Endometriosis results when tissue resembling the endometrium that lines the uterus grows elsewhere, usually in the pelvic area. This tissue swells and sheds with the menstrual cycle, as the endometrium does. But because there is no route by which these growths can be expelled when they shed, they become trapped and cause inflammation, pain, and risk infertility.

No cure currently exists for endometriosis, but hormonal treatments can help to manage disease symptoms to a certain extent.

How hormonal treatment affects endometriosis

Premenopausal women to through a monthly cycle of estrogen and progesterone secretion from the ovaries, to prepare the uterus for the possibility of an embryo growing there. If no pregnancy takes place, the endometrium sheds and the cycle starts over again. Extrauterine growths behave the same way; they swell with the hormone cycle and shed, but are trapped where they are implanted and cannot leave the body in menstrual cycles like the endometrium.

Hormonal treatments aim to control or stop the monthly hormone cycle, often by reducing estrogen levels. This can prevent or slow the growth of the endometrial tissue, easing pain and inflammation.

Different types of hormonal treatments can be used to address these symptoms of endometriosis.

Hormonal contraceptives

Many types of hormonal contraceptives, or birth control treatments, have successfully addressed the pain experienced endometriosis patients. These medications typically contain various combination dosages of the hormones estrogen and progesterone in a synthetic form.

For example, Nexplanon (etonogestrel) is an implant placed beneath the skin of the upper arm that releases small amounts of hormone over time.

Seasonique (ethinyl estradiol and levonorgestrel) is another example of hormonal contraceptive that can reduce pain associated with endometriosis.

Some hormonal contraceptives mimic mainly progesterone and are referred to specifically as progestin therapies. Example include Depo-Provera, Depo-subQ-Provera 104, and Mirena.

GnRH receptor antagonists

A different type 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 to lessen the pain associated with endometriosis.

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

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

GnRH receptor agonists

GnRH receptor agonists initially have 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 this 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), Suprefact (buserelin acetate), Zoladex (goserelin), and Synarel (nafarelin) are examples of GnRH receptor agonists.

Like other treatments that induce menopause, GnRH receptor agonists carry a risk of causing patients to develop osteoporosis.

Testosterone derivatives

Testosterone derivatives are a type of hormonal therapy that is less commonly used to treat endometriosis, as they can cause male-like (androgenic) side effects. However, they may still be prescribed when other treatments have failed.

Testosterone is a male reproductive hormone, or androgen, that acts to suppress estrogen and progesterone production. Testosterone-derivative medications contain a synthetic, or man-made, version of the androgen. Higher levels of testosterone reduce estrogen levels, which can provide relief from the symptoms of endometriosis and prevent the growth of lesions.

Examples of testosterone derivatives that can be used to treat endometriosis-associated pain include Danocrine (danazol) and gestrinone.

Aromatase inhibitors

Aromatase inhibitors are a class of medications sometimes used in combination with hormonal birth control pills or GnRH receptor agonists to ease pain linked to endometriosis.

Women also produce low levels of androgens; however, most are converted to estrogen. A key enzyme in the conversion process is aromatase, and by suppressing this enzyme, aromatase inhibitors can lower 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 and lessen the risk of fractures.

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