Episode #122: Scientific Spotlight: Journal Article Review on Metformin and PCOS

A really commonly talked about medication for PCOS is metformin. In today’s episode, I want to dive into the good, the bad, and the concerns that oftentimes arise for women with PCOS when thinking about taking metformin. So without further ado, let’s dive in.

You’re listening to the PCOS Repair Podcast, where we explore the ins and outs of PCOS and how to repair the imbalances in your hormones naturally with a little medical help sprinkled in. Hi, I’m Ashlene Korcek, and with many years of medical and personal experience with polycystic ovarian syndrome, it is my joy to watch women reverse their PCOS as they learn to nourish their body in a whole new way. With the power of our beliefs, our mindset, and our environment, and the understanding of our genetics, we can heal at the root cause.

Welcome back to the PCOS Repair podcast, where I’m excited to talk about a medication that is very helpful for PCOS, but gets a lot of bad reputation when it comes to women that have PCOS that are taking it. First of all, this is a research review episode, and so I want to start by going over the research. The whole research is going to be linked in the show notes below so that you can review any of it that you want yourself but for the purpose of the episode, I’m going to try to keep things really light and not overly scientifically worded, because I don’t particularly like reading journal articles. I find them fascinating, but I wish they would make the information a little bit more reader friendly. All right, so first of all, the article is called Metformin: A New approach and it was published in 2021. This is a fairly recent article, and it talks about the uses of metformin in general, and It also has a section that talks about it, specifically for PCOS at the end of the episode today, I will review the key takeaways and considerations. If you have taken it before, if you’ve been thinking about taking it, if you want to make an appointment and talk to a doctor about taking metformin for your PCOS, etc. The point of this episode is not to tell you to take metformin. It is simply to review some recent literature as well as to share some of my takeaways from having taken the medication as well as from clients that I’ve worked with that have taken the medication and what various women find and how best to combat any of the negative side effects.

Okay, so first of all, it has been found that metformin is very helpful in aiding in weight loss compared to the control groups in studies. The weight loss in the metformin group was significant. Side note on that, no medication is going to overcome food choices but if you’re doing everything right with your PCOS and you’re still struggling to lose weight or keep the weight off, or you feel like it’s such a struggle to lose weight, something like metformin can really help. The way that it helps is that it actually inhibits what we call the gluconeogenesis in the liver. This is where the liver is taking the stored glucose. You have blood sugar, you can send it to your cells and use it as energy right away, or you can store it. When we have excess glucose glucose, which we do pretty much every meal because we eat in chunks. We’re not just on a constant IV drip of glucose. We are eating, our body takes that and absorbs it from our intestines and then sends it to our bloodstream. Then our bloodstream signals insulin to then come and send it to where it needs to go in the body into our cells. So into our brain cells, into our muscle cells, wherever we need energy and nutrients. So that blood sugar goes in, it does the whole ATP thing that you may have heard about or you remember way back in high school chemistry. That’s where we get our energy but what if we have too much? We store it in two places. One, we store it in the liver and we have a set amount that sits in the liver and then once that store is full, then we send it to be stored as fat tissue. Then when we burn that fat tissue, we’re actually burning things a little bit different. It does not break down into glucose. It breaks down more into ketones and things like that but it’s a little bit different chemistry when we break fat but typically what we’re using on a daily basis is the food that you just consumed, and then we will break down in the liver. That’s a side note of physiology really simplified, but essentially that’s what the word gluconeogenesis is, is taking that storage out of the liver and bringing it back into the bloodstream.

Metformin inhibits that process. It’s going to start using what we have and stop storing it. Essentially, The way that not breaking down all this extra glucose from our liver allows for less blood sugar and then, of course, less insulin. We are just basically allowing our body to have breaks between meals. As long as you’re eating regular meals, this can be a really good thing because sometimes our body gets a little too excited to release more glucose before we needed it again. Metformin also slows down glucose absorption. This is going to decrease how sharp we spike our glucose as well then how much insulin is being fluttered into our system after we eat. If we are slowing down our absorption from our digestion, we can get a little bit and use it and a little bit and use it.

Then instead of having this massive flood of glucose all at once that spikes us super high and then it’s going to drop us, we can do it a little bit more gradually. Another way of thinking about this is what used to spike you really high because it was a super high sugar content is almost now acting like a food that’s maybe a little lower sugar content. Again, no medication is going to combat poor eating and poor nutrition. However, this gives us a little bit more leeway to be not quite so strict and still see results. In addition, metformin can indirectly increase our insulin sensitivity by increasing our peripheral glucose utilization. That’s all fancy jargon for basically saying the end point of our glucose use becomes more sensitive. Our muscles can take that glucose in better. Think about our insulin. If we go back to we ate something, our glucose spikes. Our metformin is helping to decrease that spike by absorbing it slower. Instead of being super high and then super crash, we have a rolling hill of blood sugar goes up. We’re slowly releasing, releasing, releasing, releasing over time, slowly, and then it starts to wane as we absorbed all of our meal and digested it.

