Progesterone: A Side Effect

As long as I’ve been reading and listening to the work of Ray Peat I’ve been hearing that progesterone has no side effects.  Progesterone is “safe in large amounts (except…can be anesthetic if hundreds of milligrams are taken at once),” Peat himself said to me in an email.

I beg to differ.

The hot flashes that I’ve been experiencing for the last 2 months became troublesome for me.  They were long, intense, and were paired with rage at times.  I couldn’t understand why I was having them – doesn’t progesterone supplementation fool your body into thinking you’re not experiencing perimenopause (or real menopause, for that matter)?  Things had been going well, and I was confused, so I asked Dr. Peat about it.  His response:

Some things that reduce hot flashes for some people are supplementing pregnenolone, interrupting the progesterone each cycle, using cynoplus only in the evenings, increased salt, and coffee. The natural ovarian cycle gives the liver time to adjust its enzymes, and with continuous progesterone supplements, the liver enzymes excrete progesterone more quickly, and weaken its effects.

I thought that was interesting about liver enzymes….maybe I was having hot flashes because I’d been dosing every day instead of just the last 2 weeks of my cycle.  I did this knowingly, attempting to reverse the hyper-estrogenation I’d inflicted on my body with the stupid and dangerous Wiley Protocol.  Of course, taking hormones in a non-physiological way is likely to cause problems at some point, so perhaps that’s what was going on.

I stopped taking the progesterone for a few days.  The hot flashes got worse.  This led me to believe it WAS perimenopause I was dealing with.  When the estrogen/progesterone ratio is too heavy in favor of estrogen, symptoms of menopause (or PMS, or other unpleasant things) occur.  So I reversed course.  I figured I’d take a LOT of progesterone, to get the hot flashes to stop.  Then I’d taper down and find my new “normal” dose, after determining the threshold below which they broke through.

So a few days ago I decided to dose 3 drops every 1-2 hours, aiming for about 30 drops across the day.  This would be 100mg of progesterone, about 5 times my normal dose, but according to Peat, still safe.  By 5:00PM I didn’t feel very good – kind of tired and tense.  I was in the habit of taking my blood pressure and pulse because I’d recently started taking beta blockers for my hypertension, which usually runs around 150/95. So I took my blood pressure and it was 165/105 – about 10 points higher than even my normally high BP, with heart rate around 105 (usually around 85).  I checked periodically throughout the evening and it remained high, but the next morning was a bit lower again. 

That next day I did the same thing – 3 drops of Progest E every 1-2 hours.  My hot flashes seemed to be getting less intense, so it seemed like the right thing to do.  Again, around 5PM I started noticing tachycardia.  I took my blood pressure and it was 164/107.  That’s when I started suspecting the progesterone had something to do with this, as I’d changed nothing else in the previous 2 days.

I hit Google and found this article about hypertension that occurs during pregnancy, which states the following:

In an article published in the July 7, 2000, issue of the journal Science, HHMI investigators Richard P. Lifton and Paul B. Sigler and colleagues at Yale University and Albert Einstein College of Medicine report that a mutation renders the mineralocorticoid receptor more sensitive to progesterone, a hormone that is produced in abundance during pregnancy. (…)

When the mineralocorticoid receptor is triggered by aldosterone, its normal binding partner, it switches on the cellular machinery that causes kidney cells to reabsorb more salt, ultimately raising blood pressure. Lifton’s group found that when women who have the faulty receptor undergo the hundred-fold rise in progesterone that occurs during pregnancy, progesterone overstimulates the receptor, causing salt retention, expansion of blood plasma volume and skyrocketing blood pressure.

So what this is saying is that some people have a protein mutation that makes them more sensitive to progesterone.  In such a person, progesterone in high amounts (such as in pregnancy….or, say, when you’re me and desperately trying to make hot flashes disappear) can cause the kidneys to retain more fluid…raising blood pressure.

