Key points from the evidence

The content of this evidence summary was up-to-date in June 2014. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Summary

In a randomised controlled trial that compared 2 low-dose intrauterine delivery systems containing 13.5 mg and 19.5 mg levonorgestrel (n=2885), the failure rate of the levonorgestrel 13.5 mg intrauterine delivery system (Jaydess: failure rate 0.4% in year 1 and 0.9% over 3 years) was similar to failure rates seen with correct and consistent use of other methods of long-acting reversible contraception. Serious adverse events were reported by 8 women (0.6%) using the levonorgestrel 13.5 mg intrauterine delivery system, including 3 ectopic pregnancies and 2 cases of pelvic inflammatory disease.

The levonorgestrel 19.5 mg intrauterine delivery system used as a comparator in the study is not licensed or available commercially, and there is insufficient evidence comparing the levonorgestrel 13.5 mg intrauterine delivery system with existing contraceptives, including the levonorgestrel 52 mg intrauterine system (Mirena). Two studies are underway comparing this device with a combined oral contraceptive containing drospirenone and ethinylestradiol (Yasmin; NCT01254292) and the progestogen-only subdermal implant (Nexplanon; NCT01397097) respectively.

Effectiveness

In women using the levonorgestrel 13.5 mg intrauterine system in Nelson et al. (2013) (n=1432):

  • 10 pregnancies occurred over 3 years (0.33 pregnancies per 100 woman-years).

  • The contraceptive failure rate was 0.4% in year 1 and 0.9% over 3 years, which is similar to failure rates seen with correct and consistent use of other methods of long-acting reversible contraception.

Safety

  • In women using the levonorgestrel 13.5 mg intrauterine system in the study:

    • 8 serious adverse events were reported (0.6%) including 3 ectopic pregnancies and 2 cases of pelvic inflammatory disease.

    • Over 3 years, the discontinuation rate for adverse events was 21.9%.

  • According to the summary of product characteristics for Jaydess, the most common adverse effects are headache, abdominal or pelvic pain, acne or seborrhoea, bleeding changes, ovarian cysts and vulvovaginitis.

User factors

  • NICE advises that women requiring contraception should be given information about and offered a choice of all methods, including long-acting reversible contraception.

  • The levonorgestrel 13.5 mg device is smaller than the levonorgestrel 52 mg device but there is insufficient evidence comparing the 2 devices in terms of pain and ease of insertion.

  • The majority of women who used the levonorgestrel 13.5 mg intrauterine system were satisfied with their treatment and bleeding patterns but comparisons with levonorgestrel 52 mg and other contraceptives are lacking.

Resource implications

  • The levonorgestrel 13.5 mg intrauterine system (Jaydess) costs £69.22 for up to 3 years' contraception

  • The levonorgestrel 52 mg intrauterine system (Mirena) costs £88.00 for up to 5 years' contraception.

  • Costs of other long-acting reversible contraceptives are listed in the costs of alternative contraceptives section of this evidence summary.

Introduction and current guidance

The NICE guideline on Long-acting reversible contraception (NICE clinical guideline 30) advises that women requiring contraception should be given information about and offered a choice of all methods, including long-acting reversible contraception. The NICE guideline offers best-practice advice for all women of reproductive age who may wish to use copper intrauterine devices, progestogen-only intrauterine systems and progestogen-only injectable contraceptives. The Faculty of Sexual and Reproductive Healthcare (FSRH) has produced clinical guidelines on various methods of contraception (processes used to produce FSRH guidance have been accredited by NICE).

This evidence summary considers the levonorgestrel 13.5 mg intrauterine delivery system (Jaydess; initial release rate 14 micrograms/24 hours, average release rate 6 micrograms/24 hours for up to 3 years). This device contains a lower dose, and is smaller than the levonorgestrel 52 mg intrauterine delivery system (Mirena; initial release rate 20 micrograms/24 hours), which has been available since March 1995.

Full text of Introduction and current guidance.

Product overview

The levonorgestrel 13.5 mg intrauterine delivery system (Jaydess) is licensed for up to 3 years' contraception. It received a marketing authorisation in January 2013 and was launched in the UK in March 2014.

Full text of Product overview.

Evidence review

This evidence summary is based on a randomised controlled trial that compared 2 low-dose intrauterine delivery systems containing 13.5 mg and 19.5 mg levonorgestrel (Nelson et al. 2013). The higher dose levonorgestrel intrauterine delivery system used in this study is not licensed or available commercially and is only briefly discussed. The study included 2885 healthy nulliparous and parous women aged 18−35 years who had regular menstrual cycles (21−35 days) and requested contraception.

  • Nelson et al. (2013) (n=2885) found that the levonorgestrel 13.5 mg intrauterine delivery system is an effective contraceptive device. The failure rate observed in the study in year 1 (0.4%) was similar to those seen with correct and consistent use of other methods of long-acting reversible contraception (Trussell 2011). Over 3 years, 10 pregnancies occurred in the levonorgestrel 13.5 mg group (0.33 pregnancies per 100 woman-years: cumulative failure rate 0.9%). Four of the pregnancies were associated with either complete or partial expulsion of the levonorgestrel intrauterine delivery system.

  • In the study, over 3 years, serious adverse events were reported by 8 women (0.6%) using the levonorgestrel 13.5 mg intrauterine delivery system. Three ectopic pregnancies and 2 cases of pelvic inflammatory disease classed as serious adverse events occurred. There were no uterine perforations. Over 3 years, 21.9% of women using the levonorgestrel 13.5 mg intrauterine delivery system discontinued treatment because of adverse events (1.0% for serious adverse events and 4.7% for bleeding disturbances including amenorrhoea).

  • According to the summary of product characteristics, the most common adverse effects of the levonorgestrel 13.5 mg intrauterine delivery system are headache, abdominal or pelvic pain, acne or seborrhoea, bleeding changes (increased or decreased menstrual bleeding, spotting, infrequent bleeding and amenorrhoea), ovarian cysts and vulvovaginitis, with an incidence of 1 in 10 or more. Adverse effects with an incidence of between 1 in 100 and 1 in 10 are depressed mood or depression, migraine, nausea, alopecia, upper genital tract infection, dysmenorrhoea, breast pain or discomfort, device expulsion (complete or partial) and genital discharge.

Full text of Evidence review.

Context

The levonorgestrel 13.5 mg intrauterine system costs £69.22 for up to 3 years' contraception. The levonorgestrel 52 mg intrauterine system (Mirena) costs £88.00 for up to 5 years' contraception. See the costs of alternative contraceptives section for details of other contraceptives.

Full text of Context.

Estimated impact for the NHS

The NICE guideline on Long-acting reversible contraception advises that women requiring contraception should be given information about and offered a choice of all methods, including long-acting reversible contraception. The place in practice of the levonorgestrel 13.5 mg intrauterine delivery system is likely to be as an alternative to other methods of long-acting reversible contraception, including the levonorgestrel 52 mg intrauterine delivery system.

There is insufficient evidence comparing the levonorgestrel 13.5 mg and 52 mg intrauterine delivery systems. An open-label phase II study by Gemzell-Danielsson et al. (2012) (n=742) included a levonorgestrel 52 mg arm and found that levonorgestrel 13.5 mg provided good contraceptive efficacy compared with the established device. However, this study was not sufficiently statistically powered to determine whether the levonorgestrel 13.5 mg intrauterine delivery system is non-inferior to the levonorgestrel 52 mg intrauterine delivery system. It is unclear whether pain and ease of insertion were improved with the levonorgestrel 13.5 mg delivery system compared with the levonorgestrel 52 mg delivery system; the investigators were not blinded and their evaluations of ease of insertion were subjective (easy, slightly difficult or very difficult). In addition, at the time the study was carried out the levonorgestrel 52 mg device had a 4.75 mm diameter insertion tube, whereas the current tube measures 4.4 mm diameter, which limits the applicability of the results.

Nelson et al. (2013) suggest that the levonorgestrel 13.5 mg intrauterine delivery system might appeal to women seeking a lower exposure to synthetic hormones. They also state that this device might be suitable for women with a narrower cervical canal, a smaller uterine cavity, or both, because it is smaller than the levonorgestrel 52 mg intrauterine delivery system. However, there is insufficient evidence to support these claims. The majority of women who used the levonorgestrel 13.5 mg intrauterine delivery system in the study were satisfied with their treatment and bleeding patterns but comparisons with the levonorgestrel 52 mg intrauterine delivery system are lacking.

Although Nelson et al. (2013) suggest that the small size of the levonorgestrel 13.5 mg intrauterine delivery system might make it suitable for use in nulliparous women and women who have never delivered vaginally, the summary of product characteristics states that it is not first-choice for contraception in nulliparous women because clinical experience is limited. Safety and efficacy of the levonorgestrel 13.5 mg intrauterine delivery system has not been confirmed in girls and young women aged under 18 years. However, a clinical study in this population is underway (NCT01434160).

The summary of product characteristics states that the levonorgestrel 13.5 mg intrauterine delivery system is not recommended for treating heavy menstrual bleeding or protecting against endometrial hyperplasia during oestrogen replacement therapy. The levonorgestrel 52 mg intrauterine delivery system (Mirena) is licensed for these indications in the UK.

There is no published evidence comparing the levonorgestrel 13.5 mg intrauterine delivery system with other methods of contraception. However, 2 studies are underway comparing this device with a combined oral contraceptive containing drospirenone and ethinylestradiol (Yasmin; NCT01254292) and the progestogen-only subdermal implant (Nexplanon; NCT01397097) respectively.

Full text of Estimated impact for the NHS.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.