Aromatase Inhibitors and Joint Pain

Discussion in 'Men's Health Forum' started by Structure, Mar 13, 2011.

  1. Structure

    Structure Member

    Are any readers of this forum taking aromatase inhibitors? If so, I'd love to hear about your experiences.

    I've been on a low dose of anastrozole for about three or so months, but it appears that I'm taking too much --- I've had wrist pain for about a month now. My morning E2 (before daily adex dose) is 15 ng / mL. In hindsight, I'm guessing it should probably be twice this value...

    I've found plenty of information about the joint problems associated with aromatase inhibitors (see for example A prospective study of aromatase inhibitor-associa... [Cancer. 2010] - PubMed result). However, none of the studies mention whether joint pain is dosage related, presumambly because the studies are done on women with breast cancer where the goal is to get rid of as much E2 as possible.

    Have any of you noticed that joint pain goes away if you lower your dose? Or is it one of those either-you-get-it-or-you-don't kind of symptoms?

    I've also posted this question in the steroid forum, since I figure a lot more of them have tried AIs that those in this forum...
     
    Last edited by a moderator: Apr 5, 2011
  2. CubbieBlue

    CubbieBlue Member

    Re: AIs and joint pain

    What happens if you stop taking it? If it's bottoming out your E2 I would stop.
     
  3. Structure

    Structure Member

    Re: AIs and joint pain

    My E2 gets into the 50's without anastrozole. My aim was to reduce it just a little (to get it into the 30's), but after introducing some other medications, it looks like my anastrozole dosage is too high (I'm currently taking 1/8th of a mg per day). I'm just wondering if I'm still going to have fucked up wrists after rebalancing my E2...

    Have you (or anyone else for that matter) ever had joint trouble from AIs?
     
  4. Structure

    Structure Member

    Re: AIs and joint pain

    Thanks for the link. That paper you cited is the second one I've seen that states that discontinuation of anastrozole leads to cessation of painful joints, which is definitely a relief... In case you're curious, here's the other one that says this: Management of menopausal symptoms in breast cancer... [Maturitas. 2011] - PubMed result

    "In the ATAC (arimidex, tamoxifen, Alone or in Combination) trial, the majority of the symptoms occurred within the first 2 years of therapy, with a peak occurrence at 6 months. Notably, half of the patients whose joint symptoms resolved were symptom-free within 6 months of the onset and in 75% of patients the symptoms spontaneously disappeared within 18 months. This implies that musculoskeletal symptoms are not due to permanent changes in the joints or joint destruction and are reversible upon AI withdrawal; indeed, this was recently shown in a prospective study using magnetic resonance imaging (MRI) of the hand."

    Hopefully, I'll be able to fix the problem by reducing my dosage instead of completely going off of anastrozole...

    To anyone not familiar with AI joint pain: it hurts like a bitch. I haven't been able to do a decent arms or chest workout in three weeks.
     
  5. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: AIs and joint pain


    I wrote and obtained the full-text article (attached) you cite:

    Henry NL, Jacobson JA, Banerjee M, et al. A prospective study of aromatase inhibitor-associated musculoskeletal symptoms and abnormalities on serial high-resolution wrist ultrasonography. Cancer 2010;116(18):4360-7. A prospective study of aromatase inhibitor-associa... [Cancer. 2010] - PubMed result

    BACKGROUND: Nearly half of women treated with aromatase inhibitors (AI) develop AI-associated musculoskeletal symptoms (AIMSS) such as arthralgias, but to the authors' knowledge the etiology is unclear. The upper extremities are frequently affected, especially the wrists, hands, and fingers. AI use may also increase the risk of developing carpal tunnel syndrome. Tendon sheath fluid and tenosynovial changes have been demonstrated by imaging symptomatic patients who were treated with AIs. The authors hypothesized that these abnormalities are correlated with AIMSS.

