98 results on '"Hannema SE"'
Search Results
2. Gonadectomy in conditions affecting sex development
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Daniel Konrad, Aneta Gawlik, Rajni Sharma, Olcay Evliyaoğlu, Dejun Li, Marek Niedziela, Jeremy W. Tomlinson, Farida Jennane, Nils Krone, Sukran Poyrazoglu, Evgenia Globa, S Faisal Ahmed, Angela K Lucas-Herald, Inas Mazen, Liat de Vries, Andreas Kyriakou, Katherine Lachlan, Wiebke Arlt, Renata Markosyan, Antonia Brooke, Olaf Hiort, Gil Guerra Júnior, Ruth Krone, Colin Johnston, Gloria Hermann, Antonio Balsamo, Corina Lichiardopol, Hedi L Claahsen-van der Grinten, Vandana Jain, Vilhelm Mladenov, Nataliya Zelinska, Naomi Weintrob, Markus Bettendorf, Simone Fica, Ieuan A. Hughes, Laura Audí, Lidka Lisa, Klaus Mohnike, Mona Ellaithi, Paul-Martin Holterhus, Lavinia Nedelea, Mars Skaeil, Rodolfo Rey, Violeta Iotova, Hannema Se, Silvano Bertelloni, Rieko Tadokoro-Cuccaro, Feyza Darendeliler, Jillian Bryce, Lloyd J.W. Tack, Tulay Guran, Odile Gaisl, Justin H Davies, Martine Cools, Anna Nordenström, Federico Baronio, Marie Lindhardt Ljubicic, Ayla Güven, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Amsterdam Gastroenterology Endocrinology Metabolism, and Pediatrics
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Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Disorders of Sex Development ,030209 endocrinology & metabolism ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Endocrinology ,SDG 3 - Good Health and Well-being ,Internal medicine ,Medicine and Health Sciences ,medicine ,Humans ,Castration ,Registries ,Young adult ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16] ,Retrospective cohort study ,General Medicine ,Middle Aged ,Diabetes and Metabolism ,Clinical Practice ,030220 oncology & carcinogenesis ,Female ,business ,Cohort study - Abstract
Objectives To determine trends in clinical practice for individuals with DSD requiring gonadectomy. Design Retrospective cohort study. Methods Information regarding age at gonadectomy according to diagnosis; reported sex; time of presentation to specialist centre; and location of centre from cases reported to the International DSD Registry and who were over 16 years old in January 2019. Results Data regarding gonadectomy were available in 668 (88%) individuals from 44 centres. Of these, 248 (37%) (median age (range) 24 (17, 75) years) were male and 420 (63%) (median age (range) 26 (16, 86) years) were female. Gonadectomy was reported from 36 centres in 351/668 cases (53%). Females were more likely to undergo gonadectomy (n = 311, P < 0.0001). The indication for gonadectomy was reported in 268 (76%). The most common indication was mitigation of tumour risk in 172 (64%). Variations in the practice of gonadectomy were observed; of the 351 cases from 36 centres, 17 (5%) at 9 centres had undergone gonadectomy before their first presentation to the specialist centre. Median age at gonadectomy of cases from high-income countries and low-/middle-income countries (LMIC) was 13.0 years (0.1, 68) years and 16.5 years (1, 28), respectively (P < 0.0001) with the likelihood of long-term retention of gonads being higher in LMIC countries. Conclusions The likelihood of gonadectomy depends on the underlying diagnosis, sex of rearing and the geographical setting. Clinical benchmarks, which can be studied across all forms of DSD will allow a better understanding of the variation in the practice of gonadectomy.
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- 2021
3. Real-World Estimates of Adrenal Insufficiency-Related Adverse Events in Children With Congenital Adrenal Hyperplasia
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Berenice B. Mendonca, Ana Vieites, Salma R Ali, Nils Krone, Martijn J J Finken, S Faisal Ahmed, Ayla Guven, Richard J. Ross, Silvia Einaudi, Violeta Iotova, Tulay Guran, Rieko Tadokoro-Cuccaro, Evelien F. Gevers, Guilherme Guaragna-Filho, Eduardo Corrêa Costa, James Lewsey, Hannema Se, Mirela C Miranda, Ruth Krone, Rita Ortolano, Niels H Birkebaek, Houra Haghpanahan, Tania A. S. S. Bachega, Andrea Luczay, Sukran Poyrazoglu, Jillian Bryce, Corina Lichiardopol, Christa E. Flück, Oliver Blankenstein, Antonio Balsamo, Ieuan A. Hughes, Claire E Higham, Liat de Vries, Feyza Darendeliler, Hedi L Claahsen-van der Grinten, Martine Cools, Hetty J. van der Kamp, Ajay Thankamony, Anna Nordenström, Navoda Atapattu, Klaus Mohnike, Heba Elsedfy, Walter Bonfig, Li En Tan, Uta Neumann, Márta Korbonits, Tatjana Milenkovic, Ali, Salma R., Bryce, Jillian, Haghpanahan, Houra, Lewsey, James D., Tan, Li En, Atapattu, Navoda, Birkebaek, Niels H., Blankenstein, Oliver, Neumann, Uta, Balsamo, Antonio, Ortolano, Rita, Bonfig, Walter, Claahsen-van der Grinten, Hedi L., Cools, Martine, Costa, Eduardo Correa, Darendeliler, Feyza, Poyrazoglu, Sukran, Elsedfy, Heba, Finken, Martijn J. J., Fluck, Christa E., Gevers, Evelien, Korbonits, Marta, Guaragna-Filho, Guilherme, Guran, Tulay, Guven, Ayla, Hannema, Sabine E., Higham, Claire, Hughes, Ieuan A., Tadokoro-Cuccaro, Rieko, Thankamony, Ajay, Iotova, Violeta, Krone, Nils P., Krone, Ruth, Lichiardopol, Corina, Luczay, Andrea, Mendonca, Berenice B., Bachega, Tania A. S. S., Miranda, Mirela C., Milenkovic, Tatjana, Mohnike, Klaus, Nordenstrom, Anna, Einaudi, Silvia, van der Kamp, Hetty, Vieites, Ana, de Vries, Liat, Ross, Richard J. M., Ahmed, S. Faisal, Pediatrics, Pediatric surgery, Amsterdam Gastroenterology Endocrinology Metabolism, and Amsterdam Reproduction & Development (AR&D)
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Male ,Pediatrics ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,registry ,Biochemistry ,Clinical biochemistry ,0302 clinical medicine ,Endocrinology ,ADOLESCENTS ,Ambulatory Care ,030212 general & internal medicine ,Registries ,Child ,CRISIS ,Geography ,Middle income countries ,Adrenal crisis ,Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16] ,Ambulatory Care/statistics & numerical data ,Hospitalization ,Child, Preschool ,Acute Disease ,Female ,medicine.symptom ,adrenal insufficiency ,AcademicSubjects/MED00250 ,Adrenal Insufficiency/complications ,medicine.medical_specialty ,Adolescent ,adrenal crisis ,030209 endocrinology & metabolism ,21-hydroxylase deficiency ,03 medical and health sciences ,Infectious illness ,All institutes and research themes of the Radboud University Medical Center ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Adrenal insufficiency ,MANAGEMENT ,Humans ,congenital adrenal hyperplasia ,Congenital adrenal hyperplasia ,Adverse effect ,Online Only Articles ,Clinical Research Articles ,Hospitalization/statistics & numerical data ,Adrenal Hyperplasia, Congenital/complications ,Adrenal Hyperplasia, Congenital ,business.industry ,Biochemistry (medical) ,Infant, Newborn ,Infant ,medicine.disease ,EXPERIENCE ,business - Abstract
Background Although congenital adrenal hyperplasia (CAH) is known to be associated with adrenal crises (AC), its association with patient- or clinician-reported sick day episodes (SDE) is less clear. Methods Data on children with classic 21-hydroxylase deficiency CAH from 34 centers in 18 countries, of which 7 were Low or Middle Income Countries (LMIC) and 11 were High Income (HIC), were collected from the International CAH Registry and analyzed to examine the clinical factors associated with SDE and AC. Results A total of 518 children—with a median of 11 children (range 1, 53) per center—had 5388 visits evaluated over a total of 2300 patient-years. The median number of AC and SDE per patient-year per center was 0 (0, 3) and 0.4 (0.0, 13.3), respectively. Of the 1544 SDE, an AC was reported in 62 (4%), with no fatalities. Infectious illness was the most frequent precipitating event, reported in 1105 (72%) and 29 (47%) of SDE and AC, respectively. On comparing cases from LMIC and HIC, the median SDE per patient-year was 0.75 (0, 13.3) vs 0.11 (0, 12.0) (P Conclusions The real-world data that are collected within the I-CAH Registry show wide variability in the reported occurrence of adrenal insufficiency–related adverse events. As these data become increasingly used as a clinical benchmark in CAH care, there is a need for further research to improve and standardize the definition of SDE.
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- 2021
4. Under-reported aspects of diagnosis and treatment addressed in the Dutch-Flemish guideline for comprehensive diagnostics in disorders/differences of sex development
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Tuula Rinne, Birgit Sikkema-Raddatz, Elfride De Baere, Conny M. A. van Ravenswaaij-Arts, Remko Hersmus, Marlies Kempers, Arianne B. Dessens, Yolande van Bever, Hedi L Claahsen-van der Grinten, Maarten F. C. M. Knapen, Hannema Se, Hennie T. Brüggenwirth, Katja P. Wolffenbuttel, Irene A.L. Groenenberg, Leendert H. J. Looijenga, Martine Cools, Clinical Genetics, Urology, Child and Adolescent Psychiatry / Psychology, Obstetrics & Gynecology, Pathology, and Pediatrics
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0301 basic medicine ,DSD POSITION PAPER ,Disorders of Sex Development ,DSD ,diagnostic ,Presentation ,0302 clinical medicine ,Pregnancy ,ADOLESCENTS ,Medicine and Health Sciences ,Genetics(clinical) ,Pathology, Molecular ,Genetics (clinical) ,media_common ,RISK ,medicine.diagnostic_test ,Sexual Development ,High-Throughput Nucleotide Sequencing ,Causality ,Europe ,NGS ,language ,Female ,guideline ,TRANSITION ,medicine.medical_specialty ,prenatal ,Referral ,DISORDERS ,media_common.quotation_subject ,AMBIGUOUS GENITALIA ,030209 endocrinology & metabolism ,Guidelines as Topic ,03 medical and health sciences ,Rare Diseases ,medicine ,Genetics ,MANAGEMENT ,Humans ,Genetic Testing ,Genetic testing ,GENETIC DIAGNOSIS ,business.industry ,Gold standard ,Guideline ,CARE ,language.human_language ,Flemish ,030104 developmental biology ,Family medicine ,UPDATE ,Suspect ,business ,Clinical Guidelines - Abstract
We present key points from the updated Dutch-Flemish guideline on comprehensive diagnostics in disorders/differences of sex development (DSD) that have not been widely addressed in the current (inter)national literature. These points are of interest to physicians working in DSD (expert) centres and to professionals who come across persons with a DSD but have no (or limited) experience in this area. The Dutch-Flemish guideline is based on internationally accepted principles. Recent initiatives striving for uniform high-quality care across Europe, and beyond, such as the completed COST action 1303 and the European Reference Network for rare endocrine conditions (EndoERN), have generated several excellent papers covering nearly all aspects of DSD. The Dutch-Flemish guideline follows these international consensus papers and covers a number of other topics relevant to daily practice. For instance, although next-generation sequencing (NGS)-based molecular diagnostics are becoming the gold standard for genetic evaluation, it can be difficult to prove variant causality or relate the genotype to the clinical presentation. Network formation and centralisation are essential to promote functional studies that assess the effects of genetic variants and to the correct histological assessment of gonadal material from DSD patients, as well as allowing for maximisation of expertise and possible cost reductions. The Dutch-Flemish guidelines uniquely address three aspects of DSD. First, we propose an algorithm for counselling and diagnostic evaluation when a DSD is suspected prenatally, a clinical situation that is becoming more common. Referral to ultrasound sonographers and obstetricians who are part of a DSD team is increasingly important here. Second, we pay special attention to healthcare professionals not working within a DSD centre as they are often the first to diagnose or suspect a DSD, but are not regularly exposed to DSDs and may have limited experience. Their thoughtful communication to patients, carers and colleagues, and the accessibility of protocols for first-line management and efficient referral are essential. Careful communication in the prenatal to neonatal period and the adolescent to adult transition are equally important and relatively under-reported in the literature. Third, we discuss the timing of (NGS-based) molecular diagnostics in the initial workup of new patients and in people with a diagnosis made solely on clinical grounds or those who had earlier genetic testing that is not compatible with current state-of-the-art diagnostics.
