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Depo Deaths - Chronicle Article

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  • Originally posted by BeeHoney View Post

    I think it's a huge mistake to compare human use of DepoProvera to the use of compounded medroxyprogesterone in horses. Just because medroxyprogesterone is safe and effective in humans does not mean that it is safe and effective in horses. Also, while the FDA does track adverse drug reactions in people, they do NOT track adverse drug reactions in horses. So, while the FDA was quick to pick up on the fact that phenylbutazone (aka bute) has dangerous side effects in humans, they would NOT likely be picking up on the fact that compounded medroxyprogesterone has been linked to an unusually high rate of fatal adverse reactions in horses.
    Let me also point out that depo has been used for decades in horses too, and although it's true that the FDA does not track equine data the same way it tracks human-- one would expect that long before now we'd have been hearing if there was a significant number of anaphylactic reactions in horses. Depo has never been OTC so it has to be ordered by/through/with the knowledge of a vet. So vets have been aware of depo use in horses for decades... if the depo itself was problematic, don't you think that would have occurred to vets from their anecdotal experience long before now?

    I'm not arguing for or against giving depo to horses (or for and against the justifications why). I'm just pointing out that there is reason to be skeptical about some of the claims in the COTH article. They seemingly got the facts wrong on part of the article, and the remainder is anecdotal data. A few vets saying "here's what I've seen." No studies, no peer reviewed data. Just some vets saying "I've seen this." Well, what they've seen looks awfully different to what doctors have seen with people. And the veterinary anecdotal data in that article is, frankly, seemingly inconsistent with the fact that depo has been used in horses for decades.

    If DEPO caused anaphylactic reactions in horses you'd expect to have hard about that long before now. These same vets would have been seeing this decades ago?! Depo use is hardly new.

    If there's a current bad batch of compounded progesterone... that's a completely different story. But people have been giving depo to horses, somewhat widely, for at least 10-15 years. Doesn't it seem odd that we're only NOW hearing these reports if it's actually the depo itself causing the problem?

    And, again, depo is just progesterone. It's not a foreign substance. It's introducing more of a naturally occurring substance into the animal/person. It's akin to insulin. People can certainly have anaphylactic reactions to insulin injections. It's not unheard of. But no more/less than any injection. Insulin has been used for a long, long time. If all of a sudden there was a rash of bad reactions following insulin injections-- would you suspect the insulin itself or something else (administration, contamination, etc.)?
    ~Veronica
    "The Son Dee Times" "Sustained" "Somerset" "Franklin Square"
    http://photobucket.com/albums/y192/vxf111/

    Comment


    • Originally posted by vxf111 View Post



      And, again, depo is just progesterone. It's not a foreign substance. It's introducing more of a naturally occurring substance into the animal/person. It's akin to insulin. People can certainly have anaphylactic reactions to insulin injections. It's not unheard of. But no more/less than any injection. Insulin has been used for a long, long time. If all of a sudden there was a rash of bad reactions following insulin injections-- would you suspect the insulin itself or something else (administration, contamination, etc.)?
      "Depo" is merely a portion of the tradename for a respository formulation of any of several compounds, including, but no limited to methylprednisolone acetate (Depo-Medrol) and medroxyprogesterone acetate (Depo-Provera).

      The active principle in the proprietary formulation Depo-Provera is the one under discussion here. Medroxyprogesterone acetate is not to my knowledge, "naturally ocurring".

      I would suspect that whatever the vehicle is for carrying the active ingredient in these compounded formulations may be the thing responsible for occasional anaphylactic reactions.

      One also wonders about the effect of the extended use of this stuff in horses with regard to bone integrity, seeing as how it is related to decreased bone density in women.
      "It's like a Russian nesting doll of train wrecks."--CaitlinandTheBay

      ...just settin' on the Group W bench.

      Comment


      • Ghazzu do different compounding pharmacies use different vehicles? To go a bit further, are the vehicles different between horse and human?

        My apologies if these questions are stupid but I don’t know much about compound pharmacies or vehicles for injections.

        Comment


        • Originally posted by TheMoo View Post
          Ghazzu do different compounding pharmacies use different vehicles? To go a bit further, are the vehicles different between horse and human?

