Can Progesterone Cause Anxiety?
Often we get reader/listener questions about their own experience with hormones. We love that readers of our blogs and listeners of the podcast (TheProgressYourHealth Podcast) reach out for more information. If they have concerns and questions, that means many, many other people have the same concerns. A lot of questions we get are hard to get answers online.
Honestly, hormones and hormone replacement is an art that should be designed around the patient. Every person taking hormone replacement has different reasons for doing so. Those hormone goals can range from weight loss, mood improvement, insomnia, bone density, energy to sex drive just to name a few. Those of you that are regular listeners/readers, I’m sure, have heard this from me a thousand times over. And I will continue on that soap box, so bear with me.
Hormone replacement is not a cookie-cutter approach where one size fits all. It needs to be tailored to the individual. This article is about a recent podcast that we did on a reader question. I feel this is an interesting question because it is about hormone replacement therapy, but there are so many nuances to tease apart. When talking about hormones, everyone is focused on the estrogen and progesterone dosing and not considering the other hormones involved that could be part of the issue.
Here is the question (we always change the names of readers and listeners to protect privacy).
From ‘Kathy’
Hi Dr. Davidson.
My question to you, is what do you suggest if a woman is on Biest and can’t take the Prometrium because it has the opposite effect and gives her anxiety?
Yes, she has a uterus, yes she is on Biest, but what if cream is her only option? Thanks in advance 🙂 – Kathy
There is a lot to tease apart here, but let’s explain a little more thoroughly about the hormone regime she is on.
Biest is an estrogen combination of estriol and estradiol. There are three main estrogens in a female’s body. Those are Estrone (E1), Estradiol (E2) and Estriol E3). Estrone is not commonly used, and it is mainly seen in younger women going through puberty or is made by adipose tissue. Adipose tissue is ‘fat’ tissue, and yes, your fat is like its own endocrine gland, secreting other hormones and estrone (lepton, adiponectin to name a few popular ones).
Biest is part of bio-identical hormone replacement, meaning the estriol and estradiol are made from plants to look exactly like what our own bodies make. So if it looks just like what our bodies make, then it will have a better response and fewer side effects.
Kathy is taking a Biest cream for her estrogen replacement, which is commonly used as a cream. She applies her biest cream topically, also called transdermally. You can apply your hormone cream to the inner thigh or back of the knee. Because all hormones are fat-soluble, and the inner thigh, as we all know, has an excellent fatty pad there, making it a great site. Applying hormones to thin tissue like the inner arms, can cause quick absorption and then it is eliminated from the system quickly. Plus, inner arms means you could share it when you hug or touch or carry pets or other humans. Some research shows that the neck and face are excellent places for transdermal absorption. But if you love giving kisses to your pets, little ones or family, you could end up sharing your hormones.
As Kathy mentioned in her question, she could not tolerate the Prometrium (an oral form of progseterone), and she has a uterus. The reason she mentions this is because it is essential to take progesterone anytime you are taking estradiol/estrogen therapy and you have a uterus. Estrogen loves to grow things, especially the uterine lining. If Kathy did not take progesterone and only took biest (estriol/estradiol), it would be a matter of time before her uterine lining started to increase. This can cause spotting, abnormal uterine bleeding, a period, and an increased risk for uterine cancer.
If you have a uterus and are taking estrogen therapy for hormone replacement it is important to take an oral form of progesterone. The oral form protects the lining much better compared to the cream. I do not think it is appropriate to take progesterone cream when taking estrogen therapy because of the risk of thickening the uterine lining. I do not prescribe less than 100mg of oral progesterone when a woman is taking a form of estrogen therapy and has a uterus. Some women may need a higher dose of progesterone, such as 125-200 mg, or even a little higher. But it really should be oral
progesterone. It was asked of me if a progesterone troche could be a replacement for oral progesterone. A troche is a sublingual tablet/gel tablet that you put under your tongue or the side of the cheek of your mouth. It is meant to be sublingually absorbed. Meaning a troche would not be an oral form of progesterone. I have found that the troches are absorbed sublingually, but there is an oral component of it as some of it will be swallowed. But even still, I do not think a troche could protect the uterus as well as a oral form.
There are a few options here.
One, would be she just could not take biest. At least in my practice, I would not feel comfortable prescribing any estrogen/estradiol therapy without oral progesterone to protect the uterus.
Two, find out if it is the oral progesterone causing the issue. I have run into this issue in the past with patients. And all the time, we find a way to take oral progesterone or find out if it is something other than the progesterone causing the anxiety. I will get into this more later in this article.
Three, let’s do bio-identical hormone replacement as rhythmic dosing instead of static dosing. The biest that Kathy is taking is considered a ‘static dose.’ Meaning she applies/takes the same dose daily, and it doesn’t change. Rhythmic dosing for estrogen and progesterone is taking the hormones in a cyclic dosing so that it mimics that ovarian natural hormonal rhythm.