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- 2020
5. Bone development in transgender adolescents treated with gnrh analogues and subsequent gender-affirming hormones
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Louis Gooren, Sebastian E.E. Schagen, Hannema Se, Peggy T. Cohen-Kettenis, Femke M. Wouters, Medical psychology, Internal medicine, Other Research, Amsterdam Gastroenterology Endocrinology Metabolism, and Pediatrics
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Male ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Biochemistry ,bone ,Gonadotropin-Releasing Hormone ,0302 clinical medicine ,Endocrinology ,Bone Density ,GnRH analogue ,Testosterone ,adolescents ,Prospective Studies ,Sexual Maturation ,Prospective cohort study ,Child ,Netherlands ,Bone mineral ,Triptorelin Pamoate ,transgender ,Female ,AcademicSubjects/MED00250 ,Gender dysphoria ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Hormone Replacement Therapy ,030209 endocrinology & metabolism ,Context (language use) ,gender dysphoria ,03 medical and health sciences ,030225 pediatrics ,Internal medicine ,medicine ,Humans ,sex steroids ,Adverse effect ,Clinical Research Articles ,Bone Development ,business.industry ,Biochemistry (medical) ,Adolescent Development ,medicine.disease ,Estrogen ,Sex Reassignment Procedures ,Observational study ,business ,bone mineral density ,Transsexualism ,Hormone - Abstract
Context Hormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual. Objective To describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones. Design Observational prospective study. Subjects 51 transgirls and 70 transboys receiving GnRHa and 36 transgirls and 42 transboys receiving GnRHa and gender-affirming hormones, subdivided into early- and late-pubertal groups. Main Outcome Measures Bone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers. Results At the start of GnRHa treatment, mean areal bone mineral density (aBMD) and BMAD values were within the normal range in all groups. In transgirls, the mean z-scores were well below the population mean. During 2 years of GnRHa treatment, BMAD stabilized or showed a small decrease, whereas z-scores decreased in all groups. During 3 years of combined administration of GnRHa and gender-affirming hormones, a significant increase of BMAD was found. Z-scores normalized in transboys but remained below zero in transgirls. In transgirls and early pubertal transboys, all bone markers decreased during GnRHa treatment. Conclusions BMAD z-scores decreased during GnRHa treatment and increased during gender-affirming hormone treatment. Transboys had normal z-scores at baseline and at the end of the study. However, transgirls had relatively low z-scores, both at baseline and after 3 years of estrogen treatment. It is currently unclear whether this results in adverse outcomes, such as increased fracture risk, in transgirls as they grow older.
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- 2020
6. Late Endocrine Effects After HSCT in Children With Nonmalignant Diseases; A Single Center Cohort Analysis
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Eileen van der Stoep-Yap, Adriaan C Lankester, Anne P J de Pagter, Erik G J von Asmuth, Liselotte C de Kloet, Hannema Se, Joëll E Bense, and Marloes Louwerens
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Oncology ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Single Center ,Text mining ,Pediatric Endocrinology ,Internal medicine ,Medicine ,Endocrine effects ,business ,Disorders of Puberty ,AcademicSubjects/MED00250 ,Cohort study - Abstract
Endocrine complications are amongst the most frequent late effects after pediatric hematopoietic stem cell transplantation (HSCT) for malignant diseases. Little is known about the prevalence and risk factors of endocrine complications in children transplanted for nonmalignant diseases. This retrospective study included 134 males and 63 females transplanted for a non-malignant disease between 1997 and 2018 with at least 2 years of follow up. Endocrine late effects and growth were evaluated. Gonadal dysfunction was defined as transient or permanent elevation of gonadotropins or hypogonadotropic hypogonadism. Median age at HSCT was 5.7 years (IQR 2.8-11.3) and median follow-up was 6.2 years (IQR 3.0-10.4). Underlying diseases were inborn errors of immunity (n=74), hemoglobinopathies (n=66) and bone marrow failure (n=57). The majority of patients had received busulfan-based conditioning (46%) or treosulfan-based conditioning (34%). Gonadal dysfunction occurred in 24/44 (post)pubertal female patients (55%) and was permanent in 19/44 (43%). 22/44 received hormonal substitution, which could be discontinued in 7. In females who received busulfan-based conditioning 16/17 (94%) developed gonadal dysfunction compared to 5/15 (33%) patients with treosulfan-based conditioning; the odds ratio for permanent gonadal dysfunction was 18.7 (3.61-135, p=0.001). Gonadal dysfunction occurred in 28/66 (post)pubertal male patients (42%) and was permanent in 23/66 (35%). 6/66 received hormonal substitution, which could be discontinued in 1. Gonadal dysfunction was more common in males (post)pubertal at HSCT, 14/21 (67%), compared to those prepubertal at HSCT, 14/45 (31%), p=0.014. 3/15 treated with a treosulfan-based regimen (20%) developed gonadal dysfunction, all transient, versus 19/39 with a busulfan-based regimen (49%), with 2 transient. 29/187 patients developed hypothyroidism (16%), 7 patients received thyroxine treatment (4%). All patients with persistent primary hypothyroidism (n=6) had positive TPO-antibodies. 17 patients received growth hormone treatment and were excluded from analysis. In patients without growth hormone treatment near adult height (NAH) was -1.2 SDS (median, IQR -2.0- -0.3) below mean parental height (MPH) in males and -0.4 SDS (median, IQR -1.6-0.3) in females. NAH below -2 SDS was seen in 13/43 males (30%) and 2/36 females (6%). The majority of these patients already had a height below -2 SDS before HSCT (73%). In conclusion, this study on late endocrine effects after HSCT in children with nonmalignant diseases indicates frequent gonadal dysfunction, present in 55% of females and 42% of males. In this cohort, risk of gonadal dysfunction in females was higher after busulfan-based conditioning than treosulfan-based conditioning. Careful long-term endocrine follow-up is indicated.
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- 2021
7. SUN-080 We Mind Your Step: Understanding and Preventing Drop-Out in the Transition from Paediatric to Adult Tertiary Endocrine Healthcare
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Karlijn Pellikaan, Judith P. van Eck, Kirsten Davidse, Janneke Baan, Erica L T van den Akker, Laura C G de Graaff-Herder, Theo C J Sas, Hannema Se, Wanda Geilvoet, Anita C. S. Hokken-Koelega, AnneLoes van Staa, and Aart-Jan van der Lely
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medicine.medical_specialty ,Pediatric Puberty, Transgender Health, and General Endocrine ,Pediatric Endocrinology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Drop out ,education ,Health care ,Medicine ,Endocrine system ,business ,Intensive care medicine ,AcademicSubjects/MED00250 - Abstract
Introduction Transition from paediatric to adult endocrinology is a challenge for adolescents, their families and their healthcare professionals. Previous studies show that up to 25% of young adults with endocrine disorders are lost to follow-up once they move out of paediatric care. This poses a health risk for young adults, as lack of medical treatment and surveillance can have both psycho-social and physical consequences. Apart from absenteeism from school or work, this can lead to serious and expensive medical complications like Addison crisis. Methods In 2019 we studied electronic medical records of 387 patients who were over 15 years old when they attended the paediatric endocrine outpatient clinic (OPC) of our medical centre in 2013-2014. We collected data from medical charts, the hospital digital agenda and medical correspondence. Results Of 387 adolescents, 161 (42%) did not need adult endocrine follow-up because paediatric endocrine care was only puberty- or growth-related. Forty-six patients did not enter regular transition because they 1) participated in a pilot to improve transition (N=10), 2) had intellectual disability (ID) and transferred to ID care (N=28), or 3) died (N=8, mostly cancer-related). Hundred-and-eighty patients entered regular transition: 49 (27%) to a regional hospital and 131 (73%) within our university hospital. Of these 131 patients, 33 (25%) were lost to follow up; in 24 of them (73%), the invitation for the adult OPC had never been sent. Loss to follow up occurred when three subsequent critical steps failed: 1) the adult endocrinologist had not received or read the paediatrician’s referral letter and/or had not invited the patient; 2) the paediatrician had not checked whether the appointment was really made and received by the patient and 3) the patients and/or caregivers had not alarmed the hospital when no invitation for an appointment was received. Conclusion We found a 25% dropout during transfer from paediatric to adult tertiary endocrine care. Starting the transition process early and in a structured manner, as well as assigning a transition coordinator, can prevent part of the dropouts. However, 73% of all dropouts appeared to be attributable to failure of practical, logistic steps. In order to prevent this part of the dropouts, we provide practical recommendations for all three parties involved: 1) the adult endocrinologist should carefully read paediatricians’ letters and check whether action is required (i.e. check whether an appointment is requested) 2) the paediatrician should ascertain whether the appointment is really made and received by the patient 3) the patients and/or caregivers should be instructed to alarm the hospital when they do not receive the appointment. These actions require relatively little effort and may prevent the part of drop-outs that is caused by logistic failures.
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- 2020
8. Disorders of Sex Development
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Chan, Yee Ming, Hannema, SE, Achermann, John, Hughes, Ieuan A., Melmed, Shlomo, Auchus, Richard J, Goldfine, Allison B, Koenig, Ronald J, and Rosen, Clifford J
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- 2020
9. Use of Fertility Preservation Among a Cohort of Transgirls in the Netherlands
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Sebastian E.E. Schagen, Tessa Brik, Martine C. de Vries, Hannema Se, A. Meissner, Lieke J.J.J. Vrouenraets, Center for Reproductive Medicine, Graduate School, APH - Personalized Medicine, APH - Quality of Care, Internal medicine, Ethics, Law & Medical humanities, and Pediatric surgery
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Gender dysphoria ,Male ,Adolescent ,medicine.medical_treatment ,media_common.quotation_subject ,Fertility ,Transgender Persons ,Intracytoplasmic sperm injection ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Medicine ,Humans ,030212 general & internal medicine ,Fertility preservation ,media_common ,Netherlands ,Retrospective Studies ,Cryopreservation ,business.industry ,Medical record ,Puberty ,Public Health, Environmental and Occupational Health ,Age Factors ,Fertility Preservation ,medicine.disease ,Semen cryopreservation ,Spermatozoa ,Psychiatry and Mental health ,Pediatrics, Perinatology and Child Health ,Cohort ,Hormone analog ,Female ,business ,Demography - Abstract
Purpose The primary aims of the study are to examine the rate of attempted fertility preservation (FP) among a Dutch cohort of transgirls who started gonadotropin-releasing hormone analog treatment and the reasons why adolescents did or did not choose to attempt FP. Methods The study was a single-center retrospective review of medical records of 35 transgirls who started gonadotropin-releasing hormone analog treatment between 2011 and 2017. Results Ninety-one percent of adolescents were counseled on the option of FP. Thirty-eight percent of counseled adolescents attempted FP, and 75% of them were able to cryopreserve sperm suitable for intrauterine insemination or intracytoplasmic sperm injection. Younger and Caucasian transgirls were less likely to attempt FP. No specific reason for declining FP was known in 33% adolescents, 32% of adolescents were not able to produce a semen sample because of early puberty, 17% felt uncomfortable with masturbation, 17% did not want to have children, and 13% wanted to adopt. Conclusions One third of adolescents attempted FP, which is much more than the percentage reported in previous studies from the United States. One third of the transgirls could not make use of FP because they were unable to produce a semen sample because of early pubertal stage. For these adolescents, alternatives need to be explored.
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- 2019
10. IGF-1 and IGF-1 SDS - Fit for purpose?
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Wilma Oostdijk, Christa M. Cobbaert, Bart E.P.B. Ballieux, Nienke R. Biermasz, J.M. Wit, T M Kuijper, S Kos, Hannema Se, and Pediatric surgery
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,business.industry ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,General Medicine ,Middle Aged ,Reference Standards ,Young Adult ,Endocrinology ,Child, Preschool ,Internal medicine ,Humans ,Medicine ,Female ,Insulin-Like Growth Factor I ,Young adult ,Child ,business ,Reference standards ,Biomarkers ,Aged - Published
- 2019
11. MANAGEMENT OF ENDOCRINE DISEASE Approach to the management of children and adolescents with Gender Dysphoria
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M.C. de Vries, Hannema Se, Laetitia Martinerie, Bremont-Weill C, A Condat, and A Bargiacchi
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Male ,Gender dysphoria ,Infertility ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,030225 pediatrics ,Internal medicine ,Transgender ,medicine ,Humans ,030212 general & internal medicine ,Child ,Gender Dysphoria ,Psychiatry ,Endocrine disease ,business.industry ,General Medicine ,medicine.disease ,United States ,Europe ,Categorization ,Female ,business ,Psychology ,Clinical psychology - Abstract
Over the past 20 years, the care for transgender adolescents has developed throughout many countries following the ‘Dutch Approach’ initiated in the 90s in pioneer countries as the Netherlands, United States and Canada, with increasing numbers of children and adolescents seeking care in transgender clinics. This medical approach has considerable positive impacts on the psychological outcomes of these adolescents, and several studies have been recently published underlining the relative safety of such treatments. This paper reviews the current standards of care for transgender children and adolescents with particular emphasis on disparities among countries and short-to-medium-term outcomes. Finally, it highlights ethical considerations regarding categorization of gender dysphoria, timing of treatment initiation, infertility and how to deal with the long-term consequences.
