title: Effect of pubertal suppression and cross-sex hormone therapy on bone turnover markers and bone mineral apparent density (BMAD) in transgender adolescents.
abstract: Puberty is highly important for the accumulation of bone mass. Bone turnover and bone mineral density (BMD) can be affected in transgender adolescents when puberty is suppressed by gonadotropin-releasing hormone analogues (GnRHa), followed by treatment with cross-sex hormone therapy (CSHT). We aimed to investigate the effect of GnRHa and CSHT on bone turnover markers (BTMs) and bone mineral apparent density (BMAD) in transgender adolescents. Gender dysphoria was diagnosed based on diagnostic criteria according to the DSM-IV (TR). Thirty four female-to-male persons (transmen) and 22 male-to-female persons (transwomen)were included. Patients were allocated to a young (bone age of <15years in transwomen or <14 in transmen) or old group (bone age of ≥15years in transwomen or ≥14years in transmen). All were treated with GnRHa triptorelin and CSHT was added in incremental doses from the age of 16years. Transmen received testosterone esters (Sustanon, MSD) and transwomen received 17-β estradiol. P1NP, osteocalcin, ICTP and BMD of lumbar spine (LS) and femoral neck (FN) were measured at three time points. In addition, BMAD and Z-scores were calculated. We found a decrease of P1NP and 1CTP during GnRHa treatment, indicating decreased bone turnover (young transmen 95% CI -74 to -50%, p=0.02, young transwomen 95% CI -73 to -43, p=0.008). The decrease in bone turnover upon GnRHa treatment was accompanied by an unchanged BMAD of FN and LS, whereas BMAD Z-scores of predominantly the LS decreased especially in the young transwomen. Twenty-four months after CSHT the BTMs P1NP and ICTP were even more decreased in all groups except for the old transmen. During CSHT BMAD increased and Z-scores returned towards normal, especially of the LS (young transwomen CI 95% 0.1 to 0.6, p=0.01, old transwomen 95% CI 0.3 to 0.8, p=0.04). To conclude, suppressing puberty by GnRHa leads to a decrease of BTMs in both transwomen and transmen transgender adolescents. The increase of BMAD and BMAD Z-scores predominantly in the LS as a result of treatment with CSHT is accompanied by decreasing BTM concentrations after 24months of CSHT. Therefore, the added value of evaluating BTMs seems to be limited and DXA-scans remain important in follow-up of bone health of transgender adolescents.
authors.affiliation: Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Department of Internal Medicine, section Endocrinology, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Mariska C
authors.initials: MC
authors.lastname: Vlot
authors.affiliation: Center of Expertise on Gender Dysphoria, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Department of Pediatric Endocrinology, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. Electronic address: d.klink@vumc.nl.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Klink
authors.affiliation: Department of Internal Medicine, section Endocrinology, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Center of Expertise on Gender Dysphoria, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. Electronic address: m.denheijer@vumc.nl.
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
authors.affiliation: Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. Electronic address: ma.blankenstein@vumc.nl.
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.affiliation: Center of Expertise on Gender Dysphoria, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Department of Pediatric Endocrinology, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. Electronic address: j.rotteveel@vumc.nl.
authors.forename: Joost
authors.initials: J
authors.lastname: Rotteveel
authors.affiliation: Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. Electronic address: a.heijboer@vumc.nl.
authors.forename: Annemieke C
authors.initials: AC
authors.lastname: Heijboer
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism*; D015519:Bone Density; D016723:Bone Remodeling; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D042341:Gonadal Hormones / Q000627:therapeutic use*; D006801:Humans; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011627:Puberty; D063106:Transgender Persons
chemical_list: D015415:Biomarkers; D042341:Gonadal Hormones; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin
keywords: Bone mineral density; Bone turnover markers; GnRHa; Puberty; Transgender