          My apologies if these questions are stupid but I don’t know much about compound pharmacies or vehicles for injections.
          I on't know the answer to that one. My suspicion is that there may be differences, but that substances that are used are regarded as safe and have been approved at some level as inactive components.
          "It's like a Russian nesting doll of train wrecks."--CaitlinandTheBay

          ...just settin' on the Group W bench.

          Comment


          • Thank you for your thoughtful response.

            Originally posted by vxf111 View Post

            Let me also point out that depo has been used for decades in horses too, and although it's true that the FDA does not track equine data the same way it tracks human-- one would expect that long before now we'd have been hearing if there was a significant number of anaphylactic reactions in horses. Depo has never been OTC so it has to be ordered by/through/with the knowledge of a vet. So vets have been aware of depo use in horses for decades... if the depo itself was problematic, don't you think that would have occurred to vets from their anecdotal experience long before now?

            I'm not arguing that the anecdotal evidence provide by the vets in the Chronicle article is particularly meaningful, but on a per veterinarian basis, if the incidence of an anaphylactic reaction is 1 out of every 700 injections, that might mean that a vet who isn't prescribing much medroxyprogesterone might not be expected to see the reaction enough to have their own meaningful anecdotal evidence. I completely agree that the anecdotal evidence described is wholly inadequate, but that's all we have right now, and it's a starting point.

            I'm not arguing for or against giving depo to horses (or for and against the justifications why). I'm just pointing out that there is reason to be skeptical about some of the claims in the COTH article. They seemingly got the facts wrong on part of the article, and the remainder is anecdotal data. A few vets saying "here's what I've seen." No studies, no peer reviewed data. Just some vets saying "I've seen this." Well, what they've seen looks awfully different to what doctors have seen with people. And the veterinary anecdotal data in that article is, frankly, seemingly inconsistent with the fact that depo has been used in horses for decades.

            If DEPO caused anaphylactic reactions in horses you'd expect to have hard about that long before now. These same vets would have been seeing this decades ago?! Depo use is hardly new.

            If there's a current bad batch of compounded progesterone... that's a completely different story. But people have been giving depo to horses, somewhat widely, for at least 10-15 years. Doesn't it seem odd that we're only NOW hearing these reports if it's actually the depo itself causing the problem?

            So, I agree that medroxyprogesterone has been around for a long time, but I don't think that it's use has been as widespread as you seem to think until recently. Personally, I think it has gained a lot of popularity in the past few years as other calming medications are no longer options (such as GABA). It's a problematic medication to give, it can make the horses very sore at the injection site, and it's terrible at controlling symptoms of estrus, so I think the main people who use it are people trying to pharmacologically calm horses down for the show ring. Again, if only one out of 700 horses has a reaction, I think it would be really easy for a prescribing vet to assume that there was an inadvertent intravascular injection or some kind of injection error.

            EVEN IF a vet were to report a problem with a compounded medication, the compounding pharmacies have NO OBLIGATION to keep track of those problems, other than to perhaps run some quality tests to make sure there were no contaminants or compounding errors, but that's it. Plus, injectable medroxyprogesterone for horses is compounded by many different pharmacies who are unlikely to correspond with their competitors regarding any issues.

            And, again, depo is just progesterone. It's not a foreign substance. It's introducing more of a naturally occurring substance into the animal/person. It's akin to insulin. People can certainly have anaphylactic reactions to insulin injections. It's not unheard of. But no more/less than any injection. Insulin has been used for a long, long time. If all of a sudden there was a rash of bad reactions following insulin injections-- would you suspect the insulin itself or something else (administration, contamination, etc.)?

            Medroxyprogesterone is a type of progesterone, but no, it is not naturally occurring in a horse's body. It absolutely can be tested for. And yes, humans can have anaphylactic reactions to DepoProvera, although as discussed that is a very rare occurrence. I have no good explanation for why it appears that horses may have a high rate of anaphylactic reactions to medroxyprogesterone, but there are many instances where animal and human reactions to medications differ greatly.
            One last point that I want to make is that many medication reactions are unreported. Many barns, trainers, and owners value their privacy. When a horse dies unexpectedly at the end of a needle, the reaction from others can have an aura of scandal. No trainer or owner wants there to be the subject of speculation or gossip regarding a bad injection. Reputation, emotions, and financial considerations are all at stake.

            Comment


            • Just for a lesson in statistics; these numbers have no concrete connection to the specific matter at hand.

