Practice Therapeutics

Newer non-oral hormonal contraception

BMJ 2013; 346 doi: (Published 14 February 2013) Cite this as: BMJ 2013;346:f341
  1. Deborah Bateson, medical director12,
  2. Kathleen McNamee, medical director34,
  3. Paula Briggs, clinical lead5
  1. 1Family Planning NSW, Sydney, NSW 2131, Australia
  2. 2Discipline of Obstetrics, Gynaecology and Neonatology, University of Sydney, Sydney, NSW 2006, Australia
  3. 3Family Planning Victoria, Box Hill, VIC 3128, Australia
  4. 4Monash Medical Centre, Department of Obstetrics and Gynaecology, Clayton, VIC 3168, Australia
  5. 5Community Sexual Health Service, Sefton, UK
  1. Correspondence to: D Bateson deborahb{at}

A 24 year old nulliparous woman asks for a repeat supply of her combined oral contraception. She mentions that she sometimes forgets to take it and asks about alternatives that don’t rely on daily pill taking. She is a non-smoker, has no contraindications to combined hormonal contraception, and had heavy menstrual bleeding before using oral contraception.

What newer non-oral hormonal contraceptive methods are available?

This article concentrates on the newer non-oral hormonal methods of contraception (table 1):

  • Medium acting combined hormonal contraception—the transdermal patch (Evra) (fig 1) and the vaginal ring (NuvaRing) (fig 2)

  • Long acting reversible methods—the levonorgestrel intrauterine system (IUS) (Mirena) (fig 3) and the single rod, progestogen-only implant (Nexplanon or Implanon NXT) (fig 4).

Table 1

Summary of newer non-oral hormonal contraceptives

View this table:

Transdermal patch (Evra). Jacek Kutyba/


Vaginal ring (NuvaRing). Permission from Family Planning NSW


Levonorgestrel intrauterine system (IUS) (Mirena). Permission from Family Planning NSW


Single rod, progestogen-only implant (Nexplanon or Implanon NXT) Permission from Family Planning NSW

How well do these methods work?

User errors are more common with methods that rely on frequent activity—for example, taking a pill daily. Table 2 summarises failure rates for different contraceptive methods (and for a useful counselling tool to use with patients, see the Web Extra figure on The efficacy of the patch (weekly activity) and the vaginal ring (monthly activity) is similar to that of the combined pill.2 An analysis of US data estimated that the combined pill has a failure rate of 0.3% for perfect use (achieved under research conditions) and 9% for typical use (which includes user error) in the first year of use.3 Long acting methods, including the progestogen-only implant and IUS, do not rely on ongoing user administration; they are thus more effective than shorter acting methods, and are sometimes referred to as “fit and forget” methods.

Table 2

Currently available contraceptive choices and estimated failure rates for typical and perfect use during the first year of use. Effectiveness is expressed as the number of unintended pregnancies occurring in a year for every 100 women using the method. Adapted from Trussell1

View this table:

How safe are these methods?

Combined hormonal contraception: patch and vaginal ring

Combined oral contraception is estimated, as a class effect, to double the risk of venous thromboembolism per 10 000 women over one year of use from 4-5 to 9 events.4 A recent national registry cohort study of Danish women suggests that use of the patch or ring may increase the risk of venous thromboembolism to 7.8 and 9.7 events respectively per 10 000 women over one year of use, compared with 6.2 events in users of pills containing levonorgestrel with 30-40 µg of ethinylestradiol and 2.1 events in non-users of hormonal contraception. After adjusting for age, calendar year of event, and level of education, the risk for use of the patch or ring was about double that for use of the combined oral contraceptive pill. This study did not control for body weight or family history and may have overestimated the risk in users.5 Unless other evidence emerges to support these findings, the ring and patch can be safely used by women without major risk factors for venous thromboembolism. The risk of venous thromboembolism in women using combined hormonal contraception is still lower than that during pregnancy and the early postpartum period, estimated respectively at 29 and 300-400 per 10 000 women exposure years.4