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- 2018
12. Changes in Adrenal Androgens During Puberty Suppression and Gender-Affirming Hormone Treatment in Adolescents With Gender Dysphoria
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Hannema Se, Paul Lustenhouwer, Sebastian E.E. Schagen, Peggy T. Cohen-Kettenis, Henriette A. Delemarre-van de Waal, VU University medical center, Medical psychology, Pediatrics, and Amsterdam Gastroenterology Endocrinology Metabolism
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Gender dysphoria ,Male ,Dehydroepiandrosterone-Sulfate ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Urology ,Endocrinology, Diabetes and Metabolism ,Gonadotropin-Releasing Hormone ,03 medical and health sciences ,chemistry.chemical_compound ,Gonadotropin-Releasing Hormone Analog ,0302 clinical medicine ,Endocrinology ,Dehydroepiandrosterone sulfate ,030225 pediatrics ,Internal medicine ,medicine ,Humans ,Testosterone ,Androstenedione ,Prospective Studies ,Sexual Maturation ,Prospective cohort study ,Child ,Gender Dysphoria ,030219 obstetrics & reproductive medicine ,Estradiol ,business.industry ,Adrenal gland ,Dehydroepiandrosterone Sulfate ,Gender Identity ,Androgen ,medicine.disease ,humanities ,Psychiatry and Mental health ,medicine.anatomical_structure ,Reproductive Medicine ,chemistry ,Androgens ,Female ,business ,Hormone - Abstract
Introduction Gender-affirming hormone treatment is known to affect adrenal androgen levels in adult individuals with gender dysphoria (GD). This may be clinically relevant because the adrenal gland plays a critical role in many different metabolic processes. Aim This study aims to assess the effects of gonadotropin-releasing hormone analogs (GnRHa) treatment and gender-affirming hormone treatment on adrenal androgen levels in adolescents with GD. Methods In this prospective study, dehydroepiandrosterone-sulfate (DHEAS) and androstenedione values were measured every 6 months during 2 years of GnRHa treatment only, and 2 years of GnRHa combined with gender-affirming hormone treatment (estradiol or testosterone) in 73 transgirls and 54 transboys. To determine trends in adrenal androgen levels a linear mixed model was used to approximate androgen levels. Main Outcome Measures DHEAS and androstenedione levels were the main outcome measures. Results DHEAS levels rose in transboys during GnRHa treatment, which may represent the normal increase during adolescence. In transgirls no change in DHEAS levels during GnRHa treatment was found. Gender-affirming hormone treatment did not affect DHEAS levels in either sex. In transboys androstenedione levels decreased during the first year of GnRHa treatment, which may reflect reduced ovarian androstenedione synthesis, and rose during the first year of gender-affirming hormone treatment, possibly due to conversion of administered testosterone. In transgirls androstenedione levels did not change during either GnRHa or gender-affirming hormone treatment. Clinical Implications No deleterious effects of treatment on adrenal androgen levels were found during approximately 4 years of follow-up. Strengths & Limitations This is one of the largest cohort of adolescents with GD, treated using a uniform protocol, with standardized follow-up. The lack of a control group is a limitation. Conclusion The changes in androstenedione levels during GnRHa and gender-affirming hormone treatment in transboys may not be of adrenal origin. The absence of changes in androstenedione levels in transgirls or DHEAS levels in either sex during gender-affirming hormone treatment suggests that gender-affirming hormone treatment does not significantly affect adrenal androgen production.
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- 2018
13. Efficacy and Safety of Pubertal Induction Using 17[beta]-Estradiol in Transgirls
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Schagen See, Delemarre-van de Waal Ha, Hannema Se, and Cohen-Kettenis Pt
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medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,medicine ,business ,17 beta estradiol - Published
- 2018
14. Birth weight in different etiologies of disorders of sex development
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Jipu Jiang, Hannema Se, Silvano Bertelloni, Jillian Bryce, Marek Niedziela, Nils Krone, S Faisal Ahmed, Feyza Darendeliler, Paul Martin Holterhus, Olaf Hiort, Lidka Lisa, An Desloovere, Tulay Guran, Martina Rodie, Hedi L Claahsen-van der Grinten, Martine Cools, Anna Nordenström, Ieuan A. Hughes, Sukran Poyrazoglu, Birgit Köhler, Pediatric surgery, Poyrazoglu, Sukran, Darendeliler, Feyza, Ahmed, S. Faisal, Hughes, Ieuan, Bryce, Jillian, Jiang, Jipu, Rodie, Martina, Hiort, Olaf, Hannema, Sabine E., Bertelloni, Silvano, Lisa, Lidka, Guran, Tulay, Cools, Martine, Desloovere, An, Grinten, Hedi L. Claahsen-van der, Nordenstrom, Anna, Holterhus, Paul-Martin, Kohler, Birgit, Niedziela, Marek, and Krone, Nils
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Male ,BOYS ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Disorders of Sex Development ,Androgen Excess ,Biochemistry ,0302 clinical medicine ,Endocrinology ,Testis ,LENGTH ,Birth Weight ,Registries ,Disorders of sex development ,Sex Characteristics ,Fetal Growth Retardation ,Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16] ,Androgen-Insensitivity Syndrome ,3. Good health ,Europe ,RECEPTOR GENE-MUTATIONS ,ANDROGEN INSENSITIVITY SYNDROME ,HEAD CIRCUMFERENCE ,Infant, Small for Gestational Age ,Androgens ,Female ,Androgen insensitivity syndrome ,medicine.medical_specialty ,Birth weight ,Gestational Age ,030209 endocrinology & metabolism ,Biology ,HYPOSPADIAS ,03 medical and health sciences ,030225 pediatrics ,Internal medicine ,Androgen deficiency ,medicine ,Humans ,COHORT ,Disorder of Sex Development, 46,XY ,Biochemistry (medical) ,Hyperandrogenism ,Infant, Newborn ,medicine.disease ,Androgen receptor ,MATERNAL RISK ,DIMORPHISM ,FETAL-GROWTH ,Small for gestational age - Abstract
Item does not contain fulltext Context: It is well established that boys are heavier than girls at birth. Although the cause of birth weight (BW) difference is unknown, it has been proposed that it could be generated from prenatal androgen action. Objective: The aim of the current study was to determine the BW of children with disorders of sex development (DSD) of different etiologies and to evaluate the effects of androgen action on BW. Methods: Data regarding diagnosis, BW, gestational age, karyotype, and concomitant conditions were collected from the International Disorders of Sex Development (I-DSD) Registry (www.i-dsd). BW standard deviation score was calculated according to gestational age. Cases were evaluated according to disorder classification in I-DSD (i.e., disorders of gonadal development, androgen excess, androgen synthesis, androgen action, nonspecific disorder of undermasculinization groups, and Leydig cell defect). Results: A total of 533 cases were available; 400 (75%) cases were 46,XY, and 133 (25%) cases were 46,XX. Eighty cases (15%) were born small for gestational age (SGA). Frequency of SGA was higher in the 46,XY group (17.8%) than in the 46,XX (6.7%) group (P = 0.001). Mean BW standard deviation scores of cases with androgen excess and androgen deficiency [in disorders of gonadal development, androgen synthesis, and Leydig cell defect groups and androgen receptor gene (AR) mutation-positive cases in disorders of androgen action groups] were similar to normal children with the same karyotype. SGA birth frequency was higher in the AR mutation-negative cases in disorders of androgen action group and in the nonspecific disorders of the undermasculinization group. Conclusions: BW dimorphism is unlikely to be explained by fetal androgen action per se. 46,XY DSDs due to nonspecific disorders of undermasculinization are more frequently associated with fetal growth restriction, SGA, and concomitant conditions.
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- 2017
15. Ovarian insufficiency and pubertal development after hematopoietic stem cell transplantation in childhood
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Hannema Se, Wouter J.W. Kollen, Dorine Bresters, J. Emons, Lynne M. Ball, Johanna G. van der Bom, Wilma Oostdijk, Johanna D.J. Bakker-Steeneveld, and Nardin Nuri
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Infertility ,medicine.medical_specialty ,Pediatrics ,business.industry ,Incidence (epidemiology) ,medicine.medical_treatment ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Single Center ,Surgery ,Pubertal stage ,surgical procedures, operative ,Oncology ,Pediatrics, Perinatology and Child Health ,medicine ,Cumulative incidence ,business ,Busulfan ,Cohort study ,medicine.drug - Abstract
Background Ovarian insufficiency (OI) and infertility are common and devastating late effects of cancer treatment and hematopoietic stem cell transplantation (HSCT). In children, gonadal insufficiency may subsequently lead to abnormal pubertal development. The aim of this study was to assess the cumulative incidence of OI and the need for hormonal induction of pubertal development after HSCT in childhood. We additionally assessed HSCT-related risk factors for OI. Procedures A single center cohort study was undertaken of female patients transplanted during childhood, surviving at least 2 years post-HSCT and who were at least 10 years old at initiation of the study. Of 141 eligible patients, 109 were included and hormone levels and clinical data of these patients during follow-up were collected. Risk factors for OI were analyzed by multivariate Cox regression analysis. Results Cumulative incidence of OI was 56% at a median follow-up of 7.2 years. Eight patients, initially diagnosed with OI, showed recovery of ovarian function over time. Hormonal induction of puberty was necessary in 44% of females who were pre-pubertal or pubertal at HSCT. In multivariate analysis, more advanced pubertal stage at HSCT was associated with OI. We found a trend for an association of busulfan with OI in patients conditioned with chemotherapy only. Conclusions The incidence of OI after HSCT was high and associated with more advanced pubertal stage at HSCT. Almost half of the females who were pre-pubertal or pubertal at HSCT required hormonal induction of pubertal development. Pediatr Blood Cancer 2014;61:2048–2053. © 2014 Wiley Periodicals, Inc.
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- 2014
16. Testicular development in the complete androgen insensitivity syndrome
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Hannema, SE, primary, Scott, IS, additional, Rajpert-De Meyts, E, additional, Skakkebæk, NE, additional, Coleman, N, additional, and Hughes, IA, additional
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- 2006
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17. Delayed hemolytic transfusion reaction with hyperhemolysis after first red blood cell transfusion in child with beta-thalassemia: challenges in treatment.
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Hannema SE, Brand A, van Meurs A, and Smiers FJ
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- 2010
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18. Temporal Trends in Acute Adrenal Insufficiency Events in Children With Congenital Adrenal Hyperplasia During 2019-2022.
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Tseretopoulou X, Ali SR, Bryce J, Amin N, Atapattu N, Bachega TASS, Baronio F, Ortolano R, Birkebaek NH, Bonfig W, Cools M, Davies JH, Thomas T, de Vries L, Elsedfy H, Amr NH, Flueck CE, Globa E, Guran T, Yavas-Abali Z, Guven A, Hannema SE, Iotova V, Konrad D, Lenherr-Taube N, Krone NP, Leka-Emiri S, Vlachopapadopoulou E, Lichiardopol C, Marginean O, Markosyan R, Neumann U, Niedziela M, Banaszak-Ziemska M, Phan-Hug F, Poyrazoglu S, Probst-Scheidegger U, Randell T, Russo G, Salerno M, Seneviratne S, Shnorhavorian M, Thankamony A, Tadokoro-Curraro R, van den Akker E, van Eck J, Vieites A, Wasniewska M, and Ahmed SF
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Background: It is unclear whether targeted monitoring of acute adrenal insufficiency (AI) related adverse events (AE) such as sick day episodes (SDEs) and hospitalization rate in congenital adrenal hyperplasia (CAH) is associated with a change in the occurrence of these events., Aim: Study temporal trends of AI related AE in the I-CAH Registry., Methods: In 2022, data on the occurrence of AI-related AE in children aged <18 years with 21-hydroxylase deficiency CAH were compared to data collected in 2019., Results: In 2022, a total of 513 children from 38 centers in 21 countries with a median of 8 children (range 1-58) per center had 2470 visits evaluated over a 3-year period (2019-2022). The median SDE per patient year in 2022 was 0 (0-2.5) compared to 0.3 (0-6) in 2019 ( P = .01). Despite adjustment for age, CAH phenotype and duration of study period, a difference in SDE rate was still apparent between the 2 cohorts. Of the 38 centers in the 2022 cohort, 21 had also participated in 2019 and a reduction in SDE rate was noted in 13 (62%), an increase was noted in 3 (14%), and in 5 (24%) the rate remained the same. Of the 474 SDEs reported in the 2022 cohort, 103 (22%) led to hospitalization compared to 299 of 1099 SDEs (27%) in the 2019 cohort ( P = .02)., Conclusion: The I-CAH Registry can be used for targeted monitoring of important clinical benchmarks in CAH. However, changes in reported benchmarks need careful interpretation and longer-term monitoring., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2024
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19. Variations in volume; Breast size in trans women in relation to timing of testosterone suppression.
