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Welcome to The Modern Midlife Collective—where midlife isn’t a crisis, it’s a rebirth. Hosted by Dr. Ade Akindipe, DNP, and Dr. Jillian Woodruff, MD, this is the podcast for women ready to unapologetically own their power, thrive through the ups and downs of hormones, weight, and self-care, and show the world that thriving at 40 and beyond isn’t just possible—it’s your birthright.
Biweekly, we bring you science-backed insights on hormones, menopause, longevity, and sexual health—real tools to empower women in midlife and beyond. With a fearless blend of functional medicine, real-life wisdom, and no-nonsense empowerment, we’re here to challenge the norms, break through the barriers, and help you step into a life of vitality, confidence, and unstoppable strength.
Ready to rise? Let’s do this.
Jillian Woodruff MD (00:27)
Okay, today we are taking on a problem that doesn't get enough attention and that is progesterone intolerance. You know, progesterone is supposed to be the calming hormone, the one that studies estrogen, counterbalances it, supports sleep, quiets the brain, decreases anxiety. What happens when instead of calm, it creates chaos?
when women don't get the calm, but instead they get the mood swings, the bloating, the headaches, migraines, even bleeding. And progesterone is supposed to prevent vaginal bleeding, uterine bleeding, but they can get it instead.
Aderonke Akindipe, DNP (00:57)
Cool.
man, yeah, we hear it from women who start hormone replacement or they want to start hormone replacement with all of these hopes because they heard that it's helping their sister, their mother, their friend, only to find out that they felt worse on them. that just completely changes the picture. So women suddenly feel worse after starting it. They're irritable, they're anxious, tired. So it's not that you're making it up. There is some truth to what's happening here. And unfortunately,
There might be times when you're not tolerating progesterone. So we're going to get into more about why this happens. So the common complaints we hear include mood swings, irritability, breast tenderness, bloating, acne, headaches, dizziness, and even fatigue, even though you're supposed to feel more drowsy and be able to go to sleep with it, unfortunately, can cause the opposite effect when you're really exhausted.
Jillian Woodruff MD (01:52)
Let's add bleeding to the list because for some women, the very problem we're trying to prevent in postmenopause actually shows up. as we talked about last time, we need to take progesterone if you have a uterus specifically to protect the uterus from being stimulated or overstimulated from estrogen therapy. And one of the ways that
or symptoms that a woman may have that shows that her uterine lining is being stimulated is she has bleeding. So we're giving progesterone to prevent that from happening, but sometimes the exact opposite happens in women have bleeding. Now it may not be due to progesterone because even if they're taking progesterone, the things we're trying to prevent can show up. You can have polyps, you can have fibroids.
Rarely you can have a cancer of the uterine lining, even if you've done everything to prevent that from happening. So bleeding isn't something to brush off, but it is so frustrating when women are taking micronized progesterone because they love it, because it helps them with sleep. They're feeling relaxed. But unfortunately, every time they take it, the micronized progesterone, they also start to have bleeding. Why is this happening? It's so frustrating.
Aderonke Akindipe, DNP (03:10)
That sounds so frustrating. We see it all the time. Women experience things like constipation, as we talked about. It does kind of relaxes you, so it does relax the GI system, the gut. But others also get diarrhea. So progesterone naturally relaxes your smooth muscles, which also means it can slow down your digestion. Some people can get reflux. Again, this is all part of your digestion. So abdominal cramping, that's another one too.
So these aren't just in your head, they're real physiological effects of what progesterone can do to the GI tract. But not to worry, we're gonna dive deep on more of what you can do. Do not give up hope because it happened that one time there's other options.
Jillian Woodruff MD (03:55)
Right, right. And some of these side effects that people have can resolve with time. You know, they may just be from initiating a therapy and they may be very temporary side effects and sometimes they're not in their signal of that intolerance. Another thing that can happen though in those who are intolerant to progesterone is fluid retention and acne. So these are
normal things that we expect to happen, but unwanted intolerance issues. Progesterone and fluid retention or bloating is a strange one because progesterone initially can act as a diuretic. So it is actually very similar in structure to aldosterone, which is our fluid releasing hormone.
And so they can bind to the same receptors. so progesterone can bind to those receptors and lead to releasing fluids. So it could really help with it to feel less puffy, less bloated, less swelling, less inflammation, less joint pain. But sometimes you can have that opposite effect because when it binds to those receptors, it can prevent the real thing from binding. And then you can get the opposite effect and be more puffy, be more full of
fluid, stop releasing the fluid. So that's pretty frustrating to get the opposite effect of what we would expect. And then if you have swollen pores too and then oils get trapped inside, that can lead to acne. So just there are some things that are not unheard of, but they may not be well known to.
all people that are prescribing progesterone. And so sometimes women are just told, yeah, that's not from that. When indeed it could be.