    METHODS: Thirty consecutive patients in whom adjuvant therapy with letrozole or exemestane was initiated on a prospective clinical trial enrolled in a pilot study evaluating tendon and joint abnormalities at baseline and after 3 months of AI therapy. Patients underwent high-resolution ultrasonography of the wrists bilaterally and completed the Health Assessment Questionnaire (HAQ) and pain Visual Analog Scale (VAS). AIMSS were defined as an increase in the HAQ or VAS score during AI therapy that exceeded a predefined cutoff.

    RESULTS: Twenty-five patients completed both the baseline and 3-month assessments. During the first 12 months of AI therapy, 15 patients developed AIMSS, and 13 discontinued therapy because of musculoskeletal symptoms. There was a trend toward an association between the presence of tendon sheath abnormalities on wrist ultrasound at baseline and the development of AIMSS (P = .06).

    CONCLUSIONS: Clinically relevant musculoskeletal symptoms develop in women treated with AIs, leading to treatment discontinuation in a substantial percentage of these patients. However, in the current study, patient-reported symptoms were not found to be associated with changes visible on wrist ultrasonography.
     

    Attached Files:

  6. Structure

    Structure Member

    Re: AIs and joint pain

    Thanks for getting this paper. I'm off to see a rheumatologist today to verify that the AI is in fact to blame...
     
  7. zkt

    zkt Member

    Re: AIs and joint pain

    I havent read all the papers refrenced but isnt the problem dose related? You are nowhere near an ER+ cancer dose.
     
  8. Structure

    Structure Member

    Re: AIs and joint pain

    That was my original question (are the effects dose related), but I haven't seen anything in print that says as much. What I have seen is that (1) the effects go away after the AI is discontinued, and (2) the exact mechanism by which this occurs is unknown.

    I was hoping to hear some anecdotal evidence of this being dose related (e.g. "I reduced my dose and the pain went away...") but no such response yet...
     
  9. chemman

    chemman Member

    Re: AIs and joint pain

    Welp, I have some experience with this.

    Basically, most guys will tell you, "dude I took too much arimidex and my joints hurt so bad I couldn't lift weights [blah blah blah], but after stopping the adex I was back to normal in [insert time frame from a few days to a few months].

    For me, I took 0.5mg/week for two weeks. A two week "experiment." I never had any joint problem besides maybe a little sciatica here and there before this. Since those two weeks, my joints have gotten so bad. All of them started cracking, creaking etc. Eventually the pain set in. And now, just under two years later, I have been diagnosed with undifferentiated seronegative spondyloarthropathy. Coincidence? I doubt it.

    My experience is probably on the extreme end of things, but you were looking for anecdotal experiences and this is mine.
     
  10. Structure

    Structure Member

    Re: AIs and joint pain

    Wow, that sounds pretty terrible.

    I took a look around to see how typical your experience is. This paper: Management of arthralgias associated with aromatase inhibitor therapy mentions that any pre-existing joint problem gets worse when an AI is taken. They go over diagnoses of various kinds of joint problems (including spondyloarthropathy), although it seems that (from other papers referenced in this thread) wrist / hand / shoulder pain is the most common.

    It also mentions that 50% recover within the first 6 months, and 75% recover within 18 months. That's a long time, but at least the changes aren't permanent. I hope your condition falls into this category...

    One other difference that makes your experience a bit extreme is that most people have to be on anastrozole for 6 months before having joint problems. Of course, I too developed issues before this (it took 3 months for mine to show up).

    My visit to the rheumatologist ended with: "either you've got early onset rheumatoid arthritis (in which case you are going to be fucked before long), or this is just a side effect from the anastrozole, and will probably go away by itself. Here's some blood tests. If they're inconclusive, we'll do an MRI." I'm paraphrasing, of course. Though that would be pretty funny if the doctor actually said "in which case you'll be fucked before long."

    I'll update as info comes in...
     
  11. chemman

    chemman Member

    Re: AIs and joint pain

    What I think happened is that I have the genetic predisposition for this autoimmune disease and arimidex set off my immune system. But it is possible that I still have imbalances in my endocrine system [like low cortisol] that could be allowing the situation to unfold.