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Boogers LS, Sardo Infirri SA, Bouchareb A, Dijkman BAM, Helder D, de Blok CJM, Liberton NPTJ, den Heijer M, van Trotsenburg ASP, Dreijerink KMA, Wiepjes CM, and Hannema SE
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Context: Breast development is an important outcome for trans women receiving gender affirming hormone therapy (GAHT). Limited breast development has been reported, possibly because of testosterone exposure during puberty. The impact of puberty suppression (PS) on breast development is unclear., Objective: To investigate the impact of PS and timing of PS prior to GAHT on breast volume and satisfaction., Design: Cross-sectional study., Setting: Tertiary gender identity clinic., Participants: 60 trans women (aged 17-57 years) after 4.5±1.7 years of GAHT were included of whom 23 initiated PS early in puberty (Tanner stage G2-3), 17 late in puberty (Tanner stage G4-5), and 20 started GAHT in adulthood without prior PS., Main Outcome Measures: Breast volume measured with a 3D scanner and breast satisfaction measured with a questionnaire. Comparisons of breast volumes were adjusted for fat percentage., Results: Median breast volume was 115ml (IQR 68; 203), i.e. bra cup-size
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- 2024
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20. Shaping the skeleton: impact of GnRH analogue and sex hormone therapy on skeletal dimensions in transgender individuals.
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Boogers LS, Sikma BT, Bouman MB, van Trotsenburg ASP, den Heijer M, Wiepjes CM, and Hannema SE
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Context: Skeletal dimensions vary between sexes. Men typically have broader shoulders and women a wider pelvis. If gender affirming hormone therapy (GAHT) with or without prior puberty suppression (PS) alters these dimensions in transgender individuals remains unclear., Objective: To investigate impact of PS and GAHT on skeletal dimensions., Design: Retrospective cross-sectional study., Setting: Gender identity clinic., Participants: Transgender individuals assigned male at birth (AMAB) and assigned female at birth (AFAB) who underwent dual-energy X-ray absorptiometry (DXA) scanning between ages 18 and 28 years were divided into four groups: Early PS (Tanner G/B2-3)+GAHT, Late PS (Tanner G/B4-5)+GAHT, GAHT only, and Untreated., Main Outcome Measures: Shoulder and pelvis dimensions measured by DXA scan were compared between groups, with adjustment for height., Results: A total of 121 individuals AMAB and 122 AFAB were included. Only in individuals AMAB who underwent early PS had smaller shoulders compared to untreated individuals AMAB (-1.3 cm; 95%CI -2.1; -0.5). In individuals AMAB from both the early and late PS group, pelvic inlet, pubic symphysis width and interischial distance were greater compared to untreated individuals AMAB resulting in dimensions comparable to untreated individuals AFAB. Only in early PS AFAB pelvic inlet width was smaller compared to untreated individuals AFAB (-1.0 cm; 95%CI -1.5; -0.6), and comparable to untreated individuals AMAB., Conclusions: The study results suggest that skeletal dimensions are only altered by GAHT if endogenous puberty has not yet been completed at start of PS. These findings enhance our understanding of hormonal effects on the skeleton and may hold clinical relevance for body image as well as for forensic anthropology. Future research should evaluate clinical implications for surgical or obstetrical outcomes in transgender individuals., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2024
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21. Time Course of Body Composition Changes in Transgender Adolescents During Puberty Suppression and Sex Hormone Treatment.
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Boogers LS, Reijtenbagh SJP, Wiepjes CM, van Trotsenburg ASP, den Heijer M, and Hannema SE
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- Humans, Adolescent, Male, Female, Retrospective Studies, Testosterone blood, Absorptiometry, Photon, Transsexualism drug therapy, Time Factors, Child, Puberty Suppression, Body Composition drug effects, Transgender Persons, Puberty physiology, Puberty drug effects, Sex Reassignment Procedures methods
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Context: Transgender adolescents can undergo puberty suppression (PS) and subsequent gender-affirming hormone therapy (GAHT) but little information is available on the expected rate of physical changes., Objective: To investigate the time course of body composition changes during PS and GAHT., Methods: In this study, retrospective data of 380 trans boys and 168 trans girls treated with PS prior to GAHT from a gender identity clinic were included. Total lean and fat mass Z-scores using birth-assigned sex as reference were determined using dual-energy X-ray absorptiometry., Results: In trans boys, lean mass Z-scores decreased (-0.32, 95% CI -0.41; -0.23) and fat mass Z-scores increased (0.31, 95% CI 0.21; 0.41) in the first year of PS and remained stable thereafter. Lean mass Z-scores increased (0.92, 95% CI 0.81; 1.04) and fat mass Z-scores decreased (-0.43, 95% CI -0.57; -0.29) only during the first year of testosterone,. In trans girls, both lean and fat mass Z-scores gradually changed over 3 years of PS (respectively -1.13, 95% CI -1.29; -0.98 and 1.06, 95% CI 0.90; 1.23). In the first year of GAHT, lean mass Z-scores decreased (-0.19, 95% CI -0.36; -0.03) while fat mass Z-scores remained unchanged after 3 years (-0.02, 95% CI -0.20; 0.16)., Conclusion: Compared with peers, trans girls experienced ongoing lean mass decrease and fat mass increase during 3 years of PS while in trans boys smaller changes were observed that stabilized after 1 year. A large increase in lean mass Z-scores occurred only during the first year of testosterone treatment. In trans girls, body composition changed only slightly during GAHT. This information can improve counseling about treatment effects., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2024
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22. Genome-wide methylation analysis in patients with proximal hypospadias - a pilot study and review of the literature.
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van Bever Y, Boers RG, Brüggenwirth HT, van IJcken WF, Magielsen FJ, de Klein A, Boers JB, Looijenga LH, Brosens E, Gribnau J, and Hannema SE
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- Humans, Male, Pilot Projects, Epigenesis, Genetic, CpG Islands, RNA, Long Noncoding genetics, Child, Child, Preschool, Infant, Genome-Wide Association Study, Case-Control Studies, DNA Methylation, Hypospadias genetics
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In patients with proximal hypospadias, often no genetic cause is identified despite extensive genetic testing. Many genes involved in sex development encode transcription factors with strict timing and dosing of the gene products. We hypothesised that there might be recurrent differences in DNA methylation in boys with hypospadias and that these might differ between patients born small versus appropriate for gestational age. Genome-wide Methylated DNA sequencing (MeD-seq) was performed on 32bp LpnPI restriction enzyme fragments after RE-digestion in leucocytes from 16 XY boys with unexplained proximal hypospadias, one with an unexplained XX testicular disorder/difference of sex development (DSD) and twelve, healthy, sex- and age-matched controls. Five of seven differentially methylated regions (DMRs) between patients and XY controls were in the Long Intergenic Non-Protein Coding RNA 665 (LINC00665; CpG24525). Three patients showed hypermethylation of MAP3K1. Finally, no DMRs in XX testicular DSD associated genes were identified in the XX boy versus XX controls. In conclusion, we observed no recognizable epigenetic signature in 16 boys with XY proximal hypospadias and no difference between children born small versus appropriate for gestational age. Comparison to previous methylation studies in individuals with hypospadias did not show consistent findings, possibly due to the use of different inclusion criteria, tissues and methods.
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- 2024
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23. Effects and Safety of Growth Hormone Treatment in Six Children with Pycnodysostosis.
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Renes JS, Sas TCJ, Clement-de Boers A, Zwaveling-Soonawala N, Hannema SE, van der Velden JAEM, van der Kaay DCM, and Hokken-Koelega ACS
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Introduction: Pycnodysostosis is an extremely rare skeletal dysplasia caused by cathepsin K deficiency. It is characterized by extreme short stature with adult height (AH) in males typically less than 150 cm and in females less than 130 cm. Our objective was to evaluate the effect and safety of growth hormone (GH) treatment in 6 patients with pycnodysostosis treated according to the Dutch national pycnodysostosis guideline., Case Presentation: Six subjects (4 boys, 2 girls) presented with pycnodysostosis, treated with GH 1.4 mg/m2/day (∼0.046 mg/kg/day) for ≥1 year. Median (IQR) age at start of GH was 10.4 years (5.7; 12.2) and median height 113.5 cm (93.3; 129.3) (-4.2 SDS [-4.8; -3.6]). All children were prepubertal at start of GH. After 1 year of GH, median height gain was 7.6 cm (6.5; 8.5) (0.3 SDS [-0.3; 0.7]). Three children are still treated with GH, and the other three subjects reached AH: 1 boy reached an AH of 157.0 cm (-3.8 SDS) after 6.3 years of GH, and 2 girls reached an AH of 138.5 cm (-5.2 SDS) after 4.8 years of GH and 148.0 cm (-3.6 SDS) after 6.4 years of GH, respectively. This last girl received additional GnRH analogue treatment. In all subjects, height SDS remained stable or improved during and after GH treatment. No serious adverse advents were found. Serum IGF-I remained below the +2 SDS., Conclusion: Our data suggest that GH may prevent the decline in height which can be observed in children with pycnodysostosis. Further research is needed to confirm this. Also, the effect of other growth-promoting strategies such as treatment with an additional GnRH analogue warrants further investigation., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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24. Response to letter to the editor: 'Gonadal tumour screening in XY gonadal dysgenesis'.
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Hannema SE, Wolffenbuttel KP, van Bever Y, Bruggenwirth HT, Hersmus R, Oosterhuis JW, and Looijenga LHJ
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- Male, Humans, Testis pathology, Gonadal Dysgenesis, 46,XY diagnosis, Testis abnormalities, Neoplasms
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- 2024
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25. A European Network for the Investigation of Gender Incongruence in adolescents.
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Boogers LS, Wiepjes CM, Staphorsius AS, Klink DT, Ciancia S, Romani A, Stolk THR, van den Boogaard E, Steensma TD, de Vries ALC, van Trotsenburg ASP, den Heijer M, Fisher AD, Cools M, and Hannema SE
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- Adult, Infant, Newborn, Humans, Male, Female, Adolescent, Gender Identity, Prospective Studies, Research Design, Transgender Persons psychology, Gender Dysphoria drug therapy, Gender Dysphoria psychology
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Background: Knowledge regarding the effects and side effects of gender-affirming hormone therapy (GAHT) in adults is rapidly growing, partly through international research networks such as the European Network for the Investigation of Gender Incongruence (ENIGI). However, data on the effects of puberty suppression (PS) and GAHT in transgender and gender diverse (TGD) youth are limited, although these data are of crucial importance, given the controversies surrounding this treatment., Aim: We sought to present a detailed overview of the design of the ENIGI Adolescents study protocol, including the first baseline data., Methods: The ENIGI Adolescents study is an ongoing multicenter prospective cohort study. This study protocol was developed by 3 European centers that provide endocrine care for TGD adolescents and were already part of the ENIGI collaboration: Amsterdam, Ghent, and Florence., Outcomes: Study outcomes include physical effects and side effects, laboratory parameters, bone mineral density, anthropometric characteristics, attitudes toward fertility and fertility preservation, and psychological well-being, which are measured in the study participants during PS and GAHT, up to 3 years after the start of GAHT., Results: Between November 2021 and May 2023, 172 TGD adolescents were included in the ENIGI Adolescents protocol, of whom 51 were assigned male at birth (AMAB) and 121 were assigned female at birth (AFAB); 3 AFAB participants reported a nonbinary gender identification. A total of 76 participants were included at the start of PS, at a median (IQR) age of 13.7 (12.9-16.5) years in AMAB and 13.5 (12.4-16.1) years in AFAB individuals. The remaining 96 participants were included at start of GAHT, at a median (IQR) age of 15.9 (15.1-17.4) years in AFAB and 16.0 (15.1-16.8) years in AMAB individuals. At the time of this report the study was open for inclusion and follow-up measurements were ongoing., Clinical Implications: In response to the rising demand for gender-affirming treatment among TGD youth, this ongoing study is fulfilling the need for prospective data on the effects and safety of PS and GAHT, thus providing a foundation for evidence-based healthcare decisions., Strengths and Limitations: This study has a strong multicenter, prospective design that allows for systematic data collection. The use of clinical and self-reported data offers a broad range of outcomes to evaluate. Nevertheless, the burden of additional measurements and questionnaires may lead to withdrawal or lower response rates. Few participants with a non-binary gender identity have been included., Conclusion: With the ENIGI Adolescents study we aim to create a comprehensive dataset that we can use for a wide range of studies to address current controversies and uncertainties and to improve healthcare for TGD adolescents., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)
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- 2024
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26. Spleen function is reduced in individuals with NR5A1 variants with or without a difference of sex development: a cross-sectional study.
