Abstract
Background: Anti-Müllerian hormone (AMH) is produced by Sertoli cells of the testes and granulosa cells of the ovary. There are limited prospective longitudinal data assessing AMH concentrations throughout childhood in both sexes.
Objective: This study aimed to examine AMH throughout childhood with particular reference to the relationship of AMH to pubertal development in both sexes.
Design: This is a prospective longitudinal non-intervention cohort study with annual sampling for participants aged 5–14 years.
Setting: Community cohort study.
Participants: A total of 307 healthy children (170 boys) recruited at 5 years from randomly selected schools in Plymouth, UK, participated in this study. Data sets are complete in 76% of the children at 14 years of age.
Main outcome measure(s): Annual measures of serum AMH, follicle stimulating hormone (FSH) and luteinising hormone (LH), Tanner stage (TS).
Results: Boys: AMH was stable from 5 to 7 years, increased slightly from 8 to 10 years, then declined at TS2. This decline was preceded by rising FSH and the appearance of LH. AMH correlated inversely with gonadotrophic hormones during puberty. Girls: AMH increased slightly between 6 and 10 years, peaking during the final prepubertal year before returning to near baseline levels at TS3. Inverse correlations between AMH and FSH were apparent during the prepubertal years.
Conclusions: Our longitudinal data clarified the development of individual AMH levels over a 10-year period. We described modest late prepubertal peaks in both boys and girls, and confirmed the pubertal decline in boys. The inverse association of AMH with gonadotrophins in young females supports its role as a marker of ovarian function, while the precise role for AMH in relation to testicular function in young males remains unclear.
Acknowledgments
We thank all the children and families who participated in the EarlyBird cohort, and all members of the research team.
Grants: EarlyBird was supported by the Bright Future Trust, the EarlyBird Diabetes Trust, the Kirby Laing Foundation, Nestlé Institute of Health Research and the Peninsula Foundation.
Disclosure summary: SMN has received honoraria to participate in advisory boards regarding AMH and to present at meetings from Beckman Coulter, Roche Diagnostics, Ferring Pharmaceuticals, Merck Serono and MSD.
Clinical trial registration: Not applicable.
References
1. Lee MM, Donahoe PK. Mullerian inhibiting substance: a gonadal hormone with multiple functions. Endocr Rev 1993;14:152–64.Suche in Google Scholar
2. Josso N, Cate RL, Picard JY, Vigier B, di CN, et al. Anti-mullerian hormone: the Jost factor. Recent Prog Horm Res 1993;48:1–59.10.1016/B978-0-12-571148-7.50005-1Suche in Google Scholar
3. Josso N, di CN. TGF-beta Family members and gonadal development. Trends Endocrinol Metab 1999;10:216–22.10.1016/S1043-2760(99)00155-1Suche in Google Scholar
4. Josso N, Lamarre I, Picard JY, Berta P, Davies N, et al. Anti-mullerian hormone in early human development. Early Hum Dev 1993;33:91–9.10.1016/0378-3782(93)90204-8Suche in Google Scholar
5. Andersen CY, Balen A, Broekmans F, Dilaver N, Fanchin R, et al. The physiology and clinical utility of anti-Mullerian hormone in women. Hum Reprod Update 2014;20:370–85.10.1093/humupd/dmt062Suche in Google Scholar
6. Fallat ME, Cook C, Siow Y, Carrillo A, Marra M. Mullerian inhibiting substance in follicular fluid and serum: a comparison on patients with tubal factor infertility, polycystic ovary syndrome, and endometriosis. Fertil Steril 1997;67:962–5.10.1016/S0015-0282(97)81417-3Suche in Google Scholar
