Danielle’s Question: So, Thank you for this article. I’m having side effects from taking 200 milligrams of oral progesterone. I take forever to wake up and feel really, really groggy. I read where you said that take it early and when I take it early and out in an hour, I can barely keep my eyes open and feel drunk or drugged. So, I usually take it in half an hour before bed. I sleep like a rock but have a hard time coming to the next day. I’m a lightweight when it comes to any medication and always thought that might be due to being clean and sober for 32 years, but I might be wrong. I’m probably just sensitive. So, should I try a hundred milligrams of oral progesterone or change it to a compound? Because currently, I am taking Prometrium. I really love the solid sleep, but it takes hours to wear off in the morning and it seems like I’m just so tired. But I do take thyroid medication and I do have low morning cortisol and take some adrenal glandular as well. So, thank you so much in advance.
Short Answer: The commercially available form of progesterone is called Prometrium. It is an instant-release medication and comes in two doses of 100 mg and 200 mg. In our experience with patients, they tend to be strong for women and not well tolerated. It is not surprising that 200 mg is causing next-day fatigue. We typically prescribe 100 mg of bioidentical, sustained-release progesterone. Some women are still sensitive but is usually very well tolerated.
PYHP 112 Full Transcript:
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 this morning we’re going to just kind of dive right in. Of course, as we always do we have a lot of listener questions. So, for the future or for those that are listening, if you’re new to the podcast you can always send us an e-mail at [email protected], [email protected]. That is if you want to keep it somewhat private and discreet. We always change everybody’s name. So, there’s no question about who is sending in the question. You know, we do get sometimes some sensitive female issues. And I’m sure people wouldn’t want that to be kind of public knowledge. So, like I said, we do try to protect everybody’s privacy as much as possible and we love the questions because that means we know people are listening. And you know, it gives us kind of an unlimited amount of topics that we can discuss in the podcast. So, Dr. Davidson won’t you just kind of dive in and let’s go through Danielle’s question.
Dr. Davidson: Sure. Sure. So this question is from Danielle, but just on a quick little side note is we love all the questions. So, if you have any concerns, please write into us. But at the same time if it’s maybe not exactly like a lot of the questions were doing or pertaining to. You can probably hear our little pup in the background. He always gets a little more, I don’t know. When we do the podcast he gets a little more rambunctious or something.
Dr. Maki: Every time. He’ll be sleeping and then we sit down to do these and he turns into a maniac.
Dr. Davidson: He’s the best, he’s the best. But if you have any topics that you’re just interested in like, “Hey, it’s not a question necessarily pertaining to me, but I’m interested in this particular topic.” So, feel free to if you want us to talk about topics or questions about yourselves or whatnot because we do really feel like this information can help others. Like, in particular, Danielle’s question. So, I’m going to jump right into Danielle or “Danielle”. So, “Thank you for this article. I’m having side effects from taking 200 milligrams of oral progesterone. I take forever to wake up and feel really, really groggy. I read where you said that take it early and when I take it early and out in an hour, I can barely keep my eyes open and feel drunk or drugged. So, I usually take it in half an hour before bed. I sleep like a rock but have a hard time coming to the next day. I’m a lightweight when it comes to any medication and always thought that might be due to being clean and sober for 32 years, but I might be wrong. I’m probably just sensitive. So, should I try a hundred milligrams of oral progesterone or change it to a compound? Because currently, I am taking Prometrium. I really love the solid sleep, but it takes hours to wear off in the morning and it seems like I’m just so tired. But I do take thyroid medication and I do have low morning cortisol and take some adrenal glandular as well. So, thank you so much in advance.”
Dr. Maki: Yeah, this certainly comes up quite often, to be honest. We run into these either questions or patient issues. Now, she makes the, you know, as you’re reading it, she makes the distinction at the end of the question compounded versus Prometrium. We don’t use a lot of Prometrium. We have some patients that either requested or do okay with it or want it. We don’t usually read out of the gate, prescribe it on at least from our standpoint. But we do have some that seem to do just fine on it. And I know you said before, there’s like two doses of either 100 milligrams or 200 milligrams. What’s the difference between Prometrium and compounded progesterone?
Dr. Davidson: You know, they both are progesterone and in compounded has a lot of different fillers. Prometrium actually has a lot of kind of weird fillers and excipients that people can be sensitive to. Some Prometrium’s have peanut oil in there. So, somebody’s allergic to peanuts. They could have an issue with that. So, I would say, you know, I do actually have a few patients on Prometrium, they do really well. And then I have a few that I put on Prometrium and they don’t do really well. And I think partly is because with Prometrium there’s very little room for changing doses. There’s only a couple of doses available. So, you know, 200 milligrams of oral progesterone is a lot of progesterone. So like, she’s saying, should I drop to a hundred, because Prometrium also comes as a 100. When you do compound, little cleaner. So, it’s more hypoallergenic. And at the same time, you can do any dose you want to. You can do 10 milligrams. You can do 50 milligrams. You can do 75 milligrams. You can do 85 milligrams. You can do 125 milligrams. You can do 150. You can do 400. There’s so many different doses you can do when you’re doing it with compound and like Danielle said is that she’s sensitive and I do think a lot of us are sensitive because in some regards when you’re doing hormone therapy, it’s not one size fits all.