    I can certainly see how low cortisol could allow the immune system to go unchecked.
     
    Burrr likes this.
  12. Structure

    Structure Member

    Excerpt: Etiology of aromatase inhibitor-induced arthralgia

    (From Din OS, Dodwell D, Wakefield RJ, Coleman RE. Aromatase inhibitor-induced arthralgia in early breast cancer: what do we know and how can we find out more? Breast Cancer Res Treat. 2010 Apr;120(3):525-38. Epub 2010 Feb 16.)

    Role of oestrogen

    The mechanism behind AIA is not clearly understood. Oestrogen deprivation is implicated as per the mechanism of action of AIs. Typical levels of oestradiol in the presence of a potent AI are less than 1 pmol/l [23]. It is known that the incidence of joint pain peaks at 50–59 years in the general population. Some preclinical studies have shown a protective effect of oestrogen in arthritis and on pro-inflammatory genes [24, 25]. Clearly, there are several possible causes of arthralgia in a non-breast cancer population, which can make it difficult to elucidate one particular cause.

    There are a number of ways that oestrogen could be implicated in the pathogenesis of AIA... ER-? has been found in normal human synovia and therefore may have a role in the function of the synovial membrane [28]. ER-? and ? are found in normal cartilage, but are present at increased levels in osteoarthritic joints [29, 30]. Type II collagen (CTX-II), the main structural protein of articular cartilage, may be influenced by oestrogen. Animal studies have investigated the effect of ovariectomy on cartilage turnover and degradation. Compared with controls, CTX-II correlated strongly with severity of surface cartilage erosion (r = 0.74, P < 0.01). Thus, oestrogen deficiency is a process that may accelerate cartilage turnover and erosion. In fact, in a review, 11 out of 16 animal studies showed that ovariectomy resulted in cartilage damage. In a further rat study, type II collagen turnover was countered by the use of oestrogen, though other studies have shown variable results for exogenous oestrogen therapy [31, 32]. However, in humans, hormone replacement therapy is not an adequate treatment of arthralgia in postmenopausal women [33].

    There is evidence that aromatase may be expressed synovial cells and chrondrocytes of articular cartilage [34, 35]. One study demonstrated synoviocytes from postmenopausal women were able to express aromatase mRNA. In addition, the authors showed that the adrenal androgen, androstenedione, was converted to estrone and estradiol in synoviocytes by aromatase and this process was positively regulated by glucocorticoids [34].

    Some of the adjuvant studies of AIs have also shown an increased prevalence of carpal tunnel syndrome. One possible explanation for this could be the presence of fluid around the flexor tendons of the wrist causing compression neuropathy of the median nerve. In a study of 23 women undergoing surgery for carpal tunnel syndrome, tissue from the transverse carpal ligament and synovium was examined and compared with four controls (undergoing hand surgery for trauma with no history of carpal tunnel syndrome). ER and PR were found to be present in these structures and to a higher degree than controls. This implicates these receptors and potentially oestrogen and progesterone in the pathogenesis of carpal tunnel syndrome. Interestingly, the number of ER positive cells in the transverse carpal ligament and synovial tissue increased with age to a peak at 55–70, decreasing thereafter [36].
     
  13. Yowzer

    Yowzer Member

    Re: Excerpt: Etiology of aromatase inhibitor-induced arthralgia

    I wish I could understand more of what teh article says but the subject is AI induced arthritis. Here is part of a previous post I made on the subject:

    " About 3 years ago, while on TRT, I had a Estradial reading come back too high. I began taking .5 mg arimidex 2 times weekly. I was 50 and had played high level tennis all my life and never experienced any hip pain whatsoever. After about 4 months on adex I experienced pain in both hips on the same day but during a month long period where I was not doing vigorous activity. A very strange "coincidence". Over the next three months I played some very hard tennis and had continued to experience some hip pain. So now after about 8 months on 2-3/week .5 mg adex I came down with serious hip pain and was diagnosed with burcitis and a small amount of arthritis. The burcitis did not resolve quickly so my activity was limited to walking and less strenuous tennis. Finally, about a year after beginning the 2/week .5 mg Adex, I had a blood test which showed Estradial <10 so it is likely it had been quite low for a year. Interestingly, I experienced no other joint pain anywhere during this time. Now, 2 1/2 years after getting my Estradial back to normal, the hip pain continues to the point where I avoid strenuous activity."

