Clinical diagnosis of endometriosis and optimal medical therapy


Volume 108, Issue 5, Pages 759–760


Hugh S. Taylor, M.D.


Reflections on "Ethinylestrdiol 20 μg/drospirenone 3 mg in a flexible extended regiment for the management of endometriosis-associted pelvic pan: a randomized, controlled trial" by Harada et al.

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Go to the profile of Tasuku Harada
over 5 years ago

Early diagnosis and treatment in AYA women with endometriosis


Tasuku Harada

Department of Obstetrics and Gynecology,
Tottori University Faculty of Medicine


We appreciate Dr Taylor’s comments and this opportunity to discuss about our recent paper as well as important issues on diagnosis and medical therapy of endometriosis. We reported a novel flexible continuous OC regimen not only to control pelvic pain associated with endometriosis but also to reduce the number of days of unwanted uterine bleeding (1).
As pointed out by Dr Taylor, we included the patients with a history of endometriosis diagnosed by laparotomy or laparoscopy, or by the identification of endometriomas, or patients with a clinical diagnosis of endometriosis who had pelvic tenderness, induration in the cul-de sac, or uterine immobility. Although we included so called “clinical diagnosis of endometriosis” in order to make recruit easier in the present clinical trial, in daily practice of Japan, we often start medical treatment to the patients with pain symptoms with endometrioma or positive clinical findings. It was reported that accuracy of clinical diagnosis of endometriosis by board qualified gynecologists was more than 80%. Imaging diagnosis using ultrasonography (US) or magnetic resonance imaging (MRI) are highly accurate, reporting that sensitivity and specificity are over 80% by US and 90% by MRI respectively (2). Furthermore, MRI become popular in Japan hospital and many patients with endometrioma are diagnosed by MRI under cover of national health insurance.

We admitted that Laparoscopic diagnosis is the gold standard for definitive diagnosis of endometriosis. It is especially essential in case of basic or clinical research to explore biological or clinical characteristics only observed in endometriosis. But in daily practice, delayed diagnosis and treatment may worsen the symptoms and allow progress of disease stage. In many occasion, the delay may also deprive future chance of pregnancy. As also suggested by Dr Taylor, new non-invasive diagnostic modalities are awaited and promising for earlier clinical diagnosis.

First line medical therapy for dysmenorrhea and endometriosis is OC. Probably this choice in the protocol of endometriosis treatment is similar all over the world. Our new continuous regimen of OC reduce not only unexpected bleeding, it may also alleviate hormone-related symptoms caused by OC, and hormone withdrawal symptoms occurred during hormone-free interval (pelvic pain, bleeding, headaches, nausea etc.). Continuous use of OC was proven to be much superior to conventional cyclic regimen in the treatment of endometriosis (3). We also showed that flexible regimen is more effective to decrease the number of day with pain associated with endometriosis. Therefore continuous regimen may be the next choice when conventional cyclic use of OC failed to control pain of endometriosis patients.

In our current randomized study, we had three arms including flexible regimen of OC, placebo and dienogest. Dienogest group was provided by requirement of Japanese health authority in phase 3 clinical trial as a reference group of bleeding evaluation. As expected, number of bleeding days was smaller in flexible regimen than dienogest group. In addition, we could compare the efficacy of  OC and Dienogest in terms of VAS. Although Dienogest had much stronger effects than OC at 24 weeks, the difference became smaller at 52 weeks (VAS change from baseline, Flexible vs Dienogest: -48.8 + 24.7 vs -57.6 + 26.8).

Earlier diagnosis of endometriosis is essential for starting earlier treatment to control propagation of the disease and to preserve future fertility in adolescent and young adult (AYA) patients. Seven to ten years delay of diagnosis suggest that onset of disease may begin during teenage in endometriosis patients (4). History of severe dysmenorrhea indicate higher risk of endometriosis in their later life (5). When we see girls having severe dysmenorrhea with no apparent findings of endometriosis, should we wait first choice OC therapy until we can confirm definite diagnosis of endometriosis?
Now we have accumulated data, although still incomplete, suggesting that we had better commence first line OC therapy either cyclic or more effective flexible continuous regimen for controlling pain in AYA women. Earlier therapy in AYA women may modify the disease’s natural history, as also mentioned by Dr Taylor. The most important point to treat AYA women at the present time is to keep their ovarian reserve until they want to have baby.  In long-term medical management for AYA women, flexible continuous regimen of OC is recommended due to lower risk of bone marrow density loss, lower cost and safer profile compare to progestin and GnRHa.  Earlier treatment using safe drugs is a key point in modern management of endometriosis.


(1)Harada T, Kosaka S, Elliesen J, Yasuda M, Ito M, Momoeda M. Ethinylestradiol 20ug/drospirenone 3mg in a flexible extended regimen for the management of endometriosis-associated pelvic pain: a randomized controlled trial. Fertil Steril 2017.

(2)Fujii S. MR imaging of endometriosis. In: Harada T ed. Endometriosis Pathogenesis and Treatment. Springer, 2014:311-320.  

(3)Muzii L, Di Tucci C, Di Donato V, Musella A, Palaia I, Panici PN. Continuous versus cyclic oral contraceptives after laparoscopic excision of ovarian endometriomas: a systematic review and metaanalysis. Am J Obstet Gynecol 2016;214:203-211. 

(4)Nnoaham KE, Hummelshoj L, Webster P, d'Hooghe T, de Cicco Nardone F, de Cicco Nardone C, Jenkinson C, Kennedy SH and Zondervan KT, Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011; 96:366–373.

(5)Chapron C, Lafay-Pillet MC, Monceau E, Borghese B, Ngo C, Souza C, deZiegler D. Questioning patients about their adolescent history can identify markers associated with deep infiltrating endometriosis. Fertil Steril 2011;95:877-81.