Menopause Matters Forum
Menopause Discussion => Other Health Discussion => Topic started by: Tc on July 11, 2019, 12:54:35 PM
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I was diagnosed in my 20's. It's a genetic disorder where the faulty gene causes bilirubin to not passed into bile at the normal rate and it builds up in the blood.
I was told although It can cause jaundice most people have few other symptoms And it's a relatively harmless condition. So as a result I have given it very ittle thought in the last 30 years. I always have high readings but normal liver function which Is a feature of it. My Gp was going through my bloods today and said "high bilirubin, but we know that's because you've got Gilberts". Not unusual, but today it set me thinking.
So I looked it up on the NHS site. Something I've never done before and it said
Symptoms inchude
Tummy pain, fatigue, dizziness, nausea, IBS, brain fog and generaly feeling unwell.
more importantly there was a list of possible triggers associated with the condition:
Dehydration, fasting, lack of sleep, infection, surgery, stress and,... wait for it ....MENSTRUATION.
A link to hormones!!
I wonder if this so called "harmless disease" which I have dismissed over the years because I wrongly thought it's only symptom was jaundice could be causing me problems now especially all my issues with HRT and particularly oral utrogestan.
I'd be interested if anyone has the condition how or if meno and HRT has affected it and vice versa. But I'd also be interested on any thoughts/ideas of you ladies who dont have it as well.
Thanks in anticipation. Xxxx
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Hello Tc,
I thought you might be interested in this https://www.ncbi.nlm.nih.gov/books/NBK470200/ particularly the Toxicokinetics.
I used to teach Genetics at Uni, many so called 'normal' enzyme deficiencies and variations are still poorly understood, because there are so many possible interactions with new chemicals (meds and xenobiotics).
On the bright side, read 'Pearls and Other Issues' :)
BeaR.
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Three of my sons and their father have been diagnosed with Gilbert's disease, two youngest are affected more severely, my youngest son can go quite a nice shade of yellow!
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Thank you bear. Just had a look. It's so interesting about the toxicokinetiks. I do wonder whether because its metabolized in the liver that could be why I'm having such severe reaction to utrogestan.
It seems to build up in my system very quickly.
. Good to see there is something actually positive to having it as well.
That mustve been such an interesting subject to teach genetics, though extremely complicated!!
Thanks for taking the time to send me the linkx
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Tinkerbell. I dont get the jaundice severe. But my dad does. Like you say it's a definite yellow and the whites of the eyes as well.
X
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I've been reading more about it. I read that studies have shown Gilbert's syndrome can affect how a drug is processed or metabolised by the body. In some cases increasing toxicity. Theres quite a lot about it online. But I cant find any mention of utrogestan. It could explain why as it accumulates in my system my symptoms get steadily worse but then suddenly it seems to get to "overload" point and I then I feel very ill very quickly.
I stopped it on Monday night after 12 days but at 10 days i felt exhausted nauseas pounding head. and by yesterday started shaking, sweating profousely and felt faint. I still felt the same this morning and at the docs she gave me diazepam cos I was shaking and sweating so much but it wasnt anxiety driven. this happens every time I take it. It's a definite pattern.
Maybe taking it orally just increases all the bad side effects for me because of the GS.
Its realy got me thinking.
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There are going to be ladies who don't like what I am going to write now because it is a somewhat controversial subject and some have voiced their opinions that it is "irresponsible". I am not sure why because it is something which can be clearly read of Professor John Studd's website regarding progesterone intolerance. He uses a 7 day regime only for utrogestan on a cycle with gel. Nick Panay (Studd's student) at Chelsea and Westminster has also used this for some of his ladies and there are those who have written about it on this website - have a look to see if you can find the posts.
Having made a bit of progress, the progesterone is obviously a problem for you in either the length of time or the dose. You should play with these before changing to Provera. Check out Studd's website, there is loads written there.
