ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Clin Endocrinol Metab. 2018 Feb 1;103(2):740-747

Polycystic ovary syndrome (PCOS) is characterized by oligo-amenorrhoea, clinical and/or biochemical hyperandrogenism, polycystic ovaries, infertility and, commonly, insulin resistance, hyperinsulinaemia, morbid obesity and type 2 diabetes. The insulin-sensitizing drug metformin ameliorates the endocrinopathy of PCOS by reducing hyperinsulinaemia-mediated hyperandrogenism, facilitating resumption of predominantly ovulatory normal menses. The use of metformin during pregnancy seems to be safe and there is no evidence that metformin is teratogenic whether given to women with type 2 diabetes mellitus, gestational diabetes or PCOS. Metformin during pregnancy in women with PCOS does not adversely affect their neonates birth weight or length, or growth in the first 18 months of life. In this study the authors examined the in-utero ultrasound measurements of the fetuses to explore the effect of metformin versus placebo on fetal and birth anthropometrics in PCOS offspring compared with those in a reference population. The results were related to maternal body mass index (BMI). The main finding was that metformin-exposed offspring had larger head circumference (HC) compared with offspring in the placebo group. This was evident already at gestational week 32. Birth weight and length did not differ between the metformin and placebo groups. The metformin effect of larger HC was seen only among offspring of mothers with hyperandrogenic phenotype; among those with normo-androgenic phenotype, there was no difference between the groups. The effect of prenatal metformin exposure seems to translate differently depending on maternal BMI and/ or metabolic status. Offspring who are exposed to metformin and born to normal-weight mothers had significantly smaller HC and were shorter and lighter than metformin-exposed offspring of overweight/obese mothers. In contrast, in the placebo group there was no difference in head size, birth length, and birth weight between offspring of normal weight and those of overweight/obese mothers. This indicates a growth restrictive effect of metformin among normal-weight mothers with PCOS.

However, because of the small sample size, a metformin effect according to maternal androgen status must be interpreted with great caution and should be addressed in future studies.