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Cools M, Grijp C, Neirinck J, Tavernier SJ, Schelstraete P, Van De Velde J, Morbée L, De Baere E, Bonroy C, van Bever Y, Bruggenwirth H, Vermont C, Hannema SE, De Rijke Y, Abdulhadi-Atwan M, Zangen D, Verdin H, and Haerynck F
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- Humans, Cross-Sectional Studies, Heterozygote, Mutation, Phenotype, Spleen diagnostic imaging, Steroidogenic Factor 1 genetics
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Objective: NR5A1 is a key regulator of sex differentiation and has been implicated in spleen development through transcription activation of TLX1. Concerns exist about hypo- or asplenism in individuals who have a difference of sex development (DSD) due to an NR5A1 disease-causing variant. We aimed to assess spleen anatomy and function in a clinical cohort of such individuals and in their asymptomatic family member carriers., Design: Cross-sectional assessment in 22 patients with a DSD or primary ovarian insufficiency and 5 asymptomatic carriers from 18 families, harboring 14 different NR5A1 variants., Methods: Spleen anatomy was assessed by ultrasound, spleen function by peripheral blood cell count, white blood cell differentiation, percentage of nonswitched memory B cells, specific pneumococcal antibody response, % pitted red blood cells, and Howell-Jolly bodies., Results: Patients and asymptomatic heterozygous individuals had significantly decreased nonswitched memory B cells compared to healthy controls, but higher than asplenic patients. Thrombocytosis and spleen hypoplasia were present in 50% of heterozygous individuals. Four out of 5 individuals homozygous for the previously described p.(Arg103Gln) variant had asplenia., Conclusions: Individuals harboring a heterozygous NR5A1 variant that may cause DSD have a considerable risk for functional hyposplenism, irrespective of their gonadal phenotype. Splenic function should be assessed in these individuals, and if affected or unknown, prophylaxis is recommended to prevent invasive encapsulated bacterial infections. The splenic phenotype associated with NR5A1 variants is more severe in homozygous individuals and is, at least for the p.(Arg103Gln) variant, associated with asplenism., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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27. Androgen Excess and Deficiency: Analytical and Diagnostic Approaches.
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Heijboer AC and Hannema SE
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- Infant, Newborn, Female, Humans, Androstenedione, Virilism, Hirsutism diagnosis, Dehydroepiandrosterone, Androgens, Testosterone
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Background: Androgens are synthesized from cholesterol through sequential conversions by enzymes in the adrenal glands and gonads. Serum levels of androgens change during the different phases of life and regulate important developmental and maturational processes. Androgen excess or deficiency can therefore present at various ages in various ways., Content: The diagnostic approach for atypical genitalia, premature pubarche, delayed pubertal onset or progression, and hirsutism or virilization, including measurement of androgens (testosterone, androstenedione, 17-OHprogesterone, dehydroepiandrosterone, and dihydrotestosterone) is discussed in the current review. Androgens can be measured in serum, saliva, urine, or dried blood spots. Techniques to measure androgens, including immunoassays and LC-MS, have their own advantages and pitfalls. In addition, pre- and postanalytical issues are important when measuring androgens., Summary: During clinical interpretation of androgen measurements, it is important to take preanalytical circumstances, such as time of blood withdrawal, into account. As immunoassays have major drawbacks, especially in samples from women and neonates, concentrations measured using these assays should be interpreted with care. Reference intervals can only be used in relation to the measurement technique and the standardization of the assay. In the near future, new androgens will probably be added to the current repertoire to further improve the diagnosis and follow-up of androgen excess or deficiency., (© Association for Diagnostics & Laboratory Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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28. Bone Mineral Density in Transgender Adolescents Treated With Puberty Suppression and Subsequent Gender-Affirming Hormones.
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van der Loos MATC, Vlot MC, Klink DT, Hannema SE, den Heijer M, and Wiepjes CM
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- Adult, Infant, Newborn, Humans, Male, Female, Adolescent, Gender Identity, Cohort Studies, Puberty, Estrogens, Gonadotropin-Releasing Hormone, Bone Density, Transgender Persons
- Abstract
Importance: Bone mineral density (BMD) z scores in transgender adolescents decrease during puberty suppression with a gonadotropin-releasing hormone (GnRH) agonist. Previous research found that after short-term use of gender-affirming hormones (GAH), pretreatment z scores were not restored. Long-term follow-up studies are lacking., Objective: To assess BMD after long-term GAH treatment in transgender adults who used puberty suppression in adolescence., Design, Setting, and Participants: This single-center cohort study with follow-up duration of 15 years selected participants from a database containing all people visiting a gender identity clinic at an academic hospital in the Netherlands between 1972 and December 31, 2018. Recruitment occurred from March 1, 2020, to August 31, 2021. A total of 75 participants diagnosed with gender dysphoria who had used puberty suppression before age 18 years prior to receiving at least 9 years of long-term GAH were included., Exposures: Puberty suppression with a GnRH agonist followed by GAH treatment., Main Outcomes and Measures: Lumbar spine, total hip, and femoral neck BMD and z scores before the start of puberty suppression, at start of GAH, and at short- and long-term follow-up., Results: Among 75 participants, 25 were assigned male at birth, and 50 were assigned female at birth. At long-term follow-up, the median (IQR) age was 28.2 (27.0-30.8) years in participants assigned male at birth and 28.2 (26.6-30.6) years in participants assigned female at birth. The median (IQR) duration of GAH treatment was 11.6 (10.1-14.7) years among those assigned male at birth and 11.9 (10.2-13.8) years among those assigned female at birth. The z scores decreased during puberty suppression. In individuals assigned male at birth, the mean (SD) z score after long-term GAH use was -1.34 (1.16; change from start of GnRH agonist: -0.87; 95% CI, -1.15 to -0.59) at the lumbar spine, -0.66 (0.75; change from start of GnRH agonist: -0.12; 95% CI, -0.31 to 0.07) at the total hip, and -0.54 (0.84; change from start of GnRH agonist: 0.01; 95% CI, -0.20 to 0.22) at the femoral neck. In individuals assigned female at birth, after long-term GAH use, the mean (SD) z score was 0.20 (1.05; change from start of GnRH agonist: 0.09; 95% CI, -0.09 to 0.27) at the lumbar spine, 0.07 (0.91; change from start of GnRH agonist: 0.10; 95% CI, -0.06 to 0.26) at the total hip, and -0.19 (0.94; change from start of GnRH agonist: -0.20; 95% CI, -0.26 to 0.06) at the femoral neck., Conclusions and Relevance: In this cohort study, after long-term use of GAH, z scores in individuals treated with puberty suppression caught up with pretreatment levels, except for the lumbar spine in participants assigned male at birth, which might have been due to low estradiol concentrations. These findings suggest that treatment with GnRH agonists followed by long-term GAH is safe with regard to bone health in transgender persons receiving testosterone, but bone health in transgender persons receiving estrogen requires extra attention and further study. Estrogen treatment should be optimized and lifestyle counseling provided to maximize bone development in individuals assigned male at birth.
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- 2023
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29. Medical decision-making competence regarding puberty suppression: perceptions of transgender adolescents, their parents and clinicians.
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Vrouenraets LJJJ, de Vries ALC, Arnoldussen M, Hannema SE, Lindauer RJL, de Vries MC, and Hein IM
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- Child, Humans, Male, Adolescent, Female, Gender Identity, Puberty, Qualitative Research, Parents, Transgender Persons
- Abstract
According to international transgender care guidelines, transgender adolescents should have medical decision-making competence (MDC) to start puberty suppression (PS) and halt endogenous pubertal development. However, MDC is a debated concept in adolescent transgender care and little is known about the transgender adolescents', their parents', and clinicians' perspectives on this. Increasing our understanding of these perspectives can improve transgender adolescent care. A qualitative interview study with adolescents attending two Dutch gender identity clinics (eight transgender adolescents who proceeded to gender-affirming hormones after PS, and six adolescents who discontinued PS) and 12 of their parents, and focus groups with ten clinicians was conducted. From thematic analysis, three themes emerged regarding transgender adolescents' MDC to start PS: (1) challenges when assessing MDC, (2) aspects that are considered when assessing MDC, and (3) MDC's relevance. The four criteria one needs to fulfill to have MDC-understanding, appreciating, reasoning, communicating a choice-were all, to a greater or lesser extent, mentioned by most participants, just as MDC being relative to a specific decision and context. Interestingly, most adolescents, parents and clinicians find understanding and appreciating PS and its consequences important for MDC. Nevertheless, most state that the adolescents did not fully understand and appreciate PS and its consequences, but were nonetheless able to decide about PS. Parents' support of their child was considered essential in the decision-making process. Clinicians find MDC difficult to assess and put into practice in a uniform way. Dissemination of knowledge about MDC to start PS would help to adequately support adolescents, parents and clinicians in the decision-making process., (© 2022. The Author(s).)
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- 2023
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30. Psychosocial Functioning in Transgender Youth after Hormones. Reply.
- Author
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de Vries ALC and Hannema SE
- Subjects
- Humans, Adolescent, Psychosocial Functioning, Hormones, Gender Identity, Transgender Persons psychology
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- 2023
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31. The dose-dependent effect of estrogen on bone mineral density in trans girls.
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Boogers LS, van der Loos MATC, Wiepjes CM, van Trotsenburg ASP, den Heijer M, and Hannema SE
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- Adolescent, Female, Humans, Retrospective Studies, Estrogens, Estradiol, Bone Density, Transgender Persons
- Abstract
Objective: Treatment in transgender girls can consist of puberty suppression (PS) with a gonadotropin-releasing hormone agonist (GnRHa) followed by gender-affirming hormonal treatment (GAHT) with estrogen. Bone mineral density (BMD) Z-scores decrease during PS and remain relatively low during GAHT, possibly due to insufficient estradiol dosage. Some adolescents receive high-dose estradiol or ethinyl estradiol (EE) to limit growth allowing comparison of BMD outcomes with different dosages., Design: Retrospective study., Methods: Adolescents treated with GnRHa for ≥1 year prior to GAHT followed by treatment with a regular estradiol dose (gradually increased to 2 mg), 6 mg estradiol or 100-200 µg EE were included to evaluate height-adjusted BMD Z-scores (HAZ scores) on DXA., Results: Eighty-seven adolescents were included. During 2.3 ± 0.7 years PS, lumbar spine HAZ scores decreased by 0.69 [95% confidence interval (CI) -0.82 to -0.56)]. During 2 years HT, lumbar spine HAZ scores hardly increased in the regular group (0.14, 95% CI -0.01 to 0.28, n = 59) vs 0.42 (95% CI 0.13 to 0.72) in the 6 mg group (n = 13), and 0.68 (95% CI 0.20 to 1.15) in the EE group (n = 15). Compared with the regular group, the increase with EE treatment was higher (0.54, 95% CI 0.05 to 1.04). After 2 years HT, HAZ scores approached baseline levels at start of PS in individuals treated with 6 mg or EE (difference in 6 mg group -0.20, 95% CI -0.50 to 0.09; in EE 0.17, 95% CI -0.16 to 0.50) but not in the regular group (-0.64, 95% CI -0.79 to -0.49)., Conclusion: Higher estrogen dosage is associated with a greater increase in lumbar spine BMD Z-scores. Increasing dosage up to 2 mg estradiol is insufficient to optimize BMD and approximately 4 mg may be required for adequate serum concentrations., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.)
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- 2023
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32. Effect of Busulfan and Treosulfan on Gonadal Function after Allogeneic Stem Cell Transplantation in Children and Adolescents with Nonmalignant Diseases Is Not Exposure-Dependent.
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van der Stoep MYEC, Bense JE, de Kloet LC, von Asmuth EGJ, de Pagter APJ, Hannema SE, Guchelaar HJ, Zwaveling J, and Lankester AC
- Subjects
- Humans, Child, Adolescent, Busulfan adverse effects, Retrospective Studies, Quality of Life, Transplantation Conditioning adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Precancerous Conditions drug therapy
- Abstract
With an increasing number of young patients surviving into adulthood after hematopoietic stem cell transplantation (HSCT), gonadal dysfunction becomes an important late effect with significant impact on quality of life. In this retrospective study, we evaluated the exposure of busulfan (Bu) and treosulfan (Treo) in relation to gonadal function in pediatric patients who underwent HSCT for a nonmalignant disease between 1997 and 2018. In the Bu group, 56 patients could be evaluated, and gonadal dysfunction was found in 35 (63%). Lower Bu exposure (ie, cumulative area under the curve [AUC] <70 mg*h/L) was not associated with a reduced risk of gonadal dysfunction (odds ratio [OR], .92; 95% confidence interval [CI], .25 to 3.49; P = .90). In the Treo cohort, 32 patients were evaluable and gonadal insufficiency occurred in 9 patients (28%). Lower Treo exposure (AUC <1750 mg*h/L on day 1) was not associated with a reduced risk of gonadal dysfunction (OR, 1.6; 95% CI, .16 to 36.6; P = .71). Our data do not support the premise that reduced-intensity Bu-based conditioning reduces the risk for gonadal toxicity, and it is unlikely that therapeutic drug monitoring-based reduced treosulfan exposure will further limit the risk of gonadal dysfunction., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2023
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33. Undetectable anti-Mullerian hormone and inhibin B do not preclude the presence of germ cell tumours in 45,X/46,XY or 46,XY gonadal dysgenesis.
