Progesterone cream and Gilberts Syndrome

by Lee
(Australia)

I have Gilbert's Syndrome and since using Natpro progesterone cream for the last 12 months the Gilbert's Syndrome has been so much worse and a recent blood test confirmed my bilirubin is at the all time highest it has ever been.

My Doctor told me that Progesterone is a trigger for Gilbert's Syndrome, can you please shed some light on this?

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Progesterone cream and Gilberts Syndrome

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Nov 07, 2010
 Progesterone cream and Gilberts Syndrome
by: Wray

Hi Lee Oestrogen is a trigger, I can find no evidence progesterone is, the reverse in fact. I'm not sure how much progesterone you are using, but it would appear too little. This sounds paradoxical. The reason being insufficient progesterone stimulates oestrogen, this would keep you in an oestrogen dominant state. I recommend 100-200mg/day, probably the higher amount would help you. Interestingly the list of symptoms for GS on this website, are, bar a few, the same symptoms for excess oestrogen/low progesterone. People with GS have a problem processing oestrogen, see here. Candida can cause bilirubin levels to rise. Candida is exacerbated by oestrogen, whereas progesterone is protective, see here. UGT's play a role in the glucuronidation of oestrogens, but as these are low in GS, oestrogen rises. Oestrogen appears to involve disruption of the membrane transport mechanisms in the hepatocytes and bile ducts. 17{beta}-Glucuronides of oestradiol and oestradiol-17-D-glucuronide are known to induce cholestasis, or malfunctioning of the liver, causing inhibition of bile flow. Unconjugated bilirubin, due to reduced activity of UGT, leads to injury of glial cells, which leads to the secretion of glutamate and inflammation. Progesterone enhances UGT1A1 transferase activity, plus it's made by glial cells and suppresses both glutamate excitation and inflammation, see here. Oestrogen activates the excitotoxic glutamate pathway, and interferes with protective adenosine inhibition of nerves. Progesterone increases the release of adenosine, see here. Excess thyroid hormone and ethinyl estradiol inhibit bilirubin glucuronidation. Interestingly cholestatic jaundice can occur in pregnancy, manifesting in the third trimester, when oestrogen is high. Jaundice and abnormal liver function can be induced with estinyl estradiol. There is evidence cholestatic jaundice increases in winter, you?ve just had a test showing high levels. It could be you have low vitamin D levels. As you live in Australia, this is more than likely, as Australia has a policy of covering up and using sunscreen. This prevents vitamin D from being made, please have a test done. For more info please see the Vitamin D council website. Take care Wray
Nov 08, 2010
 Re Gilberts Syndrome and progesterone
by: Lee

Hello Wray, thank you for your comments. I do not have low levels of vitamin D and I don't have candida both these tests were included in the large panel of tests I had just recently when I had my regular thyroid hormone test. I don't have a thyroid but my TSH, T4 & T3 are perfect at present. I have been using the high doses of the progesterone cream twice a day but I will increase it again. Thanks once again for all your info, regards, Lee, Australia.
Nov 10, 2010
 Re Gilberts Syndrome and progesterone
by: Wray

Hi Lee Glad it was of help, and relieved to hear your vitamin D is fine. Take care Wray
Jan 18, 2011
 Progesterone and bile flow
by: Al

I read everywhere that progesterone is good for bile flow and estrogen is not.

I don't know about estrogen, but the information I have found on progesterone concerning bile flow is that it actually reduces it.

''Progesterone administered as subcutaneous implants alters partitioning of hepatic bile between gallbladder and small intestine and, therefore, gallbladder filling. Progesterone also significantly impairs gallbladder emptying in response to cholecystokinin. The effects of progesterone on the sphincter of Oddi and the gallbladder may contribute to the greater prevalence of gallstones and biliary motility disorders among women.''

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1191632/

''After 3 days of pretreatment with progesterone (3 X 50 mg/kg b. w. i. p.) bile flow and TBA-excretion were diminished.''

http://www.ncbi.nlm.nih.gov/pubmed/752214

I can't find any study that says that progesterone relaxes the galbladder and increases bile flow.

Thank you.
Jan 22, 2011
 Progesterone and bile flow
by: Wray

Hi Al The first paper is confusing, as they use the word progesterone in the abstract. But reading the full paper, it says "The method of administration of progesterone used in this study was specifically chosen because of the similarity to long-acting contraceptive implants recently licensed for use in the United States." And "Further, these effects of progesterone on biliary flow dynamics raise concern regarding the risk of gallstone disease in those exposed to prolonged and sustained levels of progesterone, such as occurs with contraceptive progesterone implants." One has to assume that the 'progesterone' used was not, but was a progestin. The second paper is interesting, as it says "Progesterone administration....2 hours before bile sampling increased bile flow and bile acid excretion..." But apparently bile flow diminished after 3 days of administering it, as you've pointed out. I can't comment on this as the full paper is in German. Maybe it was not of sufficient duration, or had the progesterone stimulated the oestrogen receptors, I don't know. What I do know is that progesterone does relax smooth muscle, whereas oestrogen constricts it. The gallbladder does have progesterone receptors, so the gallbladder is relaxed under the influence of progesterone. I read this as beneficial, as the gallbladder is better able to empty itself in response to a high fat meal. Evidently the researchers query this, see here. And to compare pregnant women with their greater incidence of gall stones to men is extraordinary, better to compare with non-pregnant women, and over the full menstrual cycle too. Obviously to their mind progesterone is the culprit, but no cognisance is taken of high oestrogen levels, which can be significant, see here. This is another paper on motility, see here. Gallbladder emptying time is longer during peri-menopause. No reason for this is given, but progesterone levels are dropping during this phase, whereas oestrogen is not, see here. There is evidence oestrogen causes abnormal liver function, see here, here, here, here. Whereas progesterone increases bilary output of cholesterol, see here. Take care Wray
Nov 15, 2011
 Progesterone and bile flow
by: Al

Dear Wray, I tried progesterone cream a few times and everytime I had to stop because my liver started to feel like it was in some sort of spasm. My stools also got lighter in colour which I know is a a sign
of less bile output. So I had to stop using the cream.

Here is another study showing progesterone decreasing bile flow:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1191632/pdf/annsurg00002-0057.pdf

Would appreciate your opinion on this study.

Thanks.
Nov 15, 2011
 Progesterone and bile flow
by: Al

Hi me again. Forgot to ask you about your comment about how an insufficient progesterone dose would increase oestrogen. Thanks.

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