PROGESTERONE AND BENZOS

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.

 

http://www.ncbi.nlm.nih.gov/pubmed/16362406

 

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

 

http://www.ncbi.nlm.nih.gov/pubmed/19272715

 

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.

 

http://www.news-medical.net/news/2005/02/09/7697.aspx?page=2

 

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.

 

http://en.wikipedia.org/wiki/Benzodiazepine_dependence

 

 

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.

 

http://www.news-medical.net/news/2005/02/09/7697.aspx

 

 

Plus it has its own withdrawal syndrome.

 

http://edrv.endojournals.org/content/24/4/523.full

 

 

Thanks Perseverance. This question comes up a lot. It's good to have all this information documented here.

 

I have a friend who was put on benzos in the first place due to progesterone w/d.

Perseverance,

 

I have been on progesterone (cream) therapy for some time, since before my c/t.  I am interested in learning more about this and its effect but haven't known where to start. Thanks for the information and the links!!

 

Wow!  My doctor PUT me on bioidentical progesterone while on benzos!!!!!!!!!! (She's and integrative/holistic D.O.) Ummm...shouldn't she have known not to prescribe progesterone and the k??? No wonder I felt better when taking the progesterone...it was essentially "updosing" the K!!!!!! I stopped using it around August or Sept of last year...never knew. Man!!!

 

Thank you for posting this. I copied it, printed it off and am taking it TO her tomorrow.

You've educated me greatly about this.  I thank you.  Wonder if that's why I had such problems with the b/c pill years ago--before benzo. 

My benzo brain is spinning trying to understand this info right now.  I too will be printing it out to bring in to my doc.

 

I was started on progesterone therapy for bleeding that I was having EVERYDAY for over 3 years (-ish).  I've been on it for maybe 2 years?  Sorry, my memory is REALLY bad right now.  First I was taking it in pill form for a short time, then the cream.  Then my testosterone was off so now that's been added to my cream. 

 

Anyway, maybe you can help for now with some of these questions;

 

Is it better to wean off of it now, during my w/d?

Do I "need" it?

Can I expect the bleeding to come back?

Can I expect other benzo-type symptoms to increase?

 

I'm so confused   

I have forgotten to get my bc pill refilled for two days now.... My anxiety has been considerably less. Coincidence? I will have to take two pills tonight and two tomorrow to catch up.I'm wondering if I should just stay off it and see how I do. My progesterone is super low right now.

As a result of a contract dispute between the pharmacutical companies middlemen and my pharmacy, I was required to leave my pharmacy and move to another.  Turns out they don't carry the same generic version of my BC I have taken since 2008.  Because I have such severe PMS and the only thing that can stop my cycle and therefore my PMS I made the pharmacist SWARE ON HER MOTHER that there was no difference between the generic they carry and the generic I've been taking.  She SWORE the active incrediants BY LAW have to be IDENTICAL. I already knew there could be a variation of the inactive ingrediants of up to 20%.  But she SWORE they were the EXACT SAME THING (and behaved as if I was insane, which probably was fair.  Her condescending attitude I could have done without however)

 

Sadly, I'm two days into the switch and my body, for the first time since this happened just over a year ago, when my dose of valium was rendering my bc useless, PMS symptoms have begun.

 

This could get very very ugly...

 

And what causes me further distress is that I believe if I were off the BC my taper would possibly be easier, but my PMS would flare and visa versa.  Damned if I do and damned if I don't.

 

 

My benzo brain is spinning trying to understand this info right now.  I too will be printing it out to bring in to my doc.

 

I was started on progesterone therapy for bleeding that I was having EVERYDAY for over 3 years (-ish).  I've been on it for maybe 2 years?  Sorry, my memory is REALLY bad right now.  First I was taking it in pill form for a short time, then the cream.  Then my testosterone was off so now that's been added to my cream. 

 

Anyway, maybe you can help for now with some of these questions;

 

Is it better to wean off of it now, during my w/d?

Do I "need" it?

Can I expect the bleeding to come back?

Can I expect other benzo-type symptoms to increase?

 

I'm so confused   

Sunny,

 

If you are off the benzo now, it would be ok to start weaning off the progesterone.  It is always best to wean off one drug at a time if you are on both.  Whether you will have sx flares from weaning is hard to say since everyones experience is so individual.

 

I saw that some of you were going to bring this information to your doctors...you may also want to print off pages 1 & 3 of this thread so you can also present to your doctor the research as to why your levels are low from the benzos.

 

http://www.benzobuddies.org/forum/index.php?topic=44373.0

 

I too had bleeding so heavy I was going through 12 maxipads a day, which ended in my having a hysterectomy.  I now suspect that the heavy bleeding I was experiencing was the result of tolerance w/d from the benzos.  Ashton notes a connection between benzos and a higher rate of hysterectomies in her manual as well.  This is more than likely due to the fact that Benzodiazepines can suppress hormone production due to their effects on the Hypothalamic-Pituitary-Adrenal (HPA) Axis.  Before going off benzos my Cortisol, Testosterone, Estrogen, and DHEAS were all low due to this suppressing effect.

 

Male and female sex hormones are biosynthesized through two routes, the HPA Axis and the Hypothalamic–Pituitary–Gonadal (HPG) Axis (meaning through the testes and ovaries which are called the gonads).  In the HPA route, production begins with hormone produced by the Adrenals called DHEA, which is then synthesized first into Androstenedione, and then converted into either Estrogen or Testosterone depending on what the body requires.

 

The production of Androstenedione from DHEA in the Adrenals is especially important in post-menopausal women where all estrogens and practically all androgens, including Testosterone, are made in the peripheral tissues from adrenal DHEA.  In premenopausal women production is about 50%.  Thus the supression of the HPA Axis from the benzodiazepines can cause these levels to be low.

 

The responsible thing for any doctor to do if their patient tests low in any hormone is to investigate the underlying cause, not to simply write a prescription for hormone replacement without knowing why it is happening.

 

To rule out problems within the HPA Axis, the following tests should be ordered:

 

An ACTH stimulation test.  In this test the patient is injected with ACTH and the Adrenal outputs are monitored.  If the Adrenals respond properly you can rule out Adrenal malfunction and assume the problem lies further on up the HPA Axis (in the pituitary gland or the Paraventricular Nucleus (PVN) of the Hypothalamus) which ultimately control Adrenal outputs.

 

The PVN secretes Corticotropin Releasing Hormones (CRH) which tells the Pituitary Gland to secrete ACTH.  Having a CRH stimulation test will check to see if the Pituitary Gland is responding properly to rule it in or out.

 

If the Adrenals and Pituitary both pass these functional tests then it can be assumed that the problem lies in the PVN.  The PVN secretes CRH on in a diurnal pattern throughout the day, which is disrupted by benzodiazepine use.  Abnormalities in a 24 hour salivary test can reflect a problem here, and in that way be useful in confirmation.

 

There is a new test out now called a combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test, or DEX/CRH test, and experts are saying this is the best and most sensitive test to check for HPA Axis irregularities, and thus this test may be able to pick up the irregularities caused by benzos.

 

To rule out problems with the HPG axis, blood levels and functional tests should be ordered for Folicle Stimulating Hormone (FSH) and Luteinizing hormone (LH), to rule out the pituitary gland.

 

 

I have forgotten to get my bc pill refilled for two days now.... My anxiety has been considerably less. Coincidence? I will have to take two pills tonight and two tomorrow to catch up.I'm wondering if I should just stay off it and see how I do. My progesterone is super low right now.

Jittery,

 

It is not surprising that your progesterone is low from benzodiazepine use.  We have discussed your BC use in the past on my blog...while it is better to avoid hormone therapies in BW, one must weigh out the situation.  It would not be a good idea to become pregnant during BW...so abstaining from sex or using non-hormone contraceptive measures during the WD period would be the best approach if you are considering going off BC pills.