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Hannema SE, Wolffenbuttel KP, van Bever Y, Brüggenwirth HT, van den Berg SAA, Hersmus R, Oosterhuis JW, and Looijenga LHJ
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- Male, Female, Humans, Anti-Mullerian Hormone, Retrospective Studies, Gonadoblastoma genetics, Gonadoblastoma surgery, Dysgerminoma surgery, Gonadal Dysgenesis, 46,XY, Neoplasms, Germ Cell and Embryonal, Gonadal Dysgenesis, Ovarian Neoplasms
- Abstract
Objective: Individuals with 45,X/46,XY or 46,XY gonadal dysgenesis are at increased risk of germ cell malignancies. Therefore, prophylactic bilateral gonadectomy is advised in girls and considered in boys with atypical genitalia for undescended, macroscopically abnormal gonads. However, severely dysgenetic gonads may not contain germ cells rendering gonadectomy unnecessary. Therefore, we investigate if undetectable preoperative serum anti-Müllerian hormone (AMH) and inhibin B can predict the absence of germ cells, (pre)malignant or otherwise., Design, Patients and Measurements: Individuals who had undergone bilateral gonadal biopsy and/or gonadectomy because of suspected gonadal dysgenesis in 1999-2019 were included in this retrospective study if preoperative AMH and/or inhibin B were available. Histological material was reviewed by an experienced pathologist. Haematoxylin and eosin and immunohistochemical stainings for SOX9, OCT4, TSPY and SCF (KITL) were used., Results: Thirteen males and 16 females were included, 20 with 46,XY and 9 with 45,X/46,XY DSD. Three females had dysgerminoma alongside gonadoblastoma; two gonadoblastoma, one germ cell neoplasia in situ (GCNIS) and three males had pre-GCNIS and/or pre-gonadoblastoma. Gonadoblastoma and/or dysgerminoma were present in 3/11 individuals with undetectable AMH and inhibin B, one of whom also had non-(pre)malignant germ cells. Of the other 18, in whom AMH and/or inhibin B were detectable, only one had no germ cells., Conclusions: Undetectable serum AMH and inhibin B cannot reliably predict the absence of germ cells and germ cell tumours in individuals with 45,X/46,XY or 46,XY gonadal dysgenesis. This information should help in counselling about prophylactic gonadectomy, taking into account both the germ cell cancer risk and potential for gonadal function., (© 2023 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)
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- 2023
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34. [Children and adolescents with gender questions: dilemmas in the hormonal treatment by multidisciplinary teams].
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Claahsen-van der Grinten HL, Hannema SE, Klink D, Roeffen J, Spath MA, Verhaak C, and de Vries ALC
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- Humans, Male, Female, Adolescent, Child, Gender Identity, Netherlands, Patient Care Team, Transgender Persons psychology, Transsexualism
- Abstract
In the Netherlands but also in many other countries, there is an increasing social discussion about gender identity and gender diversity, and an increasing number of children and adolescents are seeking medical help because of questions about their gender identity. The cause of this increase is still unknown. Gender questions are diverse and require an individual approach by a multidisciplinary team. A number of adolescents have additional problems such as mood problems, autistiform symptoms and systemic problems. Diagnosis and treatment takes place in accordance with the quality standard for transgender care somatic and psychological. Hormonal treatment can help to reduce gender dysphoria and improve mental health.
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- 2023
35. Children and adolescents in the Amsterdam Cohort of Gender Dysphoria: trends in diagnostic- and treatment trajectories during the first 20 years of the Dutch Protocol.
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van der Loos MATC, Klink DT, Hannema SE, Bruinsma S, Steensma TD, Kreukels BPC, Cohen-Kettenis PT, de Vries ALC, den Heijer M, and Wiepjes CM
- Subjects
- Infant, Newborn, Humans, Male, Child, Adolescent, Female, Retrospective Studies, Gender Identity, Sex Reassignment Procedures, Gonadotropin-Releasing Hormone therapeutic use, Gender Dysphoria drug therapy, Transgender Persons
- Abstract
Background: Twenty years ago, the Dutch Protocol-consisting of a gonadotropin-releasing hormone agonist (GnRHa) to halt puberty and subsequent gender-affirming hormones (GAHs)-was implemented to treat adolescents with gender dysphoria., Aim: To study trends in trajectories in children and adolescents who were referred for evaluation of gender dysphoria and/or treated following the Dutch Protocol., Methods: The current study is based on a retrospective cohort of 1766 children and adolescents in the Amsterdam Cohort of Gender Dysphoria., Outcomes: Outcomes included trends in number of intakes, ratio of assigned sex at birth, age at intake, age at start of GnRHa and GAH, puberty stage at start of GnRHa, proportions of adolescents starting and stopping GnRHa, reasons for refraining from GnRHa, and proportions of people undergoing gender-affirming surgery., Results: A steep increase in referrals was observed over the years. A change in the AMAB:AFAB ratio (assigned male at birth to assigned female at birth) was seen over time, tipping the balance toward AFAB. Age at intake and at start of GnRHa has increased over time. Of possibly eligible adolescents who had their first visit before age 10 years, nearly half started GnRHa vs around two-thirds who had their first visit at or after age 10 years. The proportion starting GnRHa rose only for those first visiting before age 10. Puberty stage at start of GnRHa fluctuated over time. Absence of gender dysphoria diagnosis was the main reason for not starting GnRHa. Very few stopped GnRHa (1.4%), mostly because of remission of gender dysphoria. Age at start of GAH has increased mainly in the most recent years. When a change in law was made in July 2014 no longer requiring gonadectomy to change legal sex, percentages of people undergoing gonadectomy decreased in AMAB and AFAB., Clinical Implications: A substantial number of adolescents did not start medical treatment. In the ones who did, risk for retransitioning was very low, providing ongoing support for medical interventions in comprehensively assessed gender diverse adolescents., Strengths and Limitations: Important topics on transgender health care for children and adolescents were studied in a large cohort over an unprecedented time span, limited by the retrospective design., Conclusion: Trajectories in diagnostic evaluation and medical treatment in children and adolescents referred for gender dysphoria are diverse. Initiating medical treatment and need for surgical procedures depends on not only personal characteristics but societal and legal factors as well., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)
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- 2023
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36. Prenatal ultrasound finding of atypical genitalia: Counseling, genetic testing and outcomes.
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van Bever Y, Groenenberg IAL, Knapen MFCM, Dessens AB, Hannema SE, Wolffenbuttel KP, Diderich KEM, Hoefsloot LH, Srebniak MI, and Bruggenwirth HT
- Subjects
- Pregnancy, Female, Humans, Retrospective Studies, Ultrasonography, Prenatal, Counseling, Genitalia diagnostic imaging, Prenatal Diagnosis, Genetic Counseling, Genetic Testing
- Abstract
Objective: To report uptake of genetic counseling (GC) and prenatal genetic testing after the finding of atypical genitalia on prenatal ultrasound (US) and the clinical and genetic findings of these pregnancies., Methods: A retrospective cohort study (2017-2019) of atypical fetal genitalia in a large expert center for disorders/differences of sex development. We describe counseling aspects, invasive prenatal testing, genetic and clinical outcome of fetuses apparently without [group 1, n = 22 (38%)] or with [group 2, n = 36 (62%)] additional anomalies on US., Results: In group 1, 86% of parents opted for GC versus 72% in group 2, and respectively 58% and 15% of these parents refrained from invasive testing. Atypical genitalia were postnatally confirmed in 91% (group 1) and 64% (group 2), indicating a high rate of false positive US diagnosis of ambiguous genitalia. Four genetic diagnoses were established in group 1 (18%) and 10 in group 2 (28%). The total genetic diagnostic yield was 24%. No terminations of pregnancy occurred in group 1., Conclusions: For optimal care, referral for an expert fetal US scan, GC and invasive diagnostics including broad testing should be offered after prenatal detection of isolated atypical genitalia., (© 2022 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)
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- 2023
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37. Growing Evidence and Remaining Questions in Adolescent Transgender Care.
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de Vries ALC and Hannema SE
- Subjects
- Adolescent, Humans, Transgender Persons, Patient Care methods, Patient Care standards, Adolescent Health
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- 2023
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38. Just as Tall on Testosterone; a Neutral to Positive Effect on Adult Height of GnRHa and Testosterone in Trans Boys.
- Author
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Willemsen LA, Boogers LS, Wiepjes CM, Klink DT, van Trotsenburg ASP, den Heijer M, and Hannema SE
- Subjects
- Humans, Female, Male, Adult, Gonadotropin-Releasing Hormone, Testosterone pharmacology, Retrospective Studies, Gender Identity, Body Height, Human Growth Hormone pharmacology, Transgender Persons
- Abstract
Context: Growth is an important topic for many transgender boys. However, few studies have investigated the impact of puberty suppression (PS) and gender-affirming hormone treatment (GAHT) on growth and adult height., Objective: To evaluate the effect of PS and GAHT on growth and adult height., Design: Retrospective cohort study., Setting: Specialized gender identity clinic., Participants: A total of 146 transgender boys treated with GnRH analogues and testosterone who reached adult height., Main Outcome Measures: Growth, bone age (BA), adult height, and difference between adult height and predicted adult height (PAH) and midparental height., Results: In those with BA ≤14 years at start (n = 61), a decrease in growth velocity and bone maturation during PS was followed by an increase during GAHT. Adult height was 172.0 ± 6.9 cm; height SD score was similar to baseline (0.1; 95% CI, -0.2 to 0.4). Adult height was 3.9 ± 6.0 cm above midparental height and 3.0 ± 3.6 cm above PAH at start of PS. A younger BA at start PS was associated with an adult height significantly further above PAH., Conclusion: During PS, growth decelerated followed by an acceleration during GAHT. Although adult height SD score was similar to baseline, adult height was taller than predicted based on BA at baseline, especially in those who started treatment at a younger BA. It is reassuring that PS and GAHT do not have a negative impact on adult height in transgender boys and might even lead to a slightly taller adult height, especially in those who start at a younger age., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2023
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39. Continuation of gender-affirming hormones in transgender people starting puberty suppression in adolescence: a cohort study in the Netherlands.
- Author
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van der Loos MATC, Hannema SE, Klink DT, den Heijer M, and Wiepjes CM
- Subjects
- Infant, Newborn, Adolescent, Female, Male, Humans, Adult, Gender Identity, Cohort Studies, Netherlands, Puberty, Hormones, Transgender Persons
- Abstract
Background: In the Netherlands, treatment with puberty suppression is available to transgender adolescents younger than age 18 years. When gender dysphoria persists testosterone or oestradiol can be added as gender-affirming hormones in young people who go on to transition. We investigated the proportion of people who continued gender-affirming hormone treatment at follow-up after having started puberty suppression and gender-affirming hormone treatment in adolescence., Methods: In this cohort study, we used data from the Amsterdam Cohort of Gender dysphoria (ACOG), which included people who visited the gender identity clinic of the Amsterdam UMC, location Vrije Universiteit Medisch Centrum, Netherlands, for gender dysphoria. People with disorders of sex development were not included in the ACOG. We included people who started medical treatment in adolescence with a gonadotropin-releasing hormone agonist (GnRHa) to suppress puberty before the age of 18 years and used GnRHa for a minimum duration of 3 months before addition of gender-affirming hormones. We linked this data to a nationwide prescription registry supplied by Statistics Netherlands (Centraal Bureau voor de Statistiek) to check for a prescription for gender-affirming hormones at follow-up. The main outcome of this study was a prescription for gender-affirming hormones at the end of data collection (Dec 31, 2018). Data were analysed using Cox regression to identify possible determinants associated with a higher risk of stopping gender-affirming hormone treatment., Findings: 720 people were included, of whom 220 (31%) were assigned male at birth and 500 (69%) were assigned female at birth. At the start of GnRHa treatment, the median age was 14·1 (IQR 13·0-16·3) years for people assigned male at birth and 16·0 (14·1-16·9) years for people assigned female at birth. Median age at end of data collection was 20·2 (17·9-24·8) years for people assigned male at birth and 19·2 (17·8-22·0) years for those assigned female at birth. 704 (98%) people who had started gender-affirming medical treatment in adolescence continued to use gender-affirming hormones at follow-up. Age at first visit, year of first visit, age and puberty stage at start of GnRHa treatment, age at start of gender-affirming hormone treatment, year of start of gender-affirming hormone treatment, and gonadectomy were not associated with discontinuing gender-affirming hormones., Interpretation: Most participants who started gender-affirming hormones in adolescence continued this treatment into adulthood. The continuation of treatment is reassuring considering the worries that people who started treatment in adolescence might discontinue gender-affirming treatment., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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40. Mobile Phone Applications Voice Tools and Voice Pitch Analyzer Validated With LingWAVES to Measure Voice Frequency.
- Author
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Boogers LS, Chen BSJ, Coerts MJ, Rinkel RNPM, and Hannema SE
- Abstract
Objectives: Voice frequency can be measured to assess the voice change in transgender men and women during treatment. There are many applications that can analyze voice frequency. This validation study aimed to compare the ability to measure voice frequency of the mobile phone applications "Voice Tools" and "Voice Pitch Analyzer" with the registration program LingWAVES as the gold standard., Study Design: Prospective validation study., Methods: A total of 45 participants of whom 20 transgender individuals were included. They were asked to read "The North Wind and the Sun" twice. The first measurement compared voice frequency measured by Voice Tools with LingWAVES while the second measurement compared Voice Pitch Analyzer with LingWAVES. The two applications that were being compared simultaneously measured the voice frequency. Pearson's regression correlations were performed to test for correlation between the mobile phone applications and LingWAVES., Results: Significant correlations were demonstrated between the measurements of Voice Tools and LingWAVES (P < 0.001) and between Voice Pitch Analyzer and LingWAVES (P < 0.001). Voice Tools overestimated voice frequency with a median deviation of 2Hz (range -4 to 20). The overestimation was more pronounced in the high ranges. Voice Pitch Analyzer showed underestimation of voice frequency in high ranges. Median deviation was -2Hz (range -16 to 14)., Conclusions: This validation study shows that voice frequency can be reliably measured with the mobile phone applications "Voice Tools" and "Voice Pitch Analyzer". Combined with the ease of use, these applications can be used to measure voice frequency in clinical practice and for research purposes., Competing Interests: Conflict of Interest The authors have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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41. Improved growth with growth hormone treatment in children after hematopoietic stem cell transplantation.
- Author
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Hoekx CA, Bresters D, le Cessie S, Oostdijk W, and Hannema SE
- Subjects
- Adolescent, Adult, Body Height, Busulfan, Child, Female, Growth Hormone therapeutic use, Humans, Male, Retrospective Studies, Hematopoietic Stem Cell Transplantation, Human Growth Hormone therapeutic use
- Abstract
Objective: Hematopoietic stem cell transplantation (HSCT) can be a curative treatment for malignant and nonmalignant diseases in children but is associated with significant late effects including growth failure. Growth hormone treatment (GHRx) is offered to improve growth, but limited data are available on its effect on adult height (AH). We aim to evaluate the effectiveness of GHRx., Design: Single-center retrospective study., Patients: Thirty-four patients who had received GHRx for ≥1 year were matched with two controls each, without GHRx, based on sex, indication for HSCT (malignancy, benign haematological disease or immunodeficiency), age at HSCT and conditioning with/without total body irradiation (TBI). All had reached AH., Measurements: The primary outcome measure was the difference between AH and predicted AH (PAH) at start of GHRx or the equivalent age in controls (AH-PAH), calculated according to Bailey and Pinneau., Results: GHRx was started at age 12.0 ± 2.6 years; median treatment duration was 3.8 years (range 1.7-9.2). AH-PAH standard deviation score (SDS) was significantly higher in growth hormone (GH) treated boys (-0.5 ± 0.7 SDS) than in controls (-1.5 ± 1.0 SDS, p < .001). Girls also had a higher AH-PAH after GHRx (+0.5 ± 0.6 SDS) compared to controls (-0.2 SDS ±0.7, p < .01). AH remained approximately 2 SDS below target height (TH) in treated and untreated individuals. Among GH-treated children, AH-PAH was higher in those who had received busulfan-based compared to TBI-based conditioning., Conclusion: GHRx had a significant positive effect on AH compared to PAH, although AH remained far below TH. Higher AH-PAH was observed in girls and in those conditioned without TBI., (© 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)
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- 2022
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42. Late endocrine effects after hematopoietic stem cell transplantation in children with nonmalignant diseases.
- Author
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de Kloet LC, Bense JE, van der Stoep MYEC, Louwerens M, von Asmuth EGJ, Lankester AC, de Pagter APJ, and Hannema SE
- Subjects
- Adult, Child, Female, Humans, Male, Retrospective Studies, Thyroxine, Transplantation Conditioning adverse effects, Busulfan adverse effects, Busulfan analogs & derivatives, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
The number of children undergoing hematopoietic stem cell transplantation (HSCT) for nonmalignant diseases has increased in recent years. Endocrine complications are common after HSCT for malignant diseases, while little is known about long-term prevalence and risk factors in children transplanted for nonmalignant diseases. We retrospectively evaluated gonadal function, near adult height and thyroid function in 197 survivors of pediatric HSCT for hemoglobinopathies (n = 66), inborn errors of immunity/metabolism (n = 74) and bone marrow failure disorders (n = 57); median follow-up was 6.2 years (range 3.0-10.5). Gonadal dysfunction occurred in 55% of (post)pubertal females, was still present at last assessment in 43% and was more common after busulfan- than treosulfan-based conditioning (HR 10.6, CI 2.2-52.7; adjusted for HSCT indication). Gonadal dysfunction occurred in 39% of (post)pubertal males, was still present at last assessment in 32% and was less common in those who were prepubertal compared to (post)pubertal at HSCT (HR 0.11; CI 0.05-0.21). Near adult height was more than 2 SDS below mean parental height in 21% of males and 8% of females. Hypothyroidism occurred in 16% of patients; 4% received thyroxin treatment. In conclusion, endocrine complications, especially gonadal dysfunction, are common after pediatric HSCT for nonmalignant conditions. In females, treosulfan seems less gonadotoxic than busulfan. Careful long-term endocrine follow-up is indicated., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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43. We mind your step: understanding and preventing drop-out in the transfer from paediatric to adult tertiary endocrine healthcare.
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Davidse K, van Staa A, Geilvoet W, van Eck JP, Pellikaan K, Baan J, Hokken-Koelega ACS, van den Akker ELT, Sas T, Hannema SE, van der Lely AJ, and de Graaff LCG
- Abstract
Introduction: Transition from paediatric to adult endocrinology can be challenging for adolescents, their families and healthcare professionals. Previous studies have shown that up to 25% of young adults with endocrine disorders are lost to follow-up after moving out of paediatric care. This poses a health risk for young adults, which can lead to serious and expensive medical acute and long-term complications., Methods: In order to understand and prevent dropout, we studied electronic medical records of patients with endocrine disorders. These patients were over 15 years old when they attended the paediatric endocrine outpatient clinic (OPC) of our hospital in 2013-2014 and should have made the transfer to adult care at the time of the study., Results: Of 387 adolescents, 131 had an indication for adult follow-up within our university hospital. Thirty-three (25%) were lost to follow-up. In 24 of them (73%), the invitation for the adult OPC had never been sent. We describe the failures in logistic processes that eventually led to dropout in these patients., Conclusion: We found a 25% dropout during transfer from paediatric to adult tertiary endocrine care. Of all dropouts, 73% could be attributed to the failure of logistic steps. In order to prevent these dropouts, we provide practical recommendations for patients and paediatric and adult endocrinologists.
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- 2022
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44. Treatment of congenital adrenal hyperplasia in children aged 0-3 years: a retrospective multicenter analysis of salt supplementation, glucocorticoid and mineralocorticoid medication, growth and blood pressure.
- Author
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Neumann U, van der Linde A, Krone RE, Krone NP, Güven A, Güran T, Elsedfy H, Poyrazoglu S, Darendeliler F, Bachega TASS, Balsamo A, Hannema SE, Birkebaek N, Vieites A, Thankamony A, Cools M, Milenkovic T, Bonfig W, Costa EC, Atapattu N, de Vries L, Guaragna-Filho G, Korbonits M, Mohnike K, Bryce J, Ahmed SF, Voet B, Blankenstein O, and Claahsen-van der Grinten HL
- Subjects
- Blood Pressure, Child, Child, Preschool, Dietary Supplements, Fludrocortisone therapeutic use, Humans, Hydrocortisone therapeutic use, Male, Mineralocorticoids therapeutic use, Retrospective Studies, Sodium Chloride, Dietary therapeutic use, Adrenal Hyperplasia, Congenital drug therapy, Glucocorticoids therapeutic use
- Abstract
Objectives: International guidelines recommend additional salt supplementation during infancy in classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The influence of corticoid medication and growth has not been assessed., Aim: To investigate the current use of salt supplementation, fludrocortisone (FC) and hydrocortisone (HC) dosage as well as weight, height, BMI and blood pressure (BP) in CAH children aged 0-3 years., Methods: Retrospective multicentre analysis using data from the I-CAH registry. Salt-treated (ST) and non-salt-treated (NST) children were compared regarding FC and HC dosage, weight, height and BP at 0, 3, 6, 9, 12, 18, 24, 30, and 36 months., Results: We analysed 2483 visits of 331 patients born after year 2000 in 13 countries (male, n = 145) with 203 ST patients (61%). NST children had significantly higher FC dosages at 1.5-4.5 months and higher HC dosages until 1.5 months of age. No differences in weight, length and BP between subgroups were observed. Children of the whole cohort showed increased BMI-SDS during the study period and about half of the reported BP readings were >P95., Conclusion: In children treated with additional salt supplementation, FC and HC dosages are lower during the first months of life but without differences in weight, length and BP until 3 years of age compared to NST children. All children showed an increase in BMI-SDS and a high rate of BP readings >P95 until 3 years, indicating the start of weight gain and negative effects on blood pressure already in very early life.
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- 2022
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45. Optimizing the Timing of Highest Hydrocortisone Dose in Children and Adolescents With 21-Hydroxylase Deficiency.
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Schröder MAM, van Herwaarden AE, Span PN, van den Akker ELT, Bocca G, Hannema SE, van der Kamp HJ, de Kort SWK, Mooij CF, Schott DA, Straetemans S, van Tellingen V, van der Velden JA, Sweep FCGJ, and Claahsen-van der Grinten HL
- Subjects
- 17-alpha-Hydroxyprogesterone, Adolescent, Androgens therapeutic use, Child, Child, Preschool, Cross-Over Studies, Female, Humans, Male, Young Adult, Adrenal Hyperplasia, Congenital drug therapy, Hydrocortisone
- Abstract
Context: Hydrocortisone treatment of young patients with 21-hydroxylase deficiency (21OHD) is given thrice daily, but there is debate about the optimal timing of the highest hydrocortisone dose, either mimicking the physiological diurnal rhythm (morning), or optimally suppressing androgen activity (evening)., Objective: We aimed to compare 2 standard hydrocortisone timing strategies, either highest dosage in the morning or evening, with respect to hormonal status throughout the day, nocturnal blood pressure (BP), and sleep and activity scores., Methods: This 6-week crossover study included 39 patients (aged 4-19 years) with 21OHD. Patients were treated for 3 weeks with the highest hydrocortisone dose in the morning, followed by 3 weeks with the highest dose in the evening (n = 21), or vice versa (n = 18). Androstenedione (A4) and 17-hydroxyprogesterone (17OHP) levels were quantified in saliva collected at 5 am; 7 am; 3 pm; and 11 pm during the last 2 days of each treatment period. The main outcome measure was comparison of saliva 17OHP and A4 levels between the 2 treatment strategies., Results: Administration of the highest dose in the evening resulted in significantly lower 17OHP levels at 5 am, whereas the highest dose in the morning resulted in significantly lower 17OHP and A4 levels in the afternoon. The 2 treatment dose regimens were comparable with respect to averaged daily hormone levels, nocturnal BP, and activity and sleep scores., Conclusion: No clear benefit for either treatment schedule was established. Given the variation in individual responses, we recommend individually optimizing dose distribution and monitoring disease control at multiple time points., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2022
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46. Growth, puberty and testicular function in boys born small for gestational age with a nonspecific disorder of sex development.
