Hormonal intrauterine device

Last updated

IUD with progestogen
Mirena IntraUterine System.jpg
Correctly inserted IUD
Background
TypeIntrauterine
First use1990 (Mirena—currently available)
1976 (Progestasert—discontinued in 2001)
Synonyms intrauterine system (IUS), levonorgestrel intrauterine system
Trade names Mirena, Skyla, Liletta, others
AHFS/Drugs.com Professional Drug Facts
Failure rates (first year)
Perfect use0.1–0.2% [1]
Typical use0.1–0.2% [1]
Usage
Duration effect3–8 years
Reversibility2–6 months
User remindersCheck thread position monthly
Clinic reviewOne month after insertion, then annually
Advantages and disadvantages
STI protectionNo
PeriodsMenstrual irregularity, periods usually lighter or none at all
WeightPotential side effect
BenefitsNo need to remember to take daily action
Risksbenign ovarian cysts, transient risk of PID, uterine perforation (rare)

A hormonal intrauterine device (IUD), also known as an intrauterine system (IUS) with progestogen and sold under the brand name Mirena among others, is an intrauterine device that releases a progestogenic hormonal agent such as levonorgestrel into the uterus. [2] It is used for birth control, heavy menstrual periods, and to prevent excessive build of the lining of the uterus in those on estrogen replacement therapy. [2] It is one of the most effective forms of birth control with a one-year failure rate around 0.2%. [1] The device is placed in the uterus and lasts three to eight years. [3] [4] Fertility often returns quickly following removal. [2]

Contents

Side effects include irregular periods, benign ovarian cysts, pelvic pain, and depression. [2] Rarely uterine perforation may occur. [2] Use is not recommended during pregnancy but is safe with breastfeeding. [2] The IUD with progestogen is a type of long-acting reversible birth control. [5] It works by thickening the mucus at the opening of the cervix, stopping the buildup of the lining of the uterus, and occasionally preventing ovulation. [2]

The IUD with levonorgestrel was first approved for medical use in 1990 in Finland and in the United States in 2000. [6] It is on the World Health Organization's List of Essential Medicines. [7] [8]

Medical uses

Hormonal intrauterine device
Clinical data
Pregnancy
category
ATC code
  • None
Legal status
Legal status

The hormonal IUD is an extremely effective method of birth control, and a 2021 study demonstrated that it may be used for emergency contraception. [15] In addition to birth control, the hormonal IUD is used for prevention and treatment of:

Advantages:

Disadvantages:

Effectiveness

After insertion, Mirena is effective at preventing pregnancy for up to eight years. [29] Kyleena is approved for five years and Skyla is approved for three years. [30] [31]

The hormonal IUD is a long-acting reversible contraceptive, and is considered one of the most effective forms of birth control. The first year failure rate for the hormonal IUD is 0.1-0.2% and the five-year failure rate is 0.7-0.9%. [32] [29] [33] These rates are comparable to tubal sterilization, but unlike sterilization the effects of the hormonal IUD are reversible.

The hormonal IUD is considered to be more effective than other common forms of reversible contraception, such as the birth control pill, because it requires little action by the user after insertion. [23] The effectiveness of other forms of birth control is mitigated (decreased) by the users themselves. If medication regimens for contraception are not followed precisely, the method becomes less effective. IUDs require no daily, weekly, or monthly regimen, so their typical use failure rate is therefore the same as their perfect use failure rate. [23]

In a 10-year study, the levonorgestrel coil was found to be as effective as oral medicines (tranexamic acid, mefenamic acid, combined oestrogen–progestogen or progesterone alone) for heavy periods; the same proportion of women had not had surgery for heavy bleeding and had similar improvements in their quality of life. [34] [35]

In women with bicornuate uterus and in need of contraception, two IUDs are generally applied (one in each horn) due to lack of evidence of efficacy with only one IUD. [36] Evidence is lacking regarding progestogen IUD usage for menorrhagia in bicornuate uterus, but a case report showed good effect with a single IUD for this purpose. [37]

Breastfeeding

Progestogen-only contraceptives such as an IUD are not believed to affect milk supply or infant growth. [38] However, a study in the Mirena application for FDA approval found a lower continuation of breastfeeding at 75 days in hormonal IUD users (44%) versus copper IUD users (79%). [39] :37

When using Mirena, about 0.1% of the maternal dose of levonorgestrel can be transferred via milk to the nursed infant. [40] A six-year study of breastfed infants whose mothers used a levonorgestrel-only method of birth control found the infants had increased risk of respiratory infections and eye infections, though a lower risk of neurological conditions, compared to infants whose mothers used a copper IUD. [41] No longer-term studies have been performed to assess the long-term effects on infants of levonorgestrel in breast milk.

There are conflicting recommendations about use of Mirena while breastfeeding. The U.S. CDC does not recommend any hormonal method as a first choice of contraceptive for nursing mothers, although progestin-only methods, such as Mirena, may be used with close follow-up or when the benefits outweigh the risks. [42] The World Health Organization recommends against immediate postpartum insertion, citing increased expulsion rates. It also reports concerns about potential effects on the infant's liver and brain development in the first six weeks postpartum. However, it recommends offering Mirena as a contraceptive option beginning at six weeks postpartum even to nursing women. [43] [44] Planned Parenthood offers Mirena as a contraceptive option for breastfeeding women beginning at four weeks postpartum. [45]

Contraindications

A hormonal IUD should not be used by people who:

Insertion of an IUD is acceptable after a dilation and evacuation (D&E) abortion (second-trimester abortion), but may be associated with a higher expulsion rate. [48] To reduce the risk of infection, insertion of an IUD is not recommended for women that have had a medical abortion but have not yet had an ultrasound to confirm that the abortion was complete, or that have not yet had their first menstruation following the medical abortion. [45]

A full list of contraindications can be found in the WHO Medical Eligibility Criteria for Contraceptive Use and the CDC United States Medical Eligibility Criteria for Contraceptive Use. [24] [49]

Side effects

Cancer

According to a 1999 evaluation of the studies performed on progestin-only birth control by the International Agency for Research on Cancer, there is some evidence that progestin-only birth control reduces the risk of endometrial cancer. The IARC in 1999 concluded that there is no evidence progestin-only birth control increases the risk of any cancer, though the available studies were too small to be definitively conclusive. [66]

Progesterone is a hormone in the endometrium that counteracts estrogen driven growth. [67] Very low levels of progesterone will cause estrogen to act more, leading to endometrial hyperplasia and adenocarcinoma. [67] These effects can be minimized if treated with progestin, but not in very many cases.

