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  #1  
Old 12-18-2012, 10:20 PM
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Premature aging of the HPTA axis?


I've heard that use of anti-epileptic drugs, specifically the enzyme inducers, can cause "premature aging of the hypothalamic-pituitary-adrenal axis (HPA or HTPA axis)"

This got me wondering what something like that would look like? If your HPTA axis has prematurely aged due to anti-epileptic drug use, what would the symptoms be? What tests would show up abnormal if any?

I anyone out there has any info on this subject it would be greatly appreciated as I try to sift through my anti-epileptic drug choices.

Thanks.
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Old 12-19-2012, 05:04 PM
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Something similar can occur with chronic alcoholism, or chronic stress. Premature aging of the HPA axis basically means an acceleration of the aging process for the entire body. You might start to suffer from hypertension, cardiac dysrhythmia, cancers, gastrointestinal disorders, neurocognitive deficits, bone loss, and emotional disturbances -- at a younger age than would ordinarily be expected. The effect is gradual, but the net result is that you start to fall apart faster than people of comparable ages and backgrounds.

Keep in mind that while some anti-seizure medications may stress the HPA axis, chronic seizures can also have that effect.
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Old 12-20-2012, 12:54 PM
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So, are there any tests from bloodwork that might be leading indicators before your body starts to fall apart? I've had some bone loss from anti-epileptic drug use, but otherwise my body feels fine.

I do feel tired and have sexual issues, but I believe those to be from the drug I take now and therefore I am going to switch. I just wanted to know what to look for in order to identify any HPA issues before they may start.
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Old 12-20-2012, 03:55 PM
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There aren't any particular tests other than a general check-up for things like high blood pressure, or a bone density scan. If you are basically feeling fine, then that's the main thing.
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  #5  
Old 12-24-2012, 12:21 PM
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Well thats just it.. I feel like I'm not as mentally sharp as I used to be, I have some light bone loss, and some sexual effects, but I don't know if it is the drug I currently take or the result of the old drugs I took, that are more known for HPA axis issues.

So, I was looking for other signals that my help me make my decision on whether to go back to my old drugs or not. The docs just seem to look at me blankly when I bring this stuff up and they say it is my decision, since my seizures are generally controlled either way. I just didn't want to make a mistake and go back to a drug that may have done something to my HPA axis and therefore make it worse.
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Old 01-21-2013, 11:37 PM
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Nak,

I wondered if you knew what exactly causes this premature aging of the HPA, when it indeed does occur? Is it the anti-epileptic drug actually aging the hypothalums or pituitary?

Does Dilantin or other enzyme inducers affect cortisol production and; therefore, over the long term, lead to issues with HPA?

I've been researching this, but have been unable to find specificity on how Dilantin and other enzyme inducers actually cause this premature aging other than to say that it can happen though doesn't always happen.

Hope that wasn't confusing.

Thanks,

D
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Old 01-22-2013, 08:12 PM
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The Dilantin doesn't directly age the hypothalamus or the pituitary. The enzymes that it induces in the liver are steroid-metabolizing ones. As a result, corticosteroids are metabolized faster, and the rate of cortisol production speeds up in response. If you're system is stressed in other ways, the result could be elevated cortisol over the long term, which can affect the body in multiple ways.

From what I can find, the cases where Phenytoin proved problematic in this manner were patients who were already suffering from adrenal issues (such as Addison's Disease). The risk factor seems small, but if you're worried you can easily have your cortisol levels tested using the adrenal stress index (ASI), a saliva-based test. It's a very reliable measure of cortisol levels and adrenal function.
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Old 01-22-2013, 10:50 PM
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I wonder if taking Dilantin for many years and then stopping it, would cause you to notice the excess cortisol more than continuing to take the drug.

In other words, if the dilantin enzyme production catabolizes the excess cortisol, but then the drug is stopped, I am assuming this faster metabolization process would end, but your body might still be primed to produce more cortisol causing those levels to rise.

Or, as soon as the faster metabolism slows down from ending the usage of the drug, would the body would automatically stop producing more cortisol?

I bring this up because, as you know, my "not feeling right" issues didn't begin till I ended my Dilantin usage.
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Old 01-23-2013, 07:35 PM
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If they were high, your cortisol levels/production should most likely have returned to normal after you stopped using Dilantin. But the HPA axis is incredibly complex in how the different parts of the system interact. You might want to have a cortisol test done now, just to see how your levels stack up.
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  #10  
Old 01-23-2013, 10:19 PM
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If I can convince my docs to do this type of test (never easy) is there any other test that should be done besides a straight cortisol test? ACTH? Anything else?

I'd like to avoid missing any test that might be pertinent since I prefer not to have go back to the doc any more than is necessary.

Thanks.
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Old 01-24-2013, 09:23 PM
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Make sure it's the saliva cortisol test, (which is non-invasive and most accurate), and have the DHEA-S checked as well. If your doctor is hesitant, you can order the kit and do the test yourself: http://www.healthtestingcenters.com/...-test-kit.aspx
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Old 01-25-2013, 12:24 AM
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Thanks for the info. I wish my GP could do this stuff, he seems the most understanding overall.

