Intrauterine system

This article refers to the intrauterine system (IUS). For information on the copper-containing (non-hormonal) intrauterine device see the separate Intrauterine Contraceptive Device article. For information on insertion techniques see the separate Intrauterine Contraceptives (IUCD and IUS) - Management article.

Description and indication

The IUS is an intrauterine contraceptive which releases levonorgestrel (LNG). Mirena® was the first LNG-releasing IUS and has been available in the UK since 1995. It has a plastic T-shaped frame with a reservoir containing 52 mg of LNG and releasing 20 micrograms/24 hours at the outset. The Mirena® IUS has also been licensed more recently for the treatment of menorrhagia and as endometrial protection for those receiving oestrogen hormone replacement therapy (HRT). Over the past few years, some other types and brands have become available. Currently in the UK, available options are:¹

• Mirena®: contains 52 mg LNG in reservoir and releases 20 micrograms LNG/24 hours. Licensed for contraception, heavy menstrual bleeding (HMB) and endometrial protection for women using HRT. It is considered effective for five years (four years for HRT). The diameter of the Mirena® introducer is 4.4 mm.

• Levosert®: contains 52 mg LNG in reservoir and releases 20 micrograms LNG/24 hours (equivalent to Mirena® and currently cheaper). Licensed for contraception and HMB. It is effective for five years (recent licence extension). The diameter of the Levosert® intoducer is 4.8 mm and it is inserted using a two-handed technique.

• Kyleena®: contains 19.5 mg LNG in reservoir as compared to 52 mg in Mirena® and releases 17.5 micrograms/24 hours at the outset. Smaller size has been shown to make insertion easier and less painful although it may be less likely to cause amenorrhoea. Licensed for contraception only. It is effective for five years.²

• Jaydess®: contains 13.5 mg LNG in reservoir and releases 14 micrograms/24 hours. It is also smaller than Mirena®, and lasts less long (three years.) Licensed for contraception only. Again insertion has been shown to be easier and less painful.

Other brands are available in other countries.

Cost-effectiveness

• The LNG-IUS (and other methods of long-acting reversible contraception (LARC)) is more cost-effective than the combined oral contraceptive (COC) pill, even at one year of use.³ It is also more cost-effective than injectable contraceptives.

• Cost per year is currently cheapest for Levosert®, and most expensive for Jaydess®.

• The National Institute for Health and Care Excellence (NICE) advises that increasing the uptake of LARC methods will reduce the numbers of unintended pregnancies.³ It is important that women should be advised of LARC methods when seeking contraception. Over the past ten years, rates of LARC use have been rising, with data showing 41% of women attending sexual and reproductive services in England now choose LARCs - a 44% increase.⁴ 9% use an IUS.

Mode of action⁵

• The primary contraceptive effect is mediated by its suppressant effect on the endometrium, which prevents implantation: within one month of insertion, high intrauterine LNG levels cause endometrial atrophy and changes in the stroma.

• There is an increase in endometrial phagocytic cells which also prevents implantation.

• There is some decreased sperm penetration of cervical mucus and impaired sperm migration.

• There is little effect on the hypothalamic-pituitary-ovarian axis: oestrogen levels are not reduced and most women continue to ovulate.

• Amenorrhea with the IUS does not necessarily indicate anovulation. Incidence of anovulation has been shown to be lower with the 13.5 mg device than the 52 mg device.

Effectiveness

Failure rates are very low. Exact rates vary in the literature. A large European study showed the overall Pearl Index (pregnancies per 100 woman-years) to be 0.06, and demonstrated superior efficacy compared to copper devices.⁶ Comparative tables of contraceptive efficacy suggest the LNG-IUS is the most effective type of contraception other than the progestogen implant and male sterilisation, with 0.2% of women experiencing an unintended pregnancy within the first year of use.⁷ This is lower than the pregnancy rate following female sterilisation.

Duration of action⁵

Licences have been extended/subject to change over recent years, so this can be confusing and it may be worth consulting the latest relevant product information.