Estrogen and progesterone have an antagonistic relationship. Estrogen promotes the growing of endometrial lining, while progesterone limits it. [67] In the case of endometrial cancer, progesterone can negatively regulate estrogen driven growth. Tumors formed are correlated with insufficient progesterone and excess estrogen. [67] In patients with endometrial cancer who use progestin releasing IUDs concluded mixed results.

A 2020 meta-analysis by Livia Conz et al. estimated that users of levonorgestrel-releasing systems had an increased breast cancer risk in general (with an odds ratio of 1.16) and higher risk for those over age 50 (odds ratio 1.52), and suggested balancing this risk against the known benefits of long-term use. [68] Researchers cautioned against causal interpretation from this study, citing confounding effects, methodological concerns and a 2020 meta-analysis of randomized controlled trials which showed no increased risk. [69] [70] [71]

Bone density

No evidence has been identified to suggest Mirena affects bone mineral density (BMD). [72] Two small studies, limited to studying BMD in the forearm, show no decrease in BMD. [73] [74] One of the studies showed at seven years of use, similar BMD at the midshaft of the ulna and at the distal radius as nonusers matched by age and BMI. [73] In addition, BMD measurements were similar to the expected values for women in the same age group as the participants. The authors of the study said their results were predictable, since it is well established that the main factor responsible for bone loss in women is hypoestrogenism, and, in agreement with previous reports, they found estradiol levels in Mirena users to be normal. [73]

Composition and hormonal release

Mirena IUD visible on pelvic radiograph. Mirena IUD - Roe Becken ap.jpg
Mirena IUD visible on pelvic radiograph.

The hormonal IUD is a small T-shaped piece of plastic, which contains levonorgestrel, a type of progestin. [29] The cylinder of the device is coated with a membrane that regulates the release of the drug. [75] Bayer markets Skyla as Jaydess in the United Kingdom. [76] Jaydess releases six micrograms per day and lasts for three years. [77] In comparison, oral contraceptives can contain 150 micrograms of levonorgestrel. [53] The hormonal IUD releases the levonorgestrel directly into the uterus, as such its effects are mostly paracrine rather than systemic. Most of the drug stays inside the uterus, and only a small amount is absorbed into the rest of the body. [53]

Insertion and removal

Schematic depiction of vaginal ultrasonography of a Mirena. Mirena in optimal place - schematic.png
Schematic depiction of vaginal ultrasonography of a Mirena.
Vaginal ultrasonography showing a Mirena in optimal place in the uterus, as viewed from angle shown in schematic depiction. Mirena in optimal place - ultrasound.jpg
Vaginal ultrasonography showing a Mirena in optimal place in the uterus, as viewed from angle shown in schematic depiction.
Insertion of a hormonal IUD Mirena intrauterine device insertion.jpg
Insertion of a hormonal IUD
Removal of a hormonal IUD Removal of IUD with progestogen.gif
Removal of a hormonal IUD

The hormonal IUD is inserted in a similar procedure to the nonhormonal copper IUD, and can only be inserted by a qualified medical practitioner. [53] Before insertion, a pelvic exam is performed to examine the shape and position of the uterus. A current STI at the time of insertion can increase the risk of pelvic infection. [78] However, routine screening for gonorrhea and chlamydia prior to insertion is not recommended. [79] If a person needs screening and there is no evidence of infection on examination or has been previously screened, insertion of the IUD does not need to be delayed. [80]

Insertion

During the insertion, the vagina is held open with a speculum, the same device used during a pap smear. [53] A grasping instrument is used to steady the cervix, the length of the uterus is measured for proper insertion with a uterine sound for decreasing chance of uterine perforation with the IUD, and the IUD is placed using a narrow tube through the opening of the cervix into the uterus. [53] A short length of monofilament plastic/nylon string hangs down from the cervix into the vagina. The string allows physicians and patients to check to ensure the IUD is still in place and enables easy removal of the device. [53] Moderate to severe cramping can occur during the procedure, which generally takes five minutes or less. Insertion can be performed immediately postpartum and post-abortion if no infection has occurred. [24]

Misoprostol is not effective in reducing pain in IUD insertion. [81]

Removal

Removal of the device should also be performed by a qualified medical practitioner. After removal, fertility will return to previous levels relatively quickly. [82] One study found that the majority of participants returned to fertility within three months. [83]

Mechanisms of action

Levonorgestrel is a progestogen, i.e. a progesterone receptor agonist. The hormonal IUD's primary mechanism of action is to prevent fertilization. [53] [84] [85] [86] [87] The levonorgestrel intrauterine system has several contraceptive effects, although thickening of the cervical mucus appears to be the primary effect. [88] Other effects include making the inside of the uterus become fatal to sperm [86] [89] and thinning of the endometrial lining, but this is not the usual function. [90] [91]

Ovulation is not inhibited in all cases. [86] [92]

Numerous studies have demonstrated that IUDs primarily prevent fertilization, not implantation. [53] In one experiment involving tubal flushing, fertilized eggs were found in half of women not using contraception, but no fertilized eggs were found in women using IUDs. [93] IUDs also decrease the risk of ectopic pregnancy, which further implies that IUDs prevent fertilization. [53]

History

Close-up of a Mirena(r) intrauterine device Mirena IUD with hand.jpg
Close-up of a Mirena® intrauterine device

