Relationship Between Anti-Müllerian Hormone (AMH) and Insulin Levels During Different Tanner Stages in Daughters of Women With Polycystic Ovary Syndrome
Restricted accessResearch articleFirst published online April, 2012
Relationship Between Anti-Müllerian Hormone (AMH) and Insulin Levels During Different Tanner Stages in Daughters of Women With Polycystic Ovary Syndrome
Context: We have previously described increased serum levels of anti-Müllerian hormone (AMH) and stimulated insulin in daughters of women with polycystic ovary syndrome (PCOS), suggesting that these girls may have an altered ovarian follicular development which may be modulated by insulin. However, the specific relationship between serum AMH and insulin levels during each Tanner stage of puberty in this cohort has not been established. Objective: The aim of our study was to establish the relationship between AMH and poststimulated insulin serum concentrations during each stage of puberty in daughters of women with PCOS (PCOSd), compared to daughters of control women (Cd). Design: We studied 135 PCOSd and 93 Cd classified according to their Tanner stage. Gonadotrophins, sex steroids, sex hormone-binding globulin (SHBG), and AMH were determined in a fasting sample. Ovarian volume was measured by pelvic ultrasound. In addition, in both groups we performed an oral glucose tolerance test with measurements of glucose and insulin. Results: Anti-Müllerian hormone levels were significantly higher in PCOSd compared to Cd at all Tanner stages. Daughters of women with PCOS having AMH concentrations greater than 2 standard deviation (SD) above the mean AMH value for the Cd group showed decreased serum follicle-stimulating hormone (FSH) concentrations and increased stimulated levels of insulin during Tanner stages I, II, and III. Conclusions: Anti-Müllerian hormone levels are increased in PCOSd during all stages of puberty. We suggest that those PCOSd with the highest AMH levels probably represent a group of girls with more severe ovarian dysfunction and metabolic derangements.
FranksS. Polycystic ovary syndrome. N Engl J Med. 1995; 333:853–861.
2.
HomburgR. Androgen circle of polycystic ovary syndrome. Hum Reprod. 2009;24(7):1548–1555.
3.
BaillargeonJPNestlerJE. Commentary: polycystic ovary syndrome: a syndrome of ovarian hypersensitivity to insulin?. J Clin Endocrinol Metab. 2006;91(1):22–24.
4.
WebberLJStubbsSStarkJTrewGHMargaraRHardyK. Formation and early development of follicles in the polycystic ovary. Lancet. 2003;362(9389):1017–1021.
5.
CateRLMattalianoRJHeissonCTizardRFarberNMCheungA. Isolation of the bovine and human genes for Mullerian inhibiting substance and expression of the human gene in animal cells. Cell. 1986;45(5):685–698.
6.
JossoNdi ClementeN. TGF-beta Family Members and Gonadal Development. Trends Endocrinol Metab. 1999;10(6):216–222.
7.
HagenCPAksglaedeLSørensenKMainKMBoasMCleemannL. Serum levels of anti-Müllerian 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(11):5003–5010.
8.
Sir-PetermannTCodnerEMaliqueoMEchiburuBHitschfeldCCrisostoN. Increased anti-Mullerian hormone serum concentrations in prepubertal daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91(8):3105–3109.
9.
CrisostoNCodnerEMaliqueoMEchiburúBSánchezFCassorlaF. Anti-mullerian hormone levels in peri-pubertal daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007;92(7):2739–2743.
10.
Sir-PetermannTCodnerEPérezVEchiburúBMaliqueoMLadrón de GuevaraA. Metabolic and reproductive features before and during puberty in daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2009;94(6):1923–1930.
11.
ZawadzkyJKDunaifA. Diagnosis criteria: towards a rational approach. In: HershmannJM, ed. Current issues in endocrinology and metabolism. Boston, MA: Blackwell. 1992;377–384.
12.
AdamsJPolsonDWFranksS. Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism. Br Med J (Clin Res Ed). 1986;293(6543):355–359.
13.
OgdenCLKuczmarskiRJFlegalKMMeiZGuoSWeiR. Centersfor Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics. 2002;109(1):45–46.
14.
YoultonRValenzuelaC. Growth patterns in height and weight in children aged 0 to 17 years and cranial circumference in children aged 0 to 2 years from medium-high and high socioeconomic status in Santiago. Comparison with growth in children from medium-low and low status in the Northern area of Santiago. Rev Chil Pediatr1990;Spec. No:1-22.
