt sufficiently knowledgeable to assist with hormonal therapy for a male-to-female patient increased significantly, from 5% before to 71% following the lecture (χ², 24.0; degrees of freedom, 1; P<.001). The intervention increased resident knowledge about hormonal therapy for hypogonadal men (χ², 11.4; degrees of freedom, 1; P<.001) and women (χ², 9.4; degrees of freedom, 1; P = .002). The intervention made more residents agree that gender identity has a biologic basis that remains constant (P<.001) and that hormonal and surgical therapies should be offered (P = .047).Conclusion: The lecture significantly increased residents' knowledge and willingness to assist with hormonal therapy for transgender patients.Abbreviation: PGY = postgraduate year     

A Simple Curriculum Content Change Increased Medical Student Comfort with Transgender Medicine

ObjectiveA barrier to safe therapy for transgender patients is lack of access to care. Because transgender medicine is rarely taught in medical curricula, few physicians are comfortable with the treatment of transgender conditions. Our objective was to demonstrate that a simple content change in a medical school curriculum would increase students' willingness to care for transgender patients.MethodsCurriculum content was added to the endocrinology unit of the Boston University second-year pathophysiology course regarding rigidity of gender identity, treatment regimens, and monitoring requirements. All medical students received an online, anonymous questionnaire 1 month prior to and 1 month after receiving the transgender teaching. The questionnaire asked about predicted comfort using hormones to treat transgender individuals. Shifts in the views of the second-year students were compared with views of students not exposed to the curriculum change.ResultsPrior to the unit, 38% of students self-reported anticipated discomfort with caring for transgender patients. In addition, 5% of students reported that the treatment was not a part of conventional medicine. Students in the second-year class were no different than other students. Subsequent to the teaching unit, the second-year students reported a 67% drop in discomfort with providing transgender care (P<.001), and no second-year students reported the opinion that treatment was not a part of conventional medicine.ConclusionA simple change in the content of the second-year medical school curriculum significantly increased students' self-reported willingness to care for transgender patients.(Endocr Pract. 2013;19:633-637)     

Observed Deficiencies in Medical Student Knowledge of Transgender and Intersex Health

Objective: Lesbian, gay, bisexual, transgender, and intersex (LGBTI) patients face many well-documented disparities in care which among transgender and intersex people can often be traced to providers' lack of knowledge.Methods: We administered surveys to examine the self-assessed knowledge and attitudes of all medical students at Boston University regarding different LGBTI subpopulations. Survey questions were based on a Likert scale from 1 to 5; analysis was conducted with Wilcoxon rank sum tests.Results: Overall there was a response rate of 24%, with the number of responses varying by class. Three of the 4 surveyed classes reported lower knowledge about transgender health than LGB health. Every class reported significantly lower knowledge of intersex health in comparison to LGB. Comfort with transgender or with intersex patients was lower than with LGB patients for all surveyed classes. Students across all self-identified groups (LGBTI, ally, not an ally) reported significantly lower average responses for knowledge and comfort regarding transgender or intersex health in comparison to that of LGB. Students in their preclinical years reported lower levels of knowledge in comparison with students in their clinical years. Students who identified as LGBTI reported significantly higher knowledge and comfort with only LGB and transgender health when compared with students who didn't identify as LGBTI. Respondents more frequently requested additional learning opportunities in transgender and intersex health than in LGB health.Conclusion: Self-reported knowledge of transgender and intersex health lags behind knowledge of LGB health, though these deficits appear partially responsive to targeted educational intervention.Abbreviations: BUSM = Boston University School of Medicine LGB = lesbian, gay, and bisexual LGBT = lesbian, gay, bisexual, and transgender LGBTI = lesbian, gay, bisexual, transgender, and intersex M1 = first-year medical student class M2 = second-year medical student class M3 = third-year medical student class M4 = fourth-year medical student class     

Testosterone Levels Achieved by Medically Treated Transgender Women in a United States Endocrinology Clinic Cohort