I should mention, when I was pregnant I developed hypertension (not pre-eclampsia), which led to my daughter being born by C-section 3 weeks before her due date.  My blood pressure was so high she was in distress.  Before that I had not had a problem with high blood pressure, and after the pregnancy my blood pressure returned to normal.

So after finding this article I went to the drugstore and bought some diuretic pills and took one.  Within a few hours my blood pressure returned to it’s “normal” state of hypertension – 150s over 90s, and my pulse was back in the 80s.  I stopped taking the progesterone at that point – I guess that was 3 days ago now.  My hot flashes have almost vanished – just little reminders here and there.  I guess I increased my progesterone level quite a bit and it’s not dropping quickly.

I wrote to Dr. Peat to share this story and the article I found, and to ask if he’s ever encountered anything like this in his research or practice.  I haven’t heard back from him yet.  I’m trying not to make that mean anything.  He must know that everything he puts in print becomes fodder for the public so perhaps he’s choosing his words carefully.  Or maybe he’s off researching the issue intently.  Or maybe he just blew it off because it’s terribly inconvenient to have someone tell you that you were wrong and that in fact SOME people actually do have serious side effects associated with high doses of progesterone.

I developed high blood pressure while living in California, around December of 2012.  At the time I was taking high dose progesterone and estrogen supplements, a la the Wiley Protocol.  I did stop taking those in March 2013, and then there was a period of time when I wasn’t taking any hormone supplements at all, until I started with the Progest E in November 2013.  Looking back at previous blog posts I see I’ve posted various blood pressure measurements over the past year or so:

  • April 2013: 145/88
  • June 2013: 135/83
  • November 2013: 155/109 (had recently started Peat-inspired plan, had increased salt and fluids and was taking Progest E, at a pretty low dose.)

What if progesterone supplementation is behind my high blood pressure?  I wasn’t taking progesterone between April and November, and during that period my blood pressure was lower (according to this blog, anyway), with the exception of the time I tried to drink 100oz of water every day.

I’m sure progesterone is safe for most people…but I’m curious how many people have this mutation?

Am I rare?

New plan: No progesterone supplementation for a while. If I find myself needing it I’ll take a few drops, but no more than 3 per day, and only during the last 2 weeks of my cycle.  Also no more extra salt. I’m also drinking celery juice and taking Hawthorn because I understand these things can be helpful for lowering blood pressure.  I’ve tried 3 different anti-hypertensive medications – 2 caused problematic side effects and one just didn’t work.  I tried everything I’ve seen Peat recommend for high blood pressure (eating MORE salt, high dose vitamin K, bag breathing, more potassium, magnesium/epsom salt baths).

There will be other new plans too.  Stay tuned.

11 thoughts on “Progesterone: A Side Effect

  1. 100 mg of progesterone sounds a bit much. Maybe the serotonin may have something to do with the hot flashes not the lack of progesterone. Aim something in that direction. Maybe that could help your blood pressure issues also.

  2. Ella here again, Lanie you are not rare and it is a common problem. Yes, there are genetic polymorphisms but do you know for sure you possess this SNP? It seems you have been doing a lot of fiddly around with your hormones at a time in a woman’s life that hormones are in a flux. You need to check cortisol levels. Taking progesterone against a high cortisol background can cause the supplemented progesterone to convert to more cortisol. I don’t do well with progesterone but great with pregnenolone which is upstream of progesterone. You left out calcium. Are you getting enough? OJ, milk, cheese & salt? I think you need to get them in correct ratios. It is a balancing act between sodium, potassium, calcium and magnesium. Higher aldosterone hormone stimulates your kidneys to absorb more sodium and water while simultaneously releasing more potassium. Aldosterone secretion is increased by several mechanisms, including decreased blood flow to your kidneys, high serum potassium concentrations, increased acidity of your blood and falling blood pressure. Aldosterone secretion decreases as kidney blood flow increases, serum potassium levels fall, and blood volume increases. Serum sodium concentrations affect aldosterone production. A study published in the April 1985 issue of “Endocrinology” demonstrated that increased serum sodium concentrations – a direct result of increased sodium consumption – decreases aldosterone secretion. I would have the salted OJ with the cheese, and see what hapens with BP away from BP meds as they just complicate things. See if you can get your your BP right first. Remember, fermented cheeses are a good source of Vitamin K2. Diuretics are just tinkering with sodium, potassium, calcium, & magnesium to achieve salt, water and blood presssure regulation. You could get aldosterone checked with 24 hr cortisol and work from there. These are only suggestions.

  3. Indeed it is a bit much. My intention was to kick estrogen’s ass and stop the hot flashes. Peat said it was safe, and I’m aware of at least 3 people taking doses higher than this for much longer periods of time to address specific health problems. I think the hot flashes are regular old perimenopause. Serotonin doesn’t cause them, that I’m aware of. My mood is fine these days, as long as I don’t eat starches and do eat carrots daily. Nothing Peat has recommended (to my knowledge) has had an impact on my blood pressure.

  4. When I said, “Am I rare?” I meant, is it rare to have this kind of reaction to high levels of progesterone. I know perimenopause isn’t rare. Yes, I have fiddled a lot with my hormones over the last two years because my endogenous hormones were ruining my life. I was damaging every relationship and losing credibility at work due to severe mood swings. I was desperate to stabilize them. I’ve learned lots of things the hard way, unfortunately. For me a little progesterone is good. A lot is not good. I get lots of calcium – dairy is a huge part of my diet. I’m aware that eating salt decreases aldosterone. I’ve been eating lots of salt since November. It hasn’t helped my blood pressure. I get lots of K2 from cheese, dairy, and liver, and K1 from kale. I also supplement a drop or two of Thorne K2 daily. Can you explain why you think cortisol is important for me to test? I’m not following your reasoning there. Thanks for the comment. 🙂

  5. I see a lot of stuff about SSRIs being used to treat hot flashes…is that what you mean? If so, that would suggest LOW serotonin causes hot flashes and high serotonin fixes it. It doesn’t make sense in my case – if anything, my serotonin is high. Also, the hot flashes started while I was eating an easily digestible diet and feeling pretty good. They seem unrelated to diet – every diet change I’ve made over the last 2 months I’ve continued to have them at about the same frequency/intensity.

  6. Hello, I found this post when searching google for progesterone, as I have been researching ProgestE for myself. ( perimenopause) I have various drug sensitivities, so was worried about just taking it. Just recently I had a DNA test and found out that I have alterations to some of the CP450 liver enzymes that metabolize certain drugs. There are quite a few of those enzymes in the liver and one of them is CYP 2C19, that enzyme metabolizes a bunch of different drugs of which progesterone is one. For that enzyme I am an Ultra fast metabolizer which means that I will need more than the usual dose. There are others that will be a slow metabolizer who will be majorly effected by a small dose. ( I am a slow metabolizer for enzyme CYP 2D6, which metabolizes codeine ( and others also) I cannot tolerate codeine at all. I’m wondering if you are a slow metabolizer for the enzyme 2C19. Eitherway I hope this is of some help. Researching the CYP450 enzymes may help. I had the Pharmacogenetics DNA test done here in Australia it cost $199. Here is some info about the 2C19

  7. Thanks for this interesting comment. I can’t adequately respond till I’ve researched this a bit, but I appreciate all this information!

  8. Hi there! I am off Peat diet and off progest-e, and actually, my hot flushes disappeared when I started a fast…. The only moment I almost had a come back of some heat one evening, was the 1st day I tried to up fruit intake a bit! At the moment I eat a majority of raw food and a lot of proteins. Peats advices are the same all the time, and are not suiting everybody at all! The problem is that he does not say to which cases his advises correspond… I am also off coffee now. My sleep has come back. I am different in the sense that I have low pulse, low blood pressure. So there can be more than 1 problem with taking progesterone. And it is far from the truth that we can take it ad libitum!

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