Over the last few decades, metformin or glucophage has become the magic pill de jour for PCOS and type 2 diabetes, so much so that prescriptions for metformin across pregnancy are commonplace. Is it safe? To read the majority of research from early 2000 thru 2010 or so, the answer would be an unequivocal yes. Metformin during pregnancy was considered perfectly safe. Indeed, it was more than safe, it was protective against everything from pre-eclampsia to pre-term birth and it reduced the risk for gestational diabetes significantly.
Like all things too good to be true, once the appropriately sized and controlled studies were conducted researchers found that metformin was not safe. In fact, metformin increased the risk for each of the pregnancy complications it was first presumed to protect against; gestational diabetes, preclampsia and preterm labor, and added a few unexpected and more dangerous ones to boot, like an increased risk for maternal pulmonary embolism and fetal neural tube defects. And yet, it is still recommended regularly.
What has never been addressed is fetal health and long term outcomes. How can a drug that alters insulin sensitivity, a critical function in human health, and that crosses the placenta readily, with umbilical cord concentrations at amounts ranging from at least half that of mom’s to far exceeding maternal concentrations, be safe for fetal development? From a purely logical, perhaps even intuitive, gut reaction this makes absolutely no sense.
What are the consequences of maternal metformin on the developing fetus on insulin regulation and pancreatic function, on growth regulation, cardiac function, neurocognitive function and because of the close relationship between insulin and testosterone, on hormone and reproductive function? Certainly, there must be lasting biochemical changes induced during fetal development; what do we really know about the metformin children? Not much, I am afraid.
- Metformin exposure in utero induces long-term programing changes in fat metabolism and weight gain in male mice.
- In male mouse and human cells, in vitro exposure to metformin reduces testosterone production, the factors involved in the secretion of steroids, testicular size, the number of Sertoli cells – the nurse cells of the germ cells and the number of Leydig cells. Female ovarian cells were not tested.
- In female cows, metformin reduces steroidogenesis in ovarian granulosa cells and decreases both estradiol and progesterone secretion.
- Metformin exposure during pregnancy leads to heavier mamas and babies one year postpartum.
That’s about it. That’s all we know. Doctors have been giving metformin to pregnant mamas for decades without so much as a sufficiently controlled and conducted study to support its safety or efficacy. Doctors have been prescribing this drug to pregnant mamas despite the limited research. And although animal studies suggest risks to maternal health and in vitro, cell culture studies indicate potential risk to fetal biochemistry, there seems to be no impetus to cease writing prescriptions or do the research necessary to delineate risks versus benefits.
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This post was published here originally on September 26, 2013.