Hormonal IUDs were developed in the 1970s following the development of the copper IUD in the 1960s and 1970s. [94] Dr. Antonio Scommenga, working at the Michael Reese Hospital in Chicago, discovered that administering progesterone inside the uterus could have contraceptive benefits. [94] With knowledge of Scommegna's work, a Finnish doctor, Jouni Valter Tapani Luukkainen, created the T-shaped IUD that released progesterone, marketed as the Progestasert System in 1976. This IUD had a short, 1-year lifespan and never achieved widespread popularity. Following this relative lack of success, Dr. Luukkainen replaced the progesterone with the hormone levonorgestrel to be released over a five-year period, creating what is now Mirena. [95]

The Mirena IUD was studied for safety and efficacy in two clinical trials in Finland and Sweden involving 1,169 women who were all between 18 and 35 years of age at the beginning of the trials. The trials included predominantly Caucasian women who had been previously pregnant with no history of ectopic pregnancy or pelvic inflammatory disease within the previous year. Over 70% of the participants had previously used IUDs. [11]

In 2013 Skyla, a lower dose levonorgestrel IUD effective for up to three years, was approved by the FDA. [96] Skyla has a different bleeding pattern than Mirena, with only 6% of women in clinical trials becoming amenorrheic (compared to approximately 20% with Mirena).

The city of Turku, Finland, is currently the only production site for the Mirena contraceptive family. [97]

Controversies

In 2009, Bayer, the maker of Mirena, was issued an FDA Warning Letter by the United States Food and Drug Administration for overstating the efficacy, minimizing the risks of use, and making "false or misleading presentations" about the device. [98] [99] From 2000 to 2013, the federal agency received over 70,072 complaints about the device and related adverse effects. [100] [101] As of April 2014, over 1,200 lawsuits have been filed in the United States. [99] [102] [103] [104]

Related Research Articles

<span class="mw-page-title-main">Copper IUD</span> Birth control and emergency contraceptive device

A copper intrauterine device (IUD), also known as an intrauterine coil or copper coil or non-hormonal IUD, is a type of intrauterine device which contains copper. It is used for birth control and emergency contraception within five days of unprotected sex. It is one of the most effective forms of birth control with a one-year failure rate around 0.7%. The device is placed in the uterus and lasts up to twelve years. It may be used by women of all ages regardless of whether or not they have had children. Following removal, fertility quickly returns.

<span class="mw-page-title-main">Emergency contraception</span> Birth control measures taken after sexual intercourse

Emergency contraception (EC) is a birth control measure, used after sexual intercourse to prevent pregnancy.

<span class="mw-page-title-main">Combined oral contraceptive pill</span> Birth control method which is taken orally

The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. It is the oral form of combined hormonal contraception. The pill contains two important hormones: a progestin and estrogen. When taken correctly, it alters the menstrual cycle to eliminate ovulation and prevent pregnancy.

<span class="mw-page-title-main">Progestogen (medication)</span> Medication producing effects similar to progesterone

A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone.

Heavy menstrual bleeding (HMB), previously known as menorrhagia or hematomunia, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding (AUB).

<span class="mw-page-title-main">Levonorgestrel</span> Hormonal medication used for birth control

Levonorgestrel is a hormonal medication which is used in a number of birth control methods. It is combined with an estrogen to make combination birth control pills. As an emergency birth control, sold under the brand names Plan B One-Step and Julie, among others, it is useful within 72 hours of unprotected sex. The more time that has passed since sex, the less effective the medication becomes, and it does not work after pregnancy (implantation) has occurred. Levonorgestrel works by preventing ovulation or fertilization from occurring. It decreases the chances of pregnancy by 57–93%. In an intrauterine device (IUD), such as Mirena among others, it is effective for the long-term prevention of pregnancy. A levonorgestrel-releasing implant is also available in some countries.

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<span class="mw-page-title-main">Contraceptive implant</span> Implantable medical device used for birth control

