Hormone Therapy

A common class of medications used to help manage the symptoms of endometriosis are hormone-altering drugs. These medications, often called hormone therapy, impact the levels of certain hormones in the body. Many hormone therapies suppress ovarian function in one way or another. This can prevent a woman from ovulating (the process by which she releases an egg each month). Ovulation can lead to a spike in various hormones, such as estrogen and progestin. These hormones, and their high levels, are often linked to the growth, thickening, and break down of endometriosis lesions. By suppressing ovarian function and ovulation, the levels of these hormones can be stabilized, potentially shrinking endometriosis lesions and reducing pain.

Combination contraceptives

Combination contraceptives are medications intended for use by women who are sexually active but who do not wish to become pregnant. Combination contraceptives are often used off-label to treat other female reproductive system-related issues such as painful periods, endometriosis-related pelvic pain, menstrual migraines, PMS (premenstrual syndrome), and menstrual cycle irregularities. Combination contraceptives may also be used to improve bone mineral density or to treat acne. Combination contraceptives contain a synthetic estrogen and a synthetic progestin, two hormones that influence the female reproductive system and suppress ovarian function, potentially impacting endometriosis lesion growth.

Because they contain estrogen, these medications carry an increased risk of developing blood clots. These medications may also increase the risk of developing certain cancers such as breast cancer. Additionally, they may increase a woman’s risk of developing bleeding irregularities or impaired liver functioning.

Combination contraceptives make the body think that it is already pregnant, and stop it from ovulating (the process by which the ovaries release an egg each month). This suppression of ovarian function helps stabilize natural hormone levels in the body, suppressing endometriosis lesion growth. Combination contraceptives include birth control pills, the vaginal ring (NuvaRing), and the skin patch (Ortho Evra, Xulane).1,2

Progestin-only contraceptives

Progestin-only contraceptives are medications intended for use by women who are sexually active but who do not wish to become pregnant and who cannot, or should not, take estrogen-containing medications. Progestin-only contraceptives suppress ovarian function, and are often used off-label to treat the same female reproductive system-related issues as combination contraceptives. Progestin-only contraceptives can increase the risk of developing ovarian cysts, ectopic pregnancy (pregnancy outside of the womb), and issues with liver functioning. Additionally, progestin-only medications may increase the risk of developing certain cancers such as breast cancer. Progestin-only contraceptives include progestin-only birth control pills, as well as the hormonal IUD (intrauterine device, Mirena), the birth control arm implant (Nexplanon), and the progestin injection (also referred to as the birth control shot, Depo-Provera).1-3

Gn-RH agonists

Gonadotropin-releasing hormone agonists (Gn-RH agonists) are medications that suppress ovarian function by reducing levels of estrogen and other hormones in the body. Women can take Gn-RH agonists to reduce endometriosis-related pain.4,5 Other uses include preventing the recurrence or progression of certain types of cancer, and as a palliative treatment option for some breast or prostate cancers.6 They are valuable as a mechanism to reduce the painful symptoms that affect quality of life.

When women take Gn-RH agonists, the level of estrogen in their body is decreased to a menopausal-like state.7 This can lead to side effects experienced in menopause such as hot flashes, vaginal dryness, and a decreased libido (interest in sex).5 Gn-RH agonists are available in pill form, as injections, or nasal sprays.1-3

To lessen the severity or presence of some of these symptoms, Gn-RH agonists taken for endometriosis pain are often accompanied by an add-back therapy. Add-back therapy is often a supplement taken daily which contains low amounts of estrogen and progestin, or just progestin. They diminish the side effects of Gn-RH treatment including prevention of bone mineralization. Long-term use of Gn-RH agonists is typically not recommended, as they may increase the risk of developing high cholesterol, cardiovascular complications, as well as severely decreasing bone mineral density.8

Gn-RH antagonists

Gonadotropin-releasing hormone antagonists, Gn-RH antagonists, are another class of medications used to treat paid due to endometriosis. Although not a first line treatment, like nonsteroidal anti-inflammatory drugs (NSAIDs) and progestin-containing oral contraceptives, they are hormonal suppressive treatments effective for pain management.5,6,9 Well tolerated and effective after just a few doses, the effects of Gn-RH antagonists are quickly reversed after the medication is stopped.4,9