Perseverance,

 

Thank you, thank you, thank you!!!  I'm so happy you started this thread.    I feel like I am slowly putting together the pieces of the last 10 years of my life!!  All these symptoms and problems I had...and yet not finding much wrong.  Or finding things that were wrong but not knowing the cause.  Doctors treating me like "it was all in my head".  I'm angry what happened to me but so relieved to be taking control over my life!!! 

 

I'm sorry things went as far as you having to have a hysterectomy!  You seem to be very educated on this and I'm so grateful you're sharing your knowledge with us.  Thank you for explaining about the hormones, and different tests.   

 

Hi Perse,

 

I've been trying to read your research about HPA and hormone therapy. Sorry to say it is all Greek to my benzo burnt brain.

I am currently  8 months free of the benzos and still have a way to go to recover.

 

Anyway, I'm curious if you think the wd could have effected my hormones enough to cause thickened endometrial lining. I'm post menopausal. 4 months after my final period the benzos turned paradoxical on me and I had to get off. Then (break through bleeding during wd) 3months after I jumped an ultrasound showed the thickening - I waited 4 months and another US showed even more thickening. I am scheduled for a hysteroscopy next week and my fear is they'll try to treat it with progesterone therapy. I know the BZD wd has left me very shell shocked and I'm terrified to experience anything like this again. I'm sorry I can't decipher all your research, I know you worked very hard to accumulate the data, but it all just sends my head spinning.

 

Maybe I am putting the cart before the horse, but I'm curious as to your thoughts.

 

Thank you

 

Hi Perse,

 

I've been trying to read your research about HPA and hormone therapy. Sorry to say it is all Greek to my benzo burnt brain.

I am currently  8 months free of the benzos and still have a way to go to recover.

 

Anyway, I'm curious if you think the wd could have effected my hormones enough to cause thickened endometrial lining. I'm post menopausal. 4 months after my final period the benzos turned paradoxical on me and I had to get off. Then (break through bleeding during wd) 3months after I jumped an ultrasound showed the thickening - I waited 4 months and another US showed even more thickening. I am scheduled for a hysteroscopy next week and my fear is they'll try to treat it with progesterone therapy. I know the BZD wd has left me very shell shocked and I'm terrified to experience anything like this again. I'm sorry I can't decipher all your research, I know you worked very hard to accumulate the data, but it all just sends my head spinning.

 

Maybe I am putting the cart before the horse, but I'm curious as to your thoughts.

 

Thank you

 

kimba,

 

While Ashton has noted a possible corelation between benzos and an increase in the number of hysterectomies, I am unaware of any research that suggests benzos may cause thickening of the endometrial lining.  Perhaps your doctor could narrow down the exact cause of this occurrence before prescribing medication to treat it.  I personally do not think it is a good idea to prescribe medication until a cause has been determined.

 

IMO it would be a good idea to explain your benzo history and the cross tolerant aspect between benzos and Progesterone so your doctor can make an educated decision regarding your case.  You could print out any of the information I provided here on this thread, plus the two research papers I wrote on the thread below (Pages 1 & 3) to present to your doctor, as most doctors are not versed in the neuroendocrine effects from benzos.  Most of my sources are from either PubMed or Medical Journals which your doctor should recognize as credible.

 

http://www.benzobuddies.org/forum/index.php?topic=44373.0

Woah and woah.

 

I've been thinking about getting back on progesterone recently because I feel like PMS and my periods are trying to kill me.  I'm 32, been on klonopin for almost 6 years.  I have awful hot flashes, heavy bleeding & pain, extreme weakness and panic, nausea, GI pain, etc during PMS and my period.  In 2007 (I'd been on klonopin about a year) my naturopath gave me some natural progesterone topical cream to help and it sure did.  Now, this was derived from plants, was non-prescription, and non-synthetic. 