Aderonke Akindipe, DNP (05:40)
Yeah.
Yeah. And I guess the next question would be, well, if we make these hormones in our bodies naturally, why this intolerance happened in the first place? So we have to remember when you take medications, right, they have to be metabolized in some way. Now with the hormone progesterone, the liver is the starring role. It's the star. So imagine if your liver isn't optimally working.
So if it's sluggish in the first place or you have other issues, maybe fatty liver, for example, you have nutrition deficiencies. If there's illnesses, if there's infections, if there's inflammation, you know, there's a lot of things that can really get in the way of how things are metabolized. So if you are taking certain medications that are also messing with how your medication is metabolized, then of course that amplifies the kind of side effects that you get.
So remember, the liver is a multitasker. It's not just dealing with the hormone, it's dealing with everything else. If you have a glass of wine or whatever it is that you're taking into your gut, your liver is having to deal with that too. So the liver's busy doing all those other things like processing alcohol, trying to get rid of the toxins. Progesterone can get caught up in that. So that's why sometimes those symptoms like bloating, fatigue,
or even headaches might be happening. And also depending on how that was, ⁓ if it was compounded in a certain way too, if you were really sensitive to maybe like a slow release one, you know, might feel groggy in the morning because you're on something that's slowly released. So that's going to stay in your system longer.
Jillian Woodruff MD (07:17)
Right, you you talked about alcohol and there's a lot of studies of longevity now which really show that there's no safe amount of alcohol for women. And this kind of is one of the reasons that to break down and metabolize alcohol, the liver has to do a lot of work.
And so when we're in vulnerable states, which I think low hormones is a vulnerable state. And so we are taking these other hormones, try to replace what we've lost. If your liver is working so hard on breaking down that alcohol and protecting itself from alcohol, then it's not going to be able to utilize those hormones very well. And so you may not get the good benefits of the hormones. You may not have the side effects either.
but you also may not get the benefits that we're trying to provide by replacing what's, you know, has declined. Another thing with progesterone, and we didn't get into this before, is that it is converted into a neuro steroid called allopregnant alone. And this is a natural substance that calms the brain and increases our sleep quantity and quality and decreases anxiety. But some women are extra sensitive to this.
And so when they have too much activation of these GABA receptors or calming receptors, it can actually cause like way too much sedation, dizziness event, and can actually have this weird paradoxical effect where you have more anxiety instead of feeling calm. So balance, we're always talking about balance. Balance is important. And for some, you may not be able to reach that balance with specific
forums of progesterone and progesterogens, I should say.
Aderonke Akindipe, DNP (09:06)
Yeah, and that's why it's really important for hormone health. You need to have that personalized approach to each woman because not every woman is the same. So you might have the same kind of hormones, but the way you metabolize, talk about metabolism, the kinds of receptors, some are more reactive than others. And some people will react more strongly towards it than others. genetics comes into play.
So that's why two women can't, don't necessarily be on the same dose and they can be on the same dose but have different experiences. You might need a hundred milligrams of micronized progesterone to get it done. Some women might need 200 and some probably, you you might need to compound that because it's just whatever you're getting from the pharmacy is just not. So that's why I think it's great that we have different tools to help different women.
out besides just being on the oral. know, sometimes if you, especially if you don't have a uterus and you're not relying on it for uterine protection, there's other forms that may not be metabolized through the liver, for example, that you can take that may help some of those symptoms. So it really takes a lot of work and trying what would work for one symptom or the other.
I think you had mentioned that you liked, is it the cream, the progesterone that you liked? Which one did you say at the last episode for different symptoms?
Jillian Woodruff MD (10:26)
You know, it, I probably use the cream the least. But I really like most all forms of progesterone because people are so different and some women are really more likely to experience intolerance to that oral micronized progesterone. We talked about this a lot, the bioidentical form of progesterone. Some people may be more likely to experience intolerance and there's specific people
Aderonke Akindipe, DNP (10:39)
Yeah.
Jillian Woodruff MD (10:55)
One of them are women with a history of PMDD, premenstrual dysphoric disorder. They are very sensitive to progesterone in general. There are, there's one or two progesterone types that they may be more, or less likely to have side effects from, but it's not for everyone, even in their synthetic, there's synthetic
Aderonke Akindipe, DNP (11:04)
Yeah.
