Elsevier

Fertility and Sterility

Volume 95, Issue 2, February 2011, Pages 727-730
Fertility and Sterility

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

https://doi.org/10.1016/j.fertnstert.2010.08.052Get rights and content
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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 ∼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.

Key Words

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

Cited by (0)

L.I., M.D., and M.V.M. are Clinical Investigators of CIBERDEM, Madrid, Spain). A.L-B. is an Investigator of the Fund for Scientific Research I3 (Ministry of Education and Science, Spain). F.d.Z. is an Investigator of the Clinical Research Council of the University Hospital Leuven.