You take both the estradiol and progesterone as a cream, but the doses change throughout a 28-day cycle. It basically mimics the natural hormonal changes you would see in a 28-29-year-old female. In this case, the rhythmic dosing would create a monthly period. So the estradiol would thicken the uterine lining, but it would be sloughed off every month, just like a period. So there is never a long-term accumulation of the lining in the uterus. In static dosing, there should never be any spotting, bleeding, or a period.
I have run into this issue where a woman takes oral progesterone and has anxiety. There are a few issues that could be the culprit.
It could be the Prometrium that she is taking. Prometrium is considered bio-identical progesterone. But it could be the fillers, binders, or excipients in it that she is reacting to. If she were sensitive to a filler, it can cause any side effect you could imagine from
digestive distress to rashes to yes, even anxiety. Prometriums are made with peanut oil. Anyone sensitive to peanuts, ever thought they were sensitive to peanuts, thought they reacted to peanuts, or dread to think, allergic to peanuts, do NOT take Prometrium.
Instead, take a compounded progesterone made in a compounding pharmacy, where they can make sure to use fillers that you are not sensitive to.
Prometrium is an instant-release formula, and that is what Kathy is taking. Meaning that as soon as she swallows it, it goes right into her bloodstream. It could be the instant release it could be stimulating to her. Ideally, progesterone is supposed to lower cortisol and stimulate GABA. But the quick, fast, instant release could be causing a rebound of her sympathetic nervous system, causing cortisol levels to jump up and anxiety.
Ideally, oral progesterone is supposed to be taken in the evening. The evening could mean a lot of things. Personally, I am a baby, and go to bed at 8:30 and try to be asleep by 9:15 (beauty, sleep, ya all!). But other patients I have are night owls and stay up until 2 am. The last time I stayed up to 2 am was in college, and a few times (okay, every weekend), I went to dance clubs; yes, we are talking techno and 90’s dancing. Meaning that taking your progesterone at 8 pm is much different than taking it at 2 am. So, if a woman is complaining about anxiety after taking the progesterone, I have them taking it at a different time. Take it at 7 pm and go to bed at 10. It could be taking it so close to bedtime is just not enough time to let the body get into a parasympathetic state.
Yes, Prometrium is a commercially available form of bio-identical progesterone. But there are so many differences, as I mentioned above. Progesterone compounded can come as a sustained release instead of the instant release Prometrium. Sustained release is slowly absorbed and rises gently as you sleep and then drops before you wake up. I have found switching to a sustained release progesterone can help immensely with anxiety as well as sleep and the mood the next day. So honestly, my first suggestion for Kathy is to switch to a sustained-release compounded progesterone. That way the fillers she might be sensitive to are eliminated and it doesn’t instantly rise in her system after she takes it.
The dose of the prometrium could possibly be causing the anxiety Kathy is experiencing. Prometrium comes in 100mg and 200mg. It could be the 200mg is too high for her or the 100mg is too low for her. Unfortunately, you can only do 100mg or 200mg with prometrium. If she were able to do the compounded we could do any dose we wanted. Perhaps a 125mg or a 150mg she could have a better outcome.
The bio-identical hormones, inparticular the biest (estriol/estradiol) do not have a long lifespan in the body. Usually it lasts about 12 hours in the system. If Kathy were taking her biest cream once a day, that could be the issue.
If she were taking it in the morning by the time the evening comes around the biest would be out of her system. Which that can cause hot flashes. I have a lot of woman that hot flashes will cause anxiety and panic attack. I have even had quite a few women mistake a hot flashe for anxiety. I would make sure that Kathy was taking her biest twice a day (am and pm) and also taht the dose was enough for her. Checking this with her symptoms and blood work would give us good insight into if her biest dose needed to be adjusted.
Remember when I said that the progesterone could be causing a cortisol rise? Ideally, progesterone is very relaxing. It stimulates GABA and is suppose to balance cortisol levels and helps with sleep.
But progesterone can convert to 17-OH-progesterone. And 17-OH-progesterone can convert to cortisol. It would be a good idea to test Kathy’s 17-OH-progesterone and cortisol levels to see if this is the case. Not everyone converts progesterone to
17-OH-progesterone. Some very little and others there is very high conversion. That is because there is and enzyme called, 21-hydroxylase enzyme that some people can be deficient in. I won’t continue to bore you with all of the science, but it would be a good idea to check her 17-OH-progesterone and cortisol levels.
This could be another reason to switch Kathy to a sustained release. Again, another theory, and something I have noticed in practice perhaps is when taking a instant release such as Prometrium, that huge bolus of progesterone entering the system could trigger a immediate fast conversion to 17-OH-progesterone. The body is very smart. It sees a bunch of progesterone and is not quite sure what to do with it, then just converts to 17-OH-progesterone which then converts to cortisol causing anxiety.
I want to send appreciation to all of our readers and listeners for sending in their questions. If you have questions about your hormones, trust me, there are many others that have the same concern. It is great that we can all help each other and also know that we are not alone in our hormonal health.