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References

  1. 1 2 3 Trussell J (2011). "Contraceptive efficacy". In Hatcher RA, Trussell J, Nelson AL, Cates Jr W, Kowal D, Policar MS (eds.). Contraceptive technology (20th revised ed.). New York: Ardent Media. pp. 779–863. ISBN   978-1-59708-004-0. ISSN   0091-9721. OCLC   781956734. Table 26–1 = "Table 3–2 Percentage of women experiencing an unintended pregnancy during the first year of typical use and the first year of perfect use of contraception, and the percentage continuing use at the end of the first year. United States" (PDF). Archived from the original (PDF) on 15 February 2017.
  2. 1 2 3 4 5 6 7 British National Formulary: BNF 69 (69th ed.). British Medical Association. 2015. p. 556. ISBN   978-0-85711-156-2.
  3. "Levonorgestrel intrauterine system medical facts from Drugs.com". drugs.com. Archived from the original on 1 January 2017. Retrieved 1 January 2017.
  4. 1 2 3 "Hormonal IUDs". www.plannedparenthood.org. Archived from the original on 24 April 2019. Retrieved 20 April 2019.
  5. Wipf J (2015). Women's Health, An Issue of Medical Clinics of North America. Elsevier Health Sciences. p. 507. ISBN   978-0-323-37608-2. Archived from the original on 10 January 2023. Retrieved 1 September 2017.
  6. Bradley LD, Falcone T (2008). Hysteroscopy: Office Evaluation and Management of the Uterine Cavity. Elsevier Health Sciences. p. 171. ISBN   978-0-323-04101-0. Archived from the original on 12 January 2023. Retrieved 1 September 2017.
  7. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  8. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  9. 1 2 "Mirena (levonorgestrel) intrauterine device". Therapeutic Goods Administration (TGA). 17 July 2024. Retrieved 12 October 2024.
  10. "Mirena Product information". Health Canada . 22 November 2007. Archived from the original on 19 April 2024. Retrieved 19 April 2024.
  11. 1 2 "Mirena - levonorgestrel intrauterine device". Bayer Health Pharmaceuticals. May 2009. Archived from the original on 18 June 2015. Retrieved 18 June 2015.
  12. "Kyleena- levonorgestrel intrauterine device". DailyMed. 13 March 2023. Archived from the original on 22 September 2023. Retrieved 19 April 2024.
  13. "Skyla- levonorgestrel intrauterine device". DailyMed. 31 January 2023. Archived from the original on 9 December 2023. Retrieved 19 April 2024.
  14. "Liletta- levonorgestrel intrauterine device". DailyMed. 29 June 2023. Archived from the original on 29 November 2021. Retrieved 19 April 2024.
  15. "Science Update: Hormonal IUD as effective as a copper IUD at emergency contraception and with less discomfort, NICHD-funded study suggests". 4 February 2021. Archived from the original on 26 July 2021. Retrieved 26 July 2021.
  16. 1 2 3 Bahamondes L, Bahamondes MV, Monteiro I (July 2008). "Levonorgestrel-releasing intrauterine system: uses and controversies". Expert Review of Medical Devices. 5 (4): 437–445. doi:10.1586/17434440.5.4.437. PMID   18573044. S2CID   659602.
  17. Petta CA, Ferriani RA, Abrao MS, Hassan D, Rosa E, Silva JC, et al. (July 2005). "Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis". Human Reproduction. 20 (7): 1993–1998. doi: 10.1093/humrep/deh869 . PMID   15790607.
  18. Sheng J, Zhang WY, Zhang JP, Lu D (March 2009). "The LNG-IUS study on adenomyosis: a 3-year follow-up study on the efficacy and side effects of the use of levonorgestrel intrauterine system for the treatment of dysmenorrhea associated with adenomyosis". Contraception. 79 (3): 189–193. doi:10.1016/j.contraception.2008.11.004. PMID   19185671.
  19. Faundes A, Alvarez F, Brache V, Tejada AS (June 1988). "The role of the levonorgestrel intrauterine device in the prevention and treatment of iron deficiency anemia during fertility regulation". International Journal of Gynaecology and Obstetrics. 26 (3): 429–433. doi:10.1016/0020-7292(88)90341-4. PMID   2900174. S2CID   34592937.
  20. "The American College of Obstetricians and Gynecologists Committee Opinion no. 631. Endometrial intraepithelial neoplasia". Obstetrics and Gynecology. 125 (5): 1272–1278. May 2015. doi:10.1097/01.AOG.0000465189.50026.20. PMID   25932867. S2CID   46508283.
  21. Mittermeier T, Farrant C, Wise MR (September 2020). "Levonorgestrel-releasing intrauterine system for endometrial hyperplasia". The Cochrane Database of Systematic Reviews. 2020 (9): CD012658. doi:10.1002/14651858.CD012658.pub2. PMC   8200645 . PMID   32909630.
  22. Marjoribanks J, Lethaby A, Farquhar C (January 2016). "Surgery versus medical therapy for heavy menstrual bleeding". The Cochrane Database of Systematic Reviews. 2016 (1): CD003855. doi:10.1002/14651858.CD003855.pub3. PMC   7104515 . PMID   26820670.
  23. 1 2 3 Winner B, Peipert JF, Zhao Q, Buckel C, Madden T, Allsworth JE, et al. (May 2012). "Effectiveness of long-acting reversible contraception". The New England Journal of Medicine. 366 (21): 1998–2007. doi: 10.1056/NEJMoa1110855 . PMID   22621627. S2CID   16812353. Archived from the original on 11 June 2020. Retrieved 30 June 2019.
  24. 1 2 3 4 5 6 7 8 9 Curtis KM, Tepper NK, Jatlaoui TC, Berry-Bibee E, Horton LG, Zapata LB, et al. (July 2016). "U.S. Medical Eligibility Criteria for Contraceptive Use, 2016" (PDF). MMWR. Recommendations and Reports. 65 (3): 1–103. doi: 10.15585/mmwr.rr6503a1 . PMID   27467196. Archived (PDF) from the original on 16 October 2020. Retrieved 3 February 2020.
  25. "IUD". Planned Parenthood. Archived from the original on 18 June 2015. Retrieved 18 June 2015.
  26. "Convenience". Let's Talk About Mirena. Bayer. Archived from the original on 18 June 2015. Retrieved 18 June 2015.
  27. 1 2 3 "Mirena". MediResource Inc. Archived from the original on 3 July 2015. Retrieved 18 June 2015.
  28. 1 2 Hidalgo M, Bahamondes L, Perrotti M, Diaz J, Dantas-Monteiro C, Petta C (February 2002). "Bleeding patterns and clinical performance of the levonorgestrel-releasing intrauterine system (Mirena) up to two years". Contraception. 65 (2): 129–132. doi:10.1016/s0010-7824(01)00302-x. PMID   11927115.
