Endometriosis is a disease in which endometrial cells, or those that make up the lining of the uterus, are implanted and grow elsewhere, usually in other areas of the pelvis. The implanted tissue swells and sheds with the menstrual cycle, just like the normal endometrial tissue. However, because there is no exit route for these cells, they become trapped, causing inflammation, pain, and infertility.

There is currently no cure for endometriosis, but hormonal treatments can help manage symptoms.

How hormonal treatment affects endometriosis

For women, every month a cycle of estrogen and progesterone secretion from the ovaries controls the cycle of preparing the uterus for the potential implantation of an embryo. If no implantation occurs, the endometrium sheds and the cycle starts over again.

Endometrial lesions behave the same way; the lesions swell with the hormone cycle and shed, but are trapped where they are implanted and cannot be expelled like the endometrium lining the uterus.

Hormonal treatments containing progestin, estrogen, or both prevent the release of an egg from the ovaries and reduce the swelling of the endometrial tissue, which can reduce pain and inflammation.

There are different types of hormonal treatment that can be used to ease the symptoms of endometriosis.

Hormonal birth control treatments

There are many types of hormonal birth control treatments containing various dosages of hormones. Several of these have been successful in reducing pain for endometriosis patients.

For example, Depo-Provera and Depo-subQ-Provera 104 are injections that have both been shown to reduce pain caused by endometriosis. Both contain forms of progesterone.

Nexplanon (etonogestrel) is an implant placed beneath the skin of the upper arm that releases small amounts of the hormone over time. The treatment has been shown to reduce pain due to endometriosis; although the mechanism is not well-understood, it is thought to suppress the growth of endometrial implants and reduce their size.

Mirena is an implantable intrauterine device (IUD) which gradually releases a form of progesterone. Mirena is not yet approved for the treatment of endometriosis, but several small studies have indicated it may be useful in treating pain due to the condition, possibly by reducing blood flow during a woman’s period.

Continuous birth control pills (taken every day) such as Lybrel or Seasonique may also reduce menstrual bleeding; both are formulations of ethinyl estradiol and levonorgestrel.

GnRH receptor antagonists

A different kind of hormone treatment is gonadotropin-releasing hormone (GnRH) receptor antagonists. These medications act on a receptor in the pituitary gland, a region in the brain sometimes called the “master gland,” and prevent or reduce estrogen production. This reduces or suppresses the menstrual cycle and decreases the pain associated with endometriosis.

Orilissa (elagolix) a GnRH receptor antagonist, was approved by the U.S. Food and Drug Administration in July 2018.

Two other experimental GnRH receptor antagonists, Linzagolix and Relugolix, are currently undergoing clinical trials for efficacy and safety.

GnRH receptor agonists

GnRH receptor agonists have, initially, the opposite effect to GnRH receptor antagonists. They are chemically similar to GnRH and bind to the GnRH receptor in the pituitary gland, activating it and stimulating the ovaries to produce estrogen.  However, prolonged activation of the receptor causes it to become desensitized to GnRH. Between one and three weeks after beginning treatment, estrogen production stops. In essence, these treatments induce an artificial menopause.

Lupron Depot (leuprolide acetate), Zoladex (goserelin), and Synarel (nafarelin) are examples of GnRH receptor agonists.

Like other treatments that induce menopause, GnRH receptor agonists carry an increased risk of patients developing osteoporosis.

Aromatase inhibitors

Aromatase inhibitors are a class of medications sometimes used in combination with hormonal birth control pills or GnRH receptor agonists to reduce pain associated with endometriosis. Aromatase is a key enzyme that converts androgens into estrogen. By suppressing this enzyme, aromatase inhibitors can reduce the amount of estrogen being produced. Aromatase inhibitors used for endometriosis include Femara (letrozole) and Arimidex (anastrozole).

Aromatase inhibitors should not be used alone (i.e. without a hormonal birth control pill or GnRH receptor agonists), as they may stimulate the development of ovarian cysts. This class of medication is not generally prescribed to premenopausal women as it may cause osteoporosis.

Calcium, vitamin D, and a bisphosphonate, a medication that protects the bones against osteoporosis should also be taken with aromatase inhibitors to reduce bone loss.

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