Endometriosis medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Joseph Nasr, M.D.[2], Sogand Goudarzi, MD [3], Aravind Kuchkuntla, M.B.B.S[4]
Overview
The mainstay of therapy for endometriosis is pain management and regression of endometrial lesions. NSAIDs are useful for pain management. There are many therapeutic options available to reduce the size of endometrial lesions. Gonadotrophin releasing hormone agonists and danazol are widely used. Continuous oral contraceptive pill use is also helpful in patients with mild to moderate endometriosis.
Current guidelines support empiric hormonal therapy in patients with suspected endometriosis based on symptoms and imaging findings, without requiring surgical confirmation.[1]
Medical Therapy
The treatment of endometriosis is a combination of medical and surgical therapy based on the extent of the disease, the age of the patient, and the desire of the patient to conceive. The primary goal of medical therapy is the symptomatic improvement of pain and regression of the endometrial lesions.[2][3][4]
Transvaginal pelvic ultrasound is recommended as the initial imaging study prior to initiation of therapy when endometriosis is suspected.[1]
- Endometriosis occurs due to increased levels of estrogen. This may be a result of excess production in the body or exogenous estrogen intake. Therefore, the primary goal of medical therapy is to shut off the estrogen supply which is essential for the growth of the endometrial lesions.[5]
- Treatment of patients with mild to moderate pain (pain is not couse of absence) is nonsteroidal anti-inflammatory drugs (NSAIDs).[6]
- COX-2 inhibitors (celecoxib, rofecoxib, and valdecoxib) are avoided for patients desire pregnancy.[7][8]
- Among patients without medical contraindications, the best treatment is combination of estrogen-progestin contraceptives combined and NSAID.[9] Continuous administration of combined hormonal contraceptives may provide greater symptom control compared with cyclic regimens.[1]
- Progestin-only contraceptive pills such as norethindrone 0.35 mg (once daily) combined with an NSAID is used among patient who can not use estrogen therapy.[10]
- Intramuscular injection of medroxyprogesterone acetate (MPA) 150 mg can helpful every three months.[11]
- Levonorgestrel-releasing intrauterine systems are also effective for reducing endometriosis-associated pain.[12]
- Subcutaneous injection of medroxyprogesterone acetate (MPA) 104 mg can helpful every three months.[11]
- Norethindrone acetate 5 mg can be used by mouth daily (the dose can range from 2.5 mg to 15 mg daily).[13]
- Side effects of progestin treatment is:[14]
- Irregular uterine bleeding
- Spotting
- Amenorrhea
- Weight gain
- Mood changes
- Bone loss
- Reduction in high-density lipoprotein (HDL) cholesterol
- Increases in low-density lipoprotein (LDL) cholesterol and triglycerides
- There are several therapeutic agents available to decrease estrogen production. The following table is a description of different therapeutic agents available for the treatment of endometriosis.
- Endometriosis is a chronic condition, and long-term suppressive hormonal therapy may be required for symptom control.[15][16]
| Drug Class | Drugs | Duration of therapy | Mechanism of Action | Side effects of therapy |
|---|---|---|---|---|
| Gonadotrophin releasing hormone agonists | Leuprolide acetate | 3.75 mg intramuscularly once per month OR
11.25-mg depot injection every 3 months |
|
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| Nafarelin acetate | Nasal spray dose of one spray 200 μg twice a day | |||
| Goserelin acetate | 3.6 mg every 28 days in a biodegradable subcutaneous implant | |||
| Elagolix | 150 mg once daily for up to 24 months or 200 mg twice daily for up to 6 months | |||
| Oral contraceptive pills | Low dose estrogen and high dose progesterone pills | Continuous therapy for a duration of 6 to 12 months | Feedback inhibition of FSH and LH |
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| Synthetic steroid | Danazol | 200mg to 400mg orally per day for 6 to 9 months | Produces a hypoestrogenic and hyperandrogenic effect and induces atrophic changes in the endometrium |
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| Progestogens only | Medroxyprogesterone acetate | 20 to 30 mg orally per day | Feedback inhibition of FSH and LH |
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| Depo-medroxyprogesterone acetate | 150 mg intramuscularly every 3 months | |||
| Aromatase inhibitors[17] | Anastrozole | 1 mg once daily | Inhibition of aromatase expressed in the endometriomas resulting in decreased estrogen levels |
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| Letrozole | 2.5 mg once daily |
GnRH Antagonists
GnRH antagonists provide direct suppression of gonadotropin secretion and are used as second-line therapy for patients with persistent symptoms.[18]
Add-back hormonal therapy may be required to mitigate hypoestrogenic adverse effects associated with prolonged GnRH therapy.[19]
Aromatase Inhibitors
Aromatase inhibitors are generally reserved for refractory cases and are typically used in combination with other ovarian suppressive therapies.[20]
Pain Management
Nonsteroidal anti-inflammatory drugs are useful for the control of pain and help to control the amount of bleeding when used in combination with oral contraceptive pills.[21]
Endometriosis-associated pain may involve nociceptive, neuropathic, and nociplastic mechanisms.[15][16]
Hormonal suppression may not fully alleviate pain when central sensitization is present.[15][16]
Pain may persist or recur despite surgical excision of lesions, particularly when central sensitization mechanisms contribute to symptomatology.[15][16]
Referral
Referral to a gynecologist is recommended when imaging suggests deep infiltrating or extrapelvic disease, or when symptoms persist despite first-line medical therapy.[1]
References
- ↑ 1.0 1.1 1.2 1.3 Singh SS, Allaire C, Al-Nourhji O, et al. Guideline No. 449: diagnosis and impact of endometriosis—a canadian guideline. J Obstet Gynaecol Can. 2024; 46(5):102450. doi:10.1016/j.jogc.2024.102450
- ↑ Bedaiwy MA, Alfaraj S, Yong P, Casper R (2017). "New developments in the medical treatment of endometriosis". Fertil Steril. 107 (3): 555–565. doi:10.1016/j.fertnstert.2016.12.025. PMID 28139238.
- ↑ Benagiano G, Guo SW, Bianchi P, Puttemans P, Gordts S, Petraglia F; et al. (2016). "Pharmacologic treatment of the ovarian endometrioma". Expert Opin Pharmacother. 17 (15): 2019–31. doi:10.1080/14656566.2016.1229305. PMID 27615386.
- ↑ Streuli I, de Ziegler D, Santulli P, Marcellin L, Borghese B, Batteux F; et al. (2013). "An update on the pharmacological management of endometriosis". Expert Opin Pharmacother. 14 (3): 291–305. doi:10.1517/14656566.2013.767334. PMID 23356536.
- ↑ Mateo Sánez HA, Mateo Sánez E, Hernández AL, Salazar Ricarte EL (2012). "[Treatment of patients with endometriosis and infertility]". Ginecol Obstet Mex. 80 (11): 705–11. PMID 23427639.
- ↑ Brown, Julie; Crawford, Tineke J; Allen, Claire; Hopewell, Sally; Prentice, Andrew (2017). "Nonsteroidal anti-inflammatory drugs for pain in women with endometriosis". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD004753.pub4. ISSN 1465-1858.
- ↑ Pall, M. (2001). "Induction of delayed follicular rupture in the human by the selective COX-2 inhibitor rofecoxib: a randomized double-blind study". Human Reproduction. 16 (7): 1323–1328. doi:10.1093/humrep/16.7.1323. ISSN 1460-2350.
- ↑ Duffy, Diane M.; VandeVoort, Catherine A. (2011). "Maturation and fertilization of nonhuman primate oocytes are compromised by oral administration of a cyclooxygenase-2 inhibitor". Fertility and Sterility. 95 (4): 1256–1260. doi:10.1016/j.fertnstert.2010.12.048. ISSN 0015-0282.
- ↑ Bedaiwy, Mohamed A.; Allaire, Catherine; Alfaraj, Sukinah (2017). "Long-term medical management of endometriosis with dienogest and with a gonadotropin-releasing hormone agonist and add-back hormone therapy". Fertility and Sterility. 107 (3): 537–548. doi:10.1016/j.fertnstert.2016.12.024. ISSN 0015-0282.
- ↑ Allen, Rebecca; Villavicencio, Jennifer (2016). "Unscheduled bleeding and contraceptive choice: increasing satisfaction and continuation rates". Open Access Journal of Contraception: 43. doi:10.2147/OAJC.S85565. ISSN 1179-1527.
- ↑ 11.0 11.1 "DailyMed - MEDROXYPROGESTERONE ACETATE- medroxyprogesterone acetate injection, suspension".
- ↑ Practice bulletin No. 114: management of endometriosis. Obstet Gynecol. 2010;116(1):223-236. doi:10.1097/AOG.0b013e3181e8b073
- ↑ "DailyMed - AYGESTIN- norethindrone acetate tablet".
- ↑ "Menopause and Hormone Replacement - Endotext - NCBI Bookshelf".
- ↑ 15.0 15.1 15.2 15.3 Coxon L, Demetriou L, Vincent K. Current developments in endometriosis-associated pain. Cell Rep Med. 2024;5(10):101769. doi:10.1016/j. xcrm.2024.101769
- ↑ 16.0 16.1 16.2 16.3 Kaplan CM, Kelleher E, Irani A, Schrepf A, Clauw DJ, Harte SE. Deciphering nociplastic pain: clinical features, risk factors and potential mechanisms. Nat Rev Neurol. 2024;20(6):347-363. doi:10.1038/s41582-024-00966-8
- ↑ Słopień R, Męczekalski B (2016). "Aromatase inhibitors in the treatment of endometriosis". Prz Menopauzalny. 15 (1): 43–7. doi:10.5114/pm.2016.58773. PMC 4828508. PMID 27095958.
- ↑ Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Australian Clinical Practice Guideline for the Diagnosis and Management of Endometriosis. Royal Australian and New Zealand College of Obstetricians and Gynaecologists; 2021. Accessed February 10, 2025. https://ranzcog.edu.au/wp-content/uploads/+2022/02/Endometriosis-clinical-practice-guideline.+pdf
- ↑ National Institute for Health and Care Excellence. Endometriosis: Diagnosis and Management: NICE Guideline 37. Published September 6, 2017. Updated April 16, 2024. Accessed January 13, 2025. https://www.nice.org.+uk/guidance/ng73/evidence/full-guideline-pdf-+4550371315
- ↑ Becker CM, Bokor A, Heikinheimo O, et al; ESHRE Endometriosis Guideline Group. ESHRE guideline: endometriosis. Hum Reprod Open. 2022; 2022(2):hoac009. doi:10.1093/hropen/hoac009
- ↑ Brown J, Crawford TJ, Allen C, Hopewell S, Prentice A (2017). "Nonsteroidal anti-inflammatory drugs for pain in women with endometriosis". Cochrane Database Syst Rev. 1: CD004753. doi:10.1002/14651858.CD004753.pub4. PMID 28114727.