  29. 1 2 3 "Mirena IUD Homepage | Official Website". Archived from the original on 31 July 2012. Retrieved 19 July 2012., Bayer Pharmaceuticals.
  30. Highlights of Prescribing Information (Report). 9 January 2013. Archived from the original on 6 May 2016.
  31. "What are hormonal IUDs?". Planned Parenthood. Archived from the original on 24 April 2019. Retrieved 19 April 2019.
  32. Westhoff CL, Keder LM, Gangestad A, Teal SB, Olariu AI, Creinin MD (March 2020). "Six-year contraceptive efficacy and continued safety of a levonorgestrel 52 mg intrauterine system". Contraception. 101 (3): 159–161. doi:10.1016/j.contraception.2019.10.010. PMID   31786203. S2CID   208535090. Archived from the original on 10 June 2020. Retrieved 2 January 2020.
  33. Jensen JT, Creinin MD, Speroff L, eds. (2019). Speroff & Darney's clinical guide for contraception (Sixth ed.). Philadelphia, PA: Wolters Kluwer. p. 15. ISBN   978-1-9751-0728-4. OCLC   1121081247.
  34. Kai J, Dutton B, Vinogradova Y, Hilken N, Gupta J, Daniels J (October 2023). "Rates of medical or surgical treatment for women with heavy menstrual bleeding: the ECLIPSE trial 10-year observational follow-up study". Health Technology Assessment. 27 (17): 1–50. doi:10.3310/JHSW0174. PMC   10641716 . PMID   37924269. Archived from the original on 6 November 2023. Retrieved 12 April 2024.
  35. "The coil and medicines are both effective long-term treatments for heavy periods". NIHR Evidence. 8 March 2024. doi:10.3310/nihrevidence_62335. Archived from the original on 18 March 2024. Retrieved 12 April 2024.
  36. Oelschlager AM, Debiec K, Micks E, Prager S (2013). "Use of the Levonorgestrel Intrauterine System in Adolescents With Known Uterine Didelphys or Unicornuate Uterus". Journal of Pediatric and Adolescent Gynecology. 26 (2): e58. doi: 10.1016/j.jpag.2013.01.029 . ISSN   1083-3188.
  37. Acharya GP, Mills AM (July 1998). "Successful management of intractable menorrhagia with a levonorgestrel-releasing intrauterine device, in a woman with a bicornuate uterus". Journal of Obstetrics and Gynaecology. 18 (4): 392–393. doi:10.1080/01443619867263. PMID   15512123.
  38. Truitt ST, Fraser AB, Grimes DA, Gallo MF, Schulz KF (2003). Lopez LM (ed.). "Combined hormonal versus nonhormonal versus progestin-only contraception in lactation". The Cochrane Database of Systematic Reviews (2): CD003988. doi:10.1002/14651858.CD003988. PMID   12804497.
  39. 1 2 3 "Medical review of NDA 21-225: Mirena (levonorgestrel-releasing intrauterine system) Berlex Laboratories" (PDF). Center for Drug Evaluation and Research. U.S. Food and Drug Administration. December 2000. Archived from the original (PDF) on 27 February 2008.
  40. "MIRENA Data Sheet" (PDF). Bayer NZ. 11 December 2009. Archived from the original (PDF) on 6 July 2011. Retrieved 10 February 2011.
  41. Schiappacasse V, Díaz S, Zepeda A, Alvarado R, Herreros C (July 2002). "Health and growth of infants breastfed by Norplant contraceptive implants users: a six-year follow-up study". Contraception. 66 (1): 57–65. doi:10.1016/S0010-7824(02)00319-0. PMID   12169382.
  42. "Classifications for Intrauterine Devices | CDC". www.cdc.gov. 9 April 2020. Archived from the original on 15 July 2020. Retrieved 7 July 2020.
  43. World Health Organization (2015). Medical eligibility criteria for contraceptive use (5th ed.). Geneva: World Health Organization. hdl: 10665/181468 . ISBN   978-92-4-154915-8.
  44. World Health Organization (2015). "Medical eligibility criteria for contraceptive use, fifth edition 2015: executive summary". World Health Organization. hdl: 10665/172915 . Archived from the original on 28 August 2021. Retrieved 3 February 2020.
  45. 1 2 "Understanding IUDs". Planned Parenthood. July 2005. Archived from the original on 12 October 2006. Retrieved 8 October 2006.
  46. 1 2 Heavy menstrual bleeding (update). National Institute for Health and Care Excellence. 2018.
  47. 1 2 3 4 5 6 7 8 9 10 11 12 "Mirena: Consumer Medicine Information" (PDF). Bayer. March 2014. Archived (PDF) from the original on 27 April 2014. Retrieved 27 April 2014.
  48. Roe AH, Bartz D (January 2019). "Society of Family Planning clinical recommendations: contraception after surgical abortion". Contraception. 99 (1): 2–9. doi: 10.1016/j.contraception.2018.08.016 . PMID   30195718.
  49. WHO (2010). "Intrauterine devices (IUDs)". Medical Eligibility Criteria for Contraceptive Use (4th ed.). Geneva: Reproductive Health and Research, WHO. ISBN   978-92-4-156388-8. Archived from the original on 10 July 2012.
  50. Hidalgo M, Bahamondes L, Perrotti M, Diaz J, Dantas-Monteiro C, Petta C (February 2002). "Bleeding patterns and clinical performance of the levonorgestrel-releasing intrauterine system (Mirena) up to two years". Contraception. 65 (2): 129–132. doi:10.1016/S0010-7824(01)00302-X. PMID   11927115.
  51. McCarthy L (May 2006). "Levonorgestrel-Releasing Intrauterine System (Mirena) for Contraception". Am Fam Physician. 73 (10): 1799–. Archived from the original on 26 September 2007. Retrieved 4 May 2007.
  52. Rönnerdag M, Odlind V (September 1999). "Health effects of long-term use of the intrauterine levonorgestrel-releasing system. A follow-up study over 12 years of continuous use". Acta Obstetricia et Gynecologica Scandinavica. 78 (8): 716–721. doi: 10.1034/j.1600-0412.1999.780810.x . PMID   10468065.
  53. 1 2 3 4 5 6 7 8 9 10 11 12 13 Dean G, Schwarz EB (2011). "Intrauterine contraceptives (IUCs)". In Hatcher RA, Trussell J, Nelson AL, Cates Jr W, Kowal D, Policar MS (eds.). Contraceptive technology (20th revised ed.). New York: Ardent Media. pp. 147–191. ISBN   978-1-59708-004-0. ISSN   0091-9721. OCLC   781956734. p.150:
    Mechanism of action
