TY - JOUR
T1 - Gonadal function and pathology in 17beta-HSD 3 and 5alpha-reductase deficiency
AU - Boogers, Lidewij S.
AU - Brüggenwirth, Hennie T.
AU - Wolffenbuttel, Katja P.
AU - Hersmus, Remko
AU - Bryce, Jillian
AU - Ahmed, S. Faisal
AU - Lucas-Herald, Angela K.
AU - Baronio, Federico
AU - Cools, Martine
AU - Ellaithi, Mona
AU - Globa, Evgenia
AU - Güran, Tülay
AU - Hiort, Olaf
AU - Holterhus, Paul Martin
AU - MсElreavey, Kenneth
AU - Niedziela, Marek
AU - Stancampiano, Marianna Rita
AU - Tosun, Buşra G.
AU - van Bever, Yolande
AU - Oosterhuis, J. Wolter
AU - Looijenga, Leendert H.J.
AU - Hannema, Sabine E.
N1 - Publisher Copyright:
© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology.
PY - 2025/1/6
Y1 - 2025/1/6
N2 - OBJECTIVE: 17β-Hydroxysteroid dehydrogenase 3 deficiency (17β-HSDD) and 5α-reductase type 2 deficiency (5α-RD) are rare 46,XY differences of sex development (DSD). This study aims to enlarge the limited knowledge on long-term gonadal function and gonadal pathology in these conditions. DESIGN: Retrospective multicentre cohort study. METHODS: Data on phenotype, laboratory results, and hormone treatment were collected from patients aged ≥16 years at time of data collection with genetically confirmed 17β-HSDD and 5α-RD from 10 centres via the I-DSD Registry. If gonadectomy or gonadal biopsy had been performed, pathology reports and/or gonadal tissue or images were collected. RESULTS: All 16 patients with 17β-HSDD were raised female; 1 (6%) changed to male gender at age 14. Three females were treated with gonadotrophin-releasing hormone agonists (GnRHa) to prevent virilisation. Thirteen underwent gonadectomy at median age 8 (range 0-17). None had germ cell (pre)malignancies. Of 14 patients with 5α-RD, 10 (71%) were raised female. Five changed gender at age 7-23, of whom 4 to male gender. One was treated with GnRHa. Six underwent gonadectomy at median age 10 (range 0-31). None had germ cell (pre)malignancies. With gonads in situ, puberty spontaneously progressed. Three were treated with dihydrotestosterone. CONCLUSIONS: A significant percentage of individuals with 17β-HSDD and 5α-RD changed gender, and some were treated with GnRHa to prevent virilisation before making a definitive decision about gonadectomy. When left in situ, spontaneous puberty occurs and germ cell (pre)malignancies seem uncommon at least until early adulthood. Together, these data support delaying a decision about gonadectomy until late adolescence in these conditions.
AB - OBJECTIVE: 17β-Hydroxysteroid dehydrogenase 3 deficiency (17β-HSDD) and 5α-reductase type 2 deficiency (5α-RD) are rare 46,XY differences of sex development (DSD). This study aims to enlarge the limited knowledge on long-term gonadal function and gonadal pathology in these conditions. DESIGN: Retrospective multicentre cohort study. METHODS: Data on phenotype, laboratory results, and hormone treatment were collected from patients aged ≥16 years at time of data collection with genetically confirmed 17β-HSDD and 5α-RD from 10 centres via the I-DSD Registry. If gonadectomy or gonadal biopsy had been performed, pathology reports and/or gonadal tissue or images were collected. RESULTS: All 16 patients with 17β-HSDD were raised female; 1 (6%) changed to male gender at age 14. Three females were treated with gonadotrophin-releasing hormone agonists (GnRHa) to prevent virilisation. Thirteen underwent gonadectomy at median age 8 (range 0-17). None had germ cell (pre)malignancies. Of 14 patients with 5α-RD, 10 (71%) were raised female. Five changed gender at age 7-23, of whom 4 to male gender. One was treated with GnRHa. Six underwent gonadectomy at median age 10 (range 0-31). None had germ cell (pre)malignancies. With gonads in situ, puberty spontaneously progressed. Three were treated with dihydrotestosterone. CONCLUSIONS: A significant percentage of individuals with 17β-HSDD and 5α-RD changed gender, and some were treated with GnRHa to prevent virilisation before making a definitive decision about gonadectomy. When left in situ, spontaneous puberty occurs and germ cell (pre)malignancies seem uncommon at least until early adulthood. Together, these data support delaying a decision about gonadectomy until late adolescence in these conditions.
KW - 17beta-HSD deficiency
KW - 5alpha-reductase deficiency
KW - disorder of sex development
KW - germ cell cancer
KW - hypogonadism
KW - puberty
KW - testis
UR - https://www.scopus.com/pages/publications/85214930701
U2 - 10.1093/ejendo/lvae154
DO - 10.1093/ejendo/lvae154
M3 - Article
C2 - 39782875
AN - SCOPUS:85214930701
SN - 0804-4643
VL - 192
SP - 34
EP - 45
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
IS - 1
ER -