Jillian Woodruff MD (11:19)
progesterones or synthetic progestins that people with PMDD may be less likely to have side effects to. But it is something you have to be really careful with. And sometimes they do not tolerate hormones that activate their central nervous system in that way, so their brain. so oral micronized progesterone is one that is very likely to activate things in the brain.
which for many people give them good side effects. But for PMDD, we may want to do one of those synthetic progesterones or they may not do any progesterone at all because they can't tolerate it. But if they're on estrogen postmenopause, they do need a way to help the uterus actually or to prevent uterine growth and stimulation of estrogen. So what I use a lot are
progesterone-releasing IUDs. And there are progestins that are being released. It's a synthetic local progestogen that's being released in the uterus to protect it from stimulation from estrogen. But you're not going to get any of those, you know, benefits that we like from oral micronized progesterone, but not all people are seeking that. Or you may have to get those benefits from
something else, a different type of supplement or medication.
Aderonke Akindipe, DNP (12:38)
And that's why your health history really matters. Because trying to determine how your body processes and response to hormones, looking at your family history, looking at your labs, what's your liver function, all of those things really matter in how to predict. At least that's part of the story. I think hearing this episode right now, let's say you're thinking about going into hormone replacement, I think the biggest thing you can take out of this is
When you're starting, just be very patient. Understand that there's a lot of nuances, there's a lot of trial and error, and then always paying attention to those symptoms that you're experiencing and bringing it up to your provider, writing them down. Hey, I noticed X, Y, and Z can be very helpful in determining the best path forward. So it does, just because you failed with that particular one, doesn't mean that there's no other options out there. And I'm sure Dr. Jill, we're gonna talk more about the different forms and you know.
differences between the different forms and when to use them, especially you mentioned IUD.
Jillian Woodruff MD (13:36)
Yes, that's right. And so sometimes you can't take a fully systemic progesterone. You may have to do something that's more local. Another issue I can think of are people who have Ehlers Danlos, which is a connective tissue disorder. There are different types. So some people are the hypermobile ones. I can like bend their joints in.
in different positions, but not all of them are hypermobile. But with progesterone or progestogens, because they do relax smooth muscle and there's receptors for progesterone all throughout our body, high dose progesterones, progestogens are
usually not tolerated in this group of people. So it is good that we have other options, even if our favorite would be the bioidentical oral form. So I think it is important to talk about the different formulations, but I would say to go back and listen to episode 16, because we do go into detail about the different forms of progesterones and also we talk about the difference between progesterone, progesterone and progestin.
really just progestins is synthetic progesterone. It's a synthetic progesterone, but progesterone is really just talking about our natural form. And then progesterone is an overall umbrella. But I understand the different names and I unfortunately also interchange them incorrectly. So we'll keep my.
We did give you the real definition so that you can correctly use these terms, but you may just want to say natural progesterone and then synthetic. But synthetic's really called a progestin. So we have oral forms of both. We have oral natural progesterone that's identical to what our body makes. That's the oral micronized progesterone. And then we have synthetic
progestins, and there are various different oral types. But there are vaginal types. There's injectable types, those are typically only used for people who are going through fertility treatments. There are local types. So just putting an IUD, an intrauterine device, into the uterus releases local progestin. There is topical.
There's topical that you have compounded topical versions are not commercially available at CVS, Walgreens, your drug stores and the grocery stores. not available there. They have to be from a compounding pharmacy. There are also some over the counter progesterones, which do not actually, they may not have the active ingredients in them.
They may, they're usually made from wild yam, so they may act a little similarly, but they are not bioidentical products. And then even with the oral form, you can get compounded oral forms that are made differently than the one that's commercially available. So for example, if you have an allergy to peanut, oral micronized progesterone is made with peanut oil, so you can get one made without peanut oil.
Also, sometimes people have problems where the time period is a really quick acting medication, the oral micronized progesterone, it wears off quickly and they may need ⁓ a slower, longer release. So there's ways to get all of these things made as well.
And then I think, we talk about them all?
Aderonke Akindipe, DNP (17:14)
I believe we did. I mean, we did talk about progesterone creams in our previous episodes that can also be compounded from compounding pharmacies. And you talked about counter, the over-the-counter ones, but some of those, like you said, don't necessarily have what you actually need, which is the hormone in it. So what if you are taking the progesterone, let's say you go to the doctor's office, you got this prescription and you're feeling miserable on it. Here are some things that you should do.
