In my work with The Endometriosis Network Canada, I have heard many women say that their doctors told them that if their pain does not go away on Lupron, then the pain must not be from endometriosis. Lupron never has and never will be an effective tool for diagnosing whether pain is due to endometriosis. Not only does Lupron have the potential for significant side effects, which alone should abrogate its use as a diagnostic tool, but it also is not at all effective at diagnosing endometriosis and distinguishing it from other conditions.
Lupron is a synthetic version of a naturally occurring hormone called gonadotropin-releasing hormone, and its action is actually stronger than the naturally occurring GnRH. It is a long-acting medication that initially stimulates hormones in the pituitary gland that control the menstrual cycle, and then suppresses these functions. It is typically given as a 1 month or 3 month injection.
Lupron Side Effects
Lupron therapy is associated with a significant potential for side effects. One of the biggest problems with Lupron is its effect on bone density (it can decrease bone density), and this effect is not always completely reversible after Lupron is discontinued. Lupron can also cause joint pain, which in some cases is permanent. Other potential side effects include hot flashes, vaginal dryness, headaches, mood swings, decreased interest in sex, depression (in some cases severe), cognitive problems, fatigue, acne, headaches, and upset stomach. Personal stories of women’s experiences of the downside of Lupron can be found here, here, here, here, and here.
Given all of these side effects, you might be wondering: why would anyone subject themselves to the potential for at best, a month of these side effects, and at worst, a lifetime of some of them, for the purpose of diagnosis? Even from the side effect perspective, using Lupron to try to diagnose endometriosis seems like a bad idea. But now we come to the more technical part of the discussion, which will address whether Lupron could even work as a diagnostic tool for endometriosis.
How to Evaluate a Diagnostic Tool
To evaluate the effectiveness of a diagnostic tool, the two measures that are used are called sensitivity and specificity. Sensitivity addresses the question of how often the diagnostic tool will pick up the disease, in people who have that disease. Specificity addresses the question of how often the test will be positive in people who actually do not have the disease (but may have conditions other than the one you are testing for). A good diagnostic test will pick up the presence of the condition in most people who have it, while not testing positive in people who may have similar symptoms but have a different disease. In other words, a good diagnostic test will have fairly high sensitivity and specificity.
All devices or tests that are approved by regulatory agencies as diagnostics have to undergo testing to demonstrate sufficient sensitivity and specificity. Lupron has not undergone such testing, because it was not developed as a diagnostic, and is not meant to be used as one. However, given the clinical trials that were done looking at the effectiveness of Lupron as a drug therapy, it is clear that the sensitivity and specificity of it as a diagnostic would not support its use in that way.
Lupron as a Diagnostic?
The clinical trial data published by the manufacturer in its prescribing information can be illuminating when considering its sensitivity and specificity for diagnosing endometriosis. The clinical trials used several measures to assess response to the drug, such as pelvic pain, dyspareunia (pain with intercourse), dysmenorrhea (pain with periods), and pelvic tenderness. The results showed that Lupron was by far the most effective at treating dysmenorrhea, compared to the other symptoms. Almost 90 percent of study participants had dysmenorrhea before taking Lupron, and after 6 months of treatment, fewer than 10 percent still had dysmenorrhea. (Not surprisingly, within 6 months after completing treatment, about 80 percent had dysmenorrhea again.) Looking at endometriosis symptoms other than pelvic pain, about 75 percent of study participants had pelvic pain at the start of the study, and 45 percent still had pelvic pain at the end. Lupron was similarly less effective at treating other symptoms of endometriosis.
From these results, we can get an idea of what the sensitivity of Lupron as a diagnostic would be. Imagine giving Lupron to a group of women with endometriosis, whose symptoms will vary from primarily dysmenorrhea, to all different types of pelvic pain at different times (or in some cases, all times) of the menstrual cycle. Those who have primarily dysmenorrhea will feel that their pain has been treated, whereas, because it is less effective on all other types of pain and symptoms, some women may feel that their pain did not decrease at all (remember, 45 percent of women still had pelvic pain after 6 months of Lupron). This is why it is completely incorrect for any doctor to say that if a woman’s pain did not decrease on Lupron, the pain cannot be from endometriosis. Therefore, the sensitivity of Lupron as a diagnostic for endometriosis is predicted to be poor, because in a significant number of women who actually do have endometriosis, it will not treat their pain substantially.
The specificity of Lupron as a diagnostic would be even worse. Clearly Lupron is effective at treating dysmenorrhea, because by its very mechanism of action it puts a woman into chemically-induced menopause, and you cannot have dysmenorrhea when you are not having periods. However, there are many causes of dysmenorrhea other than endometriosis. So even if Lupron does work to treat a woman’s pain (by preventing periods), this does not ensure that the cause of the pain was endometriosis.
A Call for More Research
There is no doubt that women would benefit greatly from a non-invasive diagnostic test for endometriosis, given that surgery is currently the only way to definitively diagnose it. However, Lupron is not sensitive or specific enough to be useful diagnostically. New diagnostic tests have been developed for many other diseases using recent advances in technology such as imaging methods, blood biomarkers, next generation sequencing, and others. A sensitive and specific diagnostic test for endometriosis is desperately needed. However, with so little funding going to basic and applied research into endometriosis, it is unlikely that this need will be met until this funding situation improves. As Siddhartha Mukherjee said about cancer in his book The Emperor of All Maladies:
“A disease needed to be transformed politically before it could be transformed scientifically.”
This is the situation that cancer research was in, during the 1940s, and sadly this is where we are at now, with endometriosis, a disease that affects one in ten women and has for centuries, in 2016.
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This article was published originally on March 14, 2016.