The birth of an intersex child prompts a long-term management strategy that involves a myriad of professionals working with the family. There has been progress in diagnosis, surgical techniques, understanding psychosocial issues and in recognizing and accepting the place of patient advocacy. The Lawson Wilkins Paediatric Endocrine Society (LWPES) and the European Society for Paediatric Endocrinology (ESPE) considered it timely to review the management of intersex disorders from a broad perspective, to review data on longer term outcome and to formulate proposals for future studies. The methodology comprised establishing a number of working groups whose membership was drawn from 50 international experts in the field. The groups prepared prior written responses to a defined set of questions resulting from an evidence based review of the literature. At a subsequent gathering of participants, a framework for a consensus document was agreed. This paper constitutes its final form.

/pdf/consensus-statement-on-management-of-intersex-disorders-1icrsai49n.pdf

Consensus statement on management of intersex disorders

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.

Objective To update the "Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2009. Participants The participants include an Endocrine Society-appointed task force of nine experts, a methodologist, and a medical writer. Evidence This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus process Group meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines. Conclusion Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person's genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person's affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments-appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)-should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment.

/pdf/endocrine-treatment-of-gender-dysphoric-gender-incongruent-frgsgoxe8w.pdf

Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline

These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American Col- lege of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology have jointly accepted responsibility for establishing ''Allergen immunotherapy: A practice parameter third update.'' This is a complete and com- prehensive document at the current time. The medical environ- ment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individ- ual, including those who served on the Joint Task Force, is authorizedtoprovideanofficial AAAAIorACAAIinterpretation ofthesepracticeparameters.Anyrequestforinformationaboutor an interpretation of these practice parameters by the AAAAI or the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. A current list of published practice parameters of the Joint Task Force on Practice ParametersforAllergyandImmunologycanbefoundinTableE1 in this article's Online Repository at www.jacionline.org. Disclosure ofpotentialconflictofinterest:L.Coxisaconsultant forGenentech/Novartis, Hollister-Stier, and Stallergenes; is a speaker for Novartis; has received research support from Stallergenes; is on the Board of Directors for the American Board of Allergy and Immunology; and is on the US Food and Drug Administration (FDA)'s Allergenic Product Advisory Committee. H. Nelson is a consultant for Merck and Planet Biopharmaceuticals, is a Data and Safety Monitoring Board member of DBV Technologies, and has received research support from ALK-AbellM. Nelson has re- ceivedresearchsupportfromtheDepartmentofDefense,isaspeakerfortheAmerican College of Allergy, Asthma & Immunology (ACAAI), and is a member of the FDA's AdvisoryCommitteeonAllergicProducts.R.Weberisonthespeakers'bureauforAs- traZeneca and Genentech, has received research support from Novartis and Glaxo- SmithKline, and is Committee Chair of the ACAAI. D. I. Bernstein is a consultant and on the advisory board for ALK America, is on the advisory board for Merck, and has received research support from Merck and Schering-Plough. J. Blessing- Moore is a speaker for Merck-Schering/AstraZeneca, Novartis, TEVA, and Meda Alcon and has received research support from Meda. D. A. Khan is a speaker for As- traZeneca and Merck, has received research support from the Vanberg Family Foun- dation and the Sellars Family Foundation, is Conjoint Board Review Chair for the ACAAI,andisapastpresidentoftheTexasAllergy,AsthmaandImmunologySociety. D. M. Lang is a speaker and consultant for GlaxoSmithKline; is a speaker for Astra- Zeneca, Merck, TEVA, Sanofi-Aventis, and Genentech/Novartis; and has received re- search support from Genentech/Novartis. R. A. Nicklas is a fellow for the ACAAI. J. Oppenheimer is a consultant and has provided lectures for AstraZeneca, Merck, and GlaxoSmithKline; and has received research support from AstraZeneca, Merck, Glax- oSmithKline, and Genentech. J. M. Portnoy is a speaker for Phadia, Merck, and CSL Behring; hasreceived researchsupportfromtheUSDepartment ofHousingandUrban Development;andisa board memberof theACAAI board of regents.S.L. Spector has received research support from Genentech, GlaxoSmithKline, Schering-Plough, Aventis, Novartis, Pharmaxis, Boehringer Ingelheim, AstraZeneca, Johnson & John- son, Xyzal, Alcon, Centocor, Sepracor, UCB, Amgen, Capnia, and IVAX. S. Tilles isaspeakerforAlcon; isontheadvisoryboard forALK,Ista,Merck,andStallergenes; has received research support from Alcon, Amgen, Amphastar, Astellas, Boehringer Ingelheim,Ception,Genentech,Icagen, MAP Pharma, MEDA, Merck, Novartis, Rox- ane, and Sepracor; is Associate Editor of Allergy Watchand Annals of Allergy; and is a task force member for the Joint Task Force for Practice Parameters. D. Wallace is a speaker and advisor for Alcon, is a speaker for Merck and Sanofi-Aventis, and is President-Elect of the ACAAI. The rest of the authors have declared that they have no conflict of interest.