    Now the hip pain is worse than ever. By not figuring out thee cause until recently I had another period with lowish Estradial. Doing lots of fish oil, stretching, no Arimidex and things are not improving.
    Wouldn't both male and female cancer patients have their E levels reduced to near nothing for very long periods? I would think joint issues would be rampant. Checking one cancer board, a number of people with joint pain didn't know if it was due to the chemo. I can't imagine my issue not being due to the Adex.
     
  14. Structure

    Structure Member

    Re: Excerpt: Etiology of aromatase inhibitor-induced arthralgia

    I've been doing a lot of research on this because I came down with wrist pain about 6 weeks ago. I ignored it at first, and it got progressively worse. After a while, I pretty much couldn't use my thumbs because of the pain. From what I've found, here are the facts:
    • Up to 75% of anastrozole users experience joint pain. Initial estimates were 35%, but recent studies show that the number is much higher (estimates range from 50% to 75%).
    • Imaging reveals thickened tendons and changes in the tenosynovial fluid of the tendons.
    • This article talks about current research linking estrogen to joint health. It is thought that the pain results from lowering estrogen too much. This is often mentioned on the forums, but until I came across this article, I hadn't seen it explicitly stated in the research.
    • The changes in the tendons reverse after estradiol is brought back up. If you don't bring the estrogen back up, you may not reverse the changes. For example, some women with breast cancer had continued pain when they switched to tamoxifen. My pain didn't start to improve until my estradiol came back up (even after quitting anastrozole).

    My particular diagnosis is De Quervain's tenosynovitis. I still experience a lot of pain if I accidentally move my thumbs, and they frequently lock up (I have to shake my hands to unlock them). However, as I mentioned before, once I got my estradiol back up, the pain started diminishing quickly. It's always possible that the AI worsened a pre-existing condition in you, but most of the time the changes are reversible. In fact, I haven't seen any case studies on permanent problems caused by an AI, although a few papers indirectly say that it is possible to have permanent changes through the use of clever language (e.g. "almost all cases resolve upon discontinuation", etc.).

    I don't know what your bloodwork looks like currently, but if I were you, I'd try to get my E2 up a little bit to see if anything improves over a few weeks. I don't really know if this will work, but I'd sure be interested in trying it. Just use a little too much T for a month or so, which will drive your E2 up, and see if your hips improve.
     
  15. Yowzer

    Yowzer Member

    Re: Excerpt: Etiology of aromatase inhibitor-induced arthralgia

    Structure-Thanks for the info. I will try raising T further and continue with no AI since I never really had High E symptoms, just readings. What you said about tendons is very interesting since a lot of my pain has been around the outside of the hip ( as well as what feels like inside). It seems to move around all around the hip at different times so I suspect the tendons have been coming into play. I have been taking .4 cc test cyp/week so there is room to bump it up.
    It would be wonderful if you figured out something since I have been thinking I am heading to a hip replacement! Thanks!
     
  16. Structure

    Structure Member

    Re: Excerpt: Etiology of aromatase inhibitor-induced arthralgia

    Let us know how that works out. I think you stand a good chance of recovering, since I've read several papers that explicitly state that AI-induced arthralgia is not due to changes in the bone (e.g. osteoarthritis), but is rather due to reversible changes in the tendons. That would mean no need for a hip replacement for you. The trick is figuring out why you haven't recovered yet, and that's where I hope the E2 levels will help you. I took a quick look to see how often the hip is affected; the hip was the site of joint pain in 42% of the population studied in this paper (with the wrist being the most common site at 60.4%), and the hip was affected 50% of the time in this paper. So it looks like you've got plenty of company.