And I don't want you to go do this by yourself, talk with your provider about this, but you may need to lower the dose. Sometimes if you have a lower dose, you'll tolerate it just fine. Sometimes the route might need to be switched from oral to maybe vaginal. Maybe it's just the way, you know, it's metabolizing your body, you're not responding well to it. Or like Dr. Jill says, you might need to try an IUD. Changing the regimen from cyclic, where you're kind of
on it for a little while and off of it to continuous taking it or vice versa. Maybe you're taking it too much, continuous is too much for you and just making it more cyclic would work for you. And if you've had a hysterectomy and you're not tolerating the forms of progesterone, then if you're not really benefiting from it, then maybe you don't need it at all. So if you don't have a uterus and you're taking it and you feel awful, then you don't need to be on it.
If sleep is an issue, there are lots of other options for sleep that will help you instead.
Jillian Woodruff MD (18:36)
Right, because let's say you've had a hysterectomy, you can't tolerate the oral micronized progesterone, which you were prescribed for those other benefits. So you're prescribed to help you with sleep, to decrease anxiety, maybe to help with hot flashes or night sweats, especially in perimenopause, you may not be on estrogen therapy yet, actually. And so you may be starting progesterone to help with these symptoms.
If you're not getting the benefit and you're only getting side effects and you don't have a uterus, then there's no reason to try these other right formulations. When you don't have a uterus, you can't get an IUD. You don't need to be taking it topically or anything, right? But if you do have a uterus, then yes, we need to do something that's going to protect that uterine lining and see if we can by even decreasing the dose, you can still get benefits, the other benefits from
Aderonke Akindipe, DNP (19:07)
No need to torture yourself.
Jillian Woodruff MD (19:29)
⁓ a lower dose or a higher dose depending on what the issue is. Yeah. And then timing matters. So taking oral micronized progesterone at night, it does help you with sleep, sleep quality, but sometimes you were too groggy in the morning and maybe they have allowed themselves an adequate amount of time to sleep, but they still have this daytime fatigue. And so it may be that we just need a lower dose.
But you want to make sure you're taking the dose that you need for your uterine protection if you have a uterus. And so you may want to split the dose. You could take a lower dose and take half in the morning, half at night, or take a dose in the morning that doesn't cause sedation and then take your sedation dose. You know, you're more sedative. It's weird to say sedation because you're not going to be really sedated, but you'll be calmed. So take your calming dose at night and your non...
calming dose in the morning. So sometimes I have to get compounded medications for people who have a uterus, they need uterine protection, but sometimes people feel too sleepy on the dosage that leads to uterine protection. So I can compound them a dose that is like a sublingual dose that doesn't have those same effects.
Even there's some nasal dosages that you can do, nasal formulations. Yeah. Have you used those?
Aderonke Akindipe, DNP (20:47)
Yep.
love the sublinguals,
the sublinguals if they're having, some women will have that anxiety, especially during the day. That's when those perimenopausal symptoms really kick in and it's like you can't take that oral micronized during the day. So compounding the sublingual gets that, know, it goes, I guess it just bypasses everything and you just get it straight through and you're getting the benefits of that calming without the drowsy effect. So.
Jillian Woodruff MD (21:14)
because you could have absorption issues. And so when you're taking something via your GI system, some people do not absorb things as well. And so actually that brings you back to the bleeding because we mentioned bleeding before and I know I have patients that unfortunately they do have postmenopausal bleeding when they go on their progesterone. And so then they want to stop it, of course, because they're like, every time I take it, I bleed, which is not what is supposed to happen.
Aderonke Akindipe, DNP (21:17)
Hmm.
Jillian Woodruff MD (21:41)
And so I just want to go through like some potential causes of that. So it could be that the dose is not enough. So even if you're on the dose that's typically enough, it may not be enough for you or it could may not be taken long enough. So sometimes that cyclic regimen where you just take it for two weeks a month, that is done typically to have a withdrawal bleed. So people in perimenopause, have a period.
withdrawal bleed when they come off of it after they take it for two weeks. So that's typically not something that somebody wants in postmenopause. It doesn't always happen in postmenopause, but it can. So like you mentioned, you may want to switch from cyclic to continuous. Your dose may not be strong enough. You may need a stronger dose. But on the other hand, the dose may be too much for you. In postmenopause, your
your if you're taking estrogen, can stimulate the lining. So we need to have enough progesterone or progesterone in order to counteract that. But sometimes it counteracts it too much and makes the lining too thin. It's kind of fragile and it just starts to shed in a haphazard fashion. And so you can have all of this really annoying spotting. So you may not be bleeding heavily, but you're bleeding nonetheless.