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Tack LJW, van der Straaten S, Riedl S, Springer A, Holterhus PM, Hornig NC, Kolesinska Z, Niedziela M, Baronio F, Balsamo A, Hannema SE, Nordenström A, Poyrazoglu S, Darendeliler FF, Grinspon R, Rey R, Aljuraibah F, Bryce J, Ahmed F, Tadokoro-Cuccaro R, Hughes I, Guaragna-Filho G, Maciel-Guerra AT, Guerra-Junior G, and Cools M
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- Gestational Age, Humans, Infant, Newborn, Male, Retrospective Studies, Testosterone, Infant, Small for Gestational Age, Puberty
- Abstract
Objective: Being born small for gestational age (SGA) is frequently associated with unexplained disorders of sex development (nonspecific DSD) in boys. Little is known about their future growth, puberty and testicular function. Our objective is to determine the long-term endocrine outcome of boys born SGA who have a nonspecific DSD., Design: Boys with a nonspecific DSD born SGA and appropriate for GA (AGA) were retrieved through the International Disorders of Sex Development registry and retrospective data collected, based on a spreadsheet containing 102 items., Patients and Measurements: In total, 179 boys were included, of which 115 were born SGA and 64 were born AGA. Their growth and pubertal development were compared. Serum LH, FSH, testosterone, AMH and inhibin B levels in infancy and puberty were analysed to assess testicular function., Results: At 2 years of age, 30% of SGA boys had incomplete or absent catch-up growth. Boys born SGA also had higher LH during minipuberty and lower testosterone in stimulation tests (p = 0.037 and 0.040, respectively), as compared to boys born AGA. No differences were observed in timing or course of puberty or end-pubertal hormone levels., Conclusions: Almost one out of three SGA boys with a nonspecific DSD experiences insufficient catch-up growth. In addition, our data suggest dysfunction of infantile Leydig cells or altered regulation of the hypothalamic-pituitary-gonadal axis in SGA boys during childhood. Sex steroid production during puberty seems unaffected., (© 2021 John Wiley & Sons Ltd.)
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- 2022
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47. Histological study on the influence of puberty suppression and hormonal treatment on developing germ cells in transgender women.
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de Nie I, Mulder CL, Meißner A, Schut Y, Holleman EM, van der Sluis WB, Hannema SE, den Heijer M, Huirne J, van Pelt AMM, and van Mello NM
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- Adult, Child, Female, Humans, Male, Puberty, Spermatogenesis, Spermatogonia, Testis, Transgender Persons
- Abstract
Study Question: Can transgender women cryopreserve germ cells obtained from their orchiectomy specimen for fertility preservation, after having used puberty suppression and/or hormonal treatment?, Summary Answer: In the vast majority of transgender women, there were still immature germ cells present in the orchiectomy specimen, and in 4.7% of transgender women-who all initiated medical treatment in Tanner stage 4 or higher-mature spermatozoa were found, which would enable cryopreservation of spermatozoa or testicular tissue after having used puberty suppression and/or hormonal treatment., What Is Known Already: Gender affirming treatment (i.e. puberty suppression, hormonal treatment, and subsequent orchiectomy) impairs reproductive function in transgender women. Although semen cryopreservation is generally offered during the transition process, this option is not feasible for all transgender women (e.g. due to incomplete spermatogenesis when initiating treatment in early puberty, in case of inability to masturbate, or when temporary cessation of hormonal treatment is too disruptive). Harvesting mature spermatozoa, or testicular tissue harboring immature germ cells, from orchiectomy specimens obtained during genital gender-affirming surgery (gGAS) might give this group a chance of having biological children later in life. Previous studies on spermatogenesis in orchiectomy specimens showed conflicting results, ranging from complete absence of germ cells to full spermatogenesis, and did not involve transgender women who initiated medical treatment in early- or late puberty., Study Design, Size, Duration: Histological and immunohistochemical analyses were performed on orchiectomy specimens from 214 transgender women who underwent gGAS between 2006 and 2018. Six subgroups were identified, depending on pubertal stage at initiation of medical treatment (Tanner stage 2-3, Tanner stage 4-5, adult), and whether hormonal treatment was continued or temporarily stopped prior to gGAS in each of these groups., Participants/materials, Setting, Methods: All transgender women used a combination of estrogens and testosterone suppressing therapy. Orchiectomy specimen sections were stained with Mayer's hematoxylin and eosin and histologically analyzed to assess the Johnsen score and the ratio of most advanced germ cell types in at least 50 seminiferous tubular cross-sections. Subsequently, immunohistochemistry was used to validate these findings using spermatogonia, spermatocytes or spermatids markers (MAGE-A3/A4, γH2AX, Acrosin, respectively). Possibilities for fertility preservation were defined as: preservation of spermatozoa, preservation of spermatogonial stem cells or no possibilities (in case no germ cells were found). Outcomes were compared between subgroups and logistic regression analyses were used to assess the association between the duration of hormonal treatment and the possibilities for fertility preservation., Main Results and the Role of Chance: Mature spermatozoa were encountered in 4.7% of orchiectomy specimens, all from transgender women who had initiated medical treatment in Tanner stage 4 or higher. In 88.3% of the study sample orchiectomy specimens only contained immature germ cells (round spermatids, spermatocytes or spermatogonia, as most advanced germ cell type). In 7.0%, a complete absence of germ cells was observed, all these samples were from transgender women who had initiated medical treatment in adulthood. Cessation of hormonal treatment prior to gGAS did not affect the presence of germ cells or their maturation stage, nor was there an effect of the duration of hormonal treatment prior to gGAS., Limitations, Reasons for Caution: Since data on serum hormone levels on the day of gGAS were not available, we were unable to verify if the transgender women who were asked to temporarily stop hormonal treatment 4 weeks prior to surgery actually did so, and if people with full spermatogenesis were compliant to treatment., Wider Implications of the Findings: There may still be options for fertility preservation in orchiectomy specimens obtained during gGAS since a small percentage of transgender women had full spermatogenesis, which could enable cryopreservation of mature spermatozoa via a testicular sperm extraction procedure. Furthermore, the vast majority still had immature germ cells, which could enable cryopreservation of testicular tissue harboring spermatogonial stem cells. If maturation techniques like in vitro spermatogenesis become available in the future, harvesting germ cells from orchiectomy specimens might be a promising option for those who are otherwise unable to have biological children., Study Funding/competing Interest: None., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)
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- 2022
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48. Perceptions on the function of puberty suppression of transgender adolescents who continued or discontinued treatment, their parents, and clinicians.
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Vrouenraets LJJJ, de Vries MC, Hein IM, Arnoldussen M, Hannema SE, and de Vries ALC
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Purpose: Treatment of transgender adolescents with puberty suppression (PS) was developed to provide time for exploration before pursuing gender affirming medical treatment (GAMT) with irreversible effects. It may also result in a more satisfactory physical outcome for those who continue with GAMT. Despite being the current first choice treatment, little research has examined the function of PS from the perspectives of transgender adolescents, their parents, and clinicians. Insight into the perceived functions of PS will help to adequately support adolescents in their decision-making process and give them the care they need. Methods: Qualitative study using interviews with eight transgender adolescents who proceeded with GAMT after PS ("continuers"), six adolescents who discontinued PS ("discontinuers") and 12 parents, and focus groups with ten clinicians. Results: All informants considered inhibition of development of secondary sex characteristics an important function of PS. Most continuers saw PS as the first step of GAMT. Nevertheless, some were glad that the effects were reversible even if they didn't expect to change their minds. Some discontinuers did experience PS as an expanded diagnostic phase. One continuer used the time on PS to get used to living in the affirmed gender role, and several parents found the time helpful to adapt to their child's new gender role. PS provided clinicians more time for diagnostic assessment. Conclusions: Adolescents, parents and clinicians do not all report the same functions of PS. Although international guidelines emphasize providing time for exploration of gender identity as an important reason for PS, many adolescents nowadays seem to have clear ideas about their gender identity and treatment wishes, and experience PS as the first step of GAMT. For some discontinuers however, PS offered a valued period of exploration. Guidelines could be modified to provide more customized care, taking adolescents' and parents' ideas about the functions of PS into account., (© 2021 Leiden University Medical Center (LUMC). Published with license by Taylor & Francis Group, LLC.)
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- 2021
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49. Second-tier Testing for 21-Hydroxylase Deficiency in the Netherlands: A Newborn Screening Pilot Study.
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Stroek K, Ruiter A, van der Linde A, Ackermans M, Bouva MJ, Engel H, Jakobs B, Kemper EA, van den Akker ELT, van Albada ME, Bocca G, Finken MJJ, Hannema SE, Mieke Houdijk ECA, van der Kamp HJ, van Tellingen V, Paul van Trotsenburg AS, Zwaveling-Soonawala N, Bosch AM, de Jonge R, Heijboer AC, Claahsen-van der Grinten HL, and Boelen A
- Subjects
- Adrenal Hyperplasia, Congenital blood, Algorithms, False Positive Reactions, Humans, Infant, Newborn, Netherlands, Sensitivity and Specificity, 17-alpha-Hydroxyprogesterone blood, Adrenal Hyperplasia, Congenital diagnosis, Cortodoxone blood, Neonatal Screening methods, Pilot Projects
- Abstract
Context: Newborn screening (NBS) for classic congenital adrenal hyperplasia (CAH) consists of 17-hydroxyprogesterone (17-OHP) measurement with gestational age-adjusted cutoffs. A second heel puncture (HP) is performed in newborns with inconclusive results to reduce false positives., Objective: We assessed the accuracy and turnaround time of the current CAH NBS algorithm in comparison with alternative algorithms by performing a second-tier 21-deoxycortisol (21-DF) pilot study., Methods: Dried blood spots (DBS) of newborns with inconclusive and positive 17-OHP (immunoassay) first HP results were sent from regional NBS laboratories to the Amsterdam UMC Endocrine Laboratory. In 2017-2019, 21-DF concentrations were analyzed by LC-MS/MS in parallel with routine NBS. Diagnoses were confirmed by mutation analysis., Results: A total of 328 DBS were analyzed; 37 newborns had confirmed classic CAH, 33 were false-positive and 258 were categorized as negative in the second HP following the current algorithm. With second-tier testing, all 37 confirmed CAH had elevated 21-DF, while all 33 false positives and 253/258 second-HP negatives had undetectable 21-DF. The elevated 21-DF of the other 5 newborns may be NBS false negatives or second-tier false positives. Adding the second-tier results to inconclusive first HPs reduced the number of false positives to 11 and prevented all 286 second HPs. Adding the second tier to both positive and inconclusive first HPs eliminated all false positives but delayed referral for 31 CAH patients (1-4 days)., Conclusion: Application of the second-tier 21-DF measurement to inconclusive first HPs improved our CAH NBS by reducing false positives, abolishing the second HP, and thereby shortening referral time., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2021
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50. Gonadectomy in conditions affecting sex development: a registry-based cohort study.
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Lucas-Herald AK, Bryce J, Kyriakou A, Ljubicic ML, Arlt W, Audi L, Balsamo A, Baronio F, Bertelloni S, Bettendorf M, Brooke A, Claahsen van der Grinten HL, Davies JH, Hermann G, de Vries L, Hughes IA, Tadokoro-Cuccaro R, Darendeliler F, Poyrazoglu S, Ellaithi M, Evliyaoglu O, Fica S, Nedelea L, Gawlik A, Globa E, Zelinska N, Guran T, Güven A, Hannema SE, Hiort O, Holterhus PM, Iotova V, Mladenov V, Jain V, Sharma R, Jennane F, Johnston C, Guerra Junior G, Konrad D, Gaisl O, Krone N, Krone R, Lachlan K, Li D, Lichiardopol C, Lisa L, Markosyan R, Mazen I, Mohnike K, Niedziela M, Nordenstrom A, Rey R, Skaeil M, Tack LJW, Tomlinson J, Weintrob N, Cools M, and Ahmed SF
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- Adolescent, Adult, Aged, Aged, 80 and over, Disorders of Sex Development epidemiology, Female, Humans, Male, Middle Aged, Registries, Retrospective Studies, Young Adult, Castration statistics & numerical data, Disorders of Sex Development diagnosis, Disorders of Sex Development surgery
- Abstract
Objectives: To determine trends in clinical practice for individuals with DSD requiring gonadectomy., Design: Retrospective cohort study., Methods: Information regarding age at gonadectomy according to diagnosis; reported sex; time of presentation to specialist centre; and location of centre from cases reported to the International DSD Registry and who were over 16 years old in January 2019., Results: Data regarding gonadectomy were available in 668 (88%) individuals from 44 centres. Of these, 248 (37%) (median age (range) 24 (17, 75) years) were male and 420 (63%) (median age (range) 26 (16, 86) years) were female. Gonadectomy was reported from 36 centres in 351/668 cases (53%). Females were more likely to undergo gonadectomy (n = 311, P < 0.0001). The indication for gonadectomy was reported in 268 (76%). The most common indication was mitigation of tumour risk in 172 (64%). Variations in the practice of gonadectomy were observed; of the 351 cases from 36 centres, 17 (5%) at 9 centres had undergone gonadectomy before their first presentation to the specialist centre. Median age at gonadectomy of cases from high-income countries and low-/middle-income countries (LMIC) was 13.0 years (0.1, 68) years and 16.5 years (1, 28), respectively (P < 0.0001) with the likelihood of long-term retention of gonads being higher in LMIC countries., Conclusions: The likelihood of gonadectomy depends on the underlying diagnosis, sex of rearing and the geographical setting. Clinical benchmarks, which can be studied across all forms of DSD will allow a better understanding of the variation in the practice of gonadectomy.
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- 2021
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