Gn-RH receptor agonists and antagonists both bind receptors to stop the production of estrogen production using two different mechanisms. Both result in low estrogen (hypoestrogenic) conditions mimicking menopause.7 Gn-RH antagonists are non-peptide molecules that lessen the effect of Gn-RH by binding to receptors in the hypothalamus preventing the receptor from sending a message to the ovaries to produce estrogen.4

Although similar in structure to Gn-RH agonists, Gn-RH antagonists have a quicker effectiveness because of the mode of action. Gn-RH antagonists are also noted for fewer side effects. There is no initial flare of hormone levels either before or after the onset of action. This is a significant addition to the available treatment options for endometriosis-related pain.4,6

Taken in pill form by mouth, Gn-RH antagonsits are convenient to administer and achieve therapeutic effectiveness quickly.6,9 The blocking of pituitary receptors is nearly immediate, and largely reversible when the medication is stopped.4 They are well tolerated and as noted, women generally experience fewer of the Gn-RH agonist side effects including mood changes, flushing, loss of sexual drive, and vaginal dryness. For many, they can be taken without the need for add-back therapy generally required when using agonists to reduce the debilitating, life style affecting side effects.7 There are some hypoestrogenic effects that your doctor should monitor including changes in bone mineral density and lipid levels.8

Danocrine (danazol)

Danocrine (danazol) is a medication indicated for women with endometriosis to treat endometriosis-related pain. Danazol is a synthetic steroid that interacts with complex hormonal pathways. Ultimately, Danocrine suppresses ovarian function, and the pituitary-ovarian axis, which decreases the amount of estrogen in the body, among other outcomes. This decrease in estrogen can shrink endometriosis lesions, as well as potentially prevent them from thickening and breaking down, decreasing endometriosis-related pain. In addition to this, Danocrine also acts on androgen receptors, increasing male hormone levels in the body. This can lead to distressing side effects for women, such as decreased breast size and experiencing deepening of the voice.2,10

Written by: Casey Hribar | Last reviewed: January 2019
View References
  1. The American College of Obstetricians and Gynecologists. Noncontraceptive uses of hormonal contraceptives. Practice Bulletin, Clinical Management Guidelines for Obstetrician-Gynecologists. Jan 2010; 115(1), 206-218.
  2. What are the Treatments for Endometriosis? National Institutes of Health: Eunice Kennedy Shriver National Institute of Child Health and Human Development. https://www.nichd.nih.gov/health/topics/endometri/conditioninfo/treatment. Published January 31, 2017. Accessed May 1, 2018.
  3. Progestin-Only Hormonal Birth Control: Pill and Injection. The American College of Obstetricians and Gynecologists. https://www.acog.org/Patients/FAQs/Progestin-Only-Hormonal-Birth-Control-Pill-and-Injection. Published March 2018. Accessed May 1, 2018.
  4. Barbieri, RL. A Novel Oral GnRH Antagonist for Managing Endometriosis Pain. Available at: https://www.jwatch.org/na44187/2017/06/02/novel-oral-gnrh-antagonist-managing-endometriosis-pain. Accessed 2.27.19
  5. GnRH Receptor antagonists. Available at: https://endometriosisnews.com/hormonal-therapy/gnrh-receptor-antagonists/. Accessed 2.27.19
  6. Huime, JA, Lambalk, CB. Gonadotropin-releasing-hormone-receptor antagonists. Available at: https://www.ncbi.nlm.nih.gov/pubmed/11734258. Accessed 2.27.19
  7. Understanding Endometriosis and Treatment with a GnRH Agonist. Available at: https://www.abbvie.ca/content/dam/abbviecorp/ca/en/docs/MOA_Brochure_EN.pdf. Accessed 2.27.19
  8. Küpker1, W., Felberbaum, RE, et al. Use of GnRH antagonists in the treatment of endometriosis. Available at: https://www.rbmojournal.com/article/S1472-6483(10)61590-8/pdf. Accessed 2.27.19
  9. Dun, E., Taylor, H. Elagolix: a promising oral GnRH antagonist for endometriosis-associated pain. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725085/. Accessed 2.27.19
  10. Danazol Prescribing Information. National Institutes of Health. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f2c9b713-aafc-49ca-866e-334d9b5c2e2d&type=display. Published August 2017. Accessed May 1, 2018.