And so that may be that a lower dosage is needed or a different formulation. You could have just that your body isn't absorbing the typical dose and even if you're going up, it's not absorbing it orally. So that's where other populations could come into play. And then synthetic progesterones are more potent. Synthetic progestins are more potent than natural progesterones. So some women do have to
change to a synthetic progestin if they have a uterus that needs protected. But if I'm going to change to a synthetic progestin, then I'm going to prefer to do something that is not as systemic, meaning something that's just working where I need it to. So that would be the intrauterine device. And I think you said this in this episode as well, the transition period. So just in your first year of starting hormones you could have bleeding. that, did you say that tonight?
Aderonke Akindipe, DNP (23:51)
We might have mentioned it in previous episode where if you're in continuous therapy, regular bleeding or spotting is common just because of the uterine lining adjusting to that.
Jillian Woodruff MD (24:00)
Right. you know, bleeding, especially if you're having vaginal bleeding postmenopause, you have to have it evaluated. it may be, you know, okay, you may be at those first few months, but you definitely want to tell your medical provider because in some situations, they may say, let's monitor this for a bit, but you don't want to sit on something that could be a uterine cancer or atypical cells, hyperplasia.
or you have a fibroid that's growing or you're forming polyps that need to be removed. So you want to make sure that you're actually closely being followed and being evaluated when necessary.
Aderonke Akindipe, DNP (24:41)
We have spent a lot of time talking about progesterone and why? Because it's something that we see quite often in practice where there are different scenarios in the ones that you just brought up, especially the fibroid situation. And I know one particular woman who just wanted to keep going up on their progesterone dose. And I said to her, said, we need to look further into what's happening. might get some imaging done. You have a history of fibroids.
A lot of different things can cause bleeding. You don't want to just continue to just, you know, mask things and just continue to escalate dosing without looking into it. So if progesterone is making you feel worse and not fixing the problem, like we said, don't ignore it. Don't let anyone just dismiss it. You do have options. We talked about changing dosing. We talked about different formulations, different metabolism, supporting your liver.
so that you're eating good nutritionist foods, consuming less alcohol, which we should be anyway if you're navigating midlife, you gotta be very careful about that alcohol intake. And careful medication review can improve how your body handles progesterone. So if we give you a bunch of paperwork in the beginning to fill out is because we wanna know all about you so that we can help you make an informed decision on...
⁓ how to start with hormone replacement if that's what you choose to. So if you're feeling worse on progesterone and it's not in your head, ask your provider, can we try a different dose, a different route, a different formulation? And if you're just giving that one option, it might be time to seek someone else that can think outside the box and get a little creative because just because this is just one FDA approved method doesn't mean that there aren't other options.
For off-label, we talked about sublingual, which has really helped some women really calm that daytime anxiety. You don't have to take it during the day, the oral micronized one, if that's the problem. Just, you know, do you need to do it all? You know, don't have a uterus and somebody's putting you on progesterone because it has great benefits. But if it's making you feel awful, then you probably don't need to have it. You don't want to be miserable. You deserve options.
Jillian Woodruff MD (26:46)
And keep in mind that it can take time. I think that by the time women come to me, they may have seen other people, they may have shared some of the symptoms that they're experiencing. And so they're like at the end of their rope, right? And so they want to feel better. Yesterday, of course, but it takes time. It takes time. I always say it's starting your journey when you're starting.
Aderonke Akindipe, DNP (27:07)
Yeah.
Jillian Woodruff MD (27:13)
hormone therapy because the symptoms didn't, you know, the menopausal or perimenopausal symptoms did not happen overnight. All of them didn't just bam, hopefully. And so they don't just go away like that either. And then also when you're initiating therapy, you may have interesting side effects that may just be from initiating therapy and may not last. So you do want to give it time to resolve. And sometimes it could be eight to 12 weeks before
You're noticing. wait, I okay that has gone away and now I'm I'm really feeling a change So I typically when I make a change in hormones don't check those levels again for 12 weeks and I don't always check progesterone levels so Maybe and I don't even at the beginning sometimes I don't check for gestural levels, but there is utility to checking it You know, especially if there's
issues that would lie along that route of what progesterone could help with or cause. So I think if you have been complaining of symptoms or talking to your provider about symptoms, you may need to get a second opinion if you're not having any resolution.
Aderonke Akindipe, DNP (28:25)
Absolutely. With the right adjustments, whether it's the dose delivery or timing, you can still take progesterone safely. So we're not trying to scare you out taking progesterone. It's just knowing what's safe, what's comfortable. So the key is listening to your body and advocating for care that fits you. So we know many of you have strong experiences with progesterone, good and bad. We'd love to hear from you. Please email us at modernmidlifecollective.com or
You can DM us with your story. We'd love to hear from you. We may do a follow-up many episodes sharing your experiences and answering some questions. So thank you for listening.
Jillian Woodruff MD (29:01)
Thank you, bye.