Jillian Woodruff MD (00:26)
All right, today's midlife myth is this. If you don't have a uterus, you don't need progesterone. Absolutely a midlife myth, right? Modern medicine tells us a different story. Progesterone's role does not end with the uterus. Yes, progesterone is essential to protecting the uterine lining from overgrowth when women are on estrogen therapy postmenopause. But that doesn't tell the full story. And so that's what we are here to talk about today.
Aderonke Akindipe, DNP (00:57)
So yes, I think it's important for us to have this conversation because oftentimes when women come in, you know, we have to make sure that we are giving you the evidence and we know more that, you know, just because you don't have a uterus doesn't mean you don't have the benefits for progesterone. So I know that we're going to be diving deep into this so that you don't have to be confused. And when you are being told the wrong thing, you know exactly because you've heard it here.
Jillian Woodruff MD (01:20)
Right, right. Okay, so let's start with why does this myth exist? Well, yes, for women that have a uterus and were on hormone replacement therapy, traditionally, women had to be on progesterone if they have a uterus and are taking estrogen. And that is still true today, for the most part. So estrogen has many benefits. Of course, you we love estrogen as well.
The estrogen also stimulates the uterine lining. So this is really important when we are menstruating and trying to prepare for having a baby because estrogen thickens that lining, preparing it for pregnancy. After menopause, this isn't necessary, right? So whenever you're preparing for pregnancy and you're having periods, you also shed that lining every month. So you're building and shedding, building and shedding.
After menopause, you're no longer having periods, so you're no longer shedding your uterine lining. So if you're taking estrogen, that uterine lining just continues to build and thicken. And if not shedding, if it's not shedding, which it shouldn't be, then that puts you at risk for an overgrowth of the lining, atypical cells, and even cancer. So what do we do about this? We give progesterone, which really counteracts
the effects of the estrogen at the level of the uterus and it prevents that overgrowth without necessarily needing to have the outward show of bleeding and have a period. So it is preventing estrogen stimulation of the lining and thus decreasing your risk of uterine cancer. But there's more to it.
Aderonke Akindipe, DNP (03:05)
Absolutely, and that's the key word right there is counterbalance, right? So everything kind of I look at hormones as working in symphony. So if there's some kind of imbalance, you know, it'll wreak havoc in some way. So if we're going to be treating you with estrogen, we've got to make sure that you are getting the opposite counterbalancing hormone with it. So that's where progesterone comes in. So estrogen stimulates growth, like Dr. Jill says, it changes how endometrial cells grow, telling the lining, OK, you need to stop growing now.
Right? And it starts to stabilize things. So ⁓ that stabilizing signal is where what keeps, you know, your the hypoplasia we call or your cancer risk in check. So it's not necessarily that hormones cause cancer. You also don't want to increase your risk of having cancer. So that's why it's important that we're when you have to take hormones like that, you know, when you're if you don't have whether you have a uterus or not, you are prescribed
systemic estrogen therapy so that you can have those benefits.
Jillian Woodruff MD (04:10)
Right. And there's two main ways that you may be prescribed progesterone if you have a uterus. And one may be cyclic and the other is continuous. And neither is right or wrong. There's just different approaches for different providers and different approaches that work for different patients. So a continuous dosing would be that you are taking some form of progesterone every single day.
So regardless of if you're having periods, not having periods, perimenopausal, postmenopausal, continuous progesterone therapy may be given. Other people, usually people who may be taking progesterone during perimenopause, but yes, some women after menopause also do a cyclic dosing of progesterone, which is just taking progesterone for about 12 to 14 days each month.
And this is kind of mimicking your menstrual cycle that you have in your reproductive years. So you're taking progesterone during the lydial phase. So that is two weeks leading up to the period. So right after ovulation, leading up to the period, that's when you have this high progesterone and then people typically will withdraw from progesterone. Their progesterone levels fall and stimulates a period. And so some providers do like to
mimic that cycle and give you progesterone only for 12 to 14 days a month. And during postmenopause, you don't know when that phase is, so they kind of just mimic it by just choosing, you know, maybe the first 12 or 14 days per month. I'm not a fan of cyclic dosing. To me, typically people don't want to mimic the symptoms that they have with their regular cycle, right? If it's an impairment of pause, usually your symptoms may be
Aderonke Akindipe, DNP (05:58)
I
Jillian Woodruff MD (06:03)
exacerbated so I feel like it could exacerbate it more. What do you find?