/pdf/allergen-immunotherapy-a-practice-parameter-third-update-1itlwly1yo.pdf

Allergen immunotherapy: A practice parameter third update

Global health burden and needs of transgender populations: a review

Disorders of Sex Development

Background Research has highlighted the complex association between female sexual dysfunction (FSD) and distress regarding sexual activity, with decreased physical pleasure being an important mediator. The current study aims to elucidate the association between pleasurable and painful genital sensitivity and FSD, and to further investigate whether FSD may be distressing because it prevents the experience of sexual pleasure, induces pain or both. Methods: Sexually active women (n = 256; median, 22 years; range, 18–49 years) completed web-based questionnaires, including the Self-Assessment of Genital Anatomy and Sexual Function, the Female Sexual Function Index and the Female Sexual Distress Scale. Results: Women reported their clitoris to be more sensitive than their vagina in terms of having more pleasurable responses (P < 0.001), but not more painful responses (P = 0.49). In women with FSD (n = 36), impaired self-perceived genital sensation was found: they reported significantly less sexual pleasure and orgasm intensity, and more orgasm effort and discomfort within the clitoral and vaginal area than women without FSD (n = 220) (P-value < 0.05). The odds of having FSD were significantly greater in women with perceived increased discomfort in the vaginal area during stimulation (odds ratio = 5.59, P = 0.009, 95% confidence interval: 1.53–20.39), but not in the clitoral area. Conclusions: The data provide evidence of the relevance of self-perceived genital sensitivity to sexual pleasure and overall sexual experience. Enhancing the pleasurableness of genital sensations, especially during partnered sex, could decrease the likelihood of experiencing pain and concomitant FSD.

Costs of pleasure and the benefits of pain: self-perceived genital sensation, anatomy and sexual dysfunction

/pdf/caring-for-individuals-with-a-difference-of-sex-development-54ekpgt83v.pdf

Caring for individuals with a difference of sex development (DSD): a Consensus Statement

Differences of sex development and maturation (SDM) represent a heterogeneous puzzle of rare conditions with a large genetic component whose management and treatment could be improved by an accurate classification of underlying molecular conditions, and next-generation sequencing (NGS) should represent the most appropriate approach. Therefore, we conducted a survey dedicated to the use and potential outcomes of NGS for SDM disorders diagnosis among the 53 health care providers (HCP) of the European Reference Network for rare endocrine conditions. The response rate was 49% with a total of 26 HCPs from 13 countries. All HCPs, except 1, performed NGS investigations for SDM disorders on 6720 patients, 3764 (56%) with differences of sex development (DSD), including 811 unexplained primary ovarian insufficiency, and 2956 (44%) with congenital hypogonadotropic hypogonadism (CHH). The approaches varied from targeted analysis of custom gene panels (range: 11–490 genes) in 81.5% of cases or whole exome sequencing with the extraction of a virtual panel in the remaining cases. These analyses were performed for diagnostic purposes in 21 HCPs, supported by the National Health Systems in 16 cases. The likelihood of finding a variant ranged between 7 and 60%, mainly depending upon the number of analysed genes or criteria used for reporting, most HCPs also reporting variants of uncertain significance. These data illustrate the status of genetic diagnosis of DSD and CHH across Europe. In most countries, these analyses are performed for diagnostic purposes, yielding highly variable results, thus suggesting the need for harmonization and general improvements of NGS approaches.

https://ec.bioscientifica.com/downloadpdf/journals/ec/aop/ec-22-0367/ec-22-0367.pdf

Martine Cools

Papers

Disorders of Sex Development

Costs of pleasure and the benefits of pain: self-perceived genital sensation, anatomy and sexual dysfunction

Caring for individuals with a difference of sex development (DSD): a Consensus Statement

The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres

Male Gender Identity in Complete Androgen Insensitivity Syndrome