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Lady. The last gynae I saw has referred me to panay. She suggested 7 days to me. And put on my letter to doc that I can take it for 7 days until I see him. So she put it in writing. My gp.read it today and said its o.k with her as it's what my consultant has said. This consultant is in the process of heading her own meno clinic at the hospital by 2021. She knew all about panay and studd. And she recommended 7 days.
This is my own fault. I felt good at day 7 so I pushed to 12 days. Big mistake.
Xxx
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Tc, your case is very interesting (sorry, I know you're struggling) because progesterone has been shown to bind to the region (promoter) that regulates the expression of the UGT1A1 gene, enhancing its activity in a concentration dependent way. A mutation (actually several different variations) in the UGT1A1 gene is responsible for Gilbert's Syndrome.
Considering that your UGT1A1 gene is defective, an increase in activity induced by high levels of progesterone may be causing the production of intermediate metabolites (produced by a defective enzyme) that your body is not used to handle. This is only conjectural, but it's very interesting regarding progesterone intolerance.
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Bear. That is so interesting. Thank you so much for that info. I've struggled so much since ovary removal and with HRT. I was told I "dont fit into the box". In the way my body is reacting.
I've been referred to Chelsea and Westminster as they deal with eastrogen absorption and progesterone intolerance problems. I am on very high dose eastrogen and my blood seum level has actually dropped as though I'm not on any eastrogen at all. My own gynae had to admit I need more specialized help. Something unusual is happening and it so far has them stumped.
Thanks for taking the time to reply. I've learned a lot about GS today that I didnt know. Including that menopause can trigger GS symptoms!!
I was also amazed to read that
"billirubin is involved in the metabolism of eastrogen and other drugs , therefore individuals with GS may be susceptible to toxicities from these substances which require glucoronidation for metabolism "
Im not sure if that applies transdermal eastrogen although I dont seem to be metabolizing that properly either but if it applies to oral eastrogen then why not oral progesterone.
I'm intrigued.
X
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Tc, please read 'Hepatic processing of bilirubin' in this article https://www.tandfonline.com/doi/pdf/10.1080/10408363.2018.1428526
Estrogen and testosterone are inhibitors of UGT1A1. Progesterone isn't.
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Hi Tc
Have you tried the Utrogestan vaginally?
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Bear. I've read it again and seen that bit. It's a bit complicated for my little brain but does that mean that E and T can cause billirubin to rise? It doesnt mention P. I'm not sure if it only applies to oral exogenous E and T but the fact that the bodies own E and T can cause fluctuations might suggest not. I'm on E patches but I also use Testosterone gel. Thanks bear.
Northern, hiya. I tried once and it kept falling out!! I think it's the way to go. Next round I will use it vaginally and see if it makes a difference.
Xx
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Tc,
Estradiol metabolism is the same, once it reaches the bloodstream, no matter if it comes from endogenous or exogenous sources. Of course transdermal delivery bypasses first liver metabolism.
According to this estradiol patch (Estraderm) leaflet:
Metabolism
Transdermally applied oestradiol is metabolised in the same way as the endogenous hormone. Oestradiol is metabolised to oestrone, then later – primarily in the liver – to oestriol, epioestriol and catechol oestrogens, which are then conjugated to sulphates and glucoronides. Cytochrome 450 isoforms CYP1A2 and CYP3A4 catalyse the hydroxylation of oestradiol forming oestriol. Oestriol is glucuronidated by UGT1A1 and UGT2B7 in humans. Metabolic plasma clearance ranges from 650 to 900 L/(day x m²). Oestradiol metabolites are also subject to enterohepatic circulation. Oestradiol metabolites are far less active than oestradiol.
https://www.medicines.org.uk/emc/product/5838/smpc
As you can see, estriol is glucuronidated by UGT1A1, so in theory, your estriol levels are higher than expected, but that of course is not the entire picture, because the other enzyme might be doing the job.
Regarding progesterone, there is not much data. It's known that it increases UGT1A1 levels, but it's not metabolised by this enzyme.
