Early metformin therapy to delay menarche and augment height in girls with precocious pubarche

被引:52
作者
Ibanez, Lourdes [1 ,2 ]
Lopez-Bermejo, Abel [3 ]
Diaz, Marta [2 ]
Victoria Marcos, Maria [4 ]
de Zegher, Francis [5 ]
机构
[1] Univ Barcelona, Endocrinol Unit, Hosp St Joan de Deu, Barcelona 08950, Spain
[2] CIBER Diabet & Enfermedades Metab Asociadas CIBER, Madrid, Spain
[3] Dr Trueta Hosp, Girona, Spain
[4] Hosp Terrassa, Endocrinol Unit, Terrassa, Spain
[5] Univ Louvain, Dept Woman & Child, Louvain, Belgium
关键词
Metformin; menarche; insulin; IGF-I; DHEAS; puberty; pubarche; birthweight; epigenetic; androgen excess; polycystic ovary syndrome; PCOS; obesity; height; adrenarche; lipids; abdominal fat; subcutaneous fat; adiposity; hepatic fat; fatty liver; visceral fat; body composition; lean mass; LOW-BIRTH-WEIGHT; POLYCYSTIC-OVARY-SYNDROME; INSULIN SENSITIZATION; EARLY PUBERTY; VISCERAL FAT; GROWTH; SENSITIVITY; CHILDREN; RISK;
D O I
10.1016/j.fertnstert.2010.08.052
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Objective: To study the effects of early metformin treatment on menarche, height, and polycystic ovary syndrome (PCOS) markers. Low-birthweight (LBW) girls with precocious pubarche (PP) are at risk for an early menarche (< 12 years), an adult stature below target level, and PCOS. Hyperinsulinemic insulin resistance is thought to be a key factor. Design: Open-label, randomized study. Setting: University hospital. Patient(s): Thirty-eight LBW-PP girls. Intervention(s): At age 8 years, girls were randomly assigned to remain untreated or to receive metformin for 4 years; subsequently, both subgroups were followed without treatment until each girl was postmenarcheal. Main Outcome Measure(s): Age at menarche, height, weight, endocrine-metabolic state (fasting blood), body composition (by absorptiometry), abdominal fat (subcutaneous vs. visceral), and hepatic adiposity (by magnetic resonance imaging). Result(s): At last assessment, girls in each subgroup were on average 2 years beyond menarche; the mean growth velocity was below 2 cm/years. Age at menarche was 11.4 +/- 0.1 years in untreated girls and 12.5 +/- 0.2 years in metformin-treated girls; the latter girls were taller and much leaner (with less visceral and hepatic fat) and had more favorable levels of circulating insulin, androgens, and lipids. Conclusion(s): Early metformin therapy (age similar to 8-12 years) suffices to delay menarche; to augment postmenarcheal height; to reduce total, visceral, and hepatic adiposity; and to curb the endocrine-metabolic course of LBW-PP girls away from adolescent PCOS. (Fertil Steril(R) 2011;95:727-30. (C) 2011 by American Society for Reproductive Medicine.)
引用
收藏
页码:727 / 730
页数:4
相关论文
共 19 条
[1]   Adipose tissue expandability and the early origins of PCOS [J].
de Zegher, Francis ;
Lopez-Bermejo, Abel ;
Ibanez, Lourdes .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2009, 20 (09) :418-423
[2]   Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state [J].
Foretz, Marc ;
Hebrard, Sophie ;
Leclerc, Jocelyne ;
Zarrinpashneh, Elham ;
Soty, Maud ;
Mithieux, Gilles ;
Sakamoto, Kei ;
Andreelli, Fabrizio ;
Viollet, Benoit .
JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (07) :2355-2369
[3]   Age at Menarche and Risk of Type 2 Diabetes: Results From 2 Large Prospective Cohort Studies [J].
He, Chunyan ;
Zhang, Cuilin ;
Hunter, David J. ;
Hankinson, Susan E. ;
Louis, Germaine M. Buck ;
Hediger, Mary L. ;
Hu, Frank B. .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 2010, 171 (03) :334-344
[4]   Early puberty-menarche after precocious pubarche:: Relation to prenatal growth [J].
Ibáñez, L ;
Jiménez, R ;
de Zegher, F .
PEDIATRICS, 2006, 117 (01) :117-121
[5]   Anovulation after precocious pubarche:: Early markers and time course in adolescence [J].
Ibáñez, L ;
de Zegher, F ;
Potau, N .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1999, 84 (08) :2691-2695
[6]   Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls:: Relation to reduced fetal growth [J].
Ibáñez, L ;
Potau, N ;
Francois, I ;
de Zegher, F .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (10) :3558-3562
[7]   Insulin sensitization for girls with precocious pubarche and with risk for polycystic ovary syndrome:: Effects of prepubertal initiation and postpubertal discontinuation of metformin treatment [J].
Ibáñez, L ;
Valls, C ;
Marcos, MV ;
Ong, K ;
Dunger, DB ;
de Zegher, F .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (09) :4331-4337
[8]   Insulin sensitization early after menarche prevents progression from precocious pubarche to polycystic ovary syndrome [J].
Ibáñez, L ;
Ferrer, A ;
Ong, K ;
Amin, R ;
Dunger, D ;
De Zegher, F .
JOURNAL OF PEDIATRICS, 2004, 144 (01) :23-29
[9]   Polycystic ovary syndrome after precocious pubarche:: ontogeny of the low-birthweight effect [J].
Ibáñez, L ;
Valls, C ;
Potau, N ;
Marcos, MV ;
de Zegher, F .
CLINICAL ENDOCRINOLOGY, 2001, 55 (05) :667-672
[10]   Metformin treatment for four years to reduce total and visceral fat in low birth weight girls with precocious pubarche [J].
Ibanez, Lourdes ;
Lopez-Bermejo, Abel ;
Diaz, Marta ;
Victoria Marcos, Maria ;
de Zegher, Francis .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (05) :1841-1845