Data from the same cohort study on myocardial infarction and thrombotic stroke are limited by the relatively small number of ring and patch users and by the very low absolute risk of such events in women of reproductive age. The relative risk of myocardial infarction and thrombotic stroke in users of all combined hormonal contraceptives in this study ranged respectively from 1.20 to 4.31 and 0.88 to 3.15.6

As the risk of venous and arterial vascular disease increases with age5 6 women using the ring or patch are recommended to switch to a progestogen-only or non-hormonal method from the age of 50 if they need or wish to use contraception.7

Estimates for cancer risk associated with the patch and the ring are unavailable owing to the absence of long term data for these methods. A large prospective cohort study found no significant increase in cancer related mortality and a significantly lower mortality from cancers of the uterus, ovaries, and large bowel or rectum in users of the combined pill compared with never-users, but whether similar results extend to patch and ring users is not known.8

Inadvertent exposure to combined hormonal contraceptives in pregnancy is common. Most data relate to the combined pill, and although studies are limited by their observational nature and small sample size, reassuringly there have been no consistent findings of specific fetal abnormalities.9

Progestogen-only implant and IUS

The progestogen-only implant and IUS have few serious risks. The Danish cohort study found no significant increase in the risk of venous thromboembolism,5 myocardial infarction, or thrombotic stroke6 in users of the progestogen-only implant or the IUS.

Progestogen-only implant

Insertion and removal of the progestogen-only implant is associated with a small risk of local bleeding, infection, and scarring. There is no evidence that the use of the implant during pregnancy is associated with any known harm to the pregnancy or the fetus, but the National Institute for Health and Clinical Excellence (NICE) guideline recommends removal as soon as possible owing to potential virilisation of a female fetus if the woman wishes to continue the pregnancy.10


The risks associated with insertion of any intrauterine device include infection, expulsion, and perforation of the uterus.11 There is an approximate sixfold increase in pelvic infection in the 20 days after insertion. Expulsion is thought to occur with 1 in 20 insertions, and perforation of the uterus is rare, occurring on average with 2 in 1000 insertions. Perforation is more likely in postnatal and breastfeeding women. The overall risk of ectopic pregnancy is reduced in women using an IUS.11 If pregnancy occurs during use, the direct exposure to levonorgestrel in the uterus theoretically may increase the risk of teratogenesis. Removal in the first trimester is recommended to reduce this risk as well as that of miscarriage in the second trimester, preterm delivery, and sepsis.11

Training and skills

The rate of complications related to insertion and removal for the progestogen-only implant and of insertion related complications for the IUS seem to be related to the skill level of the practitioner. Appropriate training and maintenance of skills are important for all practitioners undertaking these procedures.11 12

What are the precautions?

For women with no medical contraindications, hormonal contraception can be used safely, with potential benefit far outweighing risk. The World Health Organization (WHO) developed international guidelines on medical eligibility criteria (MEC) in 2000 to ensure that women were not subjected to increased health risks when using particular contraceptive methods. These guidelines have been adapted for use in the United Kingdom13 and the United States.14 The MEC categories13 in summary are:

  • MEC 1: a condition for which there is no restriction for the use of the contraceptive method

  • MEC 2: a condition for which the advantages of using the method generally outweigh the theoretical or proved risks

  • MEC 3: a condition for which the theoretical or proved risks usually outweigh the advantages of using the method (a strong relative contraindication requiring expert clinical judgment; general practitioners should refer patients for specialist advice where possible for such conditions)

  • MEC 4: a condition for which there is an unacceptable health risk if the contraceptive method is used (an absolute contraindication).

Table 3 shows the major precautions for the patch and the ring, which are similar to those for the combined pill. Absolute contraindications include a history of migraine with aura and a personal history of a venous thromboembolism. Table 4 outlines the precautions for the progestogen-only implant and the IUS, which have few contraindications and are safe for both parous and nulliparous younger women. All hormonal methods are contraindicated for women with a history of breast cancer diagnosed within the previous five years.