    Although the precise mechanism of action is not known, currently available IUCs work primarily by preventing sperm from fertilizing ova.26 IUCs are not abortifacients: they do not interrupt an implanted pregnancy.27 Pregnancy is prevented by a combination of the "foreign body effect" of the plastic or metal frame and the specific action of the medication (copper or levonorgestrel) that is released. Exposure to a foreign body causes a sterile inflammatory reaction in the intrauterine environment that is toxic to sperm and ova and impairs implantation.28,29 The production of cytotoxic peptides and activation of enzymes lead to inhibition of sperm motility, reduced sperm capacite journal and survival, and increased phagocytosis of sperm.30,31… The progestin in the LNg IUC enhances the contraceptive action of the device by thickening cervical mucus, suppressing the endometrium, and impairing sperm function. In addition, ovulation is often impaired as a result of systemic absorption of levonorgestrel.23
    p. 162:
    Table 7-1. Myths and misconceptions about IUCs
    Myth: IUCs are abortifacients. Fact: IUCs prevent fertilization and are true contraceptives.
  54. 1 2 "IUDs—An Update". Population Reports. XXII (5). Population Information Program, Johns Hopkins School of Public Health. December 1995.
  55. "IUDs—An Update: Chapter 2.7: Expulsion". Population Reports. XXII (5). Population Information Program, Johns Hopkins School of Public Health. December 1995. Archived from the original on 5 September 2006.
  56. 1 2 "IUDs—An Update: Chapter 3.3: Postpartum Insertion". Population Reports. XXII (5). Population Information Program, Johns Hopkins School of Public Health. December 1995. Archived from the original on 29 April 2006.
  57. "IUDs—An Update: Chapter 3.4: Postabortion Insertion". Population Reports. XXII (5). Population Information Program, Johns Hopkins School of Public Health. December 1995. Archived from the original on 11 August 2006.
  58. WHO Scientific Group on the Mechanism of Action Safety and Efficacy of Intrauterine Devices, World Health Organization (1987). Mechanism of action, safety and efficacy of intrauterine devices. Geneva: World Health Organization. hdl: 10665/38182 . ISBN   92-4-120753-1. World Health Organization technical report series; no. 753.
  59. Grimes DA (September 2000). "Intrauterine device and upper-genital-tract infection". Lancet. 356 (9234): 1013–1019. doi:10.1016/S0140-6736(00)02699-4. PMID   11041414. S2CID   7760222.
  60. Teal SB, Turok DK, Chen BA, Kimble T, Olariu AI, Creinin MD (January 2019). "Five-Year Contraceptive Efficacy and Safety of a Levonorgestrel 52-mg Intrauterine System". Obstetrics and Gynecology. 133 (1): 63–70. doi:10.1097/AOG.0000000000003034. PMC   6319579 . PMID   30531565.
  61. Bahamondes L, Hidalgo M, Petta CA, Diaz J, Espejo-Arce X, Monteiro-Dantas C (August 2003). "Enlarged ovarian follicles in users of a levonorgestrel-releasing intrauterine system and contraceptive implant". The Journal of Reproductive Medicine. 48 (8): 637–640. PMID   12971147.
  62. 1 2 3 4 5 6 "Mirena". Bayer UK. 11 June 2013. Archived from the original on 18 June 2015. Retrieved 18 June 2015.
  63. Donders GG, Bellen G, Ruban K, Van Bulck B (March 2018). "Short- and long-term influence of the levonorgestrel-releasing intrauterine system (Mirena®) on vaginal microbiota and Candida". Journal of Medical Microbiology. 67 (3): 308–313. doi: 10.1099/jmm.0.000657 . PMID   29458551.
  64. Nijhuis JG, Schijf CP, Eskes TK (July 1985). "[The lost IUD: don't look too far for it]". Nederlands Tijdschrift voor Geneeskunde. 129 (30): 1409–1410. PMID   3900746.
  65. Kaplan NR (April 1976). "Letter: Lost IUD". Obstetrics and Gynecology. 47 (4): 508–509. PMID   1256735.
  66. "Hormonal Contraceptives, Progestogens Only". International Programme on Chemical Safety. 1999. Archived from the original on 28 September 2006. Retrieved 8 October 2006.
  67. 1 2 3 4 Kim JJ, Chapman-Davis E (January 2010). "Role of progesterone in endometrial cancer". Seminars in Reproductive Medicine. 28 (1): 81–90. doi:10.1055/s-0029-1242998. PMC   4767501 . PMID   20104432.
  68. Conz L, Mota BS, Bahamondes L, Teixeira Dória M, Françoise Mauricette Derchain S, Rieira R, et al. (August 2020). "Levonorgestrel-releasing intrauterine system and breast cancer risk: A systematic review and meta-analysis". Acta Obstetricia et Gynecologica Scandinavica. 99 (8). Wiley: 970–982. doi: 10.1111/aogs.13817 . PMID   31990981. S2CID   210946832.
  69. Al Kiyumi MH, Al Battashi K, Al-Riyami HA (September 2021). "Levonorgestrel-releasing intrauterine system and breast cancer; Is there an association?". Acta Obstetricia et Gynecologica Scandinavica. 100 (9). Wiley: 1749. doi: 10.1111/aogs.14188 . PMID   34021506. S2CID   235094824.
  70. Silva FR, Grande AJ, Da Rosa MI (February 2021). "Is the levonorgestrel-releasing intrauterine system a risk factor for breast cancer?". Acta Obstetricia et Gynecologica Scandinavica. 100 (2). Wiley: 363–364. doi: 10.1111/aogs.13966 . PMID   32740910. S2CID   220942002.
  71. Romero SA, Young K, Hickey M, Su HI (December 2020). "Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen". The Cochrane Database of Systematic Reviews. 12 (12): CD007245. doi: 10.1002/14651858.CD007245.pub4 . PMC   8092675 . PMID   33348436.
  72. Faculty of Family Planning and Reproductive Health Care Clinical Effectiveness Unit (April 2004). "FFPRHC Guidance (April 2004). The levonorgestrel-releasing intrauterine system (LNG-IUS) in contraception and reproductive health". The Journal of Family Planning and Reproductive Health Care. 30 (2): 99–108, quiz 109. doi: 10.1783/147118904322995474 . PMID   15086994. S2CID   31281104.
  73. 1 2 3 Wong AY, Tang LC, Chin RK (June 2010). "Levonorgestrel-releasing intrauterine system (Mirena) and Depot medroxyprogesterone acetate (Depoprovera) as long-term maintenance therapy for patients with moderate and severe endometriosis: a randomised controlled trial". The Australian & New Zealand Journal of Obstetrics & Gynaecology. 50 (3): 273–279. doi:10.1111/j.1479-828X.2010.01152.x. PMID   20618247. S2CID   22050651.
  74. Bahamondes MV, Monteiro I, Castro S, Espejo-Arce X, Bahamondes L (May 2010). "Prospective study of the forearm bone mineral density of long-term users of the levonorgestrel-releasing intrauterine system". Human Reproduction. 25 (5): 1158–1164. doi: 10.1093/humrep/deq043 . PMID   20185512.
  75. Luukkainen T (1991). "Levonorgestrel-releasing intrauterine device". Annals of the New York Academy of Sciences. 626 (1): 43–49. Bibcode:1991NYASA.626...43L. doi:10.1111/j.1749-6632.1991.tb37898.x. PMID   1905510. S2CID   39610456.
  76. Bayer Group. "What is Jaydess?". Jaydess. Bayer PLC. Archived from the original on 17 November 2016. Retrieved 16 November 2016.
  77. Römer T, Bühling KJ (2013). "Intrauterine hormonelle Kontrazeption". Gynäkologische Endokrinologie. 11 (3): 188–196. doi:10.1007/s10304-012-0532-4. S2CID   20088018.
  78. Mohllajee AP, Curtis KM, Peterson HB (February 2006). "Does insertion and use of an intrauterine device increase the risk of pelvic inflammatory disease among women with sexually transmitted infection? A systematic review". Contraception. 73 (2): 145–153. doi:10.1016/j.contraception.2005.08.007. PMID   16413845. Archived from the original on 6 February 2020. Retrieved 6 February 2020.
  79. Curtis KM, Tepper NK, Jatlaoui TC, Berry-Bibee E, Horton LG, Zapata LB, et al. (July 2016). "U.S. Medical Eligibility Criteria for Contraceptive Use, 2016". MMWR. Recommendations and Reports. 65 (3): 1–103. doi: 10.15585/mmwr.rr6503a1 . PMID   27467196.
  80. "CDC - Summary - US SPR - Reproductive Health". www.cdc.gov. 21 June 2017. Archived from the original on 13 September 2017. Retrieved 13 September 2017.
  81. Lopez LM, Bernholc A, Zeng Y, Allen RH, Bartz D, O'Brien PA, et al. (July 2015). "Interventions for pain with intrauterine device insertion". The Cochrane Database of Systematic Reviews. 2015 (7): CD007373. doi:10.1002/14651858.CD007373.pub3. PMC   9580985 . PMID   26222246.
  82. Mansour D, Gemzell-Danielsson K, Inki P, Jensen JT (November 2011). "Fertility after discontinuation of contraception: a comprehensive review of the literature". Contraception. 84 (5): 465–477. doi:10.1016/j.contraception.2011.04.002. PMID   22018120.
  83. Randic L, Vlasic S, Matrljan I, Waszak CS (September 1985). "Return to fertility after IUD removal for planned pregnancy". Contraception. 32 (3): 253–259. doi:10.1016/0010-7824(85)90048-4. PMID   4085244.
  84. Ortiz ME, Croxatto HB (June 2007). "Copper-T intrauterine device and levonorgestrel intrauterine system: biological bases of their mechanism of action". Contraception. 75 (6 Suppl): S16–S30. doi:10.1016/j.contraception.2007.01.020. PMID   17531610. p. S28:
    Conclusions
    Active substances released from the IUD or IUS, together with products derived from the inflammatory reaction present in the luminal fluids of the genital tract, are toxic for spermatozoa and oocytes, preventing the encounter of healthy gametes and the formation of viable embryos. The current data do not indicate that embryos are formed in IUD users at a rate comparable to that of nonusers. The common belief that the usual mechanism of action of IUDs in women is destruction of embryos in the uterus is not supported by empirical evidence. The bulk of the data indicate that interference with the reproductive process after fertilization has taken place is exceptional in the presence of a T-Cu or LNG-IUD and that the usual mechanism by which they prevent pregnancy in women is by preventing fertilization.
  85. ESHRE Capri Workshop Group (May–June 2008). "Intrauterine devices and intrauterine systems". Human Reproduction Update. 14 (3): 197–208. doi: 10.1093/humupd/dmn003 . PMID   18400840. p. 199:
    Mechanisms of action
    Thus, both clinical and experimental evidence suggests that IUDs can prevent and disrupt implantation. It is unlikely, however, that this is the main IUD mode of action, … The best evidence indicates that in IUD users it is unusual for embryos to reach the uterus.
    In conclusion, IUDs may exert their contraceptive action at different levels. Potentially, they interfere with sperm function and transport within the uterus and tubes. It is difficult to determine whether fertilization of the oocyte is impaired by these compromised sperm. There is sufficient evidence to suggest that IUDs can prevent and disrupt implantation. The extent to which this interference contributes to its contraceptive action is unknown. The data are scanty and the political consequences of resolving this issue interfere with comprehensive research.
    p. 205:
    Summary
    IUDs that release copper or levonorgestrel are extremely effective contraceptives... Both copper IUDs and levonorgestrel releasing IUSs may interfere with implantation, although this may not be the primary mechanism of action. The devices also create barriers to sperm transport and fertilization, and sensitive assays detect hCG in less than 1% of cycles, indicating that significant prevention must occur before the stage of implantation.
  86. 1 2 3 Speroff L, Darney PD (2011). "Intrauterine contraception". A clinical guide for contraception (5th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 239–280. ISBN   978-1-60831-610-6. pp. 246–247:
    Mechanism of action
    The contraceptive action of all IUDs is mainly in the intrauterine cavity. Ovulation is not affected, and the IUD is not an abortifacient.58–60 It is currently believed that the mechanism of action for IUDs is the production of an intrauterine environment that is spermicidal.
    Nonmedicated IUDs depend for contraception on the general reaction of the uterus to a foreign body. It is believed that this reaction, a sterile inflammatory response, produces tissue injury of a minor degree but sufficient to be spermicidal. Very few, if any, sperm reach the ovum in the fallopian tube.
