Context and Objective: Girls with precocious pubarche (PP, pubic hair < 8 yr) are at high risk for early onset and rapid progression of puberty, in particular if their prenatal growth was restrained (low birthweight, LBW) and followed by rapid postnatal catch-up of weight gain. We postulated that insulin resistance contributes to early onset and rapid progression of puberty in LBW-PP girls, and thus explored the puberty-delaying effects of insulin sensitization with metformin initiated shortly after PP diagnosis.

Setting, Design, and Patients: The study population consisted of 38 prepubertal LBW girls with PP attributed to exaggerated adrenarche [mean BW 2.4 Kg; age 7.9 yr; body mass index (BMI) 18.4 Kg/m²]; these girls were randomly assigned to remain untreated (n = 19) or to receive metformin (n = 19; 425 mg/d) for 2 yr.

Main outcome measures: Pubertal staging, age at menarche, body composition by absorptiometry, fasting insulin, glucose, lipids, leptin, insulin-like growth factor-1 (IGF-1), IGF-binding protein-1 (IGFBP-1), testosterone, dehydroepiandrosterone-sulfate (DHEAS), testosterone, sex hormone-binding globulin (SHBG).

Results: Metformin treatment was associated with a less adipose body composition (and lower serum leptin levels) and with a 0.4 yr delay in the clinical onset of puberty (Tanner B2; 9.5 yr vs. 9.1 yr; P < 0.01). These findings were corroborated by a delay of at least 1 yr in the puberty-associated rise of circulating IGF-1 (P < 0.01). Available results also point to a metformin-associated delay of menarche (P < 0.02); so far, gain in height and lean mass was not divergent between study subgroups.

Conclusion: The efficacy of early metformin treatment in PP girls is herewith extended to include not only a less adipose body composition after 2 yr, but also a less advanced onset of puberty, while height gain is maintained. These findings open the perspective that, ultimately, metformin treatment may also prove to heighten the short adult stature of LBW-PP girls.