Objective: Most transgender women depend on medical treatment alone to lower testosterone levels in order to align physical appearance with gender identity. The medical regimen in the United States typically includes spironolactone and estrogens. The purpose of this cross-sectional study was to assess the testosterone suppression achieved among transgender women treated with spironolactone and estrogens.Methods: Testosterone and estradiol levels were extracted from the electronic medical records of 98 anonymized transgender women treated with oral spironolactone and oral estrogen therapy at the Endocrinology Clinic at Boston Medical Center.Results: Patients starting therapy required about 9 months to reach a steady-state testosterone, with significant heterogeneity of levels achieved among patients. Patients with normal body mass index (BMI) had higher testosterone levels, whereas patients with obese BMI had lower testosterone levels throughout treatment. Stratification of patients by age or spironolactone dosage revealed no significant difference in testosterone levels achieved. At steady state, patients in the highest suppressing quartile were able to achieve testosterone levels of 27 ng/dL, with a standard deviation of 21 ng/dL. Measured serum estradiol levels did not change over time and did not correlate with dosage of estradiol administered.Conclusion: Among a cohort of transgender women treated with spironolactone and estrogen, the highest suppressing quartile could reliably achieve testosterone levels in the female range at virtually all times. The second highest suppressing quartile could not achieve female levels but remained below the male range virtually all of the time. One quartile was unable to achieve any significant suppression.Abbreviations:BMC = Boston Medical CenterBMI = body mass indexCPY = cyproterone acetateLC-MS/MS = liquid chromatography–tandem mass spectrometryQ = quartile     

Evidence Supporting the Biologic Nature of Gender Identity1

ObjectiveTo review current literature that supports a biologic basis of gender identity.MethodsA traditional literature review.ResultsEvidence that there is a biologic basis for gender identity primarily involves (1) data on gender identity in patients with disorders of sex development (DSDs, also known as differences of sex development) along with (2) neuroanatomical differences associated with gender identity.ConclusionsAlthough the mechanisms remain to be determined, there is strong support in the literature for a biologic basis of gender identity. (Endocr Pract. 2015;21: 199-204)     

Transgender Care by Endocrinologists in the United States

Objective: Little is known about the attitudes and practice patterns of transgender care by endocrinologists. The objective of this study was to assess the knowledge, practice patterns, access, and competency among a representative sample of endocrinologists in the mid-Atlantic region of the United States.Methods: An anonymous 19-item paper survey was administered to 80 conference attendees that included 61 adult endocrinologists, 13 endocrinology fellows, 2 pediatric endocrinologists, and 4 nurse practitioners/physician assistants.Results: The participation rate was estimated to be ~80%. Sixty-three percent of endocrinology providers were willing to provide transgender care, but the majority of providers had no current transgender patients under their care. Half of providers had read the Endocrine Society's clinical practice guidelines, with a rate of 70% among those under age 40. Nonetheless, only 20% were “very” comfortable in discussing gender identity and/or sexual orientation, and 41% described themselves as “somewhat” or “very” competent to provider transgender care.Conclusion: Endocrinologists and other providers have received more education and training on transgender care within the past decade. Nevertheless, many participants have had little opportunity to care for transgender patients, and they rate their competency to do so as low. Research is needed on how to increase comfort levels regarding gender identity among those who provider care to transgender patients.     

Children and Adolescents with Gender Dysphoria in Israel: Increasing Referral and Fertility Preservation Rates

Objective: To describe patient characteristics at presentation, management, and fertility preservation rates among a cohort of Israeli children and adolescents with gender dysphoria (GD).Methods: We performed a retrospective chart review of 106 consecutive children and adolescents with GD (<18 years) referred to and followed at the multidisciplinary Israeli Pediatric Gender Dysphoria Clinic from March 2013 through December 2018.Results: Of the 106 patients, 10 were prepubertal (9 prepubertal transgender females), and 96 were pubertal (38 pubertal transgender females). The GD population increased 11-fold since the establishment of our clinic in 2013. The subject's median age at referral was 15.5 years (range, 4.6 to 18 years). At the time of referral, 91 (95%) of the pubertal group had completed sexual maturation in their assigned gender at birth. Thirteen (13.5%) patients had attempted suicide, and 11 (11.5%) reported having had suicidal thoughts. Fourteen (45%) pubertal transgender females and 3 (6.5%) pubertal transgender males completed fertility preservation. Gonadotropin-releasing hormone analog treatment was prescribed in 77 (80%) patients at a mean age of 15.9 ± 1.6 years. Gender-affirming hormones were prescribed in 61 (64%) patients at a mean age of 16.5 ± 1.3 years. No severe side effects were recorded. Two (2%) of the pubertal group expressed regret about medical treatment.Conclusion: Children and adolescents with GD are presenting for medical attention at increasing rates. Israeli adolescents with GD have high fertility preservation rates, perhaps attributable to cultural perspectives. Taking advantage of the option to preserve fertility can be achieved when proper counseling is both available and promoted by medical personnel.Abbreviations: GAH = gender-affirming hormone; GD = gender dysphoria; GnRHa = gonadotropin-releasing hormone analog; MHP = mental health professional     

