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


METHODS
Open-label, randomized study.


METHODS
University hospital.


METHODS
Thirty-eight LBW-PP girls.


METHODS
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
Early metformin therapy (age ∼ 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.
Ibáñez
Lourdes
L
Endocrinology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, and CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Madrid, Spain. libanez@hsjdbcn.org
Lopez-Bermejo
Abel
A
Diaz
Marta
M
Marcos
Maria Victoria
MV
de Zegher
Francis
F
D001827:Body Height / Q000187:drug effects*; D002648:Child; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007230:Infant, Low Birth Weight / Q000502:physiology; D007231:Infant, Newborn; D008572:Menarche / Q000187:drug effects* / Q000502:physiology; D008687:Metformin / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000517:prevention & control; D011629:Puberty, Precocious / Q000188:drug therapy* / Q000209:etiology; D012307:Risk Factors; D013997:Time Factors
D007004:Hypoglycemic Agents; D008687:Metformin