Henrik Falhammar1,2, Louise Frisén3,4, Christina Norrby5, Catarina Almqvist5,6, Angelica Linden Hirschberg7,8, Agneta Nordenskjöld7,9,10, Anna Nordenström7,11. 1. Department of Endocrinology, Metabolism, and Diabetes, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. 2. Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden. 3. Department of Clinical Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden. 4. Child and Adolescent Psychiatry Research Center, SE-171 77 Stockholm, Sweden. 5. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 64 Stockholm, Sweden. 6. Lung and Allergy Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, SE-171 64 Stockholm, Sweden. 7. Department of Women's and Children's Health, Karolinska Institutet, SE-171 76 Stockholm, Sweden. 8. Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. 9. Center for Molecular Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden. 10. Pediatric Surgery, Astrid Lindgren Children's Hospital, Karolinska University Hospital, SE-171 64 Stockholm, Sweden. 11. Department of Pediatric Endocrinology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, SE-171 64 Stockholm, Sweden.
Abstract
Context: Fertility in males with 21-hydroxylase deficiency (21OHD) is unclear. Objective: Study fertility outcome in males with congenital adrenal hyperplasia. Design, Setting, and Participants: Males ≥15 years old with 21OHD (n = 221) were compared with controls matched for sex and year and place of birth (n = 22,024). Data were derived by linking national population-based registers. Subgroup analyses were performed regarding phenotype [salt-wasting (SW), simple virilizing (SV), and nonclassic (NC)] and CYP21A2 genotype (null, I2 splice, I172N, and P30L) and stratified by the introduction of neonatal screening. Main Outcome Measures: Number of biological and adopted children. Results: Males with 21OHD were less likely to be fathers of biological children [odds ratio (OR), 0.5; 95% confidence interval (CI), 0.4 to 0.7; after adjusting for socioeconomic characteristics: OR, 0.4; 95% CI, 0.2 to 0.5]. This was true for SW, SV, I2 splice, and I172N, but not for NC, null, and P30L groups (all adjusted). Among patients born before the neonatal screening introduction, fewer were fathers (adjusted OR, 0.3; 95% CI, 0.2 to 0.5), but this normalized in those born afterward. Adoption was more common in the 21OHD males (OR, 2.9; 95% CI, 1.0 to 7.9) and the SV and I172N subgroups. Age at becoming a father, marriage, region of residence, and education were similar, but fewer patients had high incomes. NC and I172N groups had, however, higher academic degrees and NC patients were more often married, whereas SW and I2 splice patients were more often divorced. Conclusions: 21OHD was associated with a reduced frequency of biological children and an increased frequency of adopted children, suggesting impaired fertility, although some subgroups had normal fertility.
Context: Fertility in males with 21-hydroxylase deficiency (21OHD) is unclear. Objective: Study fertility outcome in males with congenital adrenal hyperplasia. Design, Setting, and Participants: Males ≥15 years old with 21OHD (n = 221) were compared with controls matched for sex and year and place of birth (n = 22,024). Data were derived by linking national population-based registers. Subgroup analyses were performed regarding phenotype [salt-wasting (SW), simple virilizing (SV), and nonclassic (NC)] and CYP21A2 genotype (null, I2 splice, I172N, and P30L) and stratified by the introduction of neonatal screening. Main Outcome Measures: Number of biological and adopted children. Results: Males with 21OHD were less likely to be fathers of biological children [odds ratio (OR), 0.5; 95% confidence interval (CI), 0.4 to 0.7; after adjusting for socioeconomic characteristics: OR, 0.4; 95% CI, 0.2 to 0.5]. This was true for SW, SV, I2 splice, and I172N, but not for NC, null, and P30L groups (all adjusted). Among patients born before the neonatal screening introduction, fewer were fathers (adjusted OR, 0.3; 95% CI, 0.2 to 0.5), but this normalized in those born afterward. Adoption was more common in the 21OHD males (OR, 2.9; 95% CI, 1.0 to 7.9) and the SV and I172N subgroups. Age at becoming a father, marriage, region of residence, and education were similar, but fewer patients had high incomes. NC and I172N groups had, however, higher academic degrees and NC patients were more often married, whereas SW and I2 splice patients were more often divorced. Conclusions: 21OHD was associated with a reduced frequency of biological children and an increased frequency of adopted children, suggesting impaired fertility, although some subgroups had normal fertility.
Authors: Phyllis W Speiser; Wiebke Arlt; Richard J Auchus; Laurence S Baskin; Gerard S Conway; Deborah P Merke; Heino F L Meyer-Bahlburg; Walter L Miller; M Hassan Murad; Sharon E Oberfield; Perrin C White Journal: J Clin Endocrinol Metab Date: 2018-11-01 Impact factor: 5.958
Authors: Hedi L Claahsen-van der Grinten; Phyllis W Speiser; S Faisal Ahmed; Wiebke Arlt; Richard J Auchus; Henrik Falhammar; Christa E Flück; Leonardo Guasti; Angela Huebner; Barbara B M Kortmann; Nils Krone; Deborah P Merke; Walter L Miller; Anna Nordenström; Nicole Reisch; David E Sandberg; Nike M M L Stikkelbroeck; Philippe Touraine; Agustini Utari; Stefan A Wudy; Perrin C White Journal: Endocr Rev Date: 2022-01-12 Impact factor: 19.871
Authors: Henrik Falhammar; Jakob Skov; Jan Calissendorff; David Nathanson; Jonatan D Lindh; Buster Mannheimer Journal: J Clin Endocrinol Metab Date: 2020-10-01 Impact factor: 5.958