Nexplanon (etonogestrel implant) is a contraceptive developed by Merck (known as MSD outside the U.S. and Canada) and approved by the U.S. Food and Drug Administration. It is a reformulation of a similar birth control treatment called Implanon, which is no longer available.

Nexplanon can be used to treat pain caused by endometriosis.

What is endometriosis?

Endometriosis is a disease characterized by endometrial tissue, which normally lines the uterus, developing outside the uterus, usually in the abdominal cavity, forming lesions. These lesions swell and shed, just like the normal endometrial tissue, but because there is no exit route for these lesions to leave the body once they shed, they cause pain and inflammation, as well as infertility in many cases.

How Nexplanon works

Hormone cycles control the shedding of the uterine lining, and are also involved in the shedding of endometrial lesions. Controlling the secretion of estrogen, the hormone that signals for the endometrial tissue to swell, can reduce the pain caused by endometriosis. Progesterone, another hormone that is secreted following ovulation to prevent additional eggs from maturing, can also be manipulated. Progesterone levels normally rise during pregnancy, preventing menstruation.

Nexplanon is a solid implant containing etenogestrel, a compound that is structurally similar to progesterone. Etenogestrel binds to the progesterone and estrogen receptors. This binding signals to the hypothalamus (a portion of the brain considered the “master switch” for hormone control) and slows the release of the gonadotropin-releasing hormone (GnRH), which controls the release of estrogen from the ovaries. The treatment leaches out of the implant gradually over time. Eggs do not mature, and the endometrial tissue shrinks, including the tissue making up the endometrial lesions.

The implant is a small plastic rod about the size of a matchstick that is inserted under the skin of the upper arm by a doctor. He or she first numbs the skin using a topical anesthetic, inserts the rod using an applicator, and places a small bandage over the insertion site for three to five days. The patient must wear a pressure bandage over the small bandage for 24 hours.

The implant is effective for three years, but can be removed at any time.

Nexplanon in clinical trials for endometriosis

A Phase 4 clinical trial (NCT02480647) evaluated and compared the efficacy of Mirena (a uterine implant that releases levonogestrel, a synthetic progesterone-like hormone) with the Nexplanon implant in reducing chronic pelvic pain in women with endometriosis. The study involved 100 participants who were randomly assigned to one of the two treatments. Patients’ daily pain intensity and bleeding intensity were assessed over six months for each group. The results, published in the Fertility and Sterility Journal, showed that both contraceptives significantly reduced patients’ pain.

A Phase 2/3 trial (NCT02669238) to compare the Nexplanon implant with Leeloo or Minidril (daily oral birth control pills available in France) in treating pain caused by endometriosis is currently recruiting participants on the island of Reunion. Patients will be randomly assigned to either a Nexplanon implant or Leloo or Minidril. SATMED-Q, a questionnaire that measures patient satisfaction with treatments, will be used as a primary outcome measure. A survey of patient pain will be the secondary outcome measure.

Other information

Nexplanon may cause side effects, including breast pain, chills, fever, headache, and nausea. Many women do not menstruate at all or menstruate only very lightly while on Nexplanon.

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