Medication to Prevent Recurrence?

“Should I take medication to prevent recurrence of my endo?” There is no definitive answer to this question- it is an individual choice that should be discussed with your provider. However, evidence points to it not being needed if ALL endometriosis is removed with surgery. A few things to consider:

Is it truly a “recurrence” or just missed disease?

A significant factor to consider is if all endometriotic lesions were removed in the first place:

• “…findings all support that residual lesions seems to be the primary reason for the recurrence of the disease” (Selçuk & Bozdağ, 2013).  
• “Lack of complete surgical excision was another independent risk factor for recurrence of disease” (Ianieri, Mautone, & Ceccaroni, 2018).
• Deep infiltrating disease has a much lower recurrence rate with complete excision versus incomplete (3.9% versus 35.3%!) (Cao et al., 2015).
• “The experience of the surgeon is also a factor that implies the risk of recurrence” (Selçuk & Bozdağ, 2013).
• Interestingly, prior medical treatment before excision can increase the risk for recurrence (Koga et al., 2013).

Does it involve a type of endometriosis that has higher recurrence risk, such as ovarian, peritoneal, or deep infiltrating disease (stage 3 or 4)? Are you at a young age (under 21 years)?

• There is a higher recurrence risk with ovarian, peritoneal, or deep infiltrating disease (stage 3 or 4) (Selçuk & Bozdağ, 2013). Ovarian endometriomas have a recurrence rate of 11-32% (higher risk in younger patients and those with advanced disease) (Koga et al., 2013).
• Those at a younger age (under 21 years) have a higher recurrence rate (Tandoi et al., 2011).
• However, these factors depend again on the ability to remove the disease. The skill of the surgeon and having an interdisciplinary team can increase the odds of removing more advanced disease and decrease the risk of recurrence- this holds true even for younger patients (Fischer et al., 2013; Yeung et al., 2011). (See Why Excision)

Are there other conditions that can be causing continued symptoms that are similar to endometriosis symptoms (adenomyosis, interstitial cystitis, etc.)?

• Most of us with endometriosis have more than one condition that can mimic the symptoms of endometriosis. These conditions need their own specific treatment.  (See Related Conditions)

Remember, medications overall are “suppressive rather than curative” (Falcone & Flyckt, 2018). In addition, hormonal medication may not stop the progression of disease- this is particularly important where the ureters and/or bowel are involved (Barra et al., 2018; Ferrero et al., 2011; Millochau et al., 2016).

There are many studies and arguments for both sides. Here are a few:

Against it:

• “There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery.” (Sanghera et al., 2016)
• “Many studies have investigated factors determining the recurrence of endometrioma and pain after surgery [16, 19, 20]…. Regardless of the mechanism, the present and previous studies suggest that postoperative medical treatment is known to delay but not completely prevent recurrence…. In our study, we also failed to observe a benefit for postoperative medication in preventing endometrioma and/or endometriosis-related pain recurrence.” (Li et al., 2019)
• “Complete laparoscopic excision of endometriosis in teenagers–including areas of typical and atypical endometriosis–has the potential to eradicate disease. These results do not depend on postoperative hormonal suppression.” (Yeung et al., 2011)
• “A systematic review found that post-surgical hormonal treatment of endometriosis compared with surgery alone has no benefit for the outcomes of pain or pregnancy rates…it found that there is insufficient evidence to conclude that hormonal suppression in association with surgery for endometriosis is associated with a significant benefit with regard to any of the outcomes identified….Moreover, even if post-operation medication proves to be effective in reducing recurrence risk, it is questionable that ‘all’ patients would require such medication in order to reduce the risk of recurrence. It has been reported that about 9% of women with endometriosis simply do not respond to progestin treatment….Therefore, the use of post-operation medication indiscriminately may cause unnecessary side effects (and an increase in health care costs) in some patients who may intrinsically have a much lower risk than others and in others who may be simply resistant to the therapy. The identification of high-risk patients who may benefit the most from drug intervention would remain a challenge.” (Guo, 2009)
• “GnRHa administration is followed by a temporary improvement of pain in patients with incomplete surgical treatment. It seems that it has no role on post-surgical pain when the surgeon is able to completely excise DIE implants.” (Angioni et al., 2015)

For it:

• “Post-operative hormonal suppression following conservative endometriosis surgery decreases the odds of disease recurrence and results in greater reductions in pelvic pain/dysmenorrhea compared to expectant management.” (Zakhari et al., 2019)
• “Laparoscopic excision is considered as the ‘gold standard’ treatment of ovarian endometrioma. However, a frustrating aspect is that disease can recur….Regarding post-operative medical management for preventing recurrence, GnRH analogue and danazol have not been proved to be effective mainly because most trials used these drugs over short periods. In contrast, long term administration of OC is safe and tolerable and recommended for those who do not want to conceive immediately after the surgery.” (Koga et al., 2013)

References

Angioni, S., Pontis, A., Dessole, M., Surico, D., Nardone, C. D. C., & Melis, I. (2015). Pain control and quality of life after laparoscopic en-block resection of deep infiltrating endometriosis (DIE) vs. incomplete surgical treatment with or without GnRHa administration after surgery. Archives of gynecology and obstetrics, 291(2), 363-370.  Retrieved from https://link.springer.com/article/10.1007/s00404-014-3411-5