Table 3

Conditions that may pose a health risk if the combined hormonal transdermal patch or the vaginal ring is used (conditions classed as medical eligibility criteria (MEC) category 3 and 4). Adapted from Faculty of Sexual & Reproductive Healthcare13

View this table:
Table 4

Conditions that may pose a health risk if the progestogen-only implant or the levonorgestrel intrauterine system (IUS) is used (conditions classed as medical eligibility criteria (MEC) category 3 and 4). Adapted from Faculty of Sexual & Reproductive Healthcare13

View this table:

Drug interactions

The concurrent use of liver enzyme inducing medications (box) with the patch, ring, and progestogen-only implant can lead to potential method failure owing to the reduction in systemic hormone levels. The effectiveness of the IUS is not reduced by such medications.

Medications with potential liver enzyme inducing activity that may potentially lead to contraceptive failure with the patch, vaginal ring, or progestogen-only implant*

  • Antiepileptics—Carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rufinamide, topiramate

  • Antibiotics—Rifabutin, rifampicin

  • Protease inhibitors—Ritonavir and ritonavir-boosted protease inhibitors

  • Non-nucleoside reverse transcriptase inhibitors—Nevirapine, efavirenze

  • Herbal—St John’s wort (Hypericum perforatum)

  • Other—Aprepitant, bosentan, modafinil

  • *Adapted from Faculty of Sexual & Reproductive Healthcare15

The patch and ring are not usually recommended in women using lamotrigine monotherapy owing to a risk of reduced seizure control and the potential for lamotrigine toxicity in the ring-free or patch-free break.15

Adverse effects

Patch and vaginal ring

Adverse effects for the patch and ring are similar to those for combined oral contraception. Ring users generally have superior cycle control, with regular scheduled monthly bleeding compared with those using the combined pill. An increase in vaginal discharge is common in ring users.2There is no evidence of a delay in the return to fertility for patch or ring users when the method is stopped.

Progestogen-only implant and IUS

About one in five women using a progestogen-only implant are amenorrhoeic in the first year of use and others may have infrequent, frequent, or prolonged bleeding.12 Studies show the bleeding pattern in the first few months is broadly predictive of future bleeding patterns.16

In IUS users, unscheduled bleeding is most common during the first three to four months of use, with a reduction of menstrual blood loss generally within a few months of insertion. Amenorrhoea occurs in about 20-60% of regularly menstruating women and in 50-75% of women with heavy menstrual bleeding.17

Alteration in the bleeding pattern is the most common cause for early discontinuation of the progestogen-only implant12 and the IUS,11 accounting for 40-70% of removals.

Evidence is limited for the management of the bleeding irregularities related to the progestogen-only implant and the IUS. Women who have no contraindications to the use of oestrogen can be offered the combined pill for one to three months. This is likely to stop the current episode of bleeding, but evidence of a long term effect on future bleeding episodes is lacking. It is important to exclude other causes of unscheduled bleeding, including pregnancy, cervical or endometrial disease, and sexually transmitted infections.18

There is no evidence that either the progestogen-only implant or the IUS is associated with a delay in the return to fertility after removal.11 12

How are they taken and monitored?

Starting contraception

Methods that inhibit ovulation—namely, the patch, the ring, and the progestogen-only implant, can be started on day 1 to 5 of the menstrual cycle for immediate effectiveness. They can be started at any other time if the risk of a pre-existing pregnancy is considered to be low, but an additional seven days of precautions are needed before the method will become effective. A follow-up pregnancy test is important if there is a chance of a continuing pregnancy. Guidance on late application of the patch or insertion of the ring is available from the Faculty of Sexual and Reproductive Healthcare.19

The IUS is immediately effective if inserted on day 1 to 7 of the cycle. It is essential to exclude any chance of pregnancy before insertion of an IUS owing to the risk of complications if a pregnancy occurs with an IUS in situ.

Women may be prescribed a 12 month supply of the patch to reduce the risk of early discontinuation before repeat scripts can be filled. The cold chain requirement of the ring limits its supply to a maximum of three rings at any one time.


Ideally, review women three to four months after they first start using the patch or ring, to check for adverse effects or other concerns. Do an annual review to ensure ongoing eligibility for the method and to measure blood pressure and body mass index.

Routine follow-up is not required after insertion of a progestogen-only implant. If the implant is impalpable as a result of being deeply inserted into the muscle rather than the subdermal plane, refer to a specialist service for removal under high frequency ultrasound guidance. For women using an IUS, review three to six weeks after insertion to exclude complications related to insertion, such as infection or expulsion.11

Invite all women to return for review anytime they have concerns about their contraceptive method.

