To the Editor:
I read with great interest the study of Seracchioli et al (1), and I would like to start by warmly congratulating the authors. In fact, as gynecologist involved in the management of endometriosis, I have always been aware that postoperative long-term suppression of menses ought to follow the surgical procedure in order to reduce the recurrences. Now we have LE-1 data supporting the usefulness of postoperative long term medical treatment, and this is very good news for our patients!
However, I have some remarks regarding the trial. First, the authors stated that they performed an intention-to-treat analysis; however this is not true because several women were dropped out following the randomization procedure (10, 6 and 6 women in each group, representing almost 10% of the sample). I would like to highlight that the principle of the intention-to-treat is avoiding any secondary exclusion in order to guarantee the perfect comparability of the groups due to the randomization procedure.
Second, the study showed that the rate of recurrences in non-users is threefold higher than in continuous users of the contraceptive pill. In fact, I think that the difference may be even greater, because it is very likely that more than 6 non-users have actually taken a treatment because of recurrent pain. Unfortunately, the study was not double-blinded, and non-users were aware that they were not taking a hormonal treatment potentially effective in preventing recurrences. As I daily encounter women presenting with endometriosis, I cannot imagine that non-users with recurrence of cyclic pain actually used only anti-inflammatory drugs to relieve pain for several months (until the end of the study). Consequently, despite their inclusion in the non-users arm of the trial, it would be expected that several women presenting with recurrent pain and taking a hormonal treatment would have been likely to develop an endometrioma in the absence of such treatment. Furthermore, how did the authors make sure non-users were using only non-hormonal contraceptive methods during the two years of the study?
In my opinion, this study is one of the most important trials I have read in the last few years in the field of endometriosis. It clearly showed that surgery alone should no longer be proposed to patients who do not intend to get pregnant immediately after the surgical procedure, and postoperative medical treatment is useful when it is administered over the long term. I am looking forward to reading the next systematic review concerning postoperative treatment, because the study by Seracchioli et al will probably move the superior limit of the 95% IC of the OR below 1 (2), and will definitively prove that the usefulness of the postoperative treatment should is no longer up for discussion.
Horace Roman, MD, PhD
Department of Gynaecology and Obstetrics
Rouen University Hospital
1. Seracchioli R, Mabrouk M, Frascà C, Manuzzi L, Montanari G, Keramyda A, et al. Long-term cyclic and continuous oral contraceptive therapy and endometrioma recurrence: a randomized controlled trial. Fertil Steril. 2008 Oct 28.
2. Yap C, Furness S, Farquhar C. Pre and post operative medical therapy for endometriosis surgery. Cochrane Database Syst Rev. 2004;(3):CD003678.
Published online in Fertility and Sterility doi: 10.1016/j.fertnstert.2009.01.118
The Authors Respond:
We read with deep interest Dr. Roman’s letter to the editor and we would like to thank him for his rewarding comments. We agree with Dr. Roman that the methodological term of intention-to-treat cannot be precisely fit to the results published in this manuscript due to treatment drop-outs. However, in our trial women dropped out following the randomization process for initiation/discontinuation of therapy were considered for a second phase of investigation, considering endometriosis recurrence in OCP users after administration/discontinuation of the treatment.
We also agree that a double-blind design would have been better to compare the effect of therapy to a placebo. However, we believe that a good relationship and two-sided trust between the investigator and the patient are necessary, especially in a chronic disease such as endometriosis. We therefore considered as true what the women reported.
Renato Seracchioli, MD
Minimally Invasive Gynaecological Surgery Unit
Reproductive Medicine Unit
S. Orsola–Malpighi Hospital
University of Bologna
Published online in Fertility and Sterility doi: 10.1016/j.fertnstert.2009.01.119