Medical therapy for endometriosis


Oral contraceptive pills (OCPs) and progestogens are effective treatment in two-thirds of women with symptomatic endometriosis, according to a review in the Journal of Clinical Medicine.

But for those women who fail such treatment due to progesterone resistance or intolerance to these compounds, other options are needed.

The Belgian authors selected 11 published articles from a literature search of the electronic databases PubMed and Embase through December 2020. The search was limited to peer-reviewed full texts in English that reported data on medical therapy.

“It is clear that there is a need for effective long-term oral treatment capable of managing endometriosis symptoms, while mitigating the impact of side effects,” the authors wrote. “Biochemical, histological and clinical evidence show that estrogens play a critical role in the pathogenesis of endometriosis, so lowering levels of circulating estrogens should be considered an effective medical approach.”

Safety remains a concern for OCPs, though, as patients may require long periods of therapy during their advanced reproductive years. The risk of venous or arterial thrombosis also is present.

The relative risk of these 2 thromboses is predicated on the type of progestins used for estroprogestin preparation, with progestin-only preparations (norethisterone acetate [NETA] and desogestrel pills) not increasing the risk of venous thromboembolism.

In addition, patients experiencing recurrence of pelvic pain while taking an OCP may need to change to a different OCP, “supporting the notion that OCPs are not completely effective for treatment of endometriosis,” wrote the authors.

Causes of progesterone resistance include congenital, inflammation and oxidative stress, genetics and epigenetics, mesenchymal progenitors (mesenchymal stem cells) and phenotype of endometriosis.

Studies of the oral gonadotropin-releasing hormone (GnRH) antagonists linzagolix and relugolix definitively demonstrate suppression of ovarian function in a dose-dependent regimen, thus allowing modulation of estradiol (E2) levels, which may provide relief from endometriosis-associated pain, while reducing side effects caused by extreme hypoestrogenism.

The authors advocate a treatment strategy based on the different phenotypes of endometriosis, which allows clinicians to discriminate between lesions.

Appropriate patient counseling also is important. Besides healthcare providers offering a comprehensive overview of the efficacy and side effects of all available therapies, the ideal treatment should be tailored to each individual woman, according to her most bothersome symptom, like pain or infertility, and the phenotype of the disease.

The primary goal of medical therapy is to be effective and avoid unnecessary surgical intervention, according to the authors, who emphasize avoiding repeat surgery for recurrence of pain because repeat surgery is often the source of severe complications.

Long-term adherence to treatment also is key.

The cost-effectiveness of medical management of endometriosis is also an important element of care, including investigating innovative treatment options and improving women’s access to quality care.

The authors noted that both of the 2 recent Food and Drug Administration (FDA)-approved doses of elagolix for the management of moderate-to-severe pain associated with endometriosis have been shown to be less costly than leuprolide acetate over 1 to 2 years.

“There is a place for GnRH antagonists in the management of symptomatic endometriosis and clinical trials should be conducted, taking into account the different phenotypes in order to propose novel algorithms,” the authors concluded.



  1. Donnez J, Dolmans MM. Endometriosis and medical therapy: from progestogens to progesterone resistance to GnRH antagonists: a Review. J Clin Med. 2021 Mar 5;10(5):1085. doi:10.3390/jcm10051085.
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