Aderonke Akindipe, DNP (06:08)
Yeah, absolutely agree. I personally started having perimenopausal symptoms my 40s, early 40s. I'm going to be 45 now. And I tried that and wasn't really a fan of it. I think the continuous allows me from all of those benefits that I get from progesterone, just like the calming, you know, the brain not shutting off. That's one of the symptoms I had. So doing it continuously helped with sleep.
help calm the mind so that you can fall asleep and stay asleep. So I know that there are some people, I think people that struggle with those symptoms of it's not coming to me right now, but around the time of their periods tend to do better when they cycle it. But for me, when it comes to perimenopause, if you're constantly having all of these symptoms, know, night sweats, hot flashes, know, anxiety.
I think it's great to just take it every day and see how that helps you out. Now the form of it, which we're probably going to get into a little bit more, is what's going to also matter too.
Jillian Woodruff MD (07:14)
Right, absolutely. And I think, you what you just said was it some women may need it for this purpose or other women need it for a different purpose. So if you were prescribed to take it in this cyclic fashion half the month, doesn't mean that it is wrong. It's just not a personal preference of ours. But it could work for certain people in different situations. And if you were prescribed it continuously,
you know, that's absolutely fine. It's the dosage and the mode that you're taking that are going to be important. And then I think we should get into that because you brought up the sleep and relaxant properties of progesterone. So this is like the first thing that we're going to use to really knock this myth out, you know, that it's only for people who have a uterus.
Progesterone is metabolized into a neuro steroid. So that's just a steroid that acts in the brain and it activates our GABA receptors, which is like a, like a switch to relax us. And so when this switch is activated, we are able to sleep more. We have decreased anxiety. We have better quality of sleep. So it's not even just that we get a longer amount of time to sleep, but
the quality, making sure we're in that deep restorative phase of sleep is important. So these GABA receptors get activated. And this is typically with a form of progesterone that is called oral micronized progesterone. It's a bioidentical progesterone. So we've discussed bioidentical before, but just to recap, this is a chemical structure that is structurally identical.
to the progesterone that our bodies make. So it is not a little different, which is synthetic. The chemical structure is a little different, but it mimics what our body does in some ways. Whereas this bioidentical form is identical in structure. And so it should act identically as our hormones that we naturally make would act. So this is neurobiology at work.
Taking it in the oral form of micronized progesterone, which is the bioidentical progesterone, leads to this relaxing, calming, anti-anxiety feeling. So this is why it's typically given at bedtime. And this is another reason why the cyclic form may not be best for some people who are taking it because it's helping with that sleep. Do they want to sleep?
twice, you know, two weeks of the month or every night of the month is my opinion. And it also, ⁓ the other thing it does too is it helps with our vasomotor symptoms. So these are hot flashes and night sweats and things especially that plague women in perimenopause and postmenopause.
Aderonke Akindipe, DNP (10:14)
One thing I love about this hormone is that, you know, women are already battling so many other perimenopausal symptoms because of hormone decline. And one of those things that starts to happen is we are actually at more risk for of higher inflammation. When we start to lose our estrogen, that leaves room for, you know, gut changes, you know, the kind of bacteria that's in your gut and things like that. So progesterone.
can help in that it kind of helps in the immune system. It tones down inflammatory signals. So things that women will complain about like joint pain, they're tired, it's really hard for them to recover from exercise when they're trying to exercise. And also even your cardiovascular risk, where the older you get, if you're not careful, especially with these hormone changes, you're at risk for cardiovascular disease, so heart disease. So.
cardiovascular risk, those inflamed joints. It also helps with bone. Progesterone receptors sit inside osteoblasts, which are basically precursors to kind of help with bone growth. So bone building cells, by activating that, progesterone will help with bone remodeling, which is really important as you get older. Of course, hormones is just part of picture. There's other things you got to do to help with bone, but that's where estrogen and progesterone really help.
so that you have that foundation for midlife and beyond. And since cardiovascular disease is the number one killer, those vascular effects really matter. if you think about it, if you're not sleeping very well because you lack estrogen, you're constantly stressed out, those also increase your risks. it's really important to consider it if you wanted to think of hormone replacement therapy, it supports circulation.