    Here's a nice meta-analysis that summarizes the data in many other papers: Musculoskeletal Adverse Events Associated with Adjuvant Aromatase Inhibitors. Of note: most patients rate their pain as 7.5 on a 10 point scale, with about a third of them rating pain between 8-10. In other words, everyone agrees that it hurts like a bitch. Many patients continued using AIs despite the pain, and many of them recovered anyway; 50% were symptom free within 6 months, and 75% were symptom free within 18 months. In general, 20% of all women with breast cancer discontinue AI use because of joint pain.

    Perhaps naively, I'm hoping to have recovery within about 6 weeks. I've come up with this number since that's about how long it takes an injured tendon to heal. I figure as long as I keep my E2 levels high enough, it should be able to heal just like any other tendon injury. I'll let you know how that turns out...

    On a side note: I would definitely recommend that you get an MRI of your hip. The changes in the tendons are visible, and this would finally put all doubt to rest about whether or not you were suffering from osteoarthritis or AI-induced tenosynovitis. I had an MRI of my wrist done, and (with only the description "wrist pain" to guide him) the radiologist identified the affected tendons and made the diagnosis. Definitely worth the money; you can't put a price on peace of mind...
     
  17. Yowzer

    Yowzer Member

    Re: AIs and joint pain

    Just before I stopped arimidex, I was taking just 1/6th mg every 2 or 3 days and mine was down to 15 while doing .4 cc test cyp/week. Dangerous stuff.
     
  18. Yowzer

    Yowzer Member

    Re: AIs and joint pain

    Structure- Thanks for the info and encouragement. I only quit the arimidex in January after figuring out it was the proble. Problems started 3 years ago at the time of highest adex use which I maintained for a year. Hopefully the slower onset and fact that only my hips were affected indicates the levels weren't zero. Good luck to both of us! Keep us posted.
     
  19. Structure

    Structure Member

    A quick update for those that are following this thread:

    It's been about 6.5 months since this AI induced wrist pain started. I continued using anastrozole for about one month after I noticed the pain (March). Even after discontinuing, the pain continued to steadily get worse. As I mention in my previous posts, I saw a rheumatologist, had some blood tests to rule out alternatives, and had my diagnosis confirmed from a wrist / hand MRI.

    Pain peaked in the middle of April. As long as I kept my thumbs perfectly still, I had no pain at all. However, if I accidentally moved them outward (i.e. thumb "abduction") they would lock up, and the pain of unlocking them was bad --- comparable the time when I got a hairline fracture in one of my bones. Worse yet, this lockup would set back my progress for a while. It is incredibly difficult to not move your thumbs. It has been very frustrating, and at times, depressing.

    I went to a place that custom makes splints. It was expensive, but I was able to come back in a few times to have them adjusted as needed. I later graduated on to a pair of standard splints (complete with thumb spica). I was in splints until about the beginning of this month.

    I took several courses of glucocorticoids to help with the inflammation (first prednisone, then a few courses of dexamethasone). I opted not to get an injection because I didn't want to risk permanently weakening my tendons. And I made sure to keep those fucking thumbs still.

    I've been making slow but steady progress since April. I've adapted to life without thumbs for some time now (opening doors with my feet, having my wife dress me, etc.). It's been pretty extreme. Taking anastrozole was easily the biggest mistake I've ever made. I'm just glad that recovery is possible, despite how long its taking.

    I'm not completely out of the woods yet. While I don't need the splints or the steroids anymore, I still can't do a lot with my thumbs. I was a little overzealous yesterday, and today I am paying the price. Lots of ice.

    I haven't worked out my upper body in over six months now. But I'm still getting an hour of exercise every day.

    I'll update in a few months as things change.