Quantification of urinary gonadotropins by specific assays may improve the evaluation of sex-specific hormonal changes in early infancy.

follicle stimulating hormone infancy luteinizing hormone minipuberty urinary gonadotropin

Journal

Clinical endocrinology
ISSN: 1365-2265
Titre abrégé: Clin Endocrinol (Oxf)
Pays: England
ID NLM: 0346653

Informations de publication

Date de publication:
25 Apr 2024
Historique:
revised: 23 03 2024
received: 15 12 2023
accepted: 12 04 2024
medline: 26 4 2024
pubmed: 26 4 2024
entrez: 26 4 2024
Statut: aheadofprint

Résumé

The aim of this study was to investigate the feasibility of different gonadotropin assays for determining total and intact luteinizing hormone (LH), and follicle-stimulating hormone (FSH) immunoreactivity in urine (U-LH-ir and U-FSH-ir, respectively) during early infancy. Morning urine samples were obtained from 31 infants, aged between 0 and 6 months, to study the age-related course of urinary gonadotropins. Additionally, we investigated bi-hourly urine samples of a 5-day-old male neonate for 24 h to observe the course of urinary gonadotropins during a daily cycle. We employed different immunofluorometric assays for measuring total and intact U-LH-ir, and U-FSH-ir. In neonates up to 21 days of age, the U-LH-ir levels measured by the regular LH assay (also detecting hCG) were significantly higher than those determined by the total (specific) LH assays (p = .004). U-FSH-ir was higher in girls than boys during both the first and the next 5 months (p = .02 and p < .001, respectively), whereas total U-LH-ir was higher in boys until 6 months of age (p < .001). Total U-LH-ir/U-FSH-ir ratio was significantly higher in boys than girls across the first half-year (p < .001). The assessment of total U-LH-ir and U-FSH-ir, and their respective ratio constitutes a noninvasive, practical and scalable tool to investigate sex-specific changes during early infancy, with the ratio being significantly higher in boys than girls. Only highly specific LH assays detecting beta-subunit and its core fragment in addition to intact LH should be used for determining U-LH-ir in the neonatal period to avoid potential cross-reactivity with hCG of placental origin.

Identifiants

pubmed: 38664930
doi: 10.1111/cen.15064
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : The Finnish Medical Foundation (Suomen Lääketieteen Säätiö)
Organisme : The Foundation for Pediatric Research (Lastentautien tutkimussäätiö)

Informations de copyright

© 2024 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.

