This is the first study looking at TZDs in humans suffering from endometriosis-induced pelvic pain. As seen in table , when compared with currently available therapeutic options, TZDs are a well-tolerated, affordable treatment for endometriosis that can address pain without the need for add-back therapy. Moreover, and unique to TZDs, there seems to be no impedance to ovulation. While other current treatment options, such as oral contraceptives, may have favorable prices or side effect profiles, they do not offer a chance at conception. Although the data for this study are certainly limited, this case series, combined with the data gathered from studies in rats and nonhuman primates, shows promise for the potential of using TZDs in endometriosis patients desiring the chance to conceive.
Medical treatment options for endometriosis demonstrating the comparative features of pioglitazone, a thiazolidinedione class drug
A major limitation to our trial was the number of patients and the limited course of therapy. In June 2007, the New England Journal of Medicine
published a meta-analysis of rosiglitazone used for glycemic control wherein the authors concluded there was an approximately 50% increased relative risk of myocardial ischemic events (absolute difference <0.15%) [20
]. This information was widely reported in the lay press and, even though our participants were not diabetics we felt that the most prudent course of action was to suspend our trial. Because the study had to be stopped prematurely, the overall number of patients in this trial was limited and statistical analysis was prohibited. However, this study provides initial information to inform future clinical trials with larger participant recruitment. Additionally, while rosiglitazone has been given a black box warning label from the FDA due to an increased risk of cardiovascular side effects in heart failure patients, pioglitazone remains on the market and might be a viable substitute.
Since we are suggesting the possibility of using TZDs for endometriosis pain relief in conjunction with attempts to conceive, it must be understood that, under the current FDA safety classification scheme, TZDs are listed as a class C drug. There are limited studies on the potential reproductive toxicity induced by TZDs; however, animal studies show no sign of altered development and the rare human studies corroborate these findings [21
]. Furthermore, and in support of using such drugs in reproductive aged women, pioglitazone was used in a small trial as an ovulation induction agent in women with polycystic ovary syndrome. As opposed to rosiglitazone, pioglitazone produces a better overall lipid profile – reductions in serum triglycerides and increases in high-density lipoprotein cholesterol levels [23
Due to the small number of participants in this trial, definitive conclusions would be premature; in fact, due to the background placebo effect with any medical therapy this may mitigate any decisive statement from case reports. For example, a recent endometriosis study using TNF-α antibodies had a 25% overall placebo effect [25
]. Nevertheless, the preliminary positive findings of this study utilizing TZD treatment warrant larger confirmatory studies. Future studies should assess more objective measures of the extent of endometriosis using laparoscopy.