              A medication that has say a reaction rate of 1/100 per dose but is used rarely may be very acceptable and indeed that reaction rate might not be noticed, especially if the patients are being treated for other serious issues. But give it monthly to 10 horses and you're likely to see a reaction every year. Give it to 100 horses a month and you're likely to see it every month. Give it weekly and you'd likely see it every other year per horse.

              So when these medications move from rarely and specifically used to "hey, what can it hurt" and prevalently used on animals with little or no medical indication, you often find out exactly what it can hurt.
              If you are allergic to a thing, it is best not to put that thing in your mouth, particularly if the thing is cats. - Lemony Snicket

              Comment


              • Originally posted by EmilyM View Post

                so i looked up the drugs and medication brochure and not a single mention of altrenogest or regumate. i know FEI does not allow in male horses. i thought so too of USEF but I cannot find it.

                https://www.usef.org/forms-pubs/2Zp2...gs-medications
                IIRC USEF is monitoring the use of Depo to build data prior to regulating its use in competitions on male equines.

                IMO, there could be a considerable difference in the injected substance from different compounding pharmacies. I know some are very well run and ethical, others maybe not. And I know from years of personal observation some of the grooms, trainers, assistants and whoever injects the horses are well trained, careful and ethical and others are idiots.

                Some of these horses are getting Depo shots very frequently over long periods of time in combination with other drugs and substances

                Then there’s the old give the horse something to placate the owner and make it look like we are doing something. And if a little woks more is better. Right?

                Don't understand how accurate any attempt at study of it’s effect can be successful if dosage, frequency and in combination with other drugs and substances are all over the map industry wide. And don’t kid yourself, it’s not just USEF or just Hunters. Just most if the others keep it under wraps better.
                When opportunity knocks it's wearing overalls and looks like work.

                The horse world. Two people. Three opinions.

                Comment


                • Didn't check back and there are too many to reply to individually. Medroxyprogesterone (depo) is a form of progesterone. It's a derivative of what naturally occurs in the body. It's true that it is a lab synthesized version of progesterone. I guess I wasn't making the point clear. There's no reason to think synthesized progesterone would cause an unusual anaphalactic reaction. Insulin is also synthesized. There's no reason to think synthesized insulin would cause an unusual anaphalactic reaction. That's why I made the analogy.

                  I do think depo has been fairly commonly used in equines for a while. At least in some areas. I recall riding IHSA and being at a barn that gave some horses depo... and I had already heard of that happening when I learned that. So... early 2000s. Maybe it was somewhat regional/discipline specific, but by the time I got to law school I was in a different part of the country and 4 years later lots and lots of horses in that area were on it.

                  Vets would know. They have to prescribe it. Whether we can disagree as to when it become widepsread and how widespread... I think it's safe to say that within the last 5 years it was commonly used and you would expect vets to have been seeing issues long before now. That COTH article just seems very reactionary and not particularly well researched to me. It's almost click-baity.

                  I don't disagree that reporting is different for humans and horses or that maybe some vets wouldn't see patterns right away. I just think it is very odd that SUDDENLY a drug long used in people and (for some period of time) in horses is linked to deaths and the reaction being jumped to is that it's the drug causing the deaths. It just seems pretty poorly researched/thought out on the part of COTH... to the point of being misleading.
                  ~Veronica
                  "The Son Dee Times" "Sustained" "Somerset" "Franklin Square"
                  http://photobucket.com/albums/y192/vxf111/

                  Comment


                  • Originally posted by vxf111 View Post
                    ...Medroxyprogesterone (depo) is a form of progesterone. It's a derivative of what naturally occurs in the body. It's true that it is a lab synthesized version of progesterone. I guess I wasn't making the point clear. There's no reason to think synthesized progesterone would cause an unusual anaphalactic reaction. Insulin is also synthesized. There's no reason to think synthesized insulin would cause an unusual anaphalactic reaction. That's why I made the analogy...
                    Vets would know. They have to prescribe it. Whether we can disagree as to when it become widepsread and how widespread... I think it's safe to say that within the last 5 years it was commonly used and you would expect vets to have been seeing issues long before now. That COTH article just seems very reactionary and not particularly well researched to me. It's almost click-baity.