7. Sopher AB, Grigoriev G, Laura D, Cameo T, Lerner JP, et al. Anti-Mullerian hormone may be a useful adjunct in the diagnosis of polycystic ovary syndrome in nonobese adolescents. J Pediatr Endocrinol Metab 2014;27:1175–9.10.1515/jpem-2014-0128Suche in Google Scholar
8. Kelsey TW, Wright P, Nelson SM, Anderson RA, Wallace WH. A validated model of serum anti-mullerian hormone from conception to menopause. PLoS One 2011;6:e22024.10.1371/journal.pone.0022024Suche in Google Scholar
9. Kelsey TW, Anderson RA, Wright P, Nelson SM, Wallace WH. Data-driven assessment of the human ovarian reserve. Mol Hum Reprod 2012;18:79–87.10.1093/molehr/gar059Suche in Google Scholar
10. Cook CL, Siow Y, Taylor S, Fallat ME. Serum mullerian-inhibiting substance levels during normal menstrual cycles. Fertil Steril 2000;73:859–61.10.1016/S0015-0282(99)00639-1Suche in Google Scholar
11. Rajpert-De ME, Jorgensen N, Graem N, Muller J, Cate RL, et al. Expression of anti-Mullerian hormone during normal and pathological gonadal development: association with differentiation of Sertoli and granulosa cells. J Clin Endocrinol Metab 1999;84:3836–44.10.1210/jc.84.10.3836Suche in Google Scholar
12. Rey RA, Lhomme C, Marcillac I, Lahlou N, Duvillard P, et al. Antimullerian hormone as a serum marker of granulosa cell tumorsof the ovary: comparative study with serum alpha-inhibin and estradiol. Am J Obstet Gynecol 1996;174:958–65.10.1016/S0002-9378(96)70333-2Suche in Google Scholar
13. Al-Attar L, Noel K, Dutertre M, Belville C, Forest MG, et al. Hormonal and cellular regulation of Sertoli cell anti-Mullerian hormone production in the postnatal mouse. J Clin Invest 1997;100:1335–43.10.1172/JCI119653Suche in Google Scholar PubMed PubMed Central
14. Rey R, Mebarki F, Forest MG, Mowszowicz I, Cate RL, et al. Anti-mullerian hormone in children with androgen insensitivity. J Clin Endocrinol Metab 1994;79:960–4.Suche in Google Scholar
15. Aksglaede L, Sorensen K, Boas M, Mouritsen A, Hagen CP, et al. Changes in anti-Mullerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years. J Clin Endocrinol Metab 2010;95:5357–64.10.1210/jc.2010-1207Suche in Google Scholar PubMed
16. Pasqualini T, Chemes H, Rivarla MA. Testicular testosterone levels during puberty in cryptorchidism. Clin Endocrinol (Oxf) 1981;15:545–54.10.1111/j.1365-2265.1981.tb00700.xSuche in Google Scholar PubMed
17. Rey R, Lukas-Croisier C, Lasala C, Bedecarras P. AMH/MIS: what we know already about the gene, the protein and its regulation. Mol Cell Endocrinol 2003 15;211:21–31.10.1016/j.mce.2003.09.007Suche in Google Scholar PubMed
18. Lee MM, Donahoe PK, Hasegawa T, Silverman B, Crist GB, et al. Mullerian inhibiting substance in humans: normal levels from infancy to adulthood. J Clin Endocrinol Metab 1996;81:571–6.Suche in Google Scholar
19. Rey R, Lordereau-Richard I, Carel JC, Barbet P, Cate RL, et al. Anti-mullerian hormone and testosterone serum levels are inversely during normal and precocious pubertal development. J Clin Endocrinol Metab 1993;77:1220–6.Suche in Google Scholar
20. Hagen CP, Aksglaede L, Sorensen K, Main KM, Boas M, et al. Serum levels of anti-Mullerian hormone as a marker of ovarian function in 926 healthy females from birth to adulthood and in 172 Turner syndrome patients. J Clin Endocrinol Metab 2010;95:5003–10.10.1210/jc.2010-0930Suche in Google Scholar PubMed
21. Nelson SM, Messow MC, McConnachie A, Wallace H, Kelsey T, et al. External validation of nomogram for the decline in serum anti-Mullerian hormone in women: a population study of 15,834 infertility patients. Reprod Biomed Online 2011;23:204–6.10.1016/j.rbmo.2011.05.006Suche in Google Scholar PubMed
