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\title{Postoperative medical therapies for the prevention of endometrioma
recurrence -- do we now have the final answer? (Mini-commentary on
BJOG-19-1705.R2)}



\author[1]{Ertan Saridogan}%
\affil[1]{University College London Hospitals NHS Foundation Trust}%


\vspace{-1em}



  
  \date{May 23, 2024}


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Endometriosis is often described as a chronic condition. Surgical or
medical treatment approaches do not cure it, and recurrence of the
disease or its symptoms is common. Medical treatment is usually used to
achieve symptomatic control whilst surgery aims to eliminate the visible
lesions. However, recurrence is frequently seen even after very radical
surgery.

Endometriomas are frequently used for diagnosis and as a marker of
recurrence due their easy recognition on imaging. In this issue of BJOG,
Wattanayingcharoenchai et al (BJOG 2020 xxxx) present their systematic
review and network metaanalysis (NMA) on the efficacy of postoperative
medical therapies in reducing endometrioma recurrence with some mixed
messages. They conclude that evidence from randomised controlled trials
(RCTs) do not support the use of postoperative hormonal therapies,
whereas data from cohort studies indicate a significant protective
effect of levonorgestrel intrauterine system (LNG-IUS) followed by
dienogest, gonadotrophin releasing hormone agonists (GnRHa) + LNG-IUS,
continuous and cyclical oral contraceptives (OC). The most effective
postoperative therapy (although non-significant) was GnRHa+LNG-IUS,
followed by continuous OC and GnRHa based on RCTs.

Direct meta-analysis of RCTs in the Wattanayingcharoenchai et al.
article indicate an approximately 40-50\% reduction with OCs but this
remained statistically non-significant. This finding is in contrast to
an earlier meta-analysis (Vercellini et al. Acta Obstet Gynecol Scand.
2013;92:8-16) which concluded that the postoperative OC use dramatically
reduced the risk of endometrioma recurrence and international guidelines
that recommend use of hormonal contraceptives for the secondary
prevention of endometrioma (Dunselman et al. Hum Reprod.
2014;29:400-12). So what are we to believe and what should we advise
women affected by endometriosis to do?

There is a wide variation in the design of studies on which metaanalyses
and the current NMA are based on in terms of inclusion criteria,
duration of treatment and definition of recurrence. Some studies
allocate the participants on the basis of their disease stage without
taking the preoperative cyst size and bilaterality into account. The
definition of a `recurrent cyst' varies from `no definition' to
endometrioma of \textgreater{} 1 cm or \textgreater{}3 cm. These
introduce significant heterogeneity which potentially compromise the
validity of any meta-analysis. Furthermore, there is also a conceptual
difference between using medical treatment (e.g. GnRHa) for 3-6 months
postoperatively and continuing with therapy (e.g. hormonal
contraceptives) in the long term and assessing the recurrence rates at
1-5 years. In fact the ESHRE guideline (Dunselman et al.) proposed
distinguishing postoperative adjunctive treatment of \textless{} 6
months that aims to improve the outcome of surgery and longer treatments
with the intention to reduce recurrences (secondary prevention). The
former may have a significant side effect profile whereas the latter has
a good safety record.

It is very plausible that suppression of ovulation and
reducing/eliminating menstrual flow in the long term would reduce
recurrences. The current literature is too heterogeneous and fragmented
to confirm or refute this. Properly designed large scale studies with
the required power are still required. The Pre-Empt trial which is
currently ongoing in United Kingdom may give some of the answers.

\textbf{Disclosure of interest:} None. A completed disclosure of
interest form is available to view online as supporting information.

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