Carrie’s Question: 

I really liked this article about capsules versus creams. So, it was about progesterone, so bioidentical capsules or progesterone capsules versus progesterone cream. “I do have a question. I recently started 100 milligrams generic progesterone called Generic Prometrium and have had horrible side effects after almost three weeks of taking 100-milligram Prometrium pill each night. My anxiety has increased, terrible headaches the next day, very teary, exhausted the next day. Extreme brain fog like scary forgetfulness. Is it possible something could be with the fillers or the brand or maybe too high of a dose too soon? I’m being treated for very low progesterone in order to help my mood. Which sounds really sad because her mood sounds even worse on the Prometrium but anyway, My mid-luteal phase of my cycle, my levels were .9, which is very low. And should I ask for a different brand or compound capsules? Thank you.

Short Answer: 

We don’t consider Prometrium and Bioidentical Progesterone the same thing. In our experience, many women do not seem to tolerate Prometrium very well. Prometrium is an instant release. We prefer to prescribe bioidentical sustained-release progesterone.

PYHP 074 Full Transcript

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Dr. Maki: Hello, everyone. Thank you for joining us for another episode of the Progress Your Health podcast. I’m Dr. Maki. 

Dr. Davidson: And I’m Dr. Davidson. 

Dr. Maki: So, like the last episode, we answered a question from Michelle. This one we kind of follow the same trend. Like I said due to the recent Google update, we have been getting a bunch of comments and questions. That means people are finding our website, which is great. This one, we’re going to answer a question from Carrie. She’s got some concerns or questions about progesterone. 

Dr. Davidson: We love reader and listener questions. So, it’s been kind of cool, we had a little bit of a dip for a while. But then all of a sudden, all these questions came flooding in in this last week. And they take time to answer and we really do want to get back to you when you have your questions. So, we thought it would be easier if we just did some podcasts on the questions because these questions apply to a lot of other ladies that are listening to this. So, I think it would be helpful. So, this question is from Carrie, Carrie’s comment is, “I really liked this article about capsules versus creams.” So, it was about progesterone, so bioidentical capsules or progesterone capsules versus progesterone cream. “I do have a question. I recently started 100 milligrams generic progesterone called Generic Prometrium and have had horrible side effects after almost three weeks of taking 100-milligram Prometrium pill each night. My anxiety has increased, terrible headaches the next day, very teary, exhausted the next day. Extreme brain fog like scary forgetfulness. Is it possible something could be with the fillers or the brand or maybe too high of a dose too soon? I’m being treated for very low progesterone in order to help my mood.” Which sounds really sad because her mood sounds even worse on the Prometrium but anyway, “My mid-luteal phase of my cycle, my levels were .9, which is very low. And should I ask for a different brand or compound capsules? Thank you.”

Dr. Maki: Yes. So, this is something that we see quite often, for mood, for sleep or anxiety, especially like say, so mid-luteal phase just to kind of give a little backstory. The female cycle is broken up into basically three phases. The first phase is the follicular phase, then ovulation which is right around day 15, let’s say 14 to 16. And then the luteal phase which is from ovulation back to the cycle. Now, every woman’s cycle is not necessarily 28 days, but that’s what everything is based on. So, whether it’s 28, 30, 32, that same hormonal shift, the follicular phase is predominantly or almost exclusively estrogen. At ovulation there is a little bit of estrogen, some testosterone, like a surge of testosterone to increase a woman’s libido and then that’s when from ovulation when the progesterone starts to be produced by–

Dr. Davidson: And there is that increase in estrogen right before ovulation.

Dr. Maki: Right, yes.

Dr. Davidson: That’s what caused it. So, you have that estrogen in that testosterone.

Dr. Maki: Yes. And then the luteal phase is a combination of the estrogen and predominantly progesterone. So, the mid-luteal phase, when we have women go into the lab to test for something like this, we usually have them go into let’s say day 18 to 20, 21. Most gynecologist will say day 21, day 20, day 21 is fine, and that’s when the level on day 20, day 21. That level should be really high or high enough. Where would you like to see a woman’s progesterone on day 21?

Dr. Davidson: Yes, and a menstruating female. I mean, everybody’s a little different between 20s and 30s and 40s. But ideally right around that high level is you want to have that progesterone in the teens. 

Dr. Maki: Yes, right.