Mirena®: the Mirena® IUS is licensed for contraceptive use for a period of five years from insertion. The Mirena® IUS is also licensed for five years for idiopathic menorrhagia and for four years to provide endometrial protection.

Randomised controlled trials (RCTs) suggest that it provides contraceptive protection for up to seven years. Release rate of the 52 mg LNG-IUS at five years is twice that of the 13.5 mg LNG-IUS at three years, suggesting that it is likely to be effective for some time beyond its five years' licensed indication. However in general the Faculty of Sexual and Reproductive Health (FSRH) guideline does not currently recommend use outside the length of the licence other than in certain situations:

• Extended duration of use for women aged 45 years or over at the time of insertion. The guideline recommends removal when it is no longer needed (menopause) or effective (if being used for menorrhagia).

• The NICE LARC guideline initially recommended that women who have the LNG-IUS inserted at or after the age of 45 years and are amenorrhoeic may retain the LNG-IUS until the menopause.³ However the FSRH guidance supports this even where women are not amenorrhoeic.⁸

• Where women present late for a change of IUS, where this is between five and seven years after insertion, risk of pregnancy is considered low, and it may be immediately replaced subject to a negative and follow-up pregnancy test.

Levosert®: like Mirena®, Levosert® is now licensed for five years for contraception and menorrhagia. It is possible that the contraceptive licence will be extended beyond five years in future.

Kyleena®: is licensed for contraceptive use only, for five years.²

Jaydess®: is licensed for contraception alone, for a period of three years.⁹

Indications

Contraceptive use

• The LNG-IUS is a suitable option for most women who need contraception, with few conditions where risks of use outweigh benefits (see 'Contra-indications and cautions', below).

• It can be appropriate for many women, including those who traditionally offer contraceptive challenge, such as obese women, women with diabetes or epilepsy, women with migraine and women with contra-indications to oestrogen (see the separate Contraception and Special Groups article).³

• The LNG-IUS can be used at any age, and may be used in nulliparous women.

• The LNG-IUS should not be used as emergency contraception (see the separate Emergency Contraception article).

Advantages as a contraceptive method
These include:

• Rapid return of fertility post-removal.

• Reduced menstrual loss and dysmenorrhoea.

• Convenience (long-lasting method that is independent of intercourse).

• Lack of significant interactions with hepatic enzyme-inducing drugs.¹⁰

• Unlike long-acting injectable depot contraceptives there is no demonstrable effect on bone mineral density (BMD).¹¹

• Useful in the perimenopausal years where both contraception and HRT may be required together.

Disadvantages as a contraceptive method
These include:

• Initial menstrual irregularities.

• Other side-effects (see below).

• Women may dislike the idea of the invasive and uncomfortable fitting procedure.

• Fitting an IUS is technically more difficult (in view of its larger diameter) than fitting an IUCD, particularly in nulliparous or perimenopausal women. However, Kyleena® and Jaydess® may be fitted more easily, as the frame is smaller and narrower.

Non-contraceptive uses

Menorrhagia
The Mirena® LNG-IUS is the first-line pharmaceutical treatment for HMB (where there is no identified pathology or <3 cm fibroids or adenomyosis) and can reduce menstrual losses by over 90%.¹² Comparisons to alternative methods of managing this can be found in the separate Menorrhagia article. It is important to note that effectiveness of pharmacological treatments for HMB may be limited in women with fibroids that are substantially greater than 3 cm in diameter.¹²

Hormone replacement therapy (HRT)

• The Mirena® LNG-IUS is licensed for the prevention of endometrial hyperplasia during oestrogen replacement therapy for up to four years.

• It provides a means of delivering endometrial protection with minimum systemic absorption of progestogen.