So over time, that contributes to balancing out your cardiovascular system, especially when combined with estrogen.
Jillian Woodruff MD (12:11)
Right, combined. And you mentioned earlier the counterbalance and estrogen and progesterone, the yin and yang, they kind of, they work together in so many ways. You brought up the bone and I love this because we focus so much on estrogen in building bone and we kind of negate the progesterone role and the testosterone role in your bone density, really.
And, you know, thinking about our bone and how bone is laid down and how we're laying down, we're building bones until midlife, really. And then we just don't want to lose that bone, right? So it's really difficult to build it after that. But the natural cycle of bone is taking away and rebuilding, taking away and rebuilding. So if someone has low bone density, we need to slow the taking away and increase the rebuilding. And that's how estrogen and progesterone work.
together to decrease the taking away and increase the laying down of the bone tissue. the same with, you know, inflammation. Inflammation is huge. You start having all sorts of random symptoms in perimenopause. And so having progesterone to really help with that inflammation is something that everyone could use, not just somebody that has a uterus.
Aderonke Akindipe, DNP (13:35)
I can attest to that.
Jillian Woodruff MD (13:35)
as many people have, right? Historectomies
and things for different reasons. And so, what? They could still use it for all of these other purposes.
Aderonke Akindipe, DNP (13:45)
Absolutely. So yeah, the key is not it's not a blanket rule. You don't have a uterus. It's a case by case decision based on your symptoms and goals. So ladies, you're on estrogen, you have no uterus, you've heard it here, you can absolutely be on it because of all the benefits we just talked about.
Jillian Woodruff MD (14:04)
Yep. Now, if you've had a hysterectomy and you're not on estrogen therapy and you don't have sleep or anxiety issues or perimenopausal or postmenopausal issues, okay, you can skip progesterone. If you decide to start estrogen therapy and you don't have any other symptoms or maybe you couldn't tolerate progesterone, well then,
You know, lucky you, you can skip the progesterone. But is it a blanket statement that because you don't have the uterus that you should skip it? No, I wouldn't say you should skip it. Progesterone should be an option for everyone unless there's some sort of contraindication of why you can't take it. But it should be an option whether you have a uterus or not. And there's benefits whether you have a uterus or not.
So I think we should go into progesterone because there's a lot of terms that people use, progesterone, progestogens, progestins. Do you want to talk about that? You have me to talk about that.
Aderonke Akindipe, DNP (15:03)
Yes, a lot. Yeah.
I mean, there's a lot of confusion. to be honest, before I got into hormone therapy and got into the world of really understanding what it means, there was so many terms. So people say progesterone when they might actually mean progestin. And I think we need to make sure that we clear that up because it really matters and how your body is using it. So let's set the record straight now. So progesterone, progesterone, O-N-E at the end of that is the natural
hormone your body makes. So it's mostly from your ovaries. In hormone therapy, when you're given the, we call it the exogenous, it's outside of the body, it's not made inside your body, but we're giving it to you. It's like oral micronized progesterone. So that's the most bioidentical version of what your body normally produces. So it has the same chemical structure.
I like to think of it as a lock-in key. There's this one key that fits in this door, so it fits together really nicely. Same receptor binding, right? So progesterone is just a general term for progesterone kind of hormones. So it includes both the bioidentical one and all the other, we can call it synthetic ones because they don't look like the chemical structure of the micronized progesterone.
Progestin refers only to the synthetic versions. you might have seen things on your commercials on TV like Provera or Madroxyprogesterone acetate. Say that 10 times faster. Madroxyprogesterone acetate. You might see norethendrone, levonorgestrel. These are...
different forms of progestins that you might find in IUDs and birth control pills and things like that. So these are slightly different in the chemical structure than our natural or bioanatomical hormones when they were made. They are made to act very similar to protect the uterine lining, but don't actually, they don't really act like the natural progesterone in the brain or elsewhere.
Jillian Woodruff MD (17:19)
Right, right. So all progesterone is a progestogen, but not all progestogens are
Aderonke Akindipe, DNP (17:25)
Yes.