How do these methods compare with other methods?

Combined contraceptive pill

The patch and vaginal ring are equivalent to the combined pill in relation to contraindications and drug interactions.19 They have similar adverse effects2 but, unlike the combined pill, their effectiveness is not affected by vomiting, diarrhoea, or malabsorption.

Intrauterine device

Whereas the IUS is licensed for the management of heavy menstrual bleeding and is the first line recommendation for this in the NICE guideline,20 the IUD (copper-bearing intrauterine device) is associated with an increased risk of menstrual blood loss. However, the IUD has the advantage of no hormonal contraindications or adverse effects and can provide highly effective contraception for up to 10 rather than five years. Unlike the IUS, the IUD also provides postcoital emergency contraception if inserted within five days of unprotected sexual intercourse.11

Medroxyprogesterone acetate (Depo-Provera)

The three year duration of action of the progestogen-only implant compares favourably with the 12 week repeat injection schedule for medroxyprogesterone acetate. Whereas removal of the progestogen-only implant results in an immediate return to fertility, there can be a delay of up to one year after discontinuation of medroxyprogesterone acetate. Its association with a small loss of bone mineral density also means that, although medroxyprogesterone acetate may be used as a first line contraceptive in adolescents, this should follow consideration of other methods. Use of the injection is, however, more readily concealed than the implant, is associated with at least a 50% chance of amenorrhoea, and can be used concurrently with any medication without loss of efficacy.12 21

How cost effective are non-oral hormonal methods of contraception?

The newer non-oral hormonal methods of contraception are more expensive than older combined pills and non-hormonal methods at the point of purchase. However, cost effectiveness is dependent on a reduction in both unnecessary gynaecology referrals and abortions. A 2005 NICE review of long acting reversible contraceptive methods—which includes the progestogen-only implant and the IUS but not the patch or the ring—concluded that they are more cost effective than the combined pill owing to a reduction in the potential for user error.10

At one year of use, the progestogen-only implant is more cost effective than either the combined contraceptive pill or the progestogen-only injectable method. The IUS becomes more cost effective than the implant after three years of use.10 Cost effectiveness data for the patch and the ring are lacking.

Case outcome

After a discussion about all available options, the patient decides to try an IUS. This long acting, non-oral method avoids the need for taking a daily pill and is effective for the management of heavy menstrual bleeding.

Tips for patients

  • There are many contraceptive choices. These include implants, intrauterine methods, injections, pills, patches, vaginal rings, permanent sterilisation, barrier methods, and fertility awareness based methods

  • Your doctor or nurse will assess your eligibility for the different methods to help you make the right choice for your individual circumstances

  • Hormonal methods of contraception have other benefits for women with pre-existing conditions such as heavy periods. These benefits may influence which method of contraception you choose

  • Your doctor or nurse will explain how your chosen method works, how it should be used, and what side effects you might expect

  • If you are using a patch or a vaginal ring, you can miss your monthly withdrawal bleed by omitting the “patch-free” or “ring-free” break. This is similar to missing the “pill-free” break if you are using the combined pill. A patch can be applied weekly without a patch-free break. The ring can be used for up to four weeks then removed and replaced with a new ring

  • The patch, ring, progestogen-only implant, and the IUS, like all non-barrier methods of contraception, do not protect against sexually transmitted infections. Using condoms (male or female) at the same time as an effective method of contraception protects against both sexually transmitted infections and unintended pregnancy

  • If your contraceptive method fails or you are not using contraception and have unprotected sex, see a health professional to obtain emergency contraception. This includes (from most to least effective): a copper IUD (intrauterine device), ulipristal acetate (30 mg tablet), or the levonorgestrel emergency contraceptive pill


Cite this as: BMJ 2013;346:f341


  • This is one of a series of occasional articles on therapeutics for common or serious conditions, covering new drugs and old drugs with important new indications or concerns. The series advisers are Robin Ferner, honorary professor of clinical pharmacology, University of Birmingham and Birmingham City Hospital, and Albert Ferