Endometriosis: What are your treatment options?

When deciding whether or not to have a treatment, it's a good idea to find out about the pros and cons of the different treatment options first. This decision aid can help here.

Do painkillers help in endometriosis?

Painkillers known as non-steroidal anti-inflammatory drugs (NSAIDs) are often used to treat endometriosis. These painkillers include ibuprofen, diclofenac and acetylsalicylic acid (ASA – the drug in medicines like Aspirin). Lower doses of these drugs can be bought “over the counter” in pharmacies. Higher doses are only available on prescription.

Although NSAIDs have been proven to relieve period pain, there's hardly any good-quality research on their effect in women with endometriosis. They can also have side effects, particularly affecting the stomach. Acetylsalicylic acid ("Aspirin") reduces the blood's ability to clot, too. For these reasons, most women are advised not to take painkillers every day for a long time. It is better to only take them for a short while, like during a painful period. You should talk to your doctor about how best to use painkillers.

If these painkillers don't help enough, drugs known as opioids can sometimes be used. Opioids can have strong side effects, so it's important to carefully consider whether or not to use them. They can lead to drowsiness, constipation or even dependency.

Distressing, chronic pain can sometimes be treated with other kinds of medication such as antidepressants or anti-epileptic drugs – even if you don't have depression or epilepsy. There is a lack of research on their effectiveness in the treatment of endometriosis. But they can be used as part of pain management therapy to see if they help. These medications alter the perception of pain and are prescribed together with a painkiller. The pain-relieving effect may only be felt after a few weeks.

What are the hormone-based options?

Endometriosis tissue builds up and breaks down every month in the course of the menstrual cycle. Hormone-based medications lower the level of the hormone estrogen, which regulates this cycle. In this way, hormone therapy inhibits the monthly build-up of endometriosis tissue. It can also prevent ovulation (the release of an egg from the ovaries) and make your periods stop.

The hormone therapy options in endometriosis include:

• Progestins: Such as progestin tablets and the hormonal coil (IUD).
• GnRH antagonists: These are taken in the form of tablets.
• GnRH agonists: These are used in the form of injections or a nasal spray.
• Combined hormonal contraceptives, like the birth control pill ("the pill"). These contain the hormones estrogen and progestin.

Please note: GnRH antagonists and GnRH agonists are two different types of GnRH analogs.

Hormone therapy can prevent endometriosis tissue from building up, which relieves the pain. It is not clear whether these medications can also make the areas of endometriosis tissue (endometrial implants) get smaller or disappear completely, though. Endometriosis symptoms often return when women stop hormone therapy. Hormone-based treatments can also have side effects.

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Hormone therapy has a contraceptive effect, so it's not suitable for women who would like to become pregnant.

What do progestins do?

Drugs containing the hormone progestin can relieve pain in endometriosis. These include the mini-pill. Progestin tablets are often the treatment of first choice for endometriosis. They are taken every day without any breaks. That can make your period stop altogether. Progestins can have side effects such as headaches, nausea, dizziness, breast tenderness, acne or mood swings. Spotting (light bleeding) is common in the first few months. Over the long term, your bone density might decrease.

Progestins can also be used in the form of a hormonal coil (LNG-IUS or IUD, short for levonorgestrel-releasing intrauterine system or device) – particularly if there's endometriosis tissue in the wall of the womb (adenomyosis). The coil is inserted into the womb and can be left there for three to eight years, depending on the exact type. Sometimes this kind of coil is inserted after a woman has had surgery to remove endometriosis tissue. Research suggests that combining surgery and the coil in this way reduces endometriosis symptoms better than surgery does on its own. The LNG-IUS can cause side effects such as spotting, acne and breast tenderness.

Can combined contraceptives help?

The birth control pill (combination pill) can relieve endometriosis-related pain. It is taken every day, often with a one-week break each month. Then you get a period during that time. Some types of contraceptive pill can be used to suppress your monthly hormone cycle and period for a longer amount of time. To do this, they are either taken continuously, without any breaks between cycles (continuous use) – or with less frequent breaks (extended use).

Two studies found the following:

• Women who took a fake medication (placebo) reported an average pain score of 46 on a scale of 0 to 100.
• Women who took the combination pill reported an average pain score of 23 on a scale of 0 to 100.

Other types of combined hormonal contraceptives (like the vaginal ring) can be used as well, but it's not clear how effective they are in the treatment of endometriosis.

The most common side effects of combined hormonal contraceptives include headaches, nausea, dizziness, breast tenderness and mood swings. They also increase the risk of thrombosis. In terms of side effects, it makes little difference whether the pill is taken continuously or with monthly breaks.

The use of combined hormonal contraceptives in the treatment of endometriosis hasn't been approved in Germany. This means that it's considered to be off-label use when they're used for this purpose. As a result, some public health insurers in Germany may not cover the costs.

What are the pros and cons of GnRH agonists?

GnRH agonists can relieve endometriosis-related symptoms too. Like other hormone-based medications, they may cause your period to stop altogether. GnRH agonists can either be used every day in the form of a nasal spray, injected under the skin once a month, or injected into a muscle once every three months.

One study found that period pain had improved after three months in

• 44 out of 100 women who took a fake medication (placebo) and
• 99 out of 100 women who had treatment with GnRH agonists.

Other pain in the abdomen improved, too, and they had less pain during sex.

But GnRH agonists have stronger side effects than the other medications do. They reduce the production of female sex hormones so much that they often cause problems related to estrogen deficiency. These are similar to the problems women may have during menopause, such as hot flashes, sleep problems, vaginal dryness and mood swings.

When used over longer periods of time, GnRH agonists may reduce your bone density. Because of this, women are advised not to take them for longer than 3 to 6 months. They are also advised to take low doses of combined estrogen and progestin in addition to the GnRH agonists. Known as “add-back therapy,” this approach aims to reduce the problems associated with low levels of female hormones.

What do GnRH antagonists do?

GnRH antagonists reduce the amount of reproductive hormones secreted by the pituitary gland at the base of the brain. So far, only one GnRH antagonist has been approved for the treatment of endometriosis in Germany. It is a combination of the drugs relugolix, estradiol and norethindrone acetate (brand names: Ryeqo, Myfembree).

Two studies found that period pain improved in

• 29 out of 100 women who took a fake medication (placebo) and
• 75 out of 100 women who took the relugolix/estradiol/norethindrone acetate combination drug.

The combination drug is taken every day in the form of a tablet. It can be used over a longer period of time than GnRH agonists can. Its side effects include headaches, hot flashes and spotting.

GnRH antagonists can also make your periods stop altogether.

Sources

• Becker CM, Bokor A, Heikinheimo O et al. ESHRE guideline: endometriosis. Hum Reprod Open 2022; 2022(2): hoac009. [PMC free article: PMC8951218] [PubMed: 35350465]
• Brown J, Crawford TJ, Allen C et al. Nonsteroidal anti-inflammatory drugs for pain in women with endometriosis. Cochrane Database Syst Rev 2017; (1): CD004753. [PMC free article: PMC6464974] [PubMed: 28114727]
• Brown J, Crawford TJ, Datta S, Prentice A. Oral contraceptives for pain associated with endometriosis. Cochrane Database Syst Rev 2018; (5): CD001019. [PMC free article: PMC6494634] [PubMed: 29786828]
• Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG). Diagnostik und Therapie der Endometriose (S2k-Leitlinie, in Überarbeitung). AWMF-Registernr.: 015-045. 2020.
• Deutsche Gesellschaft für Psychosomatische Frauenheilkunde und Geburtshilfe (DGPFG). Chronischer Unterbauchschmerz der Frau (S2k-Leitlinie): AWMF-Registernr.: 016 - 001. 2022.
• European Medicines Agency (EMA). Ryeqo. 2024.
• Gemeinsamer Bundesausschuss (G-BA). Nutzenbewertungsverfahren zum Wirkstoff Relugolix/Estradiol/Norethisteronacetat (Neues Anwendungsgebiet: Endometriose, nach medikamentöser oder chirurgischer Behandlung). 2024.
• Gibbons T, Georgiou EX, Cheong YC, Wise MR. Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery. Cochrane Database Syst Rev 2021; (12): CD005072. [PMC free article: PMC8686684] [PubMed: 34928503]
• Marjoribanks J, Ayeleke RO, Farquhar C, Proctor M. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database Syst Rev 2015; (7): CD001751. [PMC free article: PMC6953236] [PubMed: 26224322]
• Peng C, Huang Y, Zhou Y. Dydrogesterone in the treatment of endometriosis: evidence mapping and meta-analysis. Arch Gynecol Obstet 2021; 304(1): 231-252. [PMC free article: PMC8164626] [PubMed: 33398505]
• Samy A, Taher A, Sileem SA et al. Medical therapy options for endometriosis related pain, which is better? A systematic review and network meta-analysis of randomized controlled trials. J Gynecol Obstet Hum Reprod 2020: 101798. [PubMed: 32479894]
• Veth VB, van de Kar MM, Duffy JM et al. Gonadotropin-releasing hormone analogues for endometriosis. Cochrane Database Syst Rev 2023; (6): CD014788. [PMC free article: PMC10283345] [PubMed: 37341141]

• IQWiG health information is written with the aim of helping people understand the advantages and disadvantages of the main treatment options and health care services.

  Because IQWiG is a German institute, some of the information provided here is specific to the German health care system. The suitability of any of the described options in an individual case can be determined by talking to a doctor. informedhealth.org can provide support for talks with doctors and other medical professionals, but cannot replace them. We do not offer individual consultations.

  Our information is based on the results of good-quality studies. It is written by a team of health care professionals, scientists and editors, and reviewed by external experts. You can find a detailed description of how our health information is produced and updated in our methods.