High Body Mass Index is A Significant Barrier to Gender-Confirmation Surgery for Transgender and Gender-Nonbinary Individuals

Objective: Transgender and gender-nonbinary individuals (TGNB) are disproportionately impacted by obesity. In addition to the associated health impact, obesity represents a significant barrier to accessing gender-confirmation surgery (GCS). The purpose of this study was to determine the prevalence of obesity among TGNB surgical candidates at an urban academic medical center and evaluate the efficacy of self-monitored weight management.Methods: The study was conducted at the Center for Transgender Medicine and Surgery at Mount Sinai in New York City. Data abstraction from a quality improvement database was completed for patients with a documented body mass index (BMI) and a GCS consult from October 2015 through February 2019. A total of 1,457 TGNB patients with a documented BMI and a GCS consult in the historical period of review were included in analysis. Data were abstracted to determine the prevalence of obesity among GCS candidates and evaluate the current default pre-operative self-monitored weight management protocol.Results: Of 1,457 TGNB patients, 382 (26%) were obese (BMI ≥30 kg/m²) at initial surgical consult. In addition, 369 (27%) were obese at a subsequent follow-up, suggesting no statistically significant change in the rate of obesity among evaluated TGNB despite self-monitored weight management (P = .5272).Conclusion: Obesity is a significant barrier to gender affirming surgery for transgender individuals. Self-monitored weight management is an unsuccessful strategy for improvement even among individuals who would be predicted to be motivated.Abbreviations: BMI = body mass index; CTMS = Center for Transgender Medicine and Surgery (at Mount Sinai); GCS = gender confirmation surgery; TGNB = transgender and gender-nonbinary     

Endocrinology Fellows' Perception of Their Confidence and Skill Level in Providing Transgender Healthcare

Objective: Both educational content and hours devoted to transgender health training of endocrinology fellows are suboptimal. The objective of this study was to assess the perspectives of endocrinology fellows on their training in transgender health.Methods: We evaluated the state of comfort and knowledge of transgender healthcare among endocrinology fellows attending Endocrine University. Surveys were administered to fellows before and after their participation in a case-based session on transgender health.Results: The majority of fellows felt that training in transgender health is important (95.9%, 189/197); however, only 58.9% reported inclusion of dedicated transgender content in their training programs. Fellows who had received transgender healthcare education, and those who had seen more transgender patients in their training, were more likely to be confident in treating patients with hormone therapy (P<.001 and P<.0001, respectively). Following the case-based session, 62.4 % of fellows reported that they would change their practice, 72.8% felt that their comfort level with transgender care had improved, and 91% felt that transgender content such as that provided in the educational session should be mandatory in endocrinology training programs. Methods most desired by fellows to improve their education included lectures from visiting professors (70.3%), participation in elective rotations (62.1%), online training modules (57.9%), and attendance at meetings with transgender topics (57.4%).Conclusion: Transgender health education of U.S. endocrinology fellows is suboptimal. Participation in a case-based session significantly increased the comfort level of endocrinology fellows in key areas of transgender health.Abbreviation: ACGME = Accreditation Council for Graduate Medical Education     

Meta-Analysis Shows Associations Of Digit Ratio (2D:4D) And Transgender Identity Are Small At Best

Abbreviations: 2D:4D = digit ratio; CI = confidence interval; F = female; FtM = female-to-male transgender; M = male; MtF = male-to-female transgender; TGI = transgender identity     

Prolactin Levels Do Not Rise Among Transgender Women Treated With Estradiol and Spironolactone

