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.
All content found in this blog, including text, images, audio, video, or other formats, was created for informational purposes only. The purpose of this website and blog is to promote consumer/public understanding and general knowledge of various health topics. This content is not intended to be 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 and before undertaking a new health care regimen. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. If your healthcare provider is not interested in discussing your health concern regarding this topic then it is time to find a new doctor.
Other Related Episodes:
Episode 118: When Should A Woman Take Progesterone?
Discover the common and unfamiliar symptoms that you might be experiencing. Get access to cases of real women with hormonal conditions.
In this episode, we talk about hormone treatments for perimenopause and menopause. There is a vast distinction between perimenopause and menopause when it comes to treatment options. We often see women who are being treated for menopause when they are genuinely not in menopause. Meet Linda: Linda is a listener who sent us a question […]
Recently, Catherine posted a question on our website about Biest cream, and we knew this could interest our listeners. Biest is a combination of estriol and estradiol, one of the most common forms of estrogen therapy used in bio-identical hormone replacement. There are many doses, ratios, options, and methods of using Biest, so we thought […]
Welcome to the Progress Your Health Podcast! This is a podcast that helps you learn about balancing hormones, especially during perimenopause and menopause. We love hearing from our listeners. If you have a question, please visit our website and click Ask the Doctor a question. Let’s read Brigitte’s question! I have been listening and learning […]
In this episode, we talk about the difference between perimenopause and menopause. Both Dr. Maki and I (Dr. Davidson) have worked with women in perimenopause and menopause since 2004 and sometimes get a bit myopic and technical when it comes to explaining the differences. The other day, a patient of Dr Maki’s asked the question, […]
We recently got a great question from a listener and want to share it with you. This question is about a perimenopausal 51-year-old female. She is still menstruating and having confusion about her hormone testing and the hormone therapy that she is currently taking. She is experiencing some breast tenderness and irritability related to her […]
in this episode, we answered a listener’s question. We love questions from listeners. If you have a question, please visit our website and click Ask the Doctor a question. Here is the listener’s question: I have been perimenopause for at least 4 years now I am 47 and after completing a Dutch test with a […]