22. Nelson SM, Messow MC, Wallace AM, Fleming R, McConnachie A. Nomogram for the decline in serum antimullerian hormone: a population study of 9,601 infertility patients. Fertil Steril 2011;95:736–41.10.1016/j.fertnstert.2010.08.022Suche in Google Scholar PubMed
23. Hagen CP, Aksglaede L, Sorensen K, Mouritsen A, Andersson AM, et al. Individual serum levels of anti-Mullerian hormone in healthy girls persist through childhood and adolescence: a longitudinal cohort study. Hum Reprod 2012;27:861–6.10.1093/humrep/der435Suche in Google Scholar PubMed
24. Lashen H, Dunger DB, Ness A, Ong KK. Peripubertal changes in circulating antimullerian hormone levels in girls. Fertil Steril 2013;15:10.10.1016/j.fertnstert.2013.01.139Suche in Google Scholar PubMed PubMed Central
25. Voss LD, Kirkby J, Metcalf BS, Jeffery AN, O’Riordan C, et al. Preventable factors in childhood that lead to insulin resistance, diabetes mellitus and the metabolic syndrome: the EarlyBird diabetes study 1. J Pediatr Endocrinol Metab 2003;16:1211–24.10.1515/JPEM.2003.16.9.1211Suche in Google Scholar PubMed
26. Wallace AM, Faye SA, Fleming R, Nelson SM. A multicentre evaluation of the new Beckman Coulter anti-Mullerian hormone immunoassay (AMH Gen II). Ann Clin Biochem 2011; 48(Pt 4):370–3.10.1258/acb.2011.010172Suche in Google Scholar PubMed
27. Houk CP, Kunselman AR, Lee PA. Adequacy of a single unstimulated luteinizing hormone level to diagnose central precocious puberty in girls. Pediatrics 2009;123:e1059–63.10.1542/peds.2008-1180Suche in Google Scholar PubMed
28. Taylor SJ, Whincup PH, Hindmarsh PC, Lampe F, Odoki K, et al. Performance of a new pubertal self-assessment questionnaire: a preliminary study. Paediatr Perinat Epidemiol 2001;15:88–94.10.1046/j.1365-3016.2001.00317.xSuche in Google Scholar PubMed
29. Lie FS, Visser JA, Welt CK, de Rijke YB, Eijkemans MJ, et al. Serum anti-mullerian hormone levels in healthy females: a nomogram ranging from infancy to adulthood. J Clin Endocrinol Metab 2012;97:4650–5.10.1210/jc.2012-1440Suche in Google Scholar PubMed PubMed Central
30. Boukari K, Meduri G, Brailly-Tabard S, Guibourdenche J, Ciampi ML, et al. Lack of androgen receptor expression in Sertoli cells accounts for the absence of anti-Mullerian hormone repression during early human testis development. J Clin Endocrinol Metab 2009;94:1818–25.10.1210/jc.2008-1909Suche in Google Scholar PubMed PubMed Central
31. Fleming R, Kelsey TW, Anderson RA, Wallace WH, Nelson SM. Interpreting human follicular recruitment and antimullerian hormone concentrations throughout life. Fertil Steril 2012;98: 1097–102.10.1016/j.fertnstert.2012.07.1114Suche in Google Scholar PubMed
32. Crofton PM, Evans AE, Groome NP, Taylor MR, Holland CV, et al. Dimeric inhibins in girls from birth to adulthood: relationship with age, pubertal stage, FSH and oestradiol. Clin Endocrinol (Oxf) 2002;56:223–30.10.1046/j.0300-0664.2001.01449.xSuche in Google Scholar PubMed
33. Kelsey T, Wright P, Nelson S, Anderson R, Wallace B. A validated model of serum anti-Mullerian hormone from conception to menopause. Unpublished data 2011.10.1371/journal.pone.0022024Suche in Google Scholar PubMed PubMed Central
34. Anderson RA, Themmen AP, Al-Qahtani A, Groome NP, Cameron DA. The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum Reprod 2006;21:2583–92.10.1093/humrep/del201Suche in Google Scholar PubMed
35. Arbo E, Vetori DV, Jimenez MF, Freitas FM, Lemos N, et al. Serum anti-mullerian hormone levels and follicular cohort characteristics after pituitary suppression in the late luteal phase with oral contraceptive pills. Hum Reprod 2007;22:3192–6.10.1093/humrep/dem258Suche in Google Scholar PubMed