Endometrial hyperplasiaThe Royal College of Obstetricians and Gynaecologists (RCOG) guideline recommends the LNG-IUS as the first-line of treatment for endometrial hyperplasia without atypia, as it is more effective than oral progestogens and has a more favourable profile with regard to adverse effects.^{13 14} The guideline also advises use in hyperplasia with atypia for women who are not suitable for hysterectomy or who wish to preserve fertility.

Future uses
Other potential uses of the LNG-IUS include its role in the treatment of:

• Endometriosis - studies have looked at the use of the LNG-IUS as maintenance therapy or following surgery: there is some evidence that the IUS is effective in reducing recurrence of pain.¹⁵

• Endometrial protection for women on tamoxifen - the IUS provides endometrial protection from tamoxifen-induced changes, reducing the risk of endometrial hyperplasia and benign polyps . A Cochrane review concluded that there was not yet evidence that it reduces the risk of endometrial cancer in this situation, and although there is no evidence that it affects risk of breast cancer recurrence or death, further trials are needed.¹⁶

• Endometrial carcinoma - the IUS may have a role in early-stage carcinoma and in patients unfit for surgery.¹⁷

Contra-indications and cautions¹⁰

Absolute contra-indications - UK Medical Eligibility Criteria (UKMEC) category 4 (use represents an unacceptable health risk)

• Infection: current pelvic inflammatory disease (PID) or purulent cervicitis, current symptomatic chlamydia or gonorrhoea, septic abortion or postpartum endometritis, pelvic tuberculosis.

• Current pregnancy.

• Some cancers: cervical cancer, endometrial cancer, malignant trophoblastic disease, current breast cancer.

• Undiagnosed irregular vaginal bleeding/suspicion of genital malignancy.

Relative contra-indications - UKMEC catetory 3 (risks usually outweigh benefits)

• 48 hours to four weeks postpartum (Insertion within the first 48 hours is considered safe).

• Complicated organ transplant.

• Long QT syndrome.

• Gestational trophoblastic disease with decreasing hCG levels.

• Past history of breast cancer.

• Uterine fibroids with distortion of the uterine cavity and other conditions causing distortion of the uterine cavity.

• Asymptomatic chlamydial infection.

• HIV with low CD4 count.

• Hepatocellular adenoma or carcinoma.

• Severe cirrhosis.

For women with cardiac disease, FSRH guidance suggests the decision to use intrauterine contraception should involve a cardiologist.⁵ If there is a high risk of vasovagal reaction, it should be fitted in a hospital setting (eg, women with single ventricle circulation, Eisenmenger physiology, tachycardia or pre-existing bradycardia).

Interactions
The manufacturers of Esmya® (ulipristal acetate 5 mg), which is used for the treatment of severe symptoms of uterine fibroids, advise avoiding concomitant use of a progestogen intrauterine system.¹⁸

Complications¹⁸

For complications associated directly with the insertion process, including perforation, expulsion and lost threads, see the separate Intrauterine Contraceptives (IUCD and IUS) - Management article.

Altered or abnormal bleeding¹⁹

Irregular bleeding and spotting are common in the first six months with an LNG-IUS. Explain to women that 90% will experience reduced menstrual flow ultimately and some will be amenorrhoeic. The FSRH has produced guidance on the assessment and management of problematic bleeding on hormonal contraception, including the IUS. While they recommend assessment following at least three months of persistent bleeding after insertion of IUS, they make the point that this is an arbitrary cut-off point, since persistent bleeding is common in the first six months following insertion of IUS. For full details of their recommendations, see the separate Intermenstrual and Postcoital Bleeding article.

Decision to investigate early will depend on a number of factors including risk of STIs, previous bleeding pattern, concerns of the woman and concurrent symptoms (pelvic pain, postcoital bleeding, dyspareunia, for example).

• <3 months from insertion - exclude STIs, check cervical screening history and consider the need for a pregnancy test. Where pain, discharge or lost threads occur in addition to bleeding, this requires further investigation to exclude expulsion, perforation or infection.

• >3 months from insertion (although the guidance notes that IUS-related bleeding is common up to six months) - perform a clinical examination where there is persistent bleeding, any new symptom or changed bleeding pattern, failed medical treatment, non-participation in the cervical screening programme or if requested by the woman. Abnormal clinical findings should be managed appropriately. Where findings are normal, but the woman is aged over 45 years or has risk factors for endometrial cancer, refer for further investigation (eg, ultrasound, hysteroscopy, endometrial biopsy).

Hormonal symptoms

• Acne, headaches, breast tenderness and nausea are reported by LNG-IUS users but these do not differ significantly from IUCD users, and usually settle with time.

• Serum LNG levels with an IUS are lower than with oral or subdermal administration of progestogen but there is wide individual difference, possibly explaining the variation in experience of hormonal side-effects.

Mood changes

Depression can be an issue, and may be associated with suicidal thoughts. Women should be advised to consult their GP if they develop depressive symptoms.

Pregnancy and ectopic pregnancy

• Overall rates are lower than with no contraception. If a woman does become pregnant with an LNG-IUS in situ, ectopic pregnancy risk is 1 in 20, so she should seek medical advice to exclude it. Ectopic pregnancy must be excluded although most pregnancies will be intrauterine.

• The risk of ectopic pregnancy is less for LNG-IUS than for conventional IUCDs.

• Women who become pregnant must be counselled regarding the increased risk of second-trimester miscarriage, infection and preterm delivery if the device remains in situ, and that removal reduces these outcomes but is associated with a small risk of miscarriage

• If threads are visible or retrievable in the endocervical canal the device should be removed up to 12 weeks of gestation.

• In other cases the device should be sought at delivery or termination and, if not detected at this time, an abdominal X-ray performed to ensure it is not extrauterine.

Pelvic infection

• This is most strongly related to the insertion procedure and to the background risk of STIs.

• There is a six-fold increase in risk of PID in the first 20 days following insertion.

• If pelvic infection is suspected in a woman using an IUCD/IUS then antibiotics should be started.

• The device does not routinely need to be removed, but this can be considered if symptoms do not start to resolve within 72 hours or if the woman wishes it.

• Women should be followed up and their partners treated where appropriate. Sexual health risk assessment and counselling should be offered.

Actinomyces-like organisms (ALOs)

• ALOs are commensals of the female genital tract and have been identified in women with and without intrauterine contraception

• Their role in infection in women using intrauterine contraception is not clear

• If ALOs are seen on a swab or smear, removal of the device is not indicated if the woman is asymptomatic.

• If symptoms of pelvic pain occur in conjunction with the presence of ALOs, other causes of infection should be considered and removal of the device may be advisable.

Cancer: no evidence of increased risk

Studies suggest use of the LNG-IUS is associated with significantly reduced rates of ovarian and endometrial cancer and there is currently no evidence for it being associated with any increase in breast cancer.²⁰

Removal and return of fertility

Evidence suggests that normal fertility returns as soon as an IUS is removed.¹⁸ It can, however, take some months for regular menses to resume.

Where pregnancy is desired

The LNG-IUS can be removed at any time.

Where pregnancy is not desired²²

• The LNG-IUS should be removed with menstruation or, if there has been no unprotected sexual intercourse in the previous seven days, at other times.

• Where the LNG-IUS is to be exchanged, intercourse should be avoided for the previous seven days in case re-insertion fails.

• When switching to the COC pill, remove after seven consecutive pills.

• When switching to the depot or implant progestogen methods, remove the LNG-IUS after seven days of use of the new method.

Postmenopausal removal⁸

• If inserted after the age of 45 years, the Mirena® may be used until menopause. Guidance does not currently support this extended use for other LNG-IUS devices, but this is likely to evolve.

• Similarly, if the Mirena® is being used in the management of menorrhagia (and not for contraception or with oestrogen replacement therapy), it can be retained beyond the five-year licensed duration of use if bleeding patterns are acceptable.

Dr Mary Lowth is an author or the original author of this leaflet.