Jillian Woodruff MD (17:29)
Well, let's move on to the various ways these progesterones are used in practice. So we've mentioned many times the oral micronized progesterone, and that is an FDA-approved bioidentical progesterone that's commercially available at your regular pharmacy. So whatever.
you know, big box pharmacy go to, you can pick up this prescription there. It comes in 100 milligrams or 200 milligram capsules. And it's usually taken at night because it does make you feel sleepy. So, oral micronized progesterone is also quite short acting. So, it should be gone. Those central nervous system effects of that sleepiness should be gone by the morning if you've allowed enough time to sleep in the evening. If you're taking it late in the evening.
then you may still be groggy in the morning. But if you allow enough time for sleep, then you should be fine. Important note, it is made with peanut oil. So if you have an allergy to peanuts, then this would not be the form for you to take. Also, just like any other medication, even though it is a bioidentical, there are fillers in this medication. And some people
may be sensitive to whatever fillers are in there. like, you know, there are medications that are made, a lot of medications actually are made with corn. I'm not sure about this one, but in general, some people may have sensitivities to different fillers that are in medication. So when people have reactions or side effects, I always want to check into the fillers and whether it may be to that and not actually the active medication.
Then there's the synthetic ones that you just mentioned and synthetic, there's synthetic oral progesterones as well. The ones that we may be most familiar with are the ones that are in birth control pills. Those are all synthetic forms of progesto, progestins. They're all synthetic progestins, look at me. The important thing to know about
progestins is that they are much, much more potent than bioidentical progesterones. Potency, the strength they bind to the receptors much stronger. This doesn't mean they are better in any way. It just means that they are stronger, more potent. And so their side effects also may be more potent or more unlikable, I guess. So something to keep in mind.
Micronized progesterone is, they've done multiple studies to show that it protects that uterine lining. Synthetic oral progestins, of course, also definitely protect the uterine lining because they are so potent. But you may not get, or you probably don't get those same benefits that you would get from the oral micronized form, nor do you need that much.
protection, I guess, of the uterine lining. So just to give you an idea of the potency, the oral micronized, like norepineurone acetate, it's like five milligrams is equal to 200 milligrams of oral micronized progesterone. So it is much stronger. So there's going to be some trade-offs with that and some more off-target side effects that you may have.
And then importantly, like I said, doesn't get metabolized to the neuro steroids. You're not getting that calming effect. There's also vaginal progesterone. So I don't know if you use vaginal progesterone, Dr. De. I quite like it for certain people. These are off label when it comes to using it for uterine protection. But many things we do in medicine are used off label.
These are what I recommend actually if we're using a vaginally, it's just that same oral micronized progesterone. You can put that right into the vagina. And the reason I would use this in people is if they don't tolerate taking medication orally or don't have good absorption orally, but also the trade-off is you don't get those good sedative side effects that you may really need or want. But.
like I mentioned, the oral form of the micronized progesterone is short acting. And some people may need something longer acting or may need more coverage, 24 hours. And so they could use vaginal in the daytime and use oral at the nighttime. We're almost done. There's also progesterone releasing IUDs. There's several progesterone releasing IUDs of different dosages from a very high dose to a very ⁓ low dose. So that's another way to get
These are synthetic, like I said, and they're inserted into the uterus and they also provide uterine lining protection, but also the other venus that we talked about, you don't get. And then there's topical forms. There's topical.
Progestogens, this is tricky because you can get topical forms compounded at a compounding pharmacy, and not all compounding pharmacies are the same. They have different regulations. So you want to, of course, trust your medical provider, and they need to trust a pharmacy and know about their safety regulations because they're different. They're all different. So you can compound progesterone and natural bioidentical progesterone.
been used at. These are not to be relied on for uterine protection though. So these would be for some of the other benefits of progesterone. They tend to be sequestered in fat so there is some decreased absorption issues going on with it. And then another thing to be careful of is that there is also progestogens that are over the counter. You can get them without a prescription.
And they are not actually true bioidentical products, meaning they may not actually have that active ingredient in them. So you want to look for a product that says USP so that you can make sure that you're getting something that is truly bioidentical. I don't know what experience you've had in that.
Aderonke Akindipe, DNP (23:43)
No, I think this is great because I think it's important, like you said, to point out what the difference is between bioidentical and synthetic. And more importantly, why are you taking this progesterone? Because some of them, like Dr. Jill said, do not provide uterine protection like the topical progesterone cream. You can't rely on that. So if you're not tolerating the oral form, but you're taking it for uterine protection that
cream is probably not the best way and hopefully growing to a provider that understands that and doesn't just offer you the cream to try to protect your uterus because that's probably not a lot reliable. So yes, I absolutely agree. And I think that ties down into what we're going to talk about next, which is dosing for women with a uterus who are using estrogen. So the two main ones that we are we know are backed up by evidence are one, which is continuous combined.
⁓ estrogen plus at least, we say at least, 100 milligrams of oral micronized progesterone at nighttime. So over time, most women who are still menstruating stop having monthly bleeding. Those spotting is normal in the first year. remember we talked about balance, right? So you're taking the estrogen, you're balancing it out with micronized progesterone.
So if you, let's say you were in menopause and you were on hormone replacement therapy and you started to have breakthrough, what we call breakthrough bleeding, that might mean that you probably need more of that micronized progesterone to balance that, unless you really want the bleeding, which is not good. You don't want that. you want to make sure that there's good balance there. So there's more likely that you're going to need more than a hundred milligrams of that.
Jillian Woodruff MD (25:21)
No.
Aderonke Akindipe, DNP (25:32)
The other one is Cyclic, ⁓ estrogen plus 200 milligrams micronized progesterone nightly for 12 to 14 days per month. You you take it during the second half of the cycle, which kind of mimics that luteal phase, that natural second half of your menstrual cycle. You know, that's for people who want to mimic that natural cycle of you have the bleeding, you're basically on your period. So it leads to a more predictable withdrawal. We call it withdrawal bleed.
which some women prefer. So that's, really depends on you. And this is why, you know, hormones, you know, it's, it's really personalized. It depends on what you, what's going on with you, what symptoms we're treating. Are you in pre, peri, post menopause? But it's important that any of these methods, we're looking at the safety profile, you know, for you as well. You know, what's your, your family history, what's your medical history, what symptoms you're having to figure out which one of these
progestergens would be appropriate for you.
Jillian Woodruff MD (26:34)
What do you find? find as far as dosing, you know, I do like the continuous dosing, but as far as the dosage, even though 100 milligrams may be enough to protect the uterus, I find a lot of people need the 200 milligrams for the other benefits, mostly the sleep and anxiety benefits. What do you see in your practice?
Aderonke Akindipe, DNP (26:55)
Absolutely.
Most often, and this is just anecdotally from treating women, it's just that hundred, I find that that hundred is not getting enough of all of that. Sometimes they'll say they still have problems just shutting down at night, or maybe it'll work in the beginning and it doesn't work anymore. So they just need a little bit more of that. So oftentimes I think 200 would work just fine.
Jillian Woodruff MD (27:17)
Right.
Yeah, I agree. I agree. And sometimes more. Sometimes I have women that are on more. Yeah. And that's fine.
Aderonke Akindipe, DNP (27:28)
yeah, I've seen more. Absolutely. Yeah. Yeah. At what point though,
and I think people would probably want to know, is when progesterone is considered too much.
Jillian Woodruff MD (27:38)
When you have side effects that you don't like, but also if you're having good absorption of that progesterone, then sometimes it can actually make that uterine lining too fragile. So if you have a uterus, it can make it really toothing. And sometimes you can have bleeding from it be toothed. And it's so interesting with these hormones too, because sometimes the symptoms are the same if the hormones are too high or too low.
Aderonke Akindipe, DNP (28:05)
All right.
Jillian Woodruff MD (28:06)
So balance is important
and balance is controversial because some people say there's no such thing as balancing hormones, but there sure is. It may be difficult to do or challenging, but when you're balanced, you'll know it because you're not going to have these side effects. And with progesterone, even oral progesterone, which has a lot of benefits, there's side effects that can show up that...
Aderonke Akindipe, DNP (28:16)
It sure is.