I'm very interested in the subject of pharmacogenomics, so I'm more than glad to further investigate this. It also helps me forget my persistent depressive disorder.
I think taking Utrogestan vaginally would be a good option to bypass hepatic metabolism. It is known that both oestrogen and progesterone levels are on average 3 times higher in the liver than in the bloodstream, so usual blood tests don't show the bigger picture.
BeaR.
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We R a mine of info. :thankyou:
R U getting support for the depression? :bighug:
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Hello CLKD, not yet. I am seeing a psychiatrist soon (4 weeks). Thank you for asking.
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I have a long thread somewhere about my own depressive journey. Medication has really helped me to survive. Of course, being meno-brain, can't remember the title :D ::)
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I will run a search. What type is yours? Mine is the persistent depressive type which is different from the major depressive type. It's known to be less responsive to psychotherapy and medication.
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Organic and clinical. Once I found medication .......
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Bear.
Thanks so much for taking the time with your thoughtfull replies.
My serum E blood level is lower than expected. 250.mcg of patches giving me <200pmol. Symptoms arent controlled either. Its realy what's causing the main issues. They cant understand why levels arent rising after 9 months!!
Enough about me. Its lovely to chat to you. I dont think our paths have crossed before.
Sorry to hear you are suffering PDD. Have you been treated in the past for it?
Xx
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You're welcome, Tc.
I have never been treated for depression, this is a recent diagnosis, though in hindsight I know I've been suffering since early childhood. I guess my family was in denial and I have learned to cope with it by thinking this is just a personality trait, but now I know it's not.
I love chatting on forums, much easier than facing real social interaction :)
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Have bumped my thread - now that's going some for a person with meno-brain ::)
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Thank you, CLKD. :)
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I know exactly what you mean bear did you have to wait a long time to see phychiatrist.?
You dont have to answer. Just you've been so interested in me and I've hardly asked you anything.xxx
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I have an appointment with psychiatrist in 4 weeks. I was pre-diagnosed by a psychoanalytic therapist.
I think your HRT issues are far more interesting than my depression... actually I just want to forget it, probably another of its symptoms.
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Got ya bear!! I suffer myself so I understand completely.
You realy make sense of all that baffling stuff so thanks so much. Xxxx
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You're welcome :)
Are you taking testosterone? It decreases UGT1A1 activity... just to further complicate matters!
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Yes I am. Added it about 3 months ago. Havent noticed any improvement. The gynae who referred me to the panay clinic said they should try implants for E and T but I'm not getting my Hope's up
What sort of specialist deals in these matters. I know Gilbert's comes under liver but I've often wondered if an endocrinologist might be better placed to see why I'm not processing the HRT.?
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Yes, I think an endocrinologist would be very helpful!
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I did think that. Ovary removal seems to have unbalanced my whole system. I cant ask yet as I've got to see Chelsea and Westminster first. I was quite lucky to be referred there. You know how these things work, if I ask now the GP will say "one thing at a time, let's see what they say first"
Xxx
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Ovary removal is certainly a shock to the body. There are many studies on ovariectomised animals showing that the brain response to fear, stress, anxiety and depression can be impaired. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697241/
Mr. Panay's team sounds brilliant, make sure you have all your medical history written down, including your Gilbert's diagnosis. Good luck ;)
BeaR.
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Hello.
I am picking up your feed from years ago ... maybe you are still around for me to ask you a question ... I have Gilbert's Syndrome and am on HRT. I've suffered terrible side-effects from utrogestan (depression and suicidal ideation - it was truly awful) GP's only answer was to stop prescribing me HRT unless I continue to take Utrogestan. Not great and I am afraid I have found my GP to be very poor at helping me with this.
What was the outcome of your investigations? Did you find a way to make your HRT work for you? I want a hysterectomy tbh, so that I can take HRT without progesterone element. But NHS has refused. I appealed, but they refused again. I found your thread and it's been helpful. If you are still around on the forum, I would love to know how things got resolved for you...
