metformin gestational diabetes

Pregnancy Metformin and Fetal Development

6386 views

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.

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.

Wow.

I don’t know about you, but this doesn’t give me a whole lot of confidence in medical science or medical ethics, particularly when one considers the all-too-recent history of thalidomide and DES.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter. 

This post was published here originally on September 26, 2013.  

Image by Pexels from Pixabay.

PCOS, Pregnancy, Metformin and Vitamin B12 Deficiency

8167 views

PCOS or polycystic ovarian syndrome is one of the most common hormone disorders in women. It is marked by a triad of symptoms that include: cardiovascular, metabolic and steroid hormone disturbances. Type II diabetes is common in PCOS and Metformin is the drug of choice to treat PCOS – related Type II diabetes.

In recent years, clinicians and researchers have begun to observe vitamin B12 deficiency in Metformin users. First thought to be a short term problem, researchers are now finding that with long term metformin use not only does the B12 deficiency persist, but it grows. Left alone long enough, vitamin B12 deficiency leads to a host of conditions, many that  Metformin was supposed to prevent, including:

For women, especially of reproductive age, B12 deficiency can be particularly troubling, if not downright dangerous. Vitamin B12 deficiency during pregnancy leads to an increased incidence of neural tube defects and anencephaly (the neural tube fails to close during gestation – anencephaly pictured above) . Once thought to be solely related to folate or folic acid deficiency (vitamin B9), researchers are now finding that B12 has a role in neural tube defects as well. Many women on Metformin are coming into pregnancy vitamin B12 deficient.

This is where it gets tricky. Metformin is used in women with PCOS to reduce insulin sensitivity. Metformin also tends to regulate ovulation for PCOS women and was believed to help women get pregnant (though the data here are mixed here as well). Without regular ovulation, conceiving is near impossible and so the fact that Metformin might have helped with ovulation had been seen as a breakthrough for previously infertile PCOS women. Reproductive endocrinologist embraced this new found fertility tool and as one might expect, the requisite studies (read marketing documents) flooded the esteemed peer-reviewed journals to proclaim the benefits of this new wonder drug. No wait, Metformin is not a drug, it’s a new vitamin – Vitamin M.

We now have a drug that is given liberally to women who become pregnant and then continued across the pregnancy. The drug crosses the placental barrier and there are no studies to indicate either its safety or harm to the fetus. The drug causes significant vitamin B12 deficiency, which alone poses great risk to fetal development (neural tube defects) but who knows what vitamin B12 deficiency plus the endocrine disrupting effects Metformin will have on the developing fetal insulin or cardiovascular systems. Are we looking at more transgenerational effects?  Metformin does not prevent maternal gestational diabetes (as was widely speculated) and increases pre-eclampsia, pulmonary embolism and other nasty pregnancy complications.  And yet, the major patient organizations advocate for its use across pregnancy.

Have we learned nothing from thalidomide and DES?  Apparently, not.

 

Photo credit: Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities