The intrauterine system (IUS) is an intrauterine contraceptive device (IUCD) releasing levonorgestrel (LNG). The Mirena® coil is the only LNG-releasing IUS (LNG-IUS) currently available in the UK. It has a plastic T-frame with a reservoir containing 52 mg of levonorgestrel and releasing 20 micrograms/24 hours at outset.¹ Lower-dose (10 and 14 micrograms/24 hours) and smaller-sized LNG-IUS, better suited to postmenopausal or nulliparous women, are currently under clinical development.² It has been licensed as a contraceptive in the UK since 1995 and, more recently, for the treatment of idiopathic menorrhagia and as endometrial protection for those receiving oestrogen replacement therapy.¹

Only 2-3% of contraception-using women use it as their method of choice and this has increased only slowly over the last few years despite its benefits and the National Institute for Health and Clinical Excellence (NICE) guidance that all women requesting contraception should be offered a choice including long-acting reversible methods (such as the IUS).^3,4

Mode of action⁵

As a contraceptive:

• Foreign body reaction.
• Suppression of the endometrium, preventing implantation.
• Decreased sperm penetration of cervical mucus and impaired sperm migration.
• Minimal effect on the hypothalamic-pituitary-ovarian axis (suppression of ovulation in <25% women).

Indications

Contraceptive use

• Highly efficacious with a failure rate of less than 1 per 100 women years, similar to modern non-hormonal IUCDs and male sterilisation.^4,6
• 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). Its niche to date has been as contraception for multiparous women with heavy periods. It can be appropriate for many other 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 separate article Contraception and Special Groups).^4,7
• The LNG-IUS should not be used as emergency contraception (see separate article Emergency Contraception).
• Advantages as a contraceptive method include a rapid return of fertility post-removal, reduced menstrual loss and dysmenorrhoea, convenience (long-lasting method that is independent of intercourse) and the lack of significant interactions with hepatic enzyme-inducing drugs. Also, there is no demonstrable effect on bone mineral density (BMD) with users' BMDs comparable to non-users' after 7 years' use.⁸
• Disadvantages include initial menstrual irregularities and other side-effects (see 'Side-effects', below). Also, fitting an IUS is technically more difficult in view of its larger diameter than other IUCDs, particularly in nulliparous or perimenopausal women.

Non-contraceptive uses

Menorrhagia:

• The LNG-IUS is the first-line pharmaceutical treatment for menorrhagia (where hormonal methods are acceptable and ongoing treatment of at least a year is anticipated) and can reduce menstrual losses by over 90%.^9,10
• It is effective even in the presence of fibroids, although it is not generally recommended where fibroids distort the uterine cavity, because of difficulties with insertion.
• The LNG-IUS is more effective than medical treatments for the treatment of menorrhagia. A recent meta-analysis showed its superior efficacy to oral progestogens for the treatment of idiopathic menstrual blood loss.¹¹
• A Cochrane review found that surgical treatment (hysterectomy, endometrial resection or ablation) is more effective at reducing menstrual blood loss at 1 year but the LNG-IUS is as effective at improving quality of life at 1 year.¹² Therapeutic results are comparable at two years for endometrial ablation¹³ but evidence of the LNG-IUS's effectiveness compared with surgical methods is often indirect.¹⁴
• Interestingly, there is some suggestion that sexual function is better post-hysterectomy for women with menorrhagia than for those treated with an LNG-IUS, although the risk of urinary tract infections and stress incontinence is higher in women who have had hysterectomies.^15,16
• Cost of treatment for menorrhagia is significantly lower in women with LNG-IUS compared with hysterectomy.¹⁷

• The LNG-IUS is licensed (since 2004) for the prevention of endometrial hyperplasia during oestrogen replacement therapy.
• It potentially provides a means of delivering endometrial protection with minimum systemic absorption of progestogen, given concerns regarding increased breast cancer risk associated with combined HRT.¹⁸
• A randomised controlled trial (RCT) showed that a 10 micrograms/24 hours IUS device (not currently available) was as effective as the Mirena® in providing endometrial protection in postmenopausal women on oestrogen therapy but had the advantage of easier insertion and less effect on serum lipid profiles.¹⁹

• Endometriosis and adenomyosis - studies have looked at the use of the LNG-IUS as maintenance therapy or following surgery.^20,21
• Endometrial hyperplasia - it appears effective as a treatment for non-atypical endometrial hyperplasia.^22,23
• Endometrial protection for women on tamoxifen - however a Cochrane review concluded that there was no clear evidence for its role in the prevention of endometrial hyperplasia or carcinoma, and that the risk of breast cancer recurrence warranted further investigation.²⁴
• Early-stage endometrial carcinoma in a patient unfit for surgery.²

Contra-indications and cautions²⁵

• Pregnancy.
• Recent sexually transmitted infection (STI), unless fully investigated and treated.
• Undiagnosed uterine or vaginal bleeding.
• Distorted or small uterine cavity.
• Genital malignancy.
• Active trophoblastic disease.
• Pelvic inflammatory disease.
• Marked immunosuppression.
• Current deep vein thrombosis (DVT) or pulmonary embolus (PE).
• Ischaemic heart disease.
• Active viral hepatitis, severe decompensated cirrhosis, benign liver tumours or malignant hepatomas.
• Breast cancer within the preceding 5 years.

Side-effects

Altered patterns of menstrual bleeding

Up to 60% of women stop using the LNG-IUS within 5 years - the most common reason is unacceptable vaginal bleeding. Prior to commencing use of the IUS, women should be counselled that altered patterns of menstrual bleeding are common - irregular bleeding and spotting (common in the first six months of treatment) and amenorrhoea in particular. Amenorrhoea is reported in 65% of women using the LNG-IUS after 1 year and is perceived by many as a benefit.⁴

Hormonal symptoms

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

Ectopic pregnancy

Overall, rates are lower than with no contraception. However, 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. The risk of ectopic pregnancy is less for LNG-IUS than for conventional IUCDs.²⁶

Uterine expulsion and perforation

The risk of expulsion or displacement is relatively common,(with approximately 1 in 20 women affected) and women should be encouraged to check their threads regularly.⁴ The risk of perforation is small (1-2 in 1,000 women) but significantly increased in lactating women.²⁷

Ovarian cysts

Functional, usually asymptomatic, ovarian cysts are relatively common and usually resolve spontaneously. Consider ovarian pathology in IUS-users and, if found, ultrasound monitoring is suggested.

Pelvic infection

There is a small increase in the risk of pelvic infection which occurs in the 20 days following the insertion of an LNG-IUS. Thereafter the risk of infection is the same as for those not using the device.

Insertion

Counselling

Prior to giving informed consent, women should be given verbal and written information including:

• Mode of action.
• Duration of action:²⁸
  • Contraception - 5 years.
  • Perimenopausal contraception (where aged >45 years at insertion) - 7 years/until contraception is no longer required (this is beyond the licensed use and should be discussed with the patient and documented in the notes).
  • Menorrhagia - 5 years.
  • Endometrial protection for oestrogen replacement therapy - 4 years.
• Contraceptive efficacy and failure rate.
• Reversibility and return of fertility.
• No protection against STIs (safe sex and condom use should be promoted).
• Side-effects and risks.
• Usual bleeding patterns.
• When and how to seek help.

Screening

STIs: prior to inserting an LNG-IUS, women who are at increased risk of STIs should be screened for chlamydia (and gonorrhoea in areas of prevalence). Increased risk is associated with:

• Age under 25 years.
• More than 1 sexual partner in the last 12 months.
• A previous STI or current symptoms of infection.