Why is getting the DHEA-S important in this scenario? What should I be looking for in that regard?
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Old 01-25-2013, 03:00 PM
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The DHEA-S is another indicator of adrenal health, as well as being a necessary precursor to testosterone.
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  #14  
Old 02-14-2013, 04:31 PM
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Well, I saw the endocrinologist today and he wouldn't do the DHEAs or Cortisol test. I am sick of trying to get different docs to check into things as a preventative or just to check, when there is clearly something wrong and they clearly don't know what to do.

In the meantime he flip flopped again and said I don't need testosterone and since I have slightly elevated Prolactin he noted that "if I was really desperate" I could take Cabergoline with my Keppra and see if that made any difference.

And of course, he recommends the Keppra over Dilantin.. I may be giving up on docs for awhile. A waste of time and money.
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Old 02-24-2013, 06:01 PM
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Originally Posted by Nakamova View Post:
Make sure it's the saliva cortisol test, (which is non-invasive and most accurate), and have the DHEA-S checked as well. If your doctor is hesitant, you can order the kit and do the test yourself: http://www.healthtestingcenters.com/...-test-kit.aspx
Has anyone used any of these self testing kits? Do they go through normal, trustworthy labs? And are the results considered as reliable as those ordered by docs?

My endo wouldn't do a simple DHEAs or cortisol test despite me explaining my questions shown in the previous entries of this thread..
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Old 03-13-2013, 11:16 PM
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Well, I spoke to my GP, since I'm getting my yearly physical, and he said he couldn't do the DHEAs or Cortisol either, since he wouldn't know how to interpret the results. He said an endo should do that, of course my endo didn't want to the tests, as he says they are unnecessary.

Nevermind that he didn't want to do in depth hormone testing on me either at first, since my total T is normal. But after convincing him, he now asks if anyone did those tests before I changed meds and started feeling "off." You'd think based on a question like that he'd see the benefit in just establishing a baseline prior to a drug change, regardless of whether or not he deems a particular test necessary.

I don't know what other docs to turn to get the tests. I see my GP and my neurologist at the beginning of next month, and I guess I'll just have to make the med change, yet again, without getting the full battery of tests I want done. Docs, their rules, and their lack of knowledge is absolutely frustrating and make me want to tell them all to hit the bricks.
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Old 04-12-2013, 01:14 PM
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Nak,

I finally got a DHEAs and Cortisol test. They were both blood tests (not saliva). Don't know if it matters, but I didn't sleep much at all the night before (not unusual for me on Keppra). I asked the doc about this and he said the lack of sleep might elevate the Cortisol a bit, but he thought numbers looked fine for me adrenally speaking..

Cortisol: 19 ug/dl Ref Range: 8 - 19
DHEAs: 344 ug/dl, Ref Range (males in my age range) 33 - 416

Do you have any thoughts?
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Old 04-12-2013, 09:13 PM
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I agree with the doc, those numbers are fine.

The normal cortisol range can vary depending on time of day the test was done. The levels tend to be very low at bedtime and highest just after you wake (normal morning reference range = 5 - 23). Though as you noted, the pattern can change if your sleep is off.

Your DHEAs looks good also. The typical normal range for males (according to the NIH) is shown below:

Ages 18 - 19: 108 - 441 ug/dL
Ages 20 - 29: 280 - 640 ug/dL
Ages 30 - 39: 120 - 520 ug/dL
Ages 40 - 49: 95 - 530 ug/dL
Ages 50 - 59: 70 - 310 ug/dL
Ages 60 - 69: 42 - 290 ug/dL
Ages 69 and older: 28 - 175 ug/dL
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  #19  
Old 04-12-2013, 10:17 PM
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Thanks for the info. I also had my yearly physical this past week and managed to get the GP to do a testosterone test and thyroid with TSH and T4.

The TSH: 1.461 Range:.550 - 4.780
Free T4: 1.00 Range .89 - 1.76

So, I guess with the good adrenal numbers and normal Thyroid numbers, I look okay in that regard.. I wish there was a test besides Prolactin that could verify that Pituitary was working fine and then I'd feel better about the all those things before switching drugs.

Strangely, the testosterone was lowest it has ever been... Of course, I didn't sleep hardly at all again the night before this testing as well, so I don't know if it matters or not. It was 439 on 241 - 827 reference range. I've never had one below 620 in my life and they are usually around 700..
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Old 04-05-2014, 12:24 AM
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This is an old thread, but I wanted to revisit because of the overall idea of premature aging due to anti-epileptic drugs, specifically Dilantin.

Looking back, since I switched off of Dilantin, I've seen the issues I already mentioned previously in this thread, plus overall Testosterone numbers declined (though still in the mid normal range), some loss of body hair (though others wouldn't notice it and Dilantin can increase that so maybe its just return to norm), increase in things that older guys get like more ear hair, and I've noticed some slight creasing of the ear lobes (which may or not mean anything, though some associate that with cardiac risks).

All that said my blood pressure is normal, I exercise, and I'm not overweight, and my cholesterol numbers have always been below 200 (which is what I'm told is appropriate).

I still sometimes think about going back to Dilantin (because I felt great while taking it), but wonder if it may have indeed caused me to age faster than normal.

Anyone have any thoughts? I'm just wondering aloud here..
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