Are all LHRH agonists “just the same”?


When all the drugs in the same class have the same general clinical impact, this is known as a “class effect.” As an example, all statins (hydroxymethylglutaryl–coenzyme A reductase inhibitors) will lower risk for certain types of cardiovascular event because they lower levels of cholesterol. That is a “class effect.”

Lueteinizing hormone releasing hormone or LHRH agonists (also often referred to as gonadatropin releasing hormone or GnRH agonists) also have “class effects” in that they all lower male testosterone levels and they all induce “hot flashes” (to varying degrees) in nearly all patients. However, just as different statins can have different effects on different patients, it is reasonable to believe that different LHRH agonists may also have different effects in different patients — but, as Vilar-González et al. have noted in a recent paper, there is almost no useful, comparative information on the clinical effects of the different LHRH agonists.

So what are the different LHRH agonists that have been shown to lower testosterone levels in men with progressive forms of prostate cancer. There are, in fact, six such agents:

  • Leuprolide acetate (Lupron, Eligard, Viadur)
  • Goserelin acetate (Zoladex)
  • Histrelin acetate (Vantas)
  • Triptorelin pamoate (Trelstar)
  • Buserelin acetate (Suprefact)
  • Deslorelin acetate

Neither buserelin acetate nor deslorelin acetate have ever been approved for the treatment of prostate cancer in the USA. There is also one other LHRH agonist, naferelin acetate (Synarel), which has never been tested for its ability to lower testosterone levels in men with prostate cancer. Note also that some LHRH agonists with different brand names, are in fact the same generic biologic agent. For example, Lupron and Eligard are both widely used brands of leuprolide acetate marketed by different companies around the world.

Why is any of this important? Well, if a patient doesn’t respond well to one LHRH agonist (or if he has really problematic side effects as a consequence of treatment with one particular LHRH agonist), it is possible that he may do better on a different one. Unfortunately, because there have been no direct “head to head” comparisons of these agents, we really don’t know whether there are significant differences between them.

In the USA, the majority of patients receiving an LHRH agonist will receive a form of leuprolide acetate as their first-line LHRH agonist, but it is worth remembering that there are others, and that their effects may be slightly different — just as the clinical effects of the various statins are all slighly different. Again, for purposes of comparison, when patients need a statin it is common to start them on one of the older statins (simvastatin or Mevacor). If the effects of simvastatin are insufficient, a patient may be given stronger statins such as atorvastatin (Lipitor) or rosuvastatin (Crestor). Individual patients may have the most appropriate long-term outcomes on any one of these agents.

It would be nice to know whether the differences between the various LHRH agonists were clinically signifciant insubsets of patients, thus allowing more appropriate clinical use of these agents.

It would also be interesting to know whether there were any really clinically significant risks or benefits associated with use of the LHRH antagonist degarelix (Firmagon) instead of one of the LHRH agonists as first-line hormonal therapy.

5 Responses

  1. An advantage of degarelix is it does not require an antiandrogen to precede it to prevent “flare.”

    Of interest, if a patient’s PSA is rising while he is being treated with Lupron as the prescribed LHRH, a switch to the LHRH antagonist Degarelix may reverse the trend.

    FSH (follicle-stimulating hormone) signaling is believed to contribute to the progression of androgen-independent prostate cancer (AIPC) and LHRH antagonists suppress FSH more effectively than LHRH agonists. Therefore, a change from Lupron to degarelix may prompt FSH suppression and a subsequent drop in PSA.

    The downside of degarelix is that, unlike Lupron, which can be administered every 84 or 112 days, it must be administered monthly.

  2. Chuck:

    This is all true, but we have absolutely no information about the long-term risks and benefits of using degarelix as compared to leuprolide acetate (or any other LHRH agonist). The trial that allowed for approval of degarelix in Europe and the USA only followed patients for 1 year.

  3. That is one way to look at things. However, it is impressive to be able to see a significant difference in PSA failures after only 1 year of treatment. At least this result is from a prospective, randomized, controlled trial that is designed to investigate the differences while we have no such study comparing any agonists.

    There is a far greater likelihood that this new class of drugs are different from the agonists than there would be any difference between the agonists (other than possibly administration/dose-related).

  4. I noticed my “hot flashes” we’re more frequent and more intense with Lupron. After receiving Lupron from my urologist in 6 month doses, my bones hurt and the hot flashes were almost unbearable. The urologist finally referred me to my current oncologist who changed the injection to Trelstar in 3-month doses. I asked if we could change to a 1-month dose but see him after the normal 3-month appointment, to which he said OK, whatever I’d like to do. It turns out that, after 2 years now, I’ve stayed stable with my PSA only using the lower 1-month term injection. I may be lucky with this plan but it might be worth a shot for others. The major change is no bone pain and the hot flashes are reduced in both quantity and intensity.

    Because of a vendor to the facility, my injections changed to Lupron recently, and once again, the hot flashes intensified and were more frequent. I ask why the change and after investigation we found out that the vendor changed it since it was “the same thing”. So, investigate any changes, especially if your condition changes.

    Good luck!

  5. Having used Lupron off and on for 6 years and increasingly suffered heart palpitations, I decided to try a 1-month injection of degarelix as it has been shown to have less effect on the heart. Big mistake.

    While Lupron is a time-release capsule, degarelix was two small bottles of liquid, injected by two needles on both sides of my belly button. Within an hour, my entire abdomen became horrendously painful and swollen, with two massive hard bumps at the injection sites (the size and hardness of two small apples). I could not even wear sweatpants for 4 days, and no regular pants with a belt for a week. I spent the first 3-4 days doing nothing but lying or sitting in the sofa, stretched out because of the pain and swelling. Could not bend over, could barely move without serious pain. Now, 3 weeks later, I’m able to function normally but the bumps — although shriveled — are still there and sensitive when even touched, painful if bumped.

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