Barra, F., Scala, C., Biscaldi, E., Vellone, V. G., Ceccaroni, M., Terrone, C., & Ferrero, S. (2018). Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malignant transformation and fertility. Human reproduction update, 24(6), 710-730. https://academic.oup.com/humupd/article/24/6/710/5085039?login=true

Cao, Q., Lu, F., Feng, W. W., Ding, J. X., & Hua, K. Q. (2015). Comparison of complete and incomplete excision of deep infiltrating endometriosis. International journal of clinical and experimental medicine, 8(11), 21497. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723943/

Falcone, T., & Flyckt, R. (2018). Clinical management of endometriosis. Obstetrics & Gynecology, 131(3), 557-571. Retrieved from https://journals.lww.com/greenjournal/Abstract/2018/03000/Clinical_Management_of_Endometriosis.23.aspx?context=FeaturedArticles&collectionId=4

Ferrero, S., Camerini, G., Venturini, P. L., Biscaldi, E., & Remorgida, V. (2011). Progression of bowel endometriosis during treatment with the oral contraceptive pill. Gynecological Surgery, 8(3), 311-313. Retrieved from https://link.springer.com/article/10.1007/s10397-010-0610-3

Fischer, J., Giudice, L. C., Milad, M., Mosbrucker, C., & Sinervo, K. R. (2013). Diagnosis & management of endometriosis: pathophysiology to practice. APGO Educational Series on Women’s Health Issues. Retrieved from https://www.ed.ac.uk/files/atoms/files/diagnosis_and_management_of_endometriosis_booklet.pdf

Guo, S. W. (2009). Recurrence of endometriosis and its control. Human reproduction update, 15(4), 441-461. Retrieved from http://humupd.oxfordjournals.org/content/15/4/441.full 

Ianieri, M. M., Mautone, D., & Ceccaroni, M. (2018). Recurrence in deep infiltrating endometriosis: a systematic review of the literature. Journal of minimally invasive gynecology, 25(5), 786-793. Retrieved from https://www.sciencedirect.com/science/article/pii/S1553465018300372

Koga, K., Osuga, Y., Takemura, Y., Takamura, M., & Taketani, Y. (2013). Recurrence of endometrioma after laparoscopic excision and its prevention by medical management. Front Biosci (Elite Ed), 5, 676-683.  Retrieved from https://pdfs.semanticscholar.org/2da7/5702eac08b0a32fb31bd5478be9e5d43a8b7.pdf

Li, X. Y., Chao, X. P., Leng, J. H., Zhang, W., Zhang, J. J., Dai, Y., … & Wu, Y. S. (2019). Risk factors for postoperative recurrence of ovarian endometriosis: long-term follow-up of 358 women. Journal of Ovarian Research, 12(1), 79. Retrieved from https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-019-0552-y

Millochau, J. C., Abo, C., Darwish, B., Huet, E., Dietrich, G., & Roman, H. (2016). Continuous amenorrhea may be insufficient to stop the progression of colorectal endometriosis. Journal of minimally invasive gynecology, 23(5), 839-842. Retrieved from https://www.jmig.org/article/S1553-4650(16)30047-4/abstract?fbclid=IwAR2Q7o1kJtfNNgMd0Q4_5K0BDe9_DjH1QOUTxTLK2HpgiFVgws5NT9xVdwo

Sanghera, S., Barton, P., Bhattacharya, S., Horne, A. W., & Roberts, T. E. (2016). Pharmaceutical treatments to prevent recurrence of endometriosis following surgery: a model-based economic evaluation. BMJ open, 6(4), e010580. Retrieved from http://bmjopen.bmj.com/content/6/4/e010580.long 

Selçuk, İ., & Bozdağ, G. (2013). Recurrence of endometriosis; risk factors, mechanisms and biomarkers; review of the literature. Journal of the Turkish German Gynecological Association, 14(2), 98. Retrieved from https://journals.sagepub.com/doi/full/10.2217/whe.15.56

Tandoi, I., Somigliana, E., Riparini, J., Ronzoni, S., & Candiani, M. (2011). High rate of endometriosis recurrence in young women. Journal of pediatric and adolescent gynecology, 24(6), 376-379. Retrieved from https://doi.org/10.1016/j.jpag.2011.06.012

Yeung Jr, P., Sinervo, K., Winer, W., & Albee Jr, R. B. (2011). Complete laparoscopic excision of endometriosis in teenagers: is postoperative hormonal suppression necessary?. Fertility and sterility, 95(6), 1909-1912.  Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21420081 

Zakhari, A., Delpero, E., McKeown, S., Murji, A., & Bougie, O. (2019). Long Term Outcomes of Post-Operative Hormonal Suppression in Patients with Endometriosis: A Systematic Review and Meta-Analysis. Journal of Minimally Invasive Gynecology, 26(7), S90.  Retrieved from https://www.sciencedirect.com/science/article/pii/S1553465019311641