 

Please forgive me, but I have a very hard time concentrating to read so very much info..  Can you break it down simple for me here-- do these studies suggest I should avoid even this natural progesterone?  I remember I didn't suffer at all when I stopped taking it. 

 

Thank you!  This is such a coincidence because I just found this article today: http://www.benzosupport.org/Hormones%20and%20benzo%20diazepines.htm  and felt even more like using my old cream again was a great idea.  Now...  

 

Thanks again, I am new here.

 

Warmly,

Melodie

Melodie,

 

The studies in the link you provided sum up the effects of Progesterone up nicely.  The Progesterone metabolite Allopregnanolone acts on the GABAA receptor similarly to benzodiazepines by enhancing the inhibitory action of the neurotransmitter GABA…also it is important to note the occurrence of upregulation of GABAA receptor sites upon progesterone discontinuation which is also similar to benzodiazepines.

 

It is likely you felt relief from the Progesterone as it can act similar to an increase in benzodiazepines due to its allosteric modulating effects.  It is possible that this could have negated the interdose WD effects you may have been experiencing which could be responsible for an increase in your PMS symptoms across the luteal phase.  This can happen due to the neuroendocrine effects on CRH in the brain which in turn can cause suppression of ACTH production-  which in turn negatively effects hormone production.  You can read a  detailed explanation of how this occurs on pages 1 and 3 of this thread:

 

http://www.benzobuddies.org/forum/index.php?topic=44373.0

 

In women, production of progesterone undergoes substantial changes during the menstrual cycle. Plasma levels of the steroid remain at a constant low level during the first half of the cycle. Following ovulation, secretion of progesterone by the corpus luteum increases, resulting in elevated blood plasma levels [10]. In the absence of a fertilised ovum the corpus luteum then degenerates, with an associated rapid fall in plasma progesterone production prior to menstruation.

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593562/?tool=pubmed

 

This rapid fall in progesterone levels effects the GABA system and researchers believe that this decrease is responsible for the symptoms of PMS and PMDD.  Based on this information, the decreased hormone production caused by benzodiazepines therefore can have an additive effect to these types of symptoms, in other words, make them worse.

 

Substances that work in the body as hormone replacements have these effects, regardless of whether their origin is synthetic or natural.  The reason you were able to quit the Progesterone therapy before without consequence could be due to the fact that you may not have been taking it long enough to develop tolerance.  Many people have been able to discontinue benzodiazepines without WD symptoms for this very reason.  However, once the body has begun to build up tolerance WD symptoms will most likely ensue.

 

Tolerance occurs once the body begins to make changes, called neuroadaptations, in order to counteract the increased levels of chloride produced by drugs with GABAA  Allosteric Modulating capabilities.  In order to get the body to reverse these changes so recovery can occur it is therefore vitally important not to take supplements or drugs that act as Allosteric Modulators which cause an increase in chloride by enhancing the activity of the GABA neurotransmitter.

 

This is why exogenous Progesterone is not a good idea for people trying to discontinue benzodiazepines.  I know premenstrual symptoms can be rough while in benzodiazepine tolerance or while withdrawing from them, but adding Progesterone therapy can obviously interfere with the healing process and not only can lead to Progesterone dependence, but also symptoms of tolerance and withdrawal.

 

The bottom line- there is really no easy way out of benzodiazepine dependence and unfortunately this type of suffering is part of the journey to freedom for women.  Once you have successfully completed the withdrawal recovery period your hormone levels should come back to normal and the exaggerated PMS symptoms should also decline back to pre-benzodiazepine levels.

 

I know this stuff is extremely complicated and it can be even harder to understand while withdrawing from benzodiazepines due to the drugs effect on cognition.  I hope however that this explanation did help you to better understand why it is not a good idea to take Progesterone while attempting to come off benzodiazepines.  Best of luck to you.