Dr. Maki: Yeah, right. Yeah, and you know, the other distinction too is that Prometrium is instant release where what we typically use, the compounded is sustained release. And that tends to kind of dial it back a little bit. It’s not quite as strong. Now, the good news is like I said, she’s sleeping like a rock that’s in some ways the reason for taking oral progesterone right, because it certainly does help with the sleep. But you know, clearly, if she’s having that much hard of a time waking up, she could easily try the 100 milligrams per [inaudible]. She might do just fine on that, but you know, our preference are biased in some respects would be to, just go to a 100 milligrams of bioidentical progesterone and start from there and see. Because you still get the same sleep benefit, sleeping like a rock but not so much grogginess the next morning that would be at least from our standpoint or at least from my standpoint the obvious thing to try.
Dr. Davidson: And Danielle’s right, taking progesterone does make you tired. It does make you sleepy. So, that’s why it’s great to take at night. It helps with sleep, you know, progesterone itself helps balance out if she’s taking any kind of estrogen. So, you know, there are a few markers here that we don’t know. We don’t know, is Danielle doing bioidentical hormone replacement? Because she’s menopausal in her 50s and taking some type of estrogen. Then, of course, yes, she needs some level of dosing on progesterone to balance out that estrogen. But maybe she’s more perimenopausal and she doesn’t need any estrogen, but she needs that progesterone because in perimenopause that progesterone just basically floors itself. So it could be that, you know, I always feel like less is best. Start off at 50 milligrams. How is she doing? How is she sleeping? Go up to 75 or double it up to 100. She might be, I have some people that are perfect at 125, not good at 100 and not good at 150. So, it really is a little bit individualized, but to further maybe complicate this is I love to do blood work on progesterone. When you’re taking an oral progesterone at night, there shouldn’t be too much progesterone when you do your blood draw the next morning. So, if she’s doing, taking 200 milligrams of this Prometrium at night and then she does a blood draw, say at 8:00 in the morning and her levels are pretty high like up. Like I’ve even seen people in their 20s, that might be that that progesterone is too high that it’s really staying too high in the morning which would make her tired. So usually, when I’m doing progesterone and doing blood work with progesterone, they take it the night before, maybe they go in sometime in the morning between 7:00 and 10:00 o’clock in the morning. It really should be around, you know, maybe 10:00 or maybe somewhere around there may be a little less than 10:00 because over that I do find the people have a little bit tough time waking up in the morning.
Dr. Maki: Yeah. Sure. Usually at least with bioidentical progesterone sustained release, I typically see it, you know, maybe between 2:00 to 12:00, you know, 2:00 to 8:00 something like that. Now, a menopausal woman taking progesterone, oh, a menopausal woman not taking progesterone. On lab work her progesterone is always going to be less than one. It’s going to be .5, .6, .7. In some ways this is, and I know we’ve talked about this on some of the other Biest or estrogen episodes, when she’s taking progesterone, that’s in some ways, kind of how we know she’s taking it. Because one of our rules, again, if you’re new to the podcast is you never give a woman unopposed estrogen. Now, granted if she has a uterus that’s an absolute rule. If you know, even some kind sometimes a gynecologist, a woman doesn’t have her uterus. They’re not so concerned about the progesterone, but that’s still a rule that we don’t typically break. We’ve always give women both of them. Just because of this, the progesterone does help on the sleep side, helps reduce anxiety, it helps level out the mood. So, oral progesterone still does provide some of those benefits than just taking estrogen by itself. So, the combination of those two certainly has to be taken into consideration. But you know, I’ll throw it back to you. I kind of lost my train of thought there. So, I’m trying not to stumble [crosstalk].
Dr. Davidson: We’re all human, right? We’re all human.
Dr. Maki: I’m trying not, you know, we usually do these without really editing or doing much of them.
Dr. Davidson: Never edit.
Dr. Maki: And I just ran into a wall there. So, I’m going to stop and I want to let you kind of take over.
Dr. Davidson: Well, there is something to be said because I don’t want to confuse everybody but Dr. Maki had mentioned sustained release versus instant release and Prometrium is instant release. So, what I usually find with Prometrium is people take it and it wears off too fast and they’re waking up at 2:30 in the morning and they can’t go back to sleep, which is why I do really love the sustained release. And just for full transparency, I take a sustained release progesterone at night and Dr. Maki is very very grateful for that.
Dr. Maki: I think you need to increase your dose. I say that all the time. I’m just teasing. You don’t need to change it. You’re fun. You’re perfect.
Dr. Davison: Well, thank you. Thank you very much. But I would say with Danielle, she’s taking this instant release and it’s still lingering in her system the next morning, then she’s right. It’s probably just a little bit too high. I would imagine she’s probably not on a Biest because she doesn’t mention that. She mentions the low cortisol and that she’s taking thyroid and adrenal glandulars. So, if she were on Biest or some kind of estrogen therapy, she would have told us on this question. So, I would say reducing that down maybe even keeping it to an instant release because I haven’t back just yesterday, a patient that I have on sustained release progesterone. It is lingering too long when she wants to wake up early at 5:00 in the morning that we’re going to switch it to a compounded instant release. You know, not Prometrium, but I have a different dose that I want to do because like I mentioned with compounds, you can do any milligram you could possibly even imagine. You know, tailored to fit that particular individual, but I would say for Danielle is just backing it down a little bit. And one thing that I actually want to turn back to Dr. Maki, is Danielle mentions that she has low morning cortisol.
Dr. Maki: Yeah, right. Yeah. So, I was a little awkward there a second ago and I had a little lapse there. [crosstalk]
Dr. Davidson: Stop. We’re human. Okay. [crosstalk]
Dr. Maki: But you know, it’s interesting. We used to start doing these, I would get, you know, that would be kind of like a moment to stop and then do it all over. But you know what, you know, who cares? It’s easier. It’s kind of, it’s more conversational. So again, I apologize for losing my train of thought. But lowering cortisol, you know, so I would assume maybe before the progesterone, now we’re just speculating completely here about Danielle’s case, was the morning tiredness, was that present before the progesterone? Or is it just present after starting the progesterone? Now, low morning cortisol that’s what gets us out of bed bright-eyed and bushy-tailed. It needs to be high in the morning, that’s what helps control our circadian rhythm. That’s really important and very common in this day and age to have low morning cortisol. And then in some ways now you’re not sleeping well at night. No, she says she’s sleeping like a rock. So, maybe up till the progesterone, she wasn’t sleeping very well. So, now her body is just a little bit of a transition process because we work with a lot of perimenopausal, menopausal women that the sleep that they have accrued over months and potentially years. It takes a while to work through some of that. Okay. Now, she does say she’s sensitive and so starting at 200 milligrams, obviously. And, oh, that was my point of the thing I was going to say earlier is usually what we would do in a case like this is start them at a lower dose. Let’s say, a 100 milligrams. That’s inappropriate dose for a woman in perimenopause or menopause and we just give them the autonomy to say, you know what after a couple of weeks if your sleep is unimproved, if you’re not noticing any benefit then just take 2 capsules, right? So, now you get a chance to see, they get some autonomy, they get some control over what they’re doing and they get a chance to see how they feel. And believe me, obviously, I’m not a woman. So, there are some things that I don’t understand about how women experience certain things, but a woman, and you could probably explain this a little bit better. A woman knows when there’s taking too much progesterone. They just know, right? You know, they’ll ask what are the side effects like, “Well, you know, you could have this, this or this”, but usually, you’ll just know if it’s too much and then that’s your body’s cue to say, okay, it’s time to reduce the dose. So may 200 in this case, clearly 200 is too much so they can go back a 100 or try something different.
Dr. Davidson: Exactly. And I’m thinking that because she sounds very savvy because she knows about low morning cortisol, you know, not everybody knows about that cortisol. Coming from the adrenal glands, being a diurnal curve. Not a lot of people know that and it sounds like she’s taking some adrenal glandular which is great. So, I would say really that progesterone or that Prometrium at 200 milligrams probably is just too high.
Dr. Maki: Yeah. Yeah. I mean, we’re trying to extrapolate and kind of stretch this question out so we can kind of touch a few different basis. But it’s pretty obvious, 200 milligrams, she can’t wake up. Lower the dose. Just start go to a 100 milligrams Prometrium and see what happens. If that’s still too high, now you still have another option and with the compounded progesterone you have like you said from a dosing perspective you have unlimited options. Now, the point that you made earlier, if she’s on estrogen, you want it to be at roughly, a 100 milligrams minimum of the compounded progesterone. Again, to inhibit the growth of the uterine lining. That’s kind of where we stand. We might go down to 75 for someone who’s sensitive, but we won’t go any lower than that for the most part. And wouldn’t you say 75 is kind of like the cutoff?
Dr. Davidson: Yeah. I have a few people but really, if they have a uterus and they’re on some kind of estrogen therapy, you don’t really go under a 100. And really a 100 is kind of like the usual dose. Very honestly, I have very few people on 200 milligrams of progesterone. I have quite a few on a 150. They do really good on a 150. A 125 seems to be kind of also that perfect number where that progesterone is not too low, but it’s not too high. And then, of course, you got to think about, you know, like Danielle’s saying, she’s sensitive and also she is 105 pounds or a 155 pounds. There’s also a little bit of mass versus dosage.
Dr. Maki: Yeah. Sure. And certainly, liver function, you have to take that into consideration. Some people just don’t detoxify things as quickly and especially if there’s wine and alcohol. Excuse me, alcohol and coffee on a regular basis that can put a little more burden on the liver and kind of slow down some of that detoxification as well too. So, yeah. In this one, it relatively is pretty straightforward. Just try a lower dose, see what happens. But you know, certainly, there’s, in some ways, a lot of different possibilities to maintain that sleep which then will help those adrenals kind of rebound in the morning. Now granted, with usually people have that hard time waking up. Sometimes they’re never great at waking up. But at least they can wipe the cobwebs out a little bit quicker and it doesn’t take them so long to feel somewhat normal, right? You might wake up a little groggy, but once you’re up, you’re up and then you’re fine. You know, so hopefully, that’s what she’ll experience once she tries a new dose.
Dr. Davidson: And then like I had mentioned maybe doing a little bit of blood work would be a great idea just to check the estrogen and progesterone levels in the morning.
Dr. Maki: Yeah. Yeah. Yeah. Like I said, that was what I was getting at earlier when you give a woman estrogen, progesterone and you can kind of tell because that menopausal woman, she’s not going to make any progesterone, right? So, her number is going to be really low. The perimenopausal women would make progesterone based on the time of the month, that it is, right? If it’s, you know, after ovulation, she might make some. If it’s before ovulation, she’s not going to make any so that number is going to be less than one as well. So, the timing of when they go in certainly does make a difference based on the period of life that they’re in. So, Dr. Davidson, do you have anything else to add about Danielle’s question, or are we good for now?
Dr. Davidson: No, this is great
Dr. Maki: Okay. Until next time. I’m Dr. Maki.
Dr. Davidson: And I’m Dr. Davidson.
Dr. Maki: Take care. Bye-bye.
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In this episode, we’re answering a thoughtful (and very relatable) listener question from Kari, who’s been struggling with unexpected body pain and inflammation after starting hormone therapy. She wonders if she might be hypersensitive to estrogen—something most doctors don’t talk about. Dr. Valorie Davidson and Dr. Robert Maki unpack why this happens and what to do if you suspect your body is reacting to estrogen differently than expected. In this episode, we discuss: Why some women experience increased pain, fluid retention, or inflammation on estradiol—especially starting at higher doses too quickly. The importance of starting low and increasing slowly, especially for sensitive individuals How Dr. Davidson’s personal experience with estrogen sensitivity helped shape her approach The role of the liver’s phase 1 and phase 2 detox pathways in clearing estrogen metabolites Why form, dose, and timing of hormone therapy (cream vs. patch, AM vs. PM) can affect results What to consider when adjusting your Biest ratio (80:20 vs. 90:10) or Rhythmic Dosing HRT ✉️ Here’s Kari’s full question: “I used Biest 80:20 for 3 years and suddenly stopped absorbing. I’m not sure why, but I do know I didn’t always use it the same time every day. From the moment I went on hormone therapy I’ve had body pain and thought I had fibromyalgia. When my estrogen dropped due to the absorption issue I realized the body pain completely went away. I then went on a patch because my doc said we should change the method. Immediate body pain again and even worse. Terrible. I was on 0.025 and it was tolerable, but after raising it to 0.05 it got really bad. I think I may ask to go on the compounded cream again—maybe change the site that I apply it and be more consistent. I’m very frustrated because no one talks about a subset of people that are very sensitive to estrogen. They only talk about it making joint pain go away. Do you think I should use 90:10 instead? What would you recommend that I do? I’m so sad and frustrated.” If you have a question, please visit our website and click Ask the Doctor a question. Want more insights like this? Be sure to subscribe to our newsletter for hormone Q&As, educational guides, and real-world strategies to help you feel like yourself again—especially during perimenopause and menopause. Join the Progress Your Health Newsletter Stay Connected Instagram: @drvalorie TikTok: @drvaloried Join the Hormone Community: Click here to subscribe Disclaimer: All content in this blog, including text, images, audio, video, or other formats, was created for informational purposes only. This video, website, and blog aim to promote consumer/public understanding and general knowledge of various health topics. This content is not a substitute for professional medical advice, diagnosis, or treatment. Please consult your healthcare provider with any questions or concerns you may have regarding your condition before undertaking a new healthcare regimen. Never disregard professional medical advice or delay seeking it because of something you have read on this website. If your healthcare provider is not interested in discussing your health concerns regarding this topic, then it is time to find a new doctor.
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