15.
HatchRRosenfieldRLKimMHTredwayD. Hirsutism: implications, etiology, and management. Am J Obstet Gynecol. 1981;140(7):815–830.
16.
TellezRFrenkelJ. Clinical evaluation of body hair in healthy women. Rev Med Chile. 1995;123(11):1349–1354.
17.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care Suppl. 2004;1:S5–S1.
18.
MatthewsDRHoskerJPRudenskiASNaylorBATreacherDFTurnerRC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–419.
19.
MatsudaMDeFronzoRA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22(9):1462–1470.
20.
SwansonMSauerbreiEECooperbergPL. Medical implications of ultrasonically detected polycystic ovaries. J Clin Ultrasound. 1981;9(5):219–222.
21.
ReyRACodnerEIniguezGBedecarrasPTrigoROkumaC. Low risk of impaired testicular Sertoli and Leydig cell functions in boys with isolated hypospadias. J Clin Endocrinol Metab. 2005;90(11):6035–6040.
22.
HartRDohertyDANormanRJFranksSDickinsonJEHickeyM. Serum antimullerian hormone (AMH) levels are elevated in adolescent girls with polycystic ovaries and the polycystic ovarian syndrome (PCOS). Fertil Steril. 2010;94(3):1118–1121.
23.
SampaoloPLivieriCMontanariLPaganelliASalesiALoriniR. Precocious signs of polycystic ovaries in obese girls. Ultrasound Obstet Gynecol. 1994;4(4):310–315.
24.
DunaifA. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997;18(6):774–800.
25.
WillisDMasonHGilling-SmithCFranksS. Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulose cells of normal and polycystic ovaries. J Clin Endocrinol Metab. 1996;81(1):302–309.
26.
FulghesuAMVillaPPavoneVGuidoMApaRCarusoA. The impact of insulin secretion on the ovarian response to exogenous gonadotropins in polycystic ovary syndrome. J Clin Endocrinol Metab. 1997;82(2):644–648.
27.
Sir-PetermannTEchiburúBPérezVLadrón de GuevaraAPreislerJMerinoS. Ovarian Function during Early Infancy in Daughters of Women with Polycystic Ovary Syndrome Treated with Metforming during Pregnancy. 91th Annual Meeting of Endocrine Society. 2009;P1–298.
28.
CaraJFRosenfieldRL. Insulin-like growth factor I and insulin potentiate luteinizing hormone-induced androgen synthesis by rat ovarian thecal-interstitial cells. Endocrinology. 1988; 123(2):733–739.
29.
BerghCCarlssonBOlssonJHSelleskogUHillensjöT. Regulation of androgen production in cultured human thecal cells by insulin-like growth factor I and insulin. Fertil Steril. 1993;59(2):323–331.
30.
NestlerJEJakubowiczDJde VargasAFBrikCQuinteroNMedinaF. Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J Clin Endocrinol Metab. 1998;83(6):2001–2005.
31.
RosenfieldRLBarnesRBEhrmannDA. Studies of the nature of 17-hydroxyprogesterone hyperresonsiveness to Gonadotrophin-releasing hormone agonist challenge in functional ovarian hyperandrogenism. J Clin Endocrinol Metab. 1994;79(6):1686–1692.
32.
PasqualiRPattonLPocognoliPCognigniGE, Gambineri A. 17-hydroxyprogesterone responses to Gonadotrophin-releasing hormone disclose distinct phenotypes of functional ovarian hyperandrogenism and polycystic ovary syndrome. J Clin Endocrinol Metab. 2007;92(11):4208–4217.
33.
Sir-PetermannTRabenbauerBWildtL. The effect of flutamide on pulsatile gonadotrophin secretion in hyperandrogenaemic women. Hum Reprod. 1993;8(11):1807–1812.
34.
RosenfieldRLBordiniB. Evidence that obesity and androgens have independent and opposing effects on gonadotropin production from puberty to maturity. Brain Res. 2010;1364:186–97.
35.
PioukaAFarmakiotisDKatsikisIMacutDGerouSPanidisD. Anti-Mullerian hormone levels reflect severity of PCOS but are negatively influenced by obesity: relationship with increased luteinizing hormone levels. Am J Physiol Endocrinol Metab. 2009;296(2):E238–E243.
36.
RosenfieldRL. Clinical review: identifying children at risk for polycystic ovary syndrome. J Clin Endocrinol Metab. 2007;92(3):787–96.