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Hi Joe-Bean - have U asked your GP to refer you to a dedicated menopause clinic? Not to a Gynae as they often don't know much more than some GPs seem to.
In the mean time keep a mood/food/symptom diary to chart progress. How old are U? Who over-sees your Syndrome?
Many find progesterone part of the regime difficult, I believe that 1 can have a long cycle with regular scans of the womb. Have U actually been referred for a. hyesterectomy or did your GP simply refuse to refer you? U may find 'hyster-sisters' website of use too.
Let us know how you get on.
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I don't think she's posted for a long time but she's still a member so it might be worth sending her a pm? If I remember correctly she gave up on hrt because she couldn't get oestrogen into her system. I think the last posts were about the oestrogen implant but her body formed a cyst round it so she couldn't get anything from that either.
Have you tried other forms of progestin? It's just possible you'll tolerate something else a bit better. If you haven't been referred to a meno clinic I would ask for it as this is probably beyond what a gp can deal with. Cyclogest, lutigest and provera are sometimes tolerated better than utro. I wish you luck, this thread doesn't make it sound very promising :(.
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Thanks for lovely replies. Very kind.
I was referred to Menopause Specialist Clinic, Oxford, but that was before I realised my high bilirubin levels (normal is up to 20 and mine are 48!) They weren't terribly helpful I am sorry to say. A phone call, twice over six months and the second call was a new doctor who hadn't read my notes, so was just a rerun of my first call. Plus my GP didn't send on my blood test results, even though she told me she had them but couldn't understand them and I should wait for my specialist to see them. Go figure!!
The whole experience wasn't very positive to be honest and I feel very alone in this.
My GP didn't even mention my very high bilirubin - luckily I can see my results on the NHS app because they are sky high.
So I am researching and that's how I came across this thread. I am 53 and have been suffering now for 3 years. I am self employed and have had to cut back my hours by 50% to be able to cope with life. It's difficult.
Hey ho. Onwards. There's some new dietary stuff to try and I am learning a lot. Maria Allerton in Australia has some great resources for anyone who is facing this.
Thanks for your replies. I do appreciate them.
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JoeBean - that's awful.
Sorry that the Clinic wasn't any help, that isn't good enough either >:(. No wonder you feel alone.
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I have Gilbert's Syndrome which I inherited from my father. My sister has it too.
I didn't know I had it until about 17 years ago and the levels vary on blood tests but I don't think it is without symptoms as is sometimes suggested. It certainly complicates oral HRT so it's best to go for transdermal forms. I also think the effects worsen with age particularly the fatigue and the IBS. You will find that colds affect you badly too. I never did understand how someone could have "a bit of a cold" because I always had a lot of a cold and felt absolutely dreadful for ages. One of the many reasons I moved to Spain was to avoid the endless colds I used to catch.
Do you have direct, indirect and total bilirubin checked every year? Not that there is anything you can do about it!
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Hello.
I don't routinely have my bilirubin levels checked, but I am going to start now that I realise that high bilirubin levels are a sign that your liver is not coping with what it is having to process. I also need to get the bottom of this for my lovely daughter so she doesn't suffer as I have.
Now I know more about how Gilbert's Syndrome effects my body it makes sense that I had endometriosis, an ovarian cyst the size of a cantaloupe melon (removed by oopherectomy) and heavy, painful periods with clots. These are all caused by high oestrogen levels because my liver cannot process oestrogen like women without Gilbert's Syndrome - the oestrogen stays in my system and causes problems.
For anyone else struggling with this - I have discovered that with Gilbert's Syndrome, the body is unable to process oestrogen fully, so it gets returned to the body and ends up in the gut, causing loose, pale stools and faecal urgency. The body gets overloaded, I have itchy skin flare ups too. I am exhausted and have suffered very painful joints for 3 years now.