If you have any questions, feel free to reach out and send us a message on, Ask The Dr.
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Tracy’s Question:
Episode 052 – What Biest Ratio is Best for Menopause?
This is such helpful information. I have often wondered who 80:20 is good for and who 50:50 is good for.
One thing I'm still confused by is the estrogen weight gain component. You said that estrogen (as well as menopause in general) could be the cause of her weight gain. I can relate. I was very thin my whole life, now 53 and about 30 lbs overweight. But you also said she might benefit from getting her estrogen balanced, and she was not using enough.
If too low a dose made her gain weight, won't an increased dose cause more weight gain? I have heard other podcasts and read articles that in menopause, we gain weight because our estrogen falls. Estrogen seems to be blamed for weight gain, whether it's high or low. Can you help clarify? There's something I'm not understanding. Thank you! Tracy
Short Answer:
Often estrogen has been the scapegoat for weight gain. I'm sure you have heard too much causes weight gain. Too little can pack on the pounds. It can be pretty confusing. So which is it? Is too much estrogen causing my pants to become uncomfortably tight? Or is it too little estrogen that has given me the gut I never had?
Well, it’s not that simple. Estrogen levels do have a hand in weight gain and weight loss. But it is not the only variable. It really is the combination of the balance of estrogen with other hormones in your body. To name a few main players, progesterone, insulin, and cortisol, as well as enzymes, lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL). Okay, I know that sounds vague and doesn't answer the question. Let's back up a bit and look at what women are saying about estrogen.
As soon as menopause hits, women complain that they are instantly 15-30 lbs heavier. Not because of diet or lifestyle. It's like menopause adds an unwanted 15-30 lbs overnight. Then some women are on hormone replacement therapy, taking estrogen, and are horrified because the HRT caused them to gain 10 lbs in a month. So what is it? Did the lack of estrogen in menopause cause that 20 lb weight gain? Or did that hormone replacement estrogen create rolls that were never there? Well, actually, both are true. Before you throw out your jeans in favor of high-waisted yoga pants, let’s learn about the other players in weight gain.
Progesterone will buffer estrogen. Estrogen does like to grow things'. That is why in puberty, you grow breasts and hips. Progesterone helps to balance some of the growth' that estrogen can cause. That is why in perimenopause, when the progesterone drops and the estrogen is running the show, the weight gain begins. That is also why when a woman starts estrogen therapy for menopause but not enough progesterone, there is weight gain.
Cortiso
‘Doc, I really don't feel like myself. I think it's my hormones. Could it be my hormones? Can you test my hormones?'
How many times have I heard new clients tell me this story? They go to see their GP, Gyno, or Internist, asking to have their hormones tested. Only to be told that there is no testing for hormones. Or that it's not necessary to test hormones. Only to leave feeling dismissed, with no answers to why they do not feel well.
While I understand that your GP, Gynocologist, and Primary Care Physician are not the jack of all trades,’ there are many tests for hormones. There are blood tests, urinary testing, and even saliva testing. The more difficult part of hormone testing is the interpretation. The basic lab values assigned by the labs are very vast, and without experience and training, it can be quite difficult to determine if there is a hormone imbalance.
If you are feeling like you have a hormone imbalance or having symptoms concerning your hormones, below is a list of common hormones to be tested and why. Because blood lab testing is so popular, I am going to stick to blood testing. Later we will have more labs and interpretations for urine and saliva.
To start, blood testing is just a look at one moment in time with respect to your hormone levels. In a menstruating woman, her hormone levels are changing every day. But in a menopausal woman where the ovarian function has ceased, her hormone levels are going to be pretty level day to day. So in a female that is still having her period, I like to try and aim for getting the blood drawn around day 12 and/or day 21. In a 28-day cycle, the estrogen will surge around day 12, and the progesterone will surge on day 21. This can give us better insight into her levels of progesterone and estrogen. In a menopausal woman that has not had a period or has sporadic periods with common menopausal symptoms, I will have her draw her blood any time of the month.
FSH and LH:
FSH stands for follicle-stimulating hormone, and LH stands for luteinizing hormone. These are not actually hormones. They are stimulating hormones.' Meaning both the FSH and LH are released from the pituitary gland (in your brain) in response to estrogen and progesterone production. The FSH and LH work in what is called a negative feedback loop.’ Meaning if the levels of estrogen and progesterone are high, then the FSH and LH are low. In turn, if the estrogen and progesterone levels are low, then the FSH and LH are high. It is like when you want your husband to take out the garbage. If he doesn't, you might raise your voice until he does. It is the same with all stimulating hormones. If the ovarian production of hormones is low, as in menopause or perimenopause, the FSH and LH levels will look high.
Estradiol and Progesterone:
Always test estradiol to get specific results for estrogen levels. Estradiol is much more specific for estrogen levels than simple total estrogens. Ideally, in a menstruating woman having the blood test around day 21 will give you insight if that woman is ovulating. It will so give you insight if there is progesteron
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