    The progestin-releasing IUD adds the endometrial action of the progestin to the foreign body reaction. The endometrium becomes decidualized with atrophy of the glands.65 The progestin IUD probably has two mechanisms of action: inhibition of implantation and inhibition of sperm capacite journal, penetration, and survival.
  87. Jensen JT, Mishell Jr DR (2012). "Family planning: contraception, sterilization, and pregnancy termination.". In Lentz GM, Lobo RA, Gershenson DM, Katz VL (eds.). Comprehensive gynecology. Philadelphia: Mosby Elsevier. pp. 215–272. ISBN   978-0-323-06986-1. p. 259:
    Intrauterine devices
    Mechanisms of action
    The common belief that the usual mechanism of action of IUDs in women is destruction of embryos in the uterus is not supported by empirical evidence... Because concern over mechanism of action represents a barrier to acceptance of this important and highly effective method for some women and some clinicians, it is important to point out that there is no evidence to suggest that the mechanism of action of IUDs is abortifacient.
    The LNG-IUS, like the copper device, has a very low ectopic pregnancy rate. Therefore, fertilization does not occur and its main mechanism of action is also preconceptual. Less inflammation occurs within the uterus of LNG-IUS users, but the potent progestin effect thickens cervical mucus to impede sperm penetration and access to the upper genital track.
  88. Sivin I, Stern J, Coutinho E, Mattos CE, el Mahgoub S, Diaz S, et al. (November 1991). "Prolonged intrauterine contraception: a seven-year randomized study of the levonorgestrel 20 mcg/day (LNg 20) and the Copper T380 Ag IUDS" (PDF). Contraception. 44 (5): 473–480. doi:10.1016/0010-7824(91)90149-a. PMID   1797462. Archived (PDF) from the original on 22 November 2023. Retrieved 28 December 2023.
  89. Guttinger A, Critchley HO (June 2007). "Endometrial effects of intrauterine levonorgestrel". Contraception. 75 (6 Suppl): S93–S98. doi:10.1016/j.contraception.2007.01.015. PMID   17531624.
  90. ESHRE Capri Workshop Group (2008). "Intrauterine devices and intrauterine systems". Human Reproduction Update. 14 (3): 197–208. doi: 10.1093/humupd/dmn003 . PMID   18400840. Both copper IUDs and levonorgestrel releasing IUSs may interfere with implantation
  91. Hatcher RA (2011). Contraceptive technology (20th rev. ed.). [New York, N.Y.]: Ardent Media. p. 162. ISBN   978-1-59708-004-0. Although the precise mechanism of action is not known, currently available IUCs work primarily by preventing sperm from fertilizing ova.26 IUCs are not abortifacients: they do not interrupt an implanted pregnancy.27 Pregnancy is prevented by a combination of the "foreign body effect" of the plastic or metal frame and the specific action of the medication (copper or levonorgestrel) that is released. Exposure to a foreign body causes a sterile inflammatory reaction in the intrauterine environment that is toxic to sperm and ova and impairs implantation.28,29 The production of cytotoxic peptides and activation of enzymes lead to inhibition of sperm motility, reduced sperm capacite journal and survival, and increased phagocytosis of sperm.30,31… The progestin in the LNg IUC enhances the contraceptive action of the device by thickening cervical mucus, suppressing the endometrium, and impairing sperm function. In addition, ovulation is often impaired as a result of systemic absorption of levonorgestrel
  92. Malik S (January 2013). "Levonorgestrel-IUS system and endometrial manipulation". Journal of Mid-Life Health. 4 (1): 6–7. doi: 10.4103/0976-7800.109625 . PMC   3702070 . PMID   23833526.
  93. Alvarez F, Brache V, Fernandez E, Guerrero B, Guiloff E, Hess R, et al. (May 1988). "New insights on the mode of action of intrauterine contraceptive devices in women". Fertility and Sterility. 49 (5): 768–773. doi:10.1016/S0015-0282(16)59881-1. PMID   3360166.
  94. 1 2 Thiery M (March 1997). "Pioneers of the intrauterine device". The European Journal of Contraception & Reproductive Health Care. 2 (1): 15–23. doi:10.1080/13625189709049930. PMID   9678105.
  95. Thiery M (June 2000). "Intrauterine contraception: from silver ring to intrauterine contraceptive implant". European Journal of Obstetrics, Gynecology, and Reproductive Biology. 90 (2): 145–152. doi:10.1016/s0301-2115(00)00262-1. PMID   10825633.
  96. "FDA drug approval for Skyla". Archived from the original on 13 August 2014.
  97. Laitinen K. "Bayer". businessfinland.fi. Archived from the original on 21 September 2021. Retrieved 21 September 2021.
  98. "2009 Warning Letters and Untitled Letters to Pharmaceutical Companies". U.S. Food and Drug Administration. Archived from the original on 18 June 2015. Retrieved 18 June 2015.
  99. 1 2 Bekiempis V (24 April 2014). "The Courtroom Controversy Behind Popular Contraceptive Mirena". Newsweek. Archived from the original on 18 June 2015. Retrieved 18 June 2015.
  100. Budusun S. "Thousands of women complain about dangerous complications from Mirena IUD birth control". ABC Cleveland. Archived from the original on 18 June 2015. Retrieved 18 June 2015.
  101. Colla C (21 May 2013). "Mirena birth control may be causing complications in women". ABC 15 Arizona. Archived from the original on 18 June 2015. Retrieved 18 June 2015.
  102. Bekiempis V (24 April 2014). "The Courtroom Controversy Behind Popular Contraceptive Mirena". Newsweek. Archived from the original on 15 November 2016. Retrieved 16 November 2016.
  103. "Popular contraceptive device Mirena target of lawsuits in Canada, U.S". CTV. 21 May 2014. Archived from the original on 26 October 2016. Retrieved 16 November 2016.
  104. Blackstone H (31 May 2016). "When IUDs Go Terribly Wrong". Vice. Archived from the original on 17 November 2016. Retrieved 16 November 2016.