Jillian Woodruff MD (28:33)
you know, you may want to stop it because of these side effects. some of them are GI side effects. Progesterone, we talked about before, kind of relaxes your, it relaxes smooth muscle. it helps to prevent or decrease our risk of cardiovascular disease. But in relaxing smooth muscle, you think about relaxing the smooth muscle in the GI system in your intestines. And so if it's too relaxed and there's less motility of the gut,
this can lead to some reflux or constipation issues. We see this kind of thing in pregnancy, but in pregnancy, your progesterone levels are so high, much, much higher than they are with 200 milligrams of oral micronized progesterone. And so in pregnancy, some women do have that, you know, heartburn, reflux, constipation for sure. With synthetic progestins, like we mentioned, they are much more potent than oral micronized progesterone.
So those side effects are going to be more pronounced in someone who's on synthetic progestins where they may most likely don't have those issues with oral micronized progesterone. It's a very well tolerated medication for the most part or hormone for the most part. But in some, you certainly could have it. Also in some people may have mood changes that they don't like and have bloating and may have breast tenderness.
Whereas the majority of people, have less breast tenderness when they're on progesterone, but it can work the opposite way. The same with headaches. So these are things that would be on your intolerance list that you may have a side effect that you may be able to alleviate with a different formulation or a different dosage and sometimes not. But these side effects are going to be more pronounced, like I said, with synthetic progestins.
Aderonke Akindipe, DNP (30:25)
Yeah, absolutely. think this great to see that wide profile of what could happen if you were not tolerating it or if you had some side effects. You mentioned peanut allergy. So that's something that we'll probably not even think of, right? But yes, this is something that it's made in peanut oil. So women, if you have peanut allergy,
Jillian Woodruff MD (30:41)
Mm-hmm.
Aderonke Akindipe, DNP (30:50)
can definitely find alternatives and it might need to be compounded. There are different varieties again, but we have to make sure that you're going to a trusted compounding pharmacy. And then the second is that compounding hormones can be very useful when you're using a non-peanut base, which, you know, they might have different fillers or even long acting formulations. And I've seen the long acting formulations in some women that just feel like maybe the immediate release, just the normal one you would get from the pharmacy isn't working for them.
And in some cases, it'll work. But I also err on the side of caution to make sure that if you've got a uterus, you've got to make sure that we are treating appropriately, that that lung acting isn't causing problems and not giving you urine protection. So it just requires a lot of follow up and talking to your provider. Not all compounding pharmacies are the same. We have to worry about regulations, standards.
all of that. So it's important to go to a provider that's knowledgeable and you trust and make sure that they're working in conjunction with pharmacies also that they trust.
Jillian Woodruff MD (31:53)
So let's come full circle. Today's midlife myth was if you don't have a uterus, you don't need progesterone. And while it's true that the uterus no longer needs protecting, that's not the whole picture, progesterone, progestogens, I should say, they, well actually progesterones, play beneficial roles in the brain, the bones, the blood vessels, even the immune system.
So progesterone has many other uses than protecting the uterus.
Aderonke Akindipe, DNP (32:27)
Exactly. Modern medicine, which I love so much, shows us that progesterone isn't just a sidekick to estrogen. We talk so much about estrogen, but there's other hormones like progesterone that have vital jobs. We talked about cardiovascular disease, sleep, anxiety. A lot of times women are just diagnosed and given prescriptions that they don't need. Maybe it's just hormone imbalance that they can just get replaced.
Jillian Woodruff MD (32:35)
.
Aderonke Akindipe, DNP (32:54)
start to feel better. So it makes a ⁓ huge difference in women's lives, even if you have no uterus. So that's why blanket rolls don't work. What works is individualized care.
Jillian Woodruff MD (33:07)
That is right. Okay, so Dr. Day, let's take this deeper. I think we should do another program and explore what happens when our beloved progesterone itself becomes the problem. So you're right. Yes, I think we should, because this so-called calming hormone can become chaos in our bodies sometimes too. So we can't just share the good parts. We have to share.
Aderonke Akindipe, DNP (33:23)
wow, we're going to dive deeper into this. There's a lot to tell. There is a lot to tell.
That's right.
Jillian Woodruff MD (33:36)
All right, so we're going to make it for next time, right?
Aderonke Akindipe, DNP (33:36)
Thank you so much for next time. Definitely. Please tune in. Thank you for joining us and we'll see you next time.
Jillian Woodruff MD (33:43)
Great, bye.