Objective: Existing transgender treatment guidelines suggest that there is a need to monitor prolactin levels in patients receiving transfeminine hormone treatment. Also, recent studies suggest that use of cyproterone acetate as an adjunctive anti-androgen during transgender hormone treatment may elevate serum prolactin. We sought to determine whether the reported relationship between transfeminine estradiol treatment and hyperprolactinemia would be evident when the regimen used spironolactone as the adjunctive anti-androgen.Methods: Estradiol levels, testosterone levels, prolactin levels, body mass index (BMI), and prescribed spironolactone dosage were extracted from the electronic medical records of 98 de-identified transgender women treated with estrogen therapy at the Endocrinology Clinic at Boston Medical Center (BMC). Up to 6 years of data were available for some patients.Results: We found no statistically significant relationship between prolactin and any of the other measures. No estrogen dose-associated elevations in prolactin were found. None of the patients were diagnosed with prolactinoma.Conclusion: Our data suggest that there may be no significant rise in prolactin when transgender women are treated with estrogen along with spironolactone as the adjunct anti-androgen. It may be unnecessary to monitor prolactin in patients on this treatment combination.Abbreviations: BMI = body mass index; BMC = Boston Medical Center; HT = hormone therapy     

Metabolic Effects Of Hormone Therapy In Transgender Patients

Objective: Transgender patients may seek hormone therapy to induce physical changes to simulate their expressed or experienced gender. However, many providers are uncomfortable prescribing transgender hormones due to fears over safety. The goal of this study was to determine if transgender hormone therapy with estrogen and spironolactone for male-to-female (MtF) patients or with testosterone for female-to-male (FtM) patients had adverse anthropomorphic or metabolic effects.Methods: This retrospective chart review study analyzed changes over time for 33 MtF and 19 FtM endocrine clinic patients at an academic endocrine practice with follow-up for up to 18 months after hormone initiation.Results: Compared to baseline labs obtained prior to the initiation of hormone therapy, significant changes for the MtF cohort included an increase in high-density lipoprotein (HDL) and decrease in creatinine; however, triglycerides did not show a statistically significant change. In the FtM cohort, there were significant increases in body mass index, creatinine, hemoglobin, and hematocrit. Although statistically significant, these changes were minimal for both cohorts.Conclusion: In our practice, hormone therapy was found to be safe in this retrospective study.Abbreviations:BMI = body mass indexFtM = female-to-maleHDL = high-density lipoproteinLDL = low-density lipoproteinMtF = male-to-female     

Women with Nonclassic Congenital Adrenal Hyperplasia Have Gender,Sexuality, and Quality-Of-Life Features Similar to those of Nonaffected Women

Objective: Females with the severe classic forms of congenital adrenal hyperplasia reportedly have a higher frequency of atypical gender identity, nonheterosexual sexual relationships, and cross-gender role behavior. Comparable data and quality-of-life measures among those with the milder, more prevalent form, nonclassic congenital adrenal hyperplasia, are scarce. We aimed to assess health-related quality of life, gender identity, role, and sexual orientation in women with nonclassic congenital adrenal hyperplasia via a prospective, questionnaire-based, case-control study.Methods: Thirty-eight women with nonclassic congenital adrenal hyperplasia (median age 34 years; range, 18 to 44 years) and 62 age-matched female controls were recruited. Outcome measures included the Multi-Gender Identity, Sexuality, and World Health Organization (WHO) quality-of-life questionnaires.Results: Sociodemographic parameters (marital status, number of children, and educational level) were similar for both groups, as were most measures of the Multi-Gender Identity, Sexuality, and WHO quality-of-life questionnaires. However, “sometimes-feeling-as-a-man and sometimes-feeling-as-a-woman” were more frequently reported in the study group compared to the controls (7/38 [18.4%] vs. 3/62 [4.8%], respectively; P = .02). Furthermore, more nonclassic congenital adrenal hyperplasia women reported first falling in love with a woman (4/37 [10.8%] vs. 0/58 [0%]; P = .02).Conclusion: Our findings suggest possible subtle differences in gender identity and sexual orientation between adult nonclassic congenital adrenal hyperplasia females and controls. Quality of life was not impaired in individuals within the study group. The impact of exposure to mildly elevated androgen levels during childhood and adolescence on the female brain warrants more in-depth assessment in further studies.Abbreviations: CAH = congenital adrenal hyperplasia; Multi-GIQ = Multi-Gender Identity Questionnaire; NCCAH = nonclassic congenital adrenal hyperplasia; QoL = quality of life     