Dr. Davidson: If somebody is in the teens, that’s fantastic but at .9 for Miss Carrie here that’s– and she’s right, it’s low. But it sounds like she’s being treated more about her mood where like Dr. Maki mentioned, I mean, progesterone can do a lot. It can help on lighten up periods. It can help with chronic bleeding. It can help with sleeping at night, it can definitely help with anxiety situations. So, it could be this definitely is pretty low for Carrie.

Dr. Maki: Yes. Now, one thing we don’t know is how old Carrie is, she didn’t give us her age. If she is hypothetically, let’s say she’s over the age of 40. A mid-cycle progesterone of .9 would be pretty normal.

Dr. Davidson: In some regards, yes, because your progesterone drops. 

Dr. Maki: Yes, that is not normal, but the inevitable decline of the hormone that is what we consider to be perimenopause. If she’s under the age of 40, but maybe even late 30s, this could happen where that is– but what she’s doing is still the right thing to do because her body isn’t making any progesterone. Now, there’s another kind of mechanism in the body related to stress called the pregnenolone steal when your body is under lots of stress, whether that’s lack of sleep, actual stress, job, family, work, finances, maybe too much exercise. Now, your body will shift away from making progesterone into making more cortisol because the requirement is higher and now, they have almost like an induced low progesterone 

Dr. Davidson: Because they steal the pregnenolone.

Dr. Maki: Yes, the pregnenolone which is kind of the up the chain kind of steroid. Everything’s kind of made from that it gets shifted. And now you’ll see a blood test like this and her progesterone is below one. It’s a fairly common thing to see when you run these kinds of laps.

Dr. Davidson: So, then Carrie’s pregnenolone, which is technically more of a hormone that comes with from the adrenal glands in response to like Dr. Maki said, stress, that’s probably pretty low too. 

Dr. Maki: Yes, right.

Dr. Davidson: Probably nonexistently low.

Dr. Maki: So, doing the three of those pregnenolone, DHEA sulfate or DHEA-S and progesterone labs that we typically run specifically in cases like this, because you might see a low pregnenolone, you might see a low DHEA, you might see low progesterone, all three of them might be low.

Dr. Davidson: So, then you’re differentiating between, is her progesterone low because of age or hormones or maybe just genetics with timing, or is it low because of her adrenals, or is it low because of both?

Dr. Maki: Yes, right, yes. So, it gets a little complicated and not necessary to over complicate this issue, but her question is, she should be doing the Prometrium, side effects, or she should be doing something different. Now, in most cases, we do agree with capsule progesterone, that’s usually where we start. But the dose can go anywhere from 25 milligrams, and we typically go up to 200 milligrams, we don’t really go any higher than that. Maybe in some situations, but most of the time, it’s 25 to 200, 25 to 50 milligrams would be more for a, maybe a younger female, maybe she just recently got her cycle, she’s in her teens or 20s, that would be a bit more of an appropriate dose and maybe even a, what we call a cycle dose where the dose changes throughout the month.

Dr. Davidson: Or it could be somebody that’s really sensitive. I know we’re all humans, but there’s no cookie cutter one size fits all. I have some patients that are so sensitive, that I even go lower than the 25 milligrams, and you’d think, “Oh, this isn’t going to be therapeutically effective.” But it is. And then there’s some people you kind of have to hit them with a sledgehammer to get any kind of reaction out of their system. So, it could be that maybe Carrie’s very sensitive. Honestly, we kind of talked about this question about Carrie. And wait, wait, I have to back up. Disclaimer, disclaimer, disclaimer, right? Before our attorney like waives a naughty finger at us. So, we’re not giving medical advice because Carrie is not a patient of ours, but we’re giving–

Dr. Maki: For educational purposes.

Dr. Davidson: Education stuff.

Dr. Maki: Yes. We’re just giving our opinion. We’re not advising and Carrie is not our patient. But we’re just giving our opinion on the question that she asked. So yes.

Dr. Davidson: There, there, there. So, but when we were trying to talking about this question, because I really liked it from Carrie earlier this morning. Is it probably the Prometrium to be honest. It may be a little bit with the dose, but it’s probably the Prometrium because Prometrium, hey, it is bioidentical, technically.

Dr. Maki: Supposedly.