Every peri/menopausal woman with Gilbert's Syndrome should be...
1. taking Calcium D Glucarate (helps liver function) and Zinc, but also potentially a probiotic with BIFIDO in it to help balance the gut flora that gets thrown off by all the oestrogen floating about your gut.
2. taking the lowest transdermal dose of oestrogen that you can to cope with your meno symptoms. Don't take oral oestrogen because your liver can't cope with it.
3. avoiding fat soluble vitamins like B3, A, K as they have to be processed by the liver and your liver is likely already overloaded.
4. eating no/very low saturated fat, your liver can't process it. Healthy fats all ok.
5. reducing alcohol intake to minimal amounts or none - so that you don't overload your liver.
6. avoiding taking paracetamol or ibuprofen (or any meds) unless you really have to.
7. avoiding high intensity cardio exercise as this causes bilirubin spike. Do weights, yoga and walking instead.
Progesterone doesn't seem to be processed in the same way by the body (the liver glucoridation pathway) so I am not sure why my first primary symptom was progesterone intolerance. I now take bio identical progesterone 100mg (1 x utrogestan tab) every other day, inserted vaginally (as recommended by Dr Louise Newson). This works for me. Not taking things orally reduces the stress on your liver. Perhaps progesterone was just another medication in a bodily system that was already struggling ... just too much.
GPs just don't know about this and are not interested. They just say come off HRT, but then you get all the night sweats, heart palpitations, etc that come with menopause. And if you don't take HRT you lose all the protections it gives a woman with regard to osteoperosis, Alzheimer's and heart disease.
The solution is not to come off HRT, but to find as many ways as you can to support your liver so that HRT works for you.
I really hope this helps someone else. There isn't much research around Gilbert's Syndrome as medical schools routinely teach that there are no symptoms. Sufferers can tell you that there are indeed symptoms. Serious, life-altering ones.
I am still on my journey and will report back if I find out anything new on this subject and to let you know if I finally overcome my exhaustion, brain fog, joint pain and IBS symptoms - none of which I ever had before menopause.
Thanks for this forum.
Thanks for your kindness.
xx xx
PS Here is a really helpful podcast from Australia https://www.fxmedicine.com.au/podcast/gilberts-syndrome-maria-allerton-n%C3%A9e%C2%A0shaflender
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:thankyou: .......... let us know how you get on. Which specialist would over-see this condition? Endocrinologist?
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JoBean. As I said I have Gilbert's Syndrome but don't have the problems you describe. I don't drink alcohol or take ibuprofen and I take zinc and probiotic anyway.
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JoBean. As I said I have Gilbert's Syndrome but don't have the problems you describe. I don't drink alcohol or take ibuprofen and I take zinc and probiotic anyway.
Yeah, not for you. More for anyone else who finds this thread as I did and could do with knowing what I've so far discovered. Cheers.
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Thanks JoBean, I'm sure this information will be useful to others :).
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JoBean. As I said I have Gilbert's Syndrome but don't have the problems you describe. I don't drink alcohol or take ibuprofen and I take zinc and probiotic anyway.
Yeah, not for you. More for anyone else who finds this thread as I did and could do with knowing what I've so far discovered. Cheers.
My bilirubin has never been mentioned since the day I was told I had Gilbert's syndrome. It's strange. If it wasn't that my cousin has it I'd wonder if it was a mistake
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JoeBean, thanks for all that information, it's very useful. I definitely have flare ups because very occasionally my bilirubin levels are normal. When I had a full Bupa health check at work in 2000, my bilirubin level was borderline and just about normal so it has definitely got worse since the menopause.
There are a few positives with Gilbert's and apparently it does protect you from some diseases.
Please keep up updated the your progress and on any new Gilbert's info.
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I am so glad to find this thread as was diagnosed with GS at 17 and despite too many doctors saying it's not a problem it has been totally debilitating at times of high stress and when my sleep is bad. Has HRT helped with GS symptoms?