Estrogen Levels Do Not Rise With Testosterone Treatment For Transgender Men

Objective: Existing transgender treatment guidelines suggest that for transmasculine treatment, there is a possible need for estrogen-lowering strategies adjunct to testosterone therapy. Further, guidelines advocate consideration of prophylactic female reproductive tissue surgeries for transgender men to avoid the possibility of estrogen-related health risks. Despite the paucity of objective data, some transgender men seek conversion inhibitors. We sought to determine estradiol levels in transgender men treated with testosterone therapy and the change in those levels with treatment, if any.Methods: Estradiol levels were extracted from the electronic medical records of 34 anonymized transgender men treated with testosterone therapy at the Endocrinology Clinic at Boston Medical Center. Data were sufficient to observe 6 years of follow-up.Results: With increased testosterone levels in trans-gender men, a significant decrease in estradiol levels was noted. There was a significant negative correlation between testosterone levels and body mass index, which may serve to explain part of the mechanism for the fall in estradiol levels. Even though the fall in estradiol levels was significant statistically, the actual levels remained within the normal male range, even with 6 years of follow-up.Conclusion: These data suggest that when exogenous testosterone is used to achieve normal serum male testosterone levels for transgender men, it is converted to normal male levels of estradiol, with some decline in those estradiol levels that might be attributable to a fall in fat mass. There appears to be no role for aromatase conversion inhibitors or other estrogen-reducing strategies in trans-gender men.Abbreviation: BMI = body mass index     

Clinical Characteristics and Sequelae of Severe Hypertriglyceridemia in Pediatrics

Objective: Severe hypertriglyceridemia (HTG) (i.e., plasma triglycerides [TGs] >1,000 mg/dL) in children is a rare but pernicious and understudied condition. Our objective was to evaluate the etiology, characteristics, and sequelae of severe pediatric HTG.Methods: This was a retrospective electronic medical record review of pediatric patients with severe HTG at a tertiary referral Children's hospital over a 17-year period.Results: There were a total of 124 patients with severe HTG. The etiology varied: hemato-oncologic (n = 48), diabetes and insulin resistance–related (n = 46), total parenteral nutrition (TPN)-related (n = 6), renal (n = 12), and miscellaneous (n = 12). There was considerable variability in the number of days for the plasma TGs to decrease to <1,000 mg/dL (147.7 ± 567.3 days) and to further decrease to <500 mg/dL (136.84 ± 230.9 days). Patients with diabetes required the longest time to improve their plasma TGs (165.8 ± 305.7 days) compared to other groups. There were 11 cases of pancreatitis, comorbid with diabetes (n = 5), hemato-oncologic conditions (n = 3), and TPN (n = 3). Sixty-seven patients (54%) had persistent HTG.Conclusion: Severe HTG in pediatrics is commonly due to secondary causes. Patients with diabetes tend to have a longer course of dyslipidemia. A substantial number of patients had persistent dyslipidemia, indicating underlying genetic susceptibility to HTG that is phenotypically expressed consequent to a secondary metabolic insult.Abbreviations: DKA = diabetic ketoacidosis; EMR = electronic medical record; GSD = glycogen storage disorder; HbA1c = hemoglobin A1c; HIV = human immunodeficiency virus; HTG = hypertriglyceridemia; ICD-9 = International Classification of Diseases–Ninth Revision; IV = intravenous; LCHAD = long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency; LPL = lipoprotein lipase; NPO = nothing by mouth; PCOS = polycystic ovary syndrome; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus; TG = triglyceride; TPN = total parenteral nutrition; VLDL = very-low-density lipoprotein     

Current Knowledge and Practices of Heath Care Professionals on Opioid-Induced Adrenal Insufficiency