Nulliparous women are not at increased risk of infection per se but the potential consequences of a pelvic infection may be of greater significance and this should be discussed with the patient. Where testing is not complete, prophylactic antibiotics should be given to women at increased risk of STIs prior to LNG-IUS insertion. Women may use the LNG-IUS following the full treatment and resolution of symptoms associated with a pelvic infection.²⁵

Endometrial abnormalities: endometrial biopsy or ultrasound is not routinely required prior to LNG-IUS insertion for menorrhagia. However, any vaginal bleeding should be diagnosed prior to insertion of an LNG-IUS to exclude pregnancy or an underlying pathological condition such as pelvic malignancy.²⁵

Timing

• Ideally, the LNG-IUS should be fitted within the first 7 days of a period and is effective immediately.
• If fitted beyond 7 days, the risk of a pregnancy since the last period must be excluded prior to insertion and additional contraceptive precautions should be used for the subsequent 7 days.
• The LNG-IUS can be fitted 4 weeks after a vaginal or Caesarean section delivery.
• The LNG-IUS can be fitted immediately after a first-trimester abortion or miscarriage, with immediate effect.

Fitting

• Only staff trained and up-to-date in fitting IUCDs should perform IUS insertion. Insertion is commonly undertaken in general practice (as an enhanced service) or within the context of family planning or gynaecology clinics.
• For LNG-IUS insertion technique - see separate article IUCD Insertion Technique.

Follow-up

• Routinely 3-6 weeks after fitting or after the first period to check threads and to exclude infection or perforation.
• If indication is for treatment of primary menorrhagia and there is no improvement after 6 months, consider alternative treatment.
• Further follow-up should be driven by problems or when removal is desired or necessary.

Problems

Bleeding: irregular bleeding and spotting is common in the first six months with an LNG-IUS. Counsel women that 65% of women develop amenorrhoea with the IUS and 90% experience reduced menstrual flow ultimately. Guidance for unscheduled bleeding suggests:²⁹

• <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 6 months) - perform a clinical examination where there is persistent bleeding, any new symptom or changed bleeding pattern, failed medical treatment, nonparticipation 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 (e.g. ultrasound, hysteroscopy, endometrial biopsy).

Bleeding due to the IUS may settle spontaneously within 6 months. Alternatively, a three-month trial of a first-line combined oral contraceptive pill (COCP) may be considered, although this is an off-license use. Where bleeding is not improving, refer at 6 months or, if there is menstrual flooding, remove the LNG-IUS, as the device's mechanical presence may be the cause.³⁰

Lost threads: see separate article IUCD Lost Threads and Other Problems.

Actinomyces-like organisms: these are often found coincidentally on cervical smear and should trigger an assessment for pelvic infection. If asymptomatic, the IUS can be left in situ.

Pregnancy: if a woman becomes pregnant with the IUS in situ, the IUS should be removed before the 12th week of gestation.

Removal²⁸

• Where pregnancy is desired, the LNG-IUS can be removed at any time.
• If pregnancy is not desired, the LNG-IUS should be removed with menstruation or, if there has been no unprotected sexual intercourse in the previous 7 days, at other times.
• Where the LNG-IUS is to be exchanged, intercourse should be avoided for the previous 7 days in case reinsertion fails.
• When switching to the COCP, remove after 7 consecutive pills.
• When switching to the depot or implant progestogen methods, remove the LNG-IUS after 7 days of use of the new method.

Cost

• The LNG-IUS (and other long-acting reversible contraceptives) is more cost-effective than the COCP even at one year of use.⁴
• It is also more cost-effective than injectable contraceptives.
• In the past, doctors have been reluctant to fit LNG-IUS devices on the basis of item cost but cost-effectiveness analyses show this to be a false saving when other costs are taken into account.
• It is significantly more cost-effective than endometrial ablation or hysterectomy.³¹

Document references

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3. Contraception and Sexual Health, Office for National Statistics, 2008/09
4. Long-acting reversible contraception, NICE Clinical guideline (October 2005); (the effective and appropriate use of long-acting reversible contraception)
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7. Contraception - IUS/IUD, Prodigy (Sept 2007)
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29. Management of Unscheduled Bleeding in Women Using Hormonal Contraception, Faculty of Sexual and Reproductive Healthcare (2009)
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31. Clegg JP, Guest JF, Hurskainen R; Cost-utility of levonorgestrel intrauterine system compared with hysterectomy and second generation endometrial ablative techniques in managing patients with menorrhagia in the UK. Curr Med Res Opin. 2007 Jul;23(7):1637-48. [abstract]