 

Pers,

 

You are so frigging smart. And that you impart your knowledge with such clarity and eloquence awes me

 

WWWI

I ditto that !!! :thumbsup:

Well... DARN IT

 

Thank you so much for that explanation--I needed it handed to me that way 'cause sometimes reading too much = 

 

I had thought I'd come across a fantastic way to kill two birds: benzo w/d sucks (prog could help!) and my hormones suck (prog could help!)  However, I see now that I could, just like that, create another problem for myself. 

 

This is the first I've heard that benzo's and w/d can play a part in hormones.  I thought I was simply taking after my mother with all my hormonal probs at a relatively young age.  In fact, it was before I started taking klonopin that the progesterone was giving to me, because I showed low in it.  It was immensely helpful.  But, now, whether my hormone issue exists (or existed before the benzo), it looks like I should just steer clear. 

 

I'm going to have to grieve the loss of what I thought was a brilliant idea. 

 

Thanks again, so much, for your info--I appreciate it very much!

 

Warmly,

Melodie

Melodie, glad the information helped.

 

WWWI & PG- you guys are making me blush, lol!!!  You guys are not too shabby yourselves...I always thouroughly enjoy reading your posts.

Thank you for the info Pers - sorry it took so long to get back, this cog fog has left me with the inability to read with any kind of understanding.

when I get to the end of sentence line, I find it hard to find the beginning of the next line 

 

I've printed out the info, and truly hope that I don't need the Prog.,

 

I think my hormone levels are pretty screwed up right now, this last week my depression and anxiety are high.

Could just be a wave though.  I'm fighting through it though.

 

I am amazed at how you can be so mentally adept through all of this 

You rock!

 

Thank you

Not surprising Kimba- benzos effect so many hormones.  Good to see you take the fighting attitude!

Bump

Well my symptoms got too bad during my period that I could not taper and was becoming suicidal. Tried continous bc pill  and updosed. Helped for a bit but then I think the estrogen was too much. I was trying to take it continuously and I kept on bleeding for 4 months. Stopped pill and felt better in a few days. Tried prog. cream for 2 days, made things worse. Going to try another bc pill with lower estrogen. I absolutely cannot tolerate my natural Progesterone going up and then down. Might as well quit c/t If I want to feel that bad. Just sharing my experience. Progestins don't act on GABA receptors from what I understand.

Mm

Sorry you are having a tough time with your hormones. Progesterone fluctuations do seem to be a problem for some of us in withdrawals.

 

There is evidence that the metabolites, (breakdown products) of progesterone do act on GABA A receptors, so are similar to benzos in that respect.

Please be careful if you take progesterone. I am 1.25mg of klonopin. Have been tapering for years very slowly due to cold turkey withdrawl back in 2003. I have been on estradiol/testosterone sublingual for 12 years and was doing fine until last year when my estradiol was too low. I saw my gyn and we decided to bump it up and I suggested adding in a little progesterone which is bioidentical. My doctor did tell me that it helps some and other women hate it. He added it in to my sublingual so I really didnot know what is was doing to me. I thought the estrogen was causing problems so we kept tweaking my progesterone which in turn was driving down my estradio. Anyway after 7 months of being on 60-125mg per day, we lowered to 50-100mg and started taking it alone at night. It gave me panic attacks, confusion, derealization etc. I stopped abruptly which was a huge mistake. I am a month out and still feeling like I am in a mild benzo withdrawl. Mild meaning nothing like my cold turkey. I am having awful anxiety at times, gut problems, muscle pain and twitching, insomnia, depression just to name a few. I will never take this again. I did some research that progesterone withdrawl can render benzo's not as effective. You live and learn. I really thought I had learned everything since going through the benzo mess for years. I went on a site to rate the hormone and there are so many women that have had terrible problems trying to get off progesterone. I pray that I get through pretty quick and just wanted to let everyone know the dangers of being on this for too and at a high dose.