Dr. Davidson: But it does have a lot of fillers in there. Technically, it has some kind of peanut extract. So, if someone’s allergic to peanuts, it’s not a good idea to take. And Prometrium only comes in two doses, pretty much 100 milligrams and 200 milligrams. So, like Dr. Maki said, she might need a little bit less or she might need something in between or it could be the fillers or it could be, as I kind of go on and complicate it even more, Prometrium is instant release progesterone. When I put in my mouth and swallow it, it goes right into my bloodstream at the highest-level right after you digest it and then it slowly comes down with time. So, it could be that instant release is having an effect on her system because hormones, I always call hormones, I say that they’re promiscuous. If progesterone doesn’t have a progesterone receptor site to jump into because it’s plugged up with another progesterone, it will just find a different receptor site. It can stimulate cortisol, it can stimulate testosterone receptors. So, it could be that surge in progesterone right away immediately could be stimulating other receptors or it’s just too much all at once.

Dr. Maki: Yes, so we tend to, for this particular reason, now, we do have some women that use Prometrium. Typically, most of them are menopausal, okay? So, they’re not having the hormonal swings that are menstruating female has which is at least part of maybe an explanation as to why they tolerate it better, just because of that factor, no longer menstruating. But we typically do not choose Prometrium on purpose, because of exactly what Carrie’s dealing with. We want to try to minimize the side effects and I agree with you. I think its difference between the instant release versus sustained release. Sustained release progesterone is usually extremely well-tolerated. Whatever dose is appropriate for that person, whether it’s 25 or 200. You find that sweet spot. Usually the tolerance level to that medication is going to be very, very good.

Dr. Davidson: So, I would say in just response for Carrie is she’s doing this for her mood. And it sounds like her anxiety is really high. So, progesterone is very relaxing, it’s fantastic for helping bring down cortisol, it raises up GABA, it’s great for anxiety and for mood. I’m thinking because she’s so tired the next day and she’s getting the terrible headaches. I think it’s because of the instant release, but I also think it’s probably too high.

Dr. Maki: Yes, sure. So, now if she is menstruating, a thing that we alluded to just a few minutes ago, another thing that can be helpful is to actually cycle the progesterone, again, a sustained release, let’s say 50 milligrams. Now the beginning part of her cycle, that follicular phase, you use a lower dose, the 50 milligrams, and then on day 12 she would increase to a higher dose. And to give her kind of that seven to 10 days before her period, that’s the mid-luteal phase, the seven to 10 days where most women are going through their PMS window. She’s getting more support when she really kind of needs it the most. But she’s giving herself a break in the first half of the month, that tends to be a very, if the 100 milligrams all month long is too much. It gives her kind of body a little bit of a break but not taking away completely because some women just need all month long. They just feel better that way.

Dr. Davidson: I agree, one thing is if you take too much progesterone all month long, that does suppress ovulation a bit so that’s just something that it’s not birth control, but it’s something to take into consideration, but since it’s really more about mood for Carrie is, I think Dr. Maki’s perfectly right. It’s doing a sustained release compounded progesterone capsule, but doing a lower dose that you don’t take it when you’re on your period, but maybe from day five to day 15 you would take a lower dose and from day 15 until you get your period, you would take a higher dose that would probably help a lot with Carrie, because like she said, is she had the horrible side effects after almost three weeks of taking it. So, she started taking it, she’s fine. And then after three weeks, 21 days, all of a sudden, she’s feeling horrible. So, that does lead you to say that that’s probably too high.

Dr. Maki: Yes, and progesterone, you don’t know, this is this challenging part, at least with the sustained release bioidentical progesterone, you won’t know immediately, almost similar to her three-week experiment there, you won’t know exactly if the dose is too high. Sometimes one or two or even three cycles need to go by. Unless there’s something obviously immediate, maybe with an immediate release, it takes a while because you can get some changes to the cycle. You can get more bleeding, less bleeding. The menstrual cycle itself can change, not to mention the physical symptoms that go along with that. So, you need at a time to be able to figure out is the dose too high or too low. And sometimes it’s not in a very short amount of time under one month. That’s not enough time to be able to know which way to go.