36. Nelson SM, Stewart F, Fleming R, Freeman DJ. Longitudinal assessment of antimullerian hormone during pregnancy-relationship with maternal adiposity, insulin, and adiponectin. Fertil Steril 2010;93:1356–8.10.1016/j.fertnstert.2009.07.1676Suche in Google Scholar PubMed
37. Hagen CP, Sorensen K, Anderson RA, Juul A. Serum levels of antimullerian hormone in early maturing girls before, during, and after suppression with GnRH agonist. Fertil Steril 2012;98:1326–30.10.1016/j.fertnstert.2012.07.1118Suche in Google Scholar PubMed
38. Streuli I, Fraisse T, Pillet C, Ibecheole V, Bischof P, et al. Serum antimullerian hormone levels remain stable throughout the menstrual cycle and after oral or vaginal administration of synthetic sex steroids. Fertil Steril 2008;90:395–400.10.1016/j.fertnstert.2007.06.023Suche in Google Scholar PubMed
39. Andersen CY, Schmidt KT, Kristensen SG, Rosendahl M, Byskov AG, et al. Concentrations of AMH and inhibin-B in relation to follicular diameter in normal human small antral follicles. Hum Reprod 2010;25:1282–7.10.1093/humrep/deq019Suche in Google Scholar PubMed
40. Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, et al. Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 2004;10:77–83.10.1093/molehr/gah015Suche in Google Scholar PubMed
41. Welsh P, Smith K, Nelson SM. A single-centre evaluation of two new anti-Mullerian hormone assays and comparison with the current clinical standard assay. Hum Reprod 2014;29:1035–41.10.1093/humrep/deu036Suche in Google Scholar PubMed
©2015 by De Gruyter
Artikel in diesem Heft
- Frontmatter
- Highlight: Growth hormone
- Growth hormone and growth hormone deficiency – still a lot to learn
- Dynamic changes in the hypothalamic- pituitary-adrenal axis during growth hormone therapy in children with growth hormone deficiency: a multicenter retrospective study
- Pituitary gland size is a useful marker in diagnosing isolated growth hormone deficiency in short children
- Carotid intima-media thickness in children treated with growth hormone
- The c.301_302delAG PROP1 gene mutation in Romanian patients with multiple pituitary hormone deficiency
- Growth impairment and growth hormone-IGF-1 axis in infantile anorexia nervosa
- Growth hormone deficiency in a patient with mitochondrial disease
- Perrault syndrome with growth hormone deficiency: a rare autosomal recessive disorder
- Review articles
- Phosphate homeostasis and genetic mutations of familial hypophosphatemic rickets
- Gonadal malignancy risk and prophylactic gonadectomy in disorders of sexual development
- Original articles
- Carotid intimal medial thickness and its relation to endothelial dysfunction and echocardiographic changes in adolescents with type 1 diabetes
- Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth
- Effects of adolescence-onset hypogonadism on metabolism, bone mineral density and quality of life in adulthood
- Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study
- Role of circulating adipocytokines vaspin, apelin, and visfatin in the loss of appetite in underweight children: a pilot trial
- Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family
- Waist-to-height ratio as a screening measure for identifying adolescents with hypertriglyceridemic waist phenotype
- Assessment and relation of total and regional fat mass with bone mineral content among Indian urban adolescents
- Evaluation of the relationship between serum adropin levels and blood pressure in obese children
- Swallowed glucocorticoid therapy for eosinophilic esophagitis in children does not suppress adrenal function
- Response of vitamin D binding protein and free vitamin D concentrations to vitamin D supplementation in hospitalized premature infants
- Can school health check-ups serve as screening tool for growth anomalies and obesity in children?