Objective: Opioid-induced adrenal insufficiency (OIAI) is reported in up to 29% of chronic opioid users through suppression of the hypothalamus-pituitary-adrenal axis. Unrecognized adrenal insufficiency leads to increased morbidity and potentially death; thus, healthcare provider (HCP) awareness of OIAI is crucial. The aim of the present study was to assess the knowledge and current practices of HCPs regarding OIAI and to identify factors associated with decreased awareness.Methods: We carried out a cross-sectional, anonymous survey of HCPs in internal medicine specialties that prescribe or care for patients taking chronic opioids.Results: Of 91 (30%) participants who completed the survey, 51 (56%) were men and 52 (57%) were in training. Most responders were general internal medicine providers (n = 33, 36%), followed by endocrinologists (n = 13, 14%) and various other specialties (n = 45, 49%). While 61 (67%) of respondents prescribed opioids, only 17 (19%) were comfortable in their knowledge of opioid side effects. Among nonendocrine providers, 53 (68%) identified adrenal insufficiency as a known opioid-induced endocrinopathy. Compared to other providers, endocrinologists were more likely to recognize opioid-related endocrinopathies (69% versus 24%, P = .01) and to identify the correct symptoms for OIAI (38% versus 9%, P <.001). One in four nonendocrine providers reported discomfort in managing glucocorticoid replacement therapy. The majority (60%) of providers indicated that online resources and continuing medical education lectures would improve knowledge of OIAI.Conclusion: Our study identified several deficiencies in HCP knowledge of opioid-induced endocrine effects, especially in nonendocrine providers. As many symptoms of OIAI overlap with those of underlying conditions, OIAI could be potentially missed, highlighting the need to further educate providers about opioid-induced endocrinopathies.Abbreviations: ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; CME = continuing medical education; HCP = healthcare professional; OIAI = opioid-induced adrenal insufficiency     

HbA1c and Blood Pressure Measurements: Relation with Gender,Body Mass Index,Study Field,and Lifestyle in Lebanese Students

Objective: The purpose of this study is to determine the prevalence of prediabetes/diabetes in Lebanese university students and to examine the relationship between both hemoglobin A1c (HbA1c) and blood pressure (BP) and gender, body mass index (BMI), study field, and lifestyle factors.Methods: This cross-sectional study was carried out at the Saint-Joseph University of Beirut. A total of 603 students aged 18 to 25 years were recruited from both the medical science campus (MSC) and the social science campus (SSC) between January, 2016, and May, 2018. Waist circumference (WC), BMI, and BP were determined for each student and HbA1c was measured using the Siemens vintage DCA device. Participants completed a self-administered questionnaire about their eating habits and level of physical activity.Results: The mean age of the population was 20.31 ± 1.76 years. The percentage of participants recruited from the MSC was 59.2%. The prevalence of prediabetes was 2.5%. Lower BMI, WC, and HbA1c values, and higher diastolic BP (DBP) were found in MSC students compared to SSC ones. HbA1c, systolic BP (SBP), and DBP were correlated with BMI (P = .02, P<.0001, and P = .017, respectively). HbA1c was not associated with eating habits or physical activity. DBP was inversely associated with physical activity (P = .002), while SBP was positively associated with fast food consumption (P = .003).Conclusion: The present study shows a low prevalence of prediabetes in Lebanese students. BMI and the study field are the main factors predicting HbA1c and BP. Further studies are needed to extrapolate our results to the overall young Lebanese population.Abbreviations: ADA = American Diabetes Association; BMI = body mass index; BP = blood pressure; DBP = diastolic blood pressure; HbA1c = hemoglobin A1c; HTN = hypertension; MSC = medical science campus; SBP = systolic blood pressure; SSC = social science campus; T2D = type 2 diabetes; US = United States; USJ = Saint-Joseph University; WC = waist circumference     

Bird's-Eye View of GnRH Analog use in a Pediatric Endocrinology Referral Center

Objective: Gonadotropin-releasing hormone analogs (GnRHa) are standard of care for the treatment of central precocious puberty (CPP). GnRHa have also been prescribed in other clinical settings with the hope of increasing adult stature, although evidence to support this practice is lacking. The degree to which GnRHa are being prescribed for indications other than CPP in routine clinical care has not been described. We sought to systematically examine GnRHa prescribing practices among the pediatric endocrinologists at our academic medical center.Methods: We reviewed medical records of children treated with GnRHa during a 6-year interval. Variables analyzed included gender, age at start of treatment, indication for therapy, and use of growth hormone as adjunctive treatment. Nonparametric analyses were utilized to compare treatment characteristics of those with CPP versus those without.Results: A total of 260 patients (82% female) aged 8.06 ± 2.68 years were identified. Of these, 191 (73.5%) were treated for CPP, whereas 69 (26.5%) were treated for normally timed puberty in the context of idiopathic short stature/poor predicted height (n = 37), growth hormone deficiency (n = 17), congenital adrenal hyperplasia (n = 10), primary hypothyroidism (n = 4), and developmental delay (n = 1). Of the 161 girls with CPP, GnRHa therapy was initiated at =8 years of age in 62 (39%).Conclusion: Whereas most patients were treated for CPP, ~27% were treated for other indications. Of girls with CPP, 39% were treated at an age when benefit in terms of height is unlikely. This highlights the need for rigorous studies of GnRHa use for indications beyond CPP.Abbreviations: CPP = central precocious puberty GnRHa = gonadotropin-releasing hormone analogs     