Dr. Davidson: And not to completely divert on a tangent but like Dr. Maki had mentioned earlier about that pregnenolone steal is here we are kind of downstream noticing, “Hey her progesterone is low, let’s just give her some progesterone.” But also, at the same time is working upstream on those adrenals possibly testing her pregnenolone, raising up her pregnenolone, finding out, is her cortisol too high? Doing some things to bring down that cortisol. That would want to definitely do that in tandem because one thing about pregnenolone is it does come from our adrenal glands. We do make a little bit from our brain and spinal cord, but mainly from our adrenal glands, is it’s very specific to learning. So, when someone has low pregnenolone, they are forgetful, like, “I don’t remember where my keys are. I forgot my lunch. I don’t know what I had to eat yesterday.” Their long-term memory is perfect. They can remember what shoes and dress they were at a wedding 10 years ago, but they can’t remember what they have for lunch yesterday. So, it could be a little bit about looking at the adrenals with Carrie in that pregnenolone.

Dr. Maki: Yes, and to be honest, like I said about the pregnenolone steal, a lot of PMS-related issues, whether it’s mood or physical symptoms, a lot of it is kind of a stress issue in the first place, right? So, the more pressure there is on the adrenals, the worse the female cycle is going to be. So, what things manifest as being a female hormone problem is a lot of times most of the time rooted in being an adrenal cause in the first place. So, make sure you’re sleeping well. Don’t exercise too much. Make sure your stress level is manageable, nothing crazy. And that will also help kind of ease some of those things over time as well.

Dr. Davidson: No, no, that’s perfect. But just to kind of answer Carrie here and probably a lot of people out there because I’ll have people say, “I’m on progesterone, I’m on bioidentical progesterone.” And then I looked at their bottle from the big box pharmacy and it’s Prometrium and I’d say, “Well, technically it is but there’s a lot of fillers and there’s that instant release.” Like I’d mentioned, there’s no magic “one pill fits all” so, I’d say for Carrie, she does sound sensitive. She’s not menopausal. She’s having a period, she’s cycling is she would do and I do think women that are cycling do much, much better on doing the sustained release compounded bioidentical progesterone capsule where, like Dr. Maki said, because I do have women on Prometrium and some of them do great but they’re all pretty much postmenopausal and we’re doing it for post menopause, not necessarily for a cycling female.

Dr. Maki: Yes. And just as a distinction, you cannot get bioidentical progesterone from a big box pharmacy. The big box pharmacies are not compounding pharmacies. So, if your doctor calls something in, if you’re requesting a compounded progesterone, but you still go pick it up from Walgreens or CVS. It is not a compounded progesterone. It is still a Prometrium or something generic. It has to come from a compounding pharmacy. And we work with a couple of different pharmacies that we have used for a very long time. We trust them, we like them. They make great compounds for our patients. Our patients have really good feedback about them. So, just where you pick your prescriptions up, or the type of prescription you pick up determines what pharmacy it’s going to come from. Everything for the most part at a commercial pharmacy like that is going to be a commercial drug. It has a branded name to it, it’s going to come in, like you said, for a Prometrium it comes in two doses, that’s it. Where when it comes from a compounding pharmacy, the doctor based on the patient, okay, basically, can make any prescription that they want or any dosage of a medication that they want. So, it really is tailored to the patient. I think that’s a huge benefit. You and I very rarely ever use big box pharmacies, we use exclusively compounding pharmacies for our patients because–

Dr. Davidson: For the hormones. 

Dr. Maki: Yes, right for hormones, because it’s that extra level of individualization that makes all the difference in the world, right? Hormones are an individual process. You cannot necessarily do a cookie cutter approach. All women don’t get lumped into the same category because their lives are different. Their genetics are different, their ages are different. They’re where they are in their lives are different, their goals are different. So that means their prescriptions have to be tailored to that, you can’t do it all “one size fits all” and with hormones absolutely does not work. So, anything else to add for Carrie or are we good with this one?

Dr. Davidson: No, no, thank you, Carrie. We’re going to send you a message to let you know we answered your question on the podcast and there’ll be some show notes and we are actually getting our podcast transcribed now, which I haven’t been able to read the entire thing because it makes me embarrassed and blush because I’m like, “That’s my voice but on paper.” But yes, so we also have the transcription for anybody that maybe wants to read it.

Dr. Maki: Yes. So, until next time, I’m Dr. Maki. 

Dr. Davidson: I’m Dr. Davidson.

Dr. Maki: Take care. Bye-bye.