                    I don't disagree that reporting is different for humans and horses or that maybe some vets wouldn't see patterns right away. I just think it is very odd that SUDDENLY a drug long used in people and (for some period of time) in horses is linked to deaths and the reaction being jumped to is that it's the drug causing the deaths. It just seems pretty poorly researched/thought out on the part of COTH... to the point of being misleading.
                    Insulin isn't synthesized the same way medroxyprogesterone is.
                    Insulin is a protein, and the most common current version in use is produced via recombinant DNA technology and is *identical* to human insulin.

                    Before this, beef and pork insulin were purified and used. They are not identical to human insulin, and reactions not infrequently developed over time. (FWIW, beef-derived insulin i no longer available, and pork, I am told will soon be gone, as well.)

                    Medroxyprogesterone, a steroid, is a synthetic derivative of progesterone and is not identical to the naturally occurring hormone. It has a couple of substitutions on the naturally occurring structure.

                    As others have stated, we don't have a good handle on the actual incidence (and type) of adverse reactions to medroxyprogesterone in horses because it isn't an approved drug, because compounded versions are often employed, because there is no labelled dose/schedule for administration, because folks don't tend to advertise these sorts of unfortunate events, etc.
                    It may well be the case that the incidence is small compared to the number of uses overall.

                    Still, given that the stuff is being administered in many, if not most cases, to treat a behavioral issue rather than a hormonal deficiency, I can't help but be reminded of the principle law of bioethics and medicine:

                    Primum non nocere.


                    "It's like a Russian nesting doll of train wrecks."--CaitlinandTheBay

                    ...just settin' on the Group W bench.

                    Comment


                    • Progesterone, medroxyprogesterone and medroxyprogesterone acetate (Depo-Provera) are all different molecules. The synthetic version of a naturally-occurring substance should be chemically identical to the original. And, yes, the OH group added to progesterone to make it medroxyprogesterone could make a big difference in its mode of action. Or no difference. I'm a chemist, not a pharmacologist. The acetate, (far right structure in attached file) is probably hydrolyzed pretty easily in the body to medroxyprogesterone (the middle structure) because that's what esters do. The acetate is probably a prodrug of the medroxy, in the same way that aspirin (acetylsalicylic acid) is a prodrug of salicylic acid, which is the active metabolite responsible for most of the analgesic and anti-inflammatory function of aspirin.
                      Attached Files
                      The Evil Chem Prof

                      Comment


                      • weird. I posted a reasonably lengthy response earlier today that seems to have disappeared. Oh, well.
                        "It's like a Russian nesting doll of train wrecks."--CaitlinandTheBay

                        ...just settin' on the Group W bench.

                        Comment


                        • Originally posted by Ghazzu View Post
                          weird. I posted a reasonably lengthy response earlier today that seems to have disappeared. Oh, well.
                          Ghazzu It may have gotten removed by the spam filter. No idea why it does that, but I message the mods and they restore the post for you.
                          AETERNUM VALE, INVICTUS - 7/10/2012

                          Comment


                          • Originally posted by beowulf View Post

                            Ghazzu It may have gotten removed by the spam filter. No idea why it does that, but I message the mods and they restore the post for you.
                            Huh. that's odd.

                            ETA: You were right--caught in spam filter. It's back now.
                            Last edited by Ghazzu; Oct. 21, 2019, 11:25 AM.
                            "It's like a Russian nesting doll of train wrecks."--CaitlinandTheBay

                            ...just settin' on the Group W bench.

                            Comment


                            • Originally posted by Peggy View Post
                              Progesterone, medroxyprogesterone and medroxyprogesterone acetate (Depo-Provera) are all different molecules. The synthetic version of a naturally-occurring substance should be chemically identical to the original. And, yes, the OH group added to progesterone to make it medroxyprogesterone could make a big difference in its mode of action. Or no difference. I'm a chemist, not a pharmacologist. The acetate, (far right structure in attached file) is probably hydrolyzed pretty easily in the body to medroxyprogesterone (the middle structure) because that's what esters do. The acetate is probably a prodrug of the medroxy, in the same way that aspirin (acetylsalicylic acid) is a prodrug of salicylic acid, which is the active metabolite responsible for most of the analgesic and anti-inflammatory function of aspirin.
                              I love it that COTH has some really expert people in various fields. It's always such a good place to go for help. Very much not FaceBook.
                              The armchair saddler
                              Politically Pro-Cat

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