Pharmacologic treatment of the ovarian endometrioma

ABSTRACT

Introduction: Treatment of ovarian endometriomas is commonly achieved through laparoscopic surgery and this can be effective in eliminating the disease, although a majority of recent trials documented an adverse effect of surgery on ovarian reserve markers. With the advancement in imaging techniques, ovarian endometriomas are increasingly diagnosed at an earlier stage when the endometrioma may be smaller, less fibrotic and more responsive to medical treatment, making an evaluation of medical options critically important.

Areas covered: The review focuses on currently utilized pharmacologic therapies for endometrioma (oral contraceptives, the levonorgestrel-releasing IUS, the hormone-releasing subdermal implant, Implanon); experimental and future treatments are also mentioned (GnRH antagonists, progesterone receptor modulators, antioestrogens, newer subdermal implants and intracystic administration of pharmacologic agents). Finally, the usefulness of post-operative adjuvant medical treatments is discussed

Expert opinion: Today, reliable, non-invasive diagnostic procedures of an ovarian endometrioma are available and should be utilized to identify its presence and type of pathology. In a young patient, classic medical therapies such as oral contraceptives and synthetic progestins should be tried first to alleviate symptoms. Only when these regimens fail, should a minimally invasive surgery be envisaged. Following endoscopic surgery, adjuvant medical treatment may reduce recurrence of both symptoms and the lesion.

KEYWORDS:

• Aromatase inhibitors
• combined oral contraceptives
• gonadotropin-releasing hormone analogues
• intra-uterine systems
• ovarian endometrioma
• progestins
• subdermal implants

Article highlights

• The ovarian form of endometriosis is the most frequently diagnosed variant of the disease when using modern imaging techniques.

• The condition can be considered an often progressive disease with wounds undergoing repeated tissue injury and repair, as well as platelet-driven epithelial-mesenchymal transition and fibroblast-to-myofibroblast trans-differentiation, ultimately leading to fibrosis.

• Pathology of endometriomas differs between adolescent and mature subjects due to progressive fibrosis and devascularisation of the pseudo-cyst ovarian bed. Often the early onset form represents a more haemorrhagic and less fibrotic pathology.

• Laparoscopic surgery including ablation or excision is the most common form of treatment. Surgical intervention risks causing loss of oocytes and, for this reason, its advantages and disadvantages should be very carefully considered, taking also into account psychological strain and the patient’s age.

• Today attention focuses on medical therapeutic options, both approved and still off-label. Two are the main indications for a pharmacologic management: the presence of a cystic lesion with a diameter <3 cm (especially in young patients) and recurrence and pain prevention following surgery.

• Currently available medical treatments are not therapeutic, in the sense that they cannot eliminate the disease, but can be useful to postpone surgery and reduce recurrence rate.

• In women not seeking pregnancy, approved medical therapies consist of GnRH superagonist analogues and progestins. Off-label, but widely utilized are combined oral contraceptives.

• Two long-acting progestin-releasing devices have been clinically tested: the levonorgestrel-releasing intra-uterine system, Mirena^© and the etonogestrel-releasing subdermal implant, Implanon®.

• A number of experimental drugs are also being tested clinically: GnRH-antagonists, selective progesterone and oestrogen receptor modulators (anti-progestins and anti-oestrogens).

• Still not tested in humans, but promising in animal models are inhibitors of NF-κB (the protein complex controlling DNA transcription), anti-thrombotic agents and histone deacetylase inhibitors.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded