Medical therapy

Medical therapy for endometriosis

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

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

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

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

The relative risk of these 2 thromboses depends on the type of progestogen used for the estrogen-progestogen preparation, with progestogen-only preparations (norethisterone acetate [NETA] and desogestrel pills) that do not increase the risk of venous thromboembolism.

Additionally, patients with recurrent pelvic pain while taking an OCP may need to switch to another OCP, “supporting the idea that OCPs are not completely effective for the treatment of endometriosis”, wrote the authors.

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

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

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

Appropriate patient counseling is also important. Along with health care providers offering a comprehensive overview of the effectiveness and side effects of all available therapies, the ideal treatment should be tailored to each woman, based on her most bothersome symptom, such as pain or infertility, and disease phenotype.

The primary goal of medical treatment is to be effective and to avoid unnecessary surgery, according to the authors, who insist on avoiding repeat surgery in the event of recurrence of pain because repeat surgery often causes serious complications.

Long-term adherence to treatment is also essential.

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

The authors noted that the two doses of elagolix recently approved by the Food and Drug Administration (FDA) for the management of moderate to severe pain associated with endometriosis were found to be less expensive than leuprolide acetate on 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 new algorithms”, conclude the authors.



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