Instead of this really sharp, just like, let it all in, let it all drop but once that blood sugar is in our system, once it has been released into our bloodstream, that glucose needs to go where it needs to end up, which is usually in our muscles and in our brain. One of the places where we can really improve our insulin sensitivity is our muscles but they have to accept that glucose. So This is where insulin comes in. Insulin is released. Our body recognizes the bloodstream has glucose in it. That blood glucose level tells our body, release the insulin but how much comes into how insulin sensitive we are. If we just need a little bit, it’s like a quiet, let the blood sugar in muscles, or do we need to shout, let the blood sugar in muscles? That’s the magnitude of how much insulin our body needs. If our body can just gently go, Hey, muscles, let the blood sugar in now, and our muscles just take that blood sugar in, we don’t need very much insulin. If we have to raise our insulin voice and scream at those muscles to let the blood sugar in, a lot more insulin needs to be released into our bloodstream.

When that happens, there’s a high concentration of insulin in our blood, and that high concentration of insulin tells our ovaries to produce more androgens. That’s where our reproductive hormones get messed up. That’s where our LH levels go up with the insulin effect, root cause of PCOS, which we talked about in a few episodes ago in a mini-series about the root causes. If you missed that, go back and listen to that but then there are some side effects, and these are the side effects that women talk about with PCOS. In fact, these side effects have been so notoriously talked about that the adherence rate to metformin has been very poor, and consequently, a lot of physicians have stopped prescribing it as heavily, especially with certain medications such as Ozempic on the market now for weight loss. Some physicians have gone more towards prescribing that. I probably should do a whole episode on that. I do not recommend that medication, I think metformin is a much better choice for root cause health of PCOS but that’s the whole side note. It’s my own opinion. I’ll do another episode on that one later. As far as the research, though, goes, there are some side effects.

The ones that are more concerning, and quite rare, are you can develop hypoglycemia with metformin. Now, as far as diabetic medications go, metformin is one of the lower-risk medications for developing hypoglycemia, but it can happen, as well as hyperinsulinemia and vitamin B deficiency and peripheral neuropathy, as well as acidosis but these were all fairly low compared to other diabetic medications. These are things that can happen. The ones that are very common, side effects, are lots of appetite, which is not highly It’s highly concerning as long as someone isn’t overly petite and would be in danger from having any a weight loss due to low appetite but it can cause some epigastric pain, so upper GI pain as well as some nausea and maybe some diarrhea. This GI discomfort, bloating, gas, nausea, diarrhea, just abdominal pain due to all of the digestive issues that can be going on. Then there’s studies that also suggest that metformin plays a role in our gut health and may promote healthy bacteria in our gut, which perhaps is how it helps to slow the digestion and so forth. That also may, my own theory aside, not in the research article here, may be why we have some GI upset at the beginning.

It’s not unlike when we start taking a pre or probiotic where we may have some bloating and some GI distress, and this is a pharmaceutical, so they’re usually a lot stronger than over-the-counter supplements. This is where, although some of these side effects can be annoying. We’ll talk about a little how to combat those and to help you determine if metformin may be something worth trying or retrying a slightly different approach. Basically, metformin has been shown to be an effective drug to reduce body weight in insulin sensitive and in insulin resistant patients, which is very exciting, but only in patients that are overweight. This isn’t something that usually creates weight loss in patients that are of healthy weight. This is where they actually have weight to lose. Also, I would put a caveat that they are probably actively following some weight loss plan, but this is making it more effective and they’re losing larger amounts over the course of the study compared to the control groups.

Then as far as PCOS and metformin, metformin has been shown in research to increase the ovulation rate in patients with PCOS as compared to the control or the placebo groups. However, it is not recommended as a first-line treatment for anovulatory cycles. Here’s the reason why something like Clomid or Letrozole is going to work so much better at focusing on the ovaries ovulating. The research is a little cloudy on whether or not it is helpful in combination. That would be like metformin and Clomid or metformin and Letrozole. That is a side research study that would probably need to be a lot larger and specifically looking at that. We don’t know if the metformin in combinations would increase the ovulation rates or not, but it’s not first-line as an ovulatory medication because clomid and letrozole are more effective. We’ll talk about more my take on PCOS and metformin as we review this article. This research article then also goes on to talk about metformin and its likelihood to either create a deficiency through lack of absorption or somehow creating deficient levels of vitamin B12. A lot of times, practitioners are monitoring for B12. Not a bad idea to take a B12 supplement if you are taking metformin but in addition to the benefits that we have already talked about, there are several cancers, and I’m not going to go into this because it’s not really the scope of this podcast, but I will list that metformin has been shown to improve breast cancer rates.

Of course, there are many different kinds of breast cancer, so not across the board, but there’s been shown to be improvement in survival rates in breast cancer, in lung cancer, in colorectal cancer. Essentially, there may be a lot of benefits to metformin beyond just the use in PCOS and diabetes as something that can create and sustain further metabolic health for people taking it. That concludes the research portion. Let’s dive into the takeaways here. First of all, I want you to think back to one of our episodes a few weeks ago that talked about all the different root causes and how connected they are. When we think about our cortisol, our insulin, and our inflammation, they are all connected. Metformin is primarily targeting the insulin system and decreasing our glucose effect as well as improving our insulin sensitivity. However, cortisol increases our insulin. Inflammation is made worse by high levels of cortisol and high levels of insulin and excess weight. Metformin does work on all of those, but it’s primarily doing it through the pathway of insulin. When we think about our root cause hormones, and then how they affect going up the pyramid towards our reproductive hormones and how they increase our androgens and throw off our cycle and create all of the side effects of PCOS and all of the problems that we see with PCOS, metformin definitely It definitely has its place in the treatment of PCOS.

The downsides are how well it’s tolerated. A couple of things that I want you to think about is if you have tried metformin, Perhaps you did this differently, and maybe that’s why it was not successful for you. You definitely want to start on a low dose. You want to slowly ease into it. You don’t want to go to a full dose right away. One reason, because you don’t want to be hypoglycemic, you don’t want to be too strong on yourself, which typically is less of a concern. So some doctors will go ahead and start you in a moderate to medium dose, and you could start a little less. So my recommendation would be to start at 500 milligrams. There’s a couple of different formulations out there, but basically 500 milligrams of metformin and I would take it in the evening with dinner. That seems to be the most tolerated. That way, you’re sleeping through some of the discomfort comfort, as well as starting with a lower dose and seeing how you tolerate it. As you tolerate it, increase it. What I personally have found and what I see repeatedly with women that tolerate it, now, I have seen women who do not tolerate it, but the ones who do end up tolerating it and having it be a non-factor as far as side effects, but very helpful as far as something that is assisting them with their goals for PCOS, is that when they start slow, they do have somewhere between three days to two weeks of discomfort.

Some women have had a little bit longer and they will push themselves a little bit longer but once that discomfort subsides, give yourself about that much time to settle in on that dose. If it took you five days to reach comfort, give yourself five days at comfort before you increase your dose to two five milligram tablets. Then from there, do the same thing till you reach the dose that your doctor wants you to be on but essentially, So you’re just starting in small increments, and then you’re giving yourself a couple of days to let your GI tract get used to it. Perhaps you take two weeks and then just steady for two weeks. There’s no race to get to that dosage. Again, we feel like I want this to work now. Well, if we overdo it, we start to go back and forth between, I’m on it, I’m not on it because I can’t tolerate it, and we want to find that sweet spot so that we can stay on it long term. If you have tried that and it did not work for you. It’s not the end all. It’s not the only drug out there, not the only option out there for your PCOS but I do want to bring it up because there’s been a lot of talk about how it’s not very friendly medication, how it has so many side effects but the couple of things I would really recommend is start extremely slow. If you felt like you could have started slower or you felt like you pushed yourself too fast, consider trying it again. The mindset piece here would be it may be for a couple of days and so take it easy on yourself, be patient with yourself, wear loose-fitting pants, don’t expect a whole lot else of yourself, take a hot bath in the evening, drink tea, don’t eat as much because the less you eat, the less they’ll be to bug your stomach, but eat enough that you’re comfortable. This also may be not the time and place to be your most healthy. It may be a time and place to be more carb-heavy. Sometimes a piece of toast digests better than eggs and bacon for breakfast or healthy omelet with lots of vegetables in it with your eggs. That’s okay because you’re trying to get yourself worked up on a medication that’s new to your system.

So be patient with yourself and do what’s needed. Typically, that doesn’t last for many days. It gets better and better as you go. For me, when I increase my dose, it takes me about three days. I don’t tend to be very sensitive to medications, and so I tend to handle things okay but if you are someone who tends to be sensitive, that doesn’t mean metformin is not going to happen for you, but definitely just start really slow. Start at the lowest dose you can. See how you do on it. As soon as you’ve had a couple of days where you’re doing well, increase it. Wait a couple more days till you level out again. Stabilize for a couple of days and then increase your dose until you reach that desired place. Also, make sure you’re taking a B12 supplement.

With that, I hope you found this article helpful. I will link the full article on the show notes on the website. It’s not when you scroll down, but when you go to the website, you’ll see all of the links in the show notes on the website. Until next time, if you have any questions, you can find me over on Instagram @nourishedtohealthy, and I look forward to talking to you there. Until our next episode. Bye for now.