EXOGENOUS TESTOSTERONE DOES NOT INDUCE OR EXACERBATE THE METABOLIC FEATURES ASSOCIATED WITH PCOS AMONG TRANSGENDER MEN

Objective: Polycystic ovary syndrome (PCOS) is a complex condition which can include menstrual irregularity, metabolic derangement, and increased androgen levels. The mechanism of PCOS is unknown. Some suggest that excess production of androgens by the ovaries may cause or exacerbate the metabolic findings. The purpose of this study was to assess the role of increased testosterone on metabolic parameters for individuals presumed to be chromosomally female by examination of these parameters in hormone-treated transgender men.Methods: In 2015 and 2016, we asked all transgender men who visited the Endocrinology Clinic at Boston Medical Center treated with testosterone for consent for a retrospective anonymous chart review. Of the 36 men, 34 agreed (94%). Serum metabolic factors and body mass index (BMI) levels for each patient were graphed over time, from initiation of therapy through 6 years of treatment. Bivariate analyses were conducted to analyze the impact of added testosterone.Results: Regressions measuring the impact of testosterone demonstrated no significant changes in levels of glycated hemoglobin (HbA1c), triglycerides, or low-density-lipoprotein cholesterol. There was a statistically significant decrease in BMI with increasing testosterone. There was also a statistically significant decrease in high-density lipoprotein levels upon initiation of testosterone therapy.Conclusion: Testosterone therapy in transgender men across a wide range of doses and over many years did not result in the dyslipidemia or abnormalities in HbA1c seen with PCOS. Instead, treatment of transgender men with testosterone resulted only in a shift of metabolic biomarkers toward the average physiologic male body.Abbreviations: BMI = body mass index; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; PCOS = polycystic ovary syndrome     

Differential Endocrine and Metabolic Effects of Testosterone Suppressive Agents in Transgender Women

Objective: Suppression of testosterone secretion and/or action in transgender women using cyproterone acetate (CPA), spironolactone, or gonadotropin-releasing hormone analogues (GA) is achieved through various mechanisms. Our objective was to characterize possible differential effects of these compounds on metabolic and endocrine variables.Methods: We conducted a historic cohort study of transgender patients treated in a tertiary referral center. A longitudinal analysis of treatment naïve patients and a cross-sectional analysis of the whole cohort at the last visit was carried out.Results: Among 126 transgender women (75 treatment-naïve), CPA was the predominant androgen suppressive therapy (70%), followed by spironolactone (17.6%), and GA (10.2%). Among those who were treatment-naïve, the increase in serum prolactin levels over baseline was greater at 3 months following CPA initiation (mean change 397 ± 335 mIU/L) than following spironolactone (20.1 ± 87 mIU/L) or GA initiation (64.6 ± 268 mIU/L; P = .0002). Prolactin levels remained higher in the CPA-treated group throughout follow-up, irrespective of estradiol levels, which were similar between the groups. A worse metabolic profile was associated with treatment with CPA than with spironolactone or GA. In the CPA compared to the spironolactone and GA groups, high-density lipoprotein-cholesterol levels were lower (47.1 ± 10.4, 54.4 ± 12.2, and 60.3 ± 13, respectively; P = .0076), while body mass index levels (24.3 ± 5, 21.7 ± 2.3, and 20.7 ± 3.1 kg/m²; P = .03), and systolic (117 ± 12.1, 109 ± 12.2, and 105 ± 13.3 mm Hg; P = .01) and diastolic (74 ± 9, 65.6 ± 5.5, and 65.4 ± 11 mm Hg; P = .0008) blood pressure levels were higher at the last visit.Conclusion: Treatment of transgender women with CPA was associated with hyperprolactinemia and a worse cardiovascular risk profile than treatment with spironolactone or GA.Abbreviations: BMI = body mass index; CPA = cyproterone acetate; E2 = estradiol; FSH = follicle-stimulating hormone; GA = gonadotropin-releasing hormone analogues; LH = luteinizing hormone