withdrawal symptoms after using progesterone daily...very scared

by Maya

Dear Wray,

I hope you can advise me, I will try to be concise but it is quite a long story. I am a 37 year old female. In 2007 I withdrew extremely slowly from an anti-depressant. Each time I lowered the dose I experienced severe withdrawal symptoms that would last 2 weeks, then would stop, and then I could do the next tiny reduction. Technically speaking, that medication was not classed as 'addictive'. But that does not exclude the occurrence of major psychological withdrawal symptoms as you wean off it. Unfortunately, the final lowering- from the smallest dose down to zero, caused an absolute catastrophe for my mental health as it triggered a new problem- severe OCD, which I have now had since 2007. It is severe but my mood is stable. I am completely housebound and cannot function independently.

It seems to be the case that my brain is VERY sensitive to the starting and subsequent stopping of any substance which has an affect on mood related brain receptors/levels of neurotransmitters. All drugs, such as the SSRIs, or agents such as Inositol or Tryptophan, which raise serotonin levels in isolation, make my anxiety worse- probably through the hyper-conversion of serotonin to melatonin, which causes depression in excess. I take vitamins, minerals, taurine and N-Acetyl cysteine.

At the start of 2012 I began for the first time to experience symptoms of oestrogen dominance- mainly heavier, red, clotted periods, breast tenderness and loss of blood sugar control. I discovered your website, read all of your pages with huge interest, including your page on anxiety, and thought it sounded brilliant. I deliberately avoided looking up any other opinions as I decided to take your word for it and trust your advice. I started the cream 4 months ago as follows-

Month 1- 40mg, 2 weeks on 2 weeks off. It did not resolve the oestrogen dominance fully. No problems stopping and starting it.

Month 2- 80 mg, 2 weeks on 2 weeks off. Improved but not fully resolved. No problems stopping and starting it.

Month 3 and 4- I decided to try your advice of taking it daily without a break for 2 months, you say that it is easy to get the cycle back afterwards, so there seemed no reason to not give it a go. I increased my dose to 160 mg daily. This resolved the oestrogen dominance symptoms- my period was now lighter, brown, excellent blood sugar control and no breast tenderness. I was delighted with this and I am sure that I am now progesterone dominant . Experiencing diarrhoea however on this dose.

So I decided to make the transition from taking it daily back to taking it on the 2 weeks on 2 weeks off basis. However I am experiencing extremely severe mental withdrawal symptoms every time I try even a 20mg reduction. I've tried now several times and get the same severe rage, verbal aggression, angry mood swings, explosive sobbing and sound sensitivity. I am not talking about the recurrence of oestrogen dominance symptoms at all, these are purely mental withdrawal symptoms. I did not experience these symptoms prior to starting the cream nor whilst taking the cream, they only occur whilst attempting to reduce the dose. In addition my OCD goes sky-high during this time. So I end up having to revert back to 160mg.

I'm hoping you can answer some questions-

1. There is no way I want to stay on 160mg daily for the rest of my life. If I try again with a 10mg or 20mg reduction, how long will these terrifying withdrawal symptoms last? Will they ever dissipate? I want to reduce it by at least half and then re-assess.

2. On your anxiety page you say that benzodiazepines, such as Valium, cause dependence and addiction and so should not be used for longer than 2 weeks; and that people with anxiety disorders are at risk of addictions. You say that Progesterone increases levels of serotonin, dopamine and activates the GABA receptors; that the anti-anxiety response is similar to that found with benzodiazepines but with no addictive risks. In reply to a post entitled 'Progesterone cream withdrawal- cold turkey or wean' posted Jul 02, you say that withdrawal from progesterone is nothing like that from the benzo drugs and that there are none of the appalling symptoms experienced with benzo withdrawal.

What are you basing this information on? As they both exert their effects by activation of GABA receptors, how can this cause dependence and addiction with Valium use and not with daily high dose progesterone use? The GABA receptors receive the same activation and reduction of activation when withdrawing from either. Also, by increasing dopamine, the 'gratification hormone', progesterone must activate the same potentially addictive 'reward pathways' in the brain as Valium and some illegal drugs. So how can withdrawing from a daily high dose of progesterone cream be any different to withdrawing from any other drug that activates these addictive 'reward pathways' in the brain?

I am experiencing exactly the same withdrawal symptoms as that described with benzo withdrawal. I think I would have been ok if I had kept taking it on a 2 week on 2 week off basis because perhaps, as with Valium use, 2 weeks is not enough time to develop a dependence. To further alarm me, I have just read on a Doctor's website that she does not use natural progesterone cream with her patients because it is addictive.

3. You say that Dr Dalton used very high doses with her anxiety patients, but does she say anything about the mental withdrawal symptoms they experienced, how long the withdrawal symptoms lasted and if they ever even managed to withdraw from daily use?

I'm sorry this is so long but I am very scared. If anybody else has experienced mental withdrawal symptoms when trying to wean off progesterone cream, please can you tell me how long they lasted and if they eventually went. Thanks.

Thanks, Maya.

Comments for withdrawal symptoms after using progesterone daily...very scared

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Aug 25, 2012
My personal experience
by: Karenina

Hi Maya,

Yes, I did try and do that two or three years ago and I went through hell, why because all my symptoms of estrogen dominance returned! The withdrawal symptoms were nothing compared to what I experienced with the return of estrogen dominance. Though I am still having problems with high estrogen levels the Natpro Progesterone cream is keeping me sane mentally while I am trying to get to the bottom of it which I now believe is due to a lot of toxins in my body. Before I came across this site I was in a very bad place and if it wasn't for Wray's constant support I would have given up a long time ago. She is an amazing woman with so much to give. I really hope you will come through this with the help of Wray. Take care. Karenina

Aug 27, 2012
withdrawal symptoms after using progesterone daily...very scared
by: Wray

Hi Maya Thanks for the kind words about the site. I'm delighted the progesterone helped you at 160mg/day, I use about 170mg/day and have for 15 years now. It's excellent for ageing, I appreciate that fact now! Progesterone isn't addictive as the benzos are. We make it daily and it's a vital part of our make up, the benzos are not. The ovaries of course, if we're still in our reproductive phase. The placenta when pregnant, up to 400ng/ml per day, the drop causing severe post natal depression in many women, something I experienced. My main symptoms being exhaustion, debilitating myopathy and rage. But the adrenals and brain are another daily source, the glial cells in the brain secreting it constantly. So it plays an integral part in activating neurotransmitter and other hormone receptors. Low progesterone, particularly if oestrogen is too high, can cause severe symptoms. Supplementing with it usually resolves them, so does this make it addictive? I don't think so. One could then argue that all the neurotransmitters and hormones are addictive, because if we lack them things go awry. If we take the precursors things normally resolve. I believe you began reducing the progesterone too soon. My suggestion of 2-3 months is merely a guideline, it's impossible for me to know the ins and outs of all the people who contact me, particularly one as sensitive as you. And that's only after the higher amounts used until feeling stable. By all accounts you weren't yet at that stage. I've found in many women it needs to be used at high amounts for 3 months at least, some need 6 months. My symptoms only fully resolved when a full 6 months had passed. I had the severe rage, mood swings, endless, exhausting crying, constant anxiety plus more that you speak of. It's interesting you experienced diarrhoea using that amount. Oestrogen causes water retention by drawing water from the gut, which leaves this lacking it. Progesterone is such an excellent diuretic over 1200mg/day is now given via IV transfusion to Traumatic Brain Injury victims to prevent the oedema and inflammation that occurs. The gut now gets the water it once had, but initially too much. You might also like to see this comment here. We do have a page on your severe rage, verbal aggression, etc, see Aggression. It seems it's caused by an excess of testosterone, usually combined with low serotonin. Each month women make more testosterone than oestrogen, but most of it is converted to oestrogen by the enzyme aromatase. Continued below.

Aug 27, 2012
withdrawal symptoms after using progesterone daily...very scared Part 3
by: Wray

Hi Maya Progesterone suppresses the production of excess testosterone, and therefore oestrogen, by increasing sex hormone binding globulin, see here. You'll notice in the paper that excess testosterone causes severe PMS. But if progesterone is not yet high enough, reducing the amount, or following the cycle again, allows this production to start up again. Often initially at an increased rate. I do know I had higher than normal testosterone during the years I experienced my worst symptoms. Not because of any test, but because I felt so 'male'. It's difficult to describe, and it was something which puzzled me greatly as I look very unlike a male, having large breasts and hips and a small waist. Thankfully it resolved once I'd started the progesterone. I take it you are now following your cycle again and have no adverse symptoms during the follicular phase? I can only advise you to use the high amount for far longer before attempting to reduce. Most women seem to settle somewhere around 120mg/day once stable. There is one thing I'd ask you to do and that's have vitamin D test done. You live in the UK where levels are generally very low. For more info on vitamin D levels, test kits etc see the Vitamin D Council, GrassrootsHealth and Birmingham Hospital websites. Blood levels should be 70-100ng/ml (175-250nmol/L) and not the 30ng/ml (75nmol/L) most labs and doctors regard as adequate. The minimum daily dose should be 5000iu's per day, although the latest research indicates it should be 10,000iu's per day, see here. Birmingham Hospital send out test kits for £25, and send the results back by email. Please ignore their 'adequate' level of 50nmol/L, even the FDA have set theirs at 75nmol/L, both too low according to the vitamin D specialists. Vitamin D is vital for mental health, see here, here, here, here and here. Continued below.

Aug 27, 2012
withdrawal symptoms after using progesterone daily...very scared Part 2
by: Wray

Hi Maya And more here,
here, here, here, here and here. Dr Dalton didn't mention withdrawal symptoms, but then she had women on very high amounts, and until symptoms had resolved, see here. You were only using 160mg/day for 2 months, she used levels of 400mg, 800mg up to 2400mg for her patients with post natal psychosis. She doesn't mention oestrogen dominance in any of her papers or books, simply because her patients never got it. I met her a few times while still alive, she practiced in Harley Street, and she never once warned me to be cautious about it. Women who use the low amounts, i.e. 20mg/day do get it. I'm surprised you didn't respond well to inositol, as I prefer to recommend that rather than tryptophan. It's excellent for OCD, doses of 18g per day have been given, see here, here, here and here. Take care Wray

Aug 28, 2012
by: Critic

I absolutely agree: It was too soon to withdraw the progesterone at all. I have been using it every day for two years now and feel I still need it. But I have been using 500 mg a day and more, orally - because of cancer, which I am cured of now. But progesteron does lower testosterone and if you quit using it, testosterone rises immediately and so does estrogen. The first makes you aggressive, the second weepy. Serotonin on the other hand is responsible for the feeling of hopelessness and helplessness. I strongly suggest reading www.raypeat.com on this and all other issues. Do not quit using progesterone! There is no reason for it. It might save your love or just make it worth living.

Aug 30, 2012
by: Wray

Hi Critic I'm delighted the cancer has gone, wonderful news. Thanks for your words of encouragement, it does need to be used until stable and not reduced too quickly. Ray Peat's site is so worth looking through too, I love his controversial views. Take care Wray

Aug 30, 2012
My personal experience
by: Wray

Hi Karenina Bless you for your support! Your patience has been amazing too, it must be well over 2 years you've been trying to get to the bottom of it all. All too often we have to go it alone, as you have resorted to, I wish it wasn't so. Take care Wray

Sep 01, 2012
Bless you!
by: Karenina

Bless you Wray....will speak to you soon. Take care and hugs to you.x Karenina

Sep 18, 2012
What to do now?
by: Terrie

Also, I wanted to add that my blood levels were --- prog. 3.5 ng/ml and est. was 228 pg/ml. These results were taken while still on oral dosages of both. Am I right in understanding that you say you have to divide the 228 of the estrogen by 1000 to get the proper ratio before looking at the ratio of the est. / prog.? If that is so, then it makes my prog. 3.5 to est. of .228. I guess I find that odd as I thought that the prog. was affected because of the liver but not the estrogen. I would have thought that the ratio would have been a whole lot different.

Sep 19, 2012
What to do now?
by: Wray

Hi Terrie It appears you must have made another comment somewhere as you say " I wanted to add ...". But I haven't seen it. You are right in saying the pg/ml which oestrogen is measured in must be converted to ng/ml to match the progesterone. This is 0.228. But you then divide the progesterone of 3.5ng/ml by this figure and you get a ratio of 15:1, which is very low. Even going by ratios the labs use. We've found from Saliva Tests we run, that's it's best if the ratio is 600:1 and over to feel well. I'm not sure what you mean by the progesterone being affected by the liver. Do you mean it's metabolised and excreted by it? If taken orally it's estimated that 90% of progesterone entering the gut and liver is metabolised by these tissues, see here. But both the liver and kidney play a role in excreting it, plus oestrogen too. Take care Wray

Jul 18, 2015
Progesterone can cause withdrawal
by: Anonymous

Not everything is from estrogen dominance when coming off of progesterone cream.This is simply not true and for many women the withdrawal they experience when coming off of progesterone is VERY similar to that of benzodiazepines.There are several studies and links that show the relationship between the two and if one can alleviate the withdrawal symptoms of another that means that they work in very similar ways and can cause very similar withdrawal symptoms.I wish I had known this before reading this site and following the advice here as well.

Not everyone will experience this effect but just because the ladies here might not have experienced it or either havnt tried to come off of it yet does not mean that this is not what is happening with many women.The information is out there that shows it can cause pretty serious withdrawal even when tapered. What the woman is describing above is not estrogen dominance.It is a gaba-ergic withdrawal syndrome that rivals benzodiazepines.I take it that she gave up posting back here because she realized no one here was really understanding what she was going through. It mustve been incredibly frustrating and scary for her. I can relate as I am now going through this as well and I have never been on benzos before but what I feel has been absolute hell, far worse than my estrogen dominance symptoms that I had before progesterone cream, no not even close.Even if you choose not to publish these comments I wanted you to have the information. Thanks,

Cross tolerance

Benzodiazepines share a similar mechanism of action with various sedative compounds that act by enhancing the GABAA receptor. Cross tolerance means that one drug will alleviate the withdrawal effects of another. It also means that tolerance of one drug will result in tolerance of another similarly-acting drug. Benzodiazepines are often used for this reason to detoxify alcohol-dependent patients and can have life-saving properties in preventing and/or treating severe life-threatening withdrawal syndromes from alcohol, such as delirium tremens. However, although benzodiazepines can be very useful in the acute detoxification of alcoholics, benzodiazepines in themselves act as positive reinforcers in alcoholics, by increasing the desire for alcohol. Low doses of benzodiazepines were found to significantly increase the level of alcohol consumed in alcoholics.[20] Alcoholics dependent on benzodiazepines should not be abruptly withdrawn but be very slowly withdrawn from benzodiazepines, as over-rapid withdrawal is likely to produce severe anxiety or panic, which is well known for being a relapse risk factor in recovering alcoholics.[21]

There is cross tolerance between alcohol, the benzodiazepines, the barbiturates, the nonbenzodiazepine drugs, and corticosteroids, which all act by enhancing the GABAA receptor's function via modulating the chloride ion channel function of the GABAA receptor.[22][23][24][25][26]

Neuroactive steroids, e.g., progesterone and its active metabolite allopregnanolone, are positive modulators of the GABAA receptor and are cross tolerant with benzodiazepines.[27] The active metabolite of progesterone has been found to enhance the binding of benzodiazepines to the benzodiazepine binding sites on the GABAA receptor.[28] The cross-tolerance between GABAA receptor positive modulators occurs because of the similar mechanism of action and the subunit changes that occur from chronic use from one or more of these compounds in expressed receptor isoforms. Abrupt withdrawal from any of these compounds, e.g., barbiturates, benzodiazepines, alcohol, corticosteroids, neuroactive steroids, and nonbenzodiazepines, precipitate similar withdrawal effects characterized by central nervous system hyper-excitability, resulting in symptoms such as increased seizure susceptibility and anxiety.[29] While many of the neuroactive steroids do not produce full tolerance to their therapeutic effects, cross-tolerance to benzodiazepines still occurs as had been demonstrated between the neuroactive steroid ganaxolone and diazepam. Alterations of levels of neuroactive steroids in the body during the menstrual cycle, menopause, pregnancy, and stressful circumstances can lead to a reduction in the effectiveness of benzodiazepines and a reduced therapeutic effect. During withdrawal of neuroactive steroids, benzodiazepines become less effective.[30]

I wanted to post this information for anyone thinking about Progesterone therapy. I am not on the forum much anymore, but wanted to make sure that everyone was aware of this information to avoid any pitfalls in their recovery by taking some form of progesterone, which is cross tolerant to benzos:

The metabolites of progesterone, allopregnolone and pregnolone, act on the GABA receptors the same way that benzos do, thus it can have the same effect as a benzo dosage increase. Here are a few articles that explain how they act in the same way as benzos on the GABAA receptor:

The steroids most studied are allopregnanolone (ALLO), tetrahydrodesoxycorticosterone (THDOC), pregnenolone sulfate (PS) dihydroepiandrosteronesulfate (DHEAS), and estradiol (E2). ALLO and THDOC are called gamma-aminobutyric acid (GABA) steroids as they are positive modulators of the GABAA receptor in a similar way as benzodiazepines, barbiturates, and alcohol.


The positive modulators of the GABA(A) receptor include allopregnanolone and pregnanolone, both neuroactive metabolites of progesterone, as well as benzodiazepines, barbiturates, and alcohol.


Previous studies have determined that allopregnanolone enhances the activity of GABA, the main inhibitory neurotransmitter in the central nervous system, at its receptors throughout the brain. This mechanism, Toufexis said, likely accounts for progesterone's blunting effect on the brain's stress system.


So you can see from that why progesterone is categorized as being cross tolerant to benzos, because it modulates the GABAA receptor in the same manner.

Neuroactive steroids, e.g., progesterone and its active metabolite allopregnanolone, are positive modulators of the GABAA receptor and are cross tolerant with benzodiazepines.[27] The active metabolite of progesterone has been found to enhance the binding of benzodiazepines to the benzodiazepine binding sites on the GABAA receptor.[28] The cross-tolerance between GABAA receptor positive modulators occurs because of the similar mechanism of action and the subunit changes that occur from chronic use from one or more of these compounds in expressed receptor isoforms. Abrupt withdrawal from any of these compounds, e.g., barbiturates, benzodiazepines, alcohol, corticosteroids, neuroactive steroids, and nonbenzodiazepines, precipitate similar withdrawal effects characterized by central nervous system hyper-excitability, resulting in symptoms such as increased seizure susceptibility and anxiety.


Another thing it has in common with benzos is its effects on the corticotropin-releasing factor (CRF), also called the corticotropin-releasing hormone (CRH).
(NOTE: You can read more about the CRF/CRH involvement on this thread: http://www.benzobuddies.org/forum/index.php?topic=44373.0 )

The scientists found evidence that the progesterone metabolite allopregnanolone reduces the brain's response to corticotropin-releasing factor (CRF), a peptide hormone that plays an important role in the stress response in animals.


Plus it has its own withdrawal syndrome.


Oct 23, 2015
Progesterone cream withdrawal same as benzo withdrawal
by: Anonymous

I have currently had to go onto valium in order to go onto a slow taper in order to cope with progesterone cream withdrawal. I have had benzo withdrawal (cold turkey) before 8 years ago and like this it was hell - burning skin, severe anxiety and agitation, an inability to sit still, eat or sleep. The cream is highly lipophilic so is hard to taper from as you dont know exactly how much of each dose goes directly into the blood - hence the choice to bin the cream and go straight on valium (8mg is my start dose). I had only been using 20mg of compounded cream per day for just over 2 months and in the last few weeks suffered continual hot flashes, sweating, a raging thirst and a constant headache. I assumed this to indicate a drop in oestrogen so I had my oestrogen and progesterone levels tested. This was done on capillary blood which gives the most accurate reading cf venous blood or saliva (see BMJ for studies - venous tests give low results when prog is at toxic levels, capillary readings often x100 higher). My progesterone reading was off the chart - x10 normal levels. I immediately stopped the cream and within a week I had the full gamut of benzo withdrawal symptoms and was now on course to not be able to hold down a job or look after my children. Last time in benzo cold turkey I could'nt live independently. Luckily for me having gone through a successful benzo taper before and responding well to it I was able to persuade a reluctant doctor and I feel normal again but with a long roller coaster of a taper to endure. Progesterone acts as a GABA agonist just like benzos - just cos its 'natural' it makes no difference.

Oct 27, 2015
I am in the exact same boat
by: Anonymous

Hi I am the one who posted the above comment before yours. Ive of course read the research but hearing this from other real life experiences terrifies me even more since I know I am hooked badly but also have a very severe disease and am in such a weakened state that I know that I wouldnt be able to withstand the withdrawal.The small bit that I have felt before after just trying to come off of 20 mg rivaled coming off of the worst gaba agonists that a person could withdrawal from.And I have been using 100 mg of the cream daily for around two years.This has REALLY put me a bad place since my disease causes allergic type reactions to even medications and so I cant even take most prescription medications to help cover the withdrawal.I cannot stress enough to people thinking about taking on the advice of the site to do your homework first. Just because some people are fine doesnt mean you will be when you try and come off it. It can make you feel like your losing your mind and no not from estrogen dominance but from benzodiazepine withdrawal and if you ask any doctor they will tell you its the worst withdrawal a person could ever endure.

Oct 30, 2015
Benz withdrawal not always so bad
by: Anonymous

Hi there,

I have withdrawn from benzos before and had a reasonably easy ride of it but the key was slow and very small cuts - the best advice I ever had. My worst days were in the beginning of the taper. I am not really looking forward to doing it again and would prefer not to but I have no choice, I have made a small cut (0.5mg so now on 7mg per day) and am feeling fine and miles better than I felt at any point on progesterone which made me feel like crap even before I was toxic with it - for me its better the devil I know there was no way I was cold turkeying again - 5 months of benzo cold turkey almost killed me.

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