pcos, metformin, anencephaly

PCOS, Pregnancy, Metformin and Vitamin B12 Deficiency

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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

Chandler Marrs MS, MA, PhD spent the last dozen years in women’s health research with a focus on steroid neuroendocrinology and mental health. She has published and presented several articles on her findings. As a graduate student, she founded and directed the UNLV Maternal Health Lab, mentoring dozens of students while directing clinical and Internet-based research. Post graduate, she continued at UNLV as an adjunct faculty member, teaching advanced undergraduate psychopharmacology and health psychology (stress endocrinology). Dr. Marrs received her BA in philosophy from the University of Redlands; MS in Clinical Psychology from California Lutheran University; and, MA and PhD in Experimental Psychology/ Neuroendocrinology from the University of Nevada, Las Vegas.


  1. Hi Dr. Marrs,

    I got diagnosed with PCOS last November based on the results of AMH test and was prescribed Metformin, 1000mg/day. I got pregnant fairly quickly (within 3 months of starting the prescription and within 6 months of trying overall). Once I learned that I got pregnant, I stopped metformin because I was concerned about its safety for pregnancy. I never was a big fan putting chemicals with undefined consequences in my body, especially when pregnant. I wasn’t aware at the time about DES tragedies but was trying to prevent similar consequences. So I adjusted my diet and excluded all sweets. I couldn’t exercise though because I was struggling with a cold for about 4 weeks (no fevers).

    I miscarried at 7.5 weeks (I am still waiting on karyotyping results). My guess would be that it was because of problems with uterine lining – because the baby had a heartbeat even when my bleeding was increasing, and even 24 hours before miscarriage took place.

    My question is – we are going to keep trying to get pregnant, and we still want to avoid taking metformin during pregnancy. What do I need to do to maximize my chances to carry the next pregnancy to term?

    My background information: I am turning 36 in July, and I have a 3-year old daughter delivered naturally.

    Also, are there any studies on metformin alternatives (Berberine, etc.) or healthy lifestyle impact on miscarriage rates?

    Thank you.

    • Heather, I am not sure what you are asking? Can you get pregnant on metformin, yes? Should you get pregnant on metformin, maybe not. Metformin during pregnancy increases the risk of neural tube defects in the child b/c of the vitamin b12 deficit. We have additional articles showing it also damages mitochondria by depleting thiamine and coQ10 – two necessary cofactors for energy production. Without these, all sorts of things can go wrong. Please read the other articles on metformin before you make your decision.

  2. Not sure if this helps or if anyone is interested but I recently heard about a new oral prescription alternative to the injections called Eligen B12. I recently read that it works even if you don’t have intrinsic factor (so even if you don’t have normal gut absorption), which would mean no more shots. Apparently it came out a month or two ago. Has anyone tried it??

  3. This is a thought-provoking piece that I hope garners the attention it deserves. I have known that metformin and vitamin B12 do not play well in the sandbox. However, adding PCOS and pregnancy to the mix clearly may further exacerbate women’s (pregnant or not) health. Metformin prescriptions are being doled out as candy, and they should not be. More medical professionals need to understand how to treat the body as a complex system, not simple applying a “Band-Aid” to a symptom or two.

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