- The spectrum of 46XY disorders of sex development in a University centre in Saudi Arabia
- Clinical and molecular characterization of five Spanish kindreds with X-linked adrenal hypoplasia congenita: atypical findings and a novel mutation in NR0B1
- Clinical characteristics of children referred for signs of early puberty before age 3
- Effects of GnRH analogue treatment on anterior pituitary hormones in children with central precocious puberty
- Anti-Müllerian hormone in children: a ten-year prospective longitudinal study (EarlyBird 39)
- Patient reports
- A rare cause of fatal pulmonary alveolar proteinosis: Niemann-Pick disease type C2 and a novel mutation
- Migratory polyarthritis as an adverse effect of thiamazole use in a 13-year-old girl with Graves’ disease
- Dyshormonogenesis seems to be more frequent in a group of Cameroonian children with congenital hypothyroidism
- Primary systemic carnitine deficiency: a Turkish case with a novel homozygous SLC22A5 mutation and 14 years follow-up
- Cerebral infarction and femoral venous thrombosis detected in a patient with diabetic ketoacidosis and heterozygous factor V Leiden G1691A and PAI-1 4G/5G mutations
- Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency
- Short communication
- Tamoxifen-associated hirsutism: an unusual side effect in a 5-year-old girl with McCune-Albright syndrome
- Letters to the Editor
- Psychiatric disorders are associated with increased risk for developing hyponatraemia in children
- Rett syndrome and precocious puberty association
Artikel in diesem Heft
- Frontmatter
- Highlight: Growth hormone
- Growth hormone and growth hormone deficiency – still a lot to learn
- Dynamic changes in the hypothalamic- pituitary-adrenal axis during growth hormone therapy in children with growth hormone deficiency: a multicenter retrospective study
- Pituitary gland size is a useful marker in diagnosing isolated growth hormone deficiency in short children
- Carotid intima-media thickness in children treated with growth hormone
- The c.301_302delAG PROP1 gene mutation in Romanian patients with multiple pituitary hormone deficiency
- Growth impairment and growth hormone-IGF-1 axis in infantile anorexia nervosa
- Growth hormone deficiency in a patient with mitochondrial disease
- Perrault syndrome with growth hormone deficiency: a rare autosomal recessive disorder
- Review articles
- Phosphate homeostasis and genetic mutations of familial hypophosphatemic rickets
- Gonadal malignancy risk and prophylactic gonadectomy in disorders of sexual development
- Original articles
- Carotid intimal medial thickness and its relation to endothelial dysfunction and echocardiographic changes in adolescents with type 1 diabetes
- Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth
- Effects of adolescence-onset hypogonadism on metabolism, bone mineral density and quality of life in adulthood
- Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study
- Role of circulating adipocytokines vaspin, apelin, and visfatin in the loss of appetite in underweight children: a pilot trial
- Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family
- Waist-to-height ratio as a screening measure for identifying adolescents with hypertriglyceridemic waist phenotype
- Assessment and relation of total and regional fat mass with bone mineral content among Indian urban adolescents
- Evaluation of the relationship between serum adropin levels and blood pressure in obese children
- Swallowed glucocorticoid therapy for eosinophilic esophagitis in children does not suppress adrenal function
- Response of vitamin D binding protein and free vitamin D concentrations to vitamin D supplementation in hospitalized premature infants
- Can school health check-ups serve as screening tool for growth anomalies and obesity in children?
- The spectrum of 46XY disorders of sex development in a University centre in Saudi Arabia
- Clinical and molecular characterization of five Spanish kindreds with X-linked adrenal hypoplasia congenita: atypical findings and a novel mutation in NR0B1
- Clinical characteristics of children referred for signs of early puberty before age 3
- Effects of GnRH analogue treatment on anterior pituitary hormones in children with central precocious puberty
- Anti-Müllerian hormone in children: a ten-year prospective longitudinal study (EarlyBird 39)
- Patient reports
- A rare cause of fatal pulmonary alveolar proteinosis: Niemann-Pick disease type C2 and a novel mutation
- Migratory polyarthritis as an adverse effect of thiamazole use in a 13-year-old girl with Graves’ disease
- Dyshormonogenesis seems to be more frequent in a group of Cameroonian children with congenital hypothyroidism
- Primary systemic carnitine deficiency: a Turkish case with a novel homozygous SLC22A5 mutation and 14 years follow-up
- Cerebral infarction and femoral venous thrombosis detected in a patient with diabetic ketoacidosis and heterozygous factor V Leiden G1691A and PAI-1 4G/5G mutations
- Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency
- Short communication
- Tamoxifen-associated hirsutism: an unusual side effect in a 5-year-old girl with McCune-Albright syndrome
- Letters to the Editor
- Psychiatric disorders are associated with increased risk for developing hyponatraemia in children
- Rett syndrome and precocious puberty association