AMH concentrations in infancy and mid-childhood predict ovarian activity in adolescence: A long-term longitudinal study of healthy girls
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AMH concentrations in infancy and mid-childhood predict ovarian activity in adolescence : A long-term longitudinal study of healthy girls. / Hagen, Casper P.; Fischer, Margit Bistrup; Wohlfahrt-Veje, Christine; Assens, Maria; Busch, Alexander S.; Pedersen, Anette Tønnes; Juul, Anders; Main, Katharina M.
I: EClinicalMedicine, Bind 55, 101742, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - AMH concentrations in infancy and mid-childhood predict ovarian activity in adolescence
T2 - A long-term longitudinal study of healthy girls
AU - Hagen, Casper P.
AU - Fischer, Margit Bistrup
AU - Wohlfahrt-Veje, Christine
AU - Assens, Maria
AU - Busch, Alexander S.
AU - Pedersen, Anette Tønnes
AU - Juul, Anders
AU - Main, Katharina M.
N1 - Publisher Copyright: © 2022 The Authors
PY - 2023
Y1 - 2023
N2 - Background: Anti-Müllerian hormone (AMH) is produced by granulosa cells in small growing ovarian follicles. In adult women, serum concentrations of AMH reflect the ovarian reserve of resting primordial follicles, and low AMH is associated with risk of early menopause. In contrast, patients with polycystic ovary syndrome (PCOS) have elevated AMH. The primary aim of this study was to evaluate the individual tracking of serum AMH concentrations, as well as whether AMH in early childhood reflects ovarian activity in adolescence. Methods: In this large longitudinal study of healthy girls were examined from infancy to adolescence (1997–2019) including physical examination, assessment of serum concentrations of reproductive hormones (in infancy, median age 0.3 yrs; mid-childhood, 7.2 yrs; puberty, 11.3 yrs; and adolescence, 15.9 yrs), transabdominal ultrasound (TAUS, puberty and adolescence) and magnetic resonance imaging (MRI, puberty) of the ovaries. Findings: Each girl maintained her relative AMH concentration (expressed as standard deviation (SD) scores) over time; mean variation of individual age adjusted AMH concentrations was 0.56 ± 0.31 SD. Serum concentrations of AMH in adolescence correlated with AMH in infancy and childhood; infancy: r = 0.347; mid-childhood: r = 0.637; puberty: r = 0.675, all p < 0.001. AMH correlated negatively with FSH concentrations in all age groups (infancy: r = −0.645, p < 0.001; mid-childhood: r = −0.222, p < 0.001; puberty: r = −0.354, p < 0.001; adolescence: n = 275, r = −0.175, p = 0.004). Serum AMH concentrations in mid-childhood correlated with the number of follicles in puberty (TAUS and MRI) as well as in adolescence (TAUS); e.g. total number of follicles: TAUS puberty (r = 0.607), MRI puberty (r = 0.379), TAUS adolescence (r = 0.414), all p < 0.001. AMH concentration in infancy as well as in mid-childhood predicted low AMH (<10 pmol/L) in adolescence; AMH infancy <7.5 pmol/L as predictor of low AMH in adolescence: sensitivity 0.71, specificity 0.70, AUC 0.759; AMH mid-childhood < 8.4 pmol/L as predictor of low AMH in adolescence: sensitivity 0.88, specificity 0.87, AUC 0.949. Girls with high serum AMH concentration in mid-childhood (AMH >30.0 pmol/L vs. other girls) had higher adolescent LH (median 4.53 vs. 3.29 U/L p = 0.041), LH/FSH ratio (1.00 vs 0.67, p = 0.019), testosterone (1.05 vs 0.81 nmol/L, p = 0.005), total number of follicles (23 vs. 19, p = 0.004), and higher prevalence of irregular cycles (10/15 = 67% vs. 28/113 = 25%, p = 0.002). Interpretation: The present findings suggest remarkably stable ovarian activity from small growing follicles in healthy girls, supporting AMH in early life as a useful clinical tool to predict future ovarian activity. Funding: The work was supported by The Center on Endocrine Disruptors (CeHoS) under The Danish Environmental Protection Agency and The Ministry of Environment and Food (grant number: MST-621-00 065), the EU ( QLK4-CT1999-01422; QLK4-2001-00269), the Novo Nordisk Foundation and The Danish Ministry of Science Technology and Innovation ( 2107-05-0006). A.S.B. is funded by the Deutsche Forschungsgemeinschaft ( DFG, German Research Foundation) – 464240267. KM receives honoraria from Novo Nordisk A/S for teaching at the Danish annual postgraduate course of pituitary diseases.
AB - Background: Anti-Müllerian hormone (AMH) is produced by granulosa cells in small growing ovarian follicles. In adult women, serum concentrations of AMH reflect the ovarian reserve of resting primordial follicles, and low AMH is associated with risk of early menopause. In contrast, patients with polycystic ovary syndrome (PCOS) have elevated AMH. The primary aim of this study was to evaluate the individual tracking of serum AMH concentrations, as well as whether AMH in early childhood reflects ovarian activity in adolescence. Methods: In this large longitudinal study of healthy girls were examined from infancy to adolescence (1997–2019) including physical examination, assessment of serum concentrations of reproductive hormones (in infancy, median age 0.3 yrs; mid-childhood, 7.2 yrs; puberty, 11.3 yrs; and adolescence, 15.9 yrs), transabdominal ultrasound (TAUS, puberty and adolescence) and magnetic resonance imaging (MRI, puberty) of the ovaries. Findings: Each girl maintained her relative AMH concentration (expressed as standard deviation (SD) scores) over time; mean variation of individual age adjusted AMH concentrations was 0.56 ± 0.31 SD. Serum concentrations of AMH in adolescence correlated with AMH in infancy and childhood; infancy: r = 0.347; mid-childhood: r = 0.637; puberty: r = 0.675, all p < 0.001. AMH correlated negatively with FSH concentrations in all age groups (infancy: r = −0.645, p < 0.001; mid-childhood: r = −0.222, p < 0.001; puberty: r = −0.354, p < 0.001; adolescence: n = 275, r = −0.175, p = 0.004). Serum AMH concentrations in mid-childhood correlated with the number of follicles in puberty (TAUS and MRI) as well as in adolescence (TAUS); e.g. total number of follicles: TAUS puberty (r = 0.607), MRI puberty (r = 0.379), TAUS adolescence (r = 0.414), all p < 0.001. AMH concentration in infancy as well as in mid-childhood predicted low AMH (<10 pmol/L) in adolescence; AMH infancy <7.5 pmol/L as predictor of low AMH in adolescence: sensitivity 0.71, specificity 0.70, AUC 0.759; AMH mid-childhood < 8.4 pmol/L as predictor of low AMH in adolescence: sensitivity 0.88, specificity 0.87, AUC 0.949. Girls with high serum AMH concentration in mid-childhood (AMH >30.0 pmol/L vs. other girls) had higher adolescent LH (median 4.53 vs. 3.29 U/L p = 0.041), LH/FSH ratio (1.00 vs 0.67, p = 0.019), testosterone (1.05 vs 0.81 nmol/L, p = 0.005), total number of follicles (23 vs. 19, p = 0.004), and higher prevalence of irregular cycles (10/15 = 67% vs. 28/113 = 25%, p = 0.002). Interpretation: The present findings suggest remarkably stable ovarian activity from small growing follicles in healthy girls, supporting AMH in early life as a useful clinical tool to predict future ovarian activity. Funding: The work was supported by The Center on Endocrine Disruptors (CeHoS) under The Danish Environmental Protection Agency and The Ministry of Environment and Food (grant number: MST-621-00 065), the EU ( QLK4-CT1999-01422; QLK4-2001-00269), the Novo Nordisk Foundation and The Danish Ministry of Science Technology and Innovation ( 2107-05-0006). A.S.B. is funded by the Deutsche Forschungsgemeinschaft ( DFG, German Research Foundation) – 464240267. KM receives honoraria from Novo Nordisk A/S for teaching at the Danish annual postgraduate course of pituitary diseases.
KW - AMH
KW - Anti-Müllerian hormone
KW - Female reproductive endocrinology
KW - Girls
KW - Ovarian function
U2 - 10.1016/j.eclinm.2022.101742
DO - 10.1016/j.eclinm.2022.101742
M3 - Journal article
C2 - 36386030
AN - SCOPUS:85141797154
VL - 55
JO - EClinicalMedicine
JF - EClinicalMedicine
SN - 2589-5370
M1 - 101742
ER -
ID: 334306270