Références

Forest MG, Cathiard AM. Pattern of plasma testosterone and Δ4‐androstenedione in normal newborns: evidence for testicular activity at birth. J Clin Endocrinol Metab. 1975;41(5):977‐980.
Forest MG, Cathiard AM, Bertrand JA. Evidence of testicular activity in early infancy. J Clin Endocrinol Metab. 1973;37(1):148‐151.
Forest MG, Sizonenko PC, Cathiard AM, Bertrand J. Hypophyso‐gonadal function in humans during the first year of life. J Clin Invest. 1974;53(3):819‐828.
Corbier P, Dehennin L, Castanier M, Mebazaa A, Edwards DA, Roffi J. Sex differences in serum luteinizing hormone and testosterone in the human neonate during the first few hours after birth. J Clin Endocrinol Metab. 1990;71(5):1344‐1348.
Schmidt H, Schwarz H. Serum concentrations of LH and FSH in the healthy newborn. Eur J Endocrinol. 2000;143(2):213‐215.
Winter JSD, Faiman C, Hobson WC, Prasad AV, Reyes FI. Pituitary‐gonadal relations in infancy. I. Patterns of serum gonadotropin concentrations from birth to four years of age in man and chimpanzee. J Clin Endocrinol Metab. 1975;40(4):545‐551.
Andersson AM. Longitudinal reproductive hormone profiles in infants: peak of inhibin B levels in infant boys exceeds levels in adult men. J Clin Endocrinol Metab. 1998;83(2):675‐681.
Kuiri‐Hänninen T, Seuri R, Tyrväinen E, et al. Increased activity of the hypothalamic‐pituitary‐testicular axis in infancy results in increased androgen action in premature boys. J Clin Endocrinol Metab. 2011;96(1):98‐105.
Kuiri‐Hänninen T, Kallio S, Seuri R, et al. Postnatal developmental changes in the pituitary‐ovarian axis in preterm and term infant girls. J Clin Endocrinol Metab. 2011;96(11):3432‐3439.
Bergada I, Milani C, Bedecarras P, et al. Time course of the serum gonadotropin surge, inhibins, and anti‐Mullerian hormone in normal newborn males during the first month of life. J Clin Endocrinol Metab. 2006;91(10):4092‐4098.
Shinkawa O, Furuhashi N, Fukaya T, Suzuki M, Kono H, Tachibana Y. Changes of serum gonadotropin levels and sex differences in premature and mature infant during neonatal life. J Clin Endocrinol Metab. 1983;56(6):1327‐1331.
Ibáñez L, Valls C, Cols M, Ferrer A, Marcos MV, De Zegher F. Hypersecretion of FSH in infant boys and girls born small for gestational age. J Clin Endocrinol Metab. 2002;87(5):1986‐1988.
Ljubicic ML, Busch AS, Upners EN, et al. Dynamic changes in LH/FSH ratios in infants with normal sex development. Eur J Endocrinol. 2022;187(1):135‐142.
Kuiri‐Hänninen T, Sankilampi U, Dunkel L. Activation of the hypothalamic‐pituitary‐gonadal axis in infancy: minipuberty. Horm Res Paediatr. 2014;82(2):73‐80.
Swee DS, Quinton R. Managing congenital hypogonadotrophic hypogonadism: a contemporary approach directed at optimizing fertility and long‐term outcomes in males. Ther Adv Endocrinol Metab. 2019;10:204201881982688.
Demir A, Hero M, Juul A, Main KM. Sex‐independent timing of the onset of central puberty revealed by nocturnal luteinizing hormone concentrations. Clin Endocrinol. 2023;99(6):552‐558.
Demir A, Buyukgebiz A, Aydin A, Hero M. Quantification of overnight urinary gonadotropin excretion predicts imminent puberty in girls: a semi‐longitudinal study. Hormones (Athens). 2024;23(1):141‐250.
Xu D, Zhou X, Wang J, Cao X, Liu T. The value of urinary gonadotropins in the diagnosis of central precocious puberty: a meta‐analysis. BMC Pediatr. 2022;22(1):453.
Demir A, Aydın A, Büyükgebiz A, Stenman UH, Hero M. Urinary gonadotropin measurements by enhanced luminometric assays (LIA) for the evaluation of pubertal development. J Pediatr Endocrinol Metab. 2021;34(7):859‐866.
Kolby N, Busch AS, Aksglaede L, et al. Nocturnal urinary excretion of FSH and LH in children and adolescents with normal and early puberty. J Clin Endocrinol Metab. 2017;102(10):3830‐3838.
Lucaccioni L, McNeilly J, Mason A, et al. The measurement of urinary gonadotropins for assessment and management of pubertal disorder. Hormones (Athens). 2016;15(3):377‐384.
Demir A, Voutilainen R, Stenman UH, Dunkel L, Albertsson‐Wikland K, Norjavaara E. First‐morning‐voided urinary gonadotropin measurements as an alternative to the GnRH test. Horm Rese Paediatr. 2016;85(5):301‐308.
Kuijper EAM, Houwink EJF, van Weissenbruch MM, et al. Urinary gonadotropin measurements in neonates: a valuable non‐invasive method. Ann Clin Biochem. 2006;43(Pt 4):320‐322.
Demir A, Demir A, Voutilainen R, et al. Increase in first morning voided urinary luteinizing hormone levels precedes the physical onset of puberty. J Clin Endocrinol Metab. 1996;81(8):2963‐2967.
Demir A, Alfthan H, Stenman UH, Voutilainen R. A clinically useful method for detecting gonadotropins in children: assessment of luteinizing hormone and follicle‐stimulating hormone from urine as an alternative to serum by ultrasensitive time‐resolved immunofluorometric assays. Pediatr Res. 1994;36(2):221‐226.
Demir A, Hero M, Alfthan H, Passioni A, Tapanainen JS, Stenman UH. Intact luteinizing hormone (LH), LHβ, and LHβ core fragment in urine of menstruating women. Minerva Endocrinol (Torino). Published online February 15, 2022. doi:10.23736/S2724‐6507.22.03565‐5
Demir A, Hero M, Alfthan H, Passioni A, Tapanainen JS, Stenman UH. Identification of the LH surge by measuring intact and total immunoreactivity in urine for prediction of ovulation time. Hormones. 2022;21(3):413‐420.
Demir A, Hero M, Holopainen E, Juul A. Quantification of urinary total luteinizing hormone immunoreactivity may improve the prediction of ovulation time. Front Endocrinol. 2022;13:903831.
Koysombat K, Dhillo WS, Abbara A. Assessing hypothalamic pituitary gonadal function in reproductive disorders. Clin Sci. 2023;137(11):863‐879.
Demir A, Dunkel L, Stenman UH, Voutilainen R. Age‐related course of urinary gonadotropins in children. J Clin Endocrinol Metab. 1995;80(4):1457‐1460.
Stenman UH, Alfthan H. Determination of human chorionic gonadotropin. Best Pract Res Clin Endocrinol Metab. 2013;27(6):783‐793.
Pettersson K, Ding YQ, Huhtaniemi I. An immunologically anomalous luteinizing hormone variant in a healthy woman. J Clin Endocrinol Metab. 1992;74(1):164‐171.
Iles RK, Javid MK, Gunn LK, Chard T. Cross‐reaction with luteinizing hormone β‐core is responsible for the age‐dependent increase of immunoreactive β‐core fragment of human chorionic gonadotropin in women with nonmalignant conditions. Clin Chem. 1999;45(4):532‐538.
Johannsen TH, Main KM, Ljubicic ML, et al. Sex differences in reproductive hormones during mini‐puberty in infants with normal and disordered sex development. J Clin Endocrinol Metab. 2018;103(8):3028‐3037.

Auteurs

And Demir (A)

Pediatric Research Center, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Raimo Voutilainen (R)

Department of Pediatrics, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.

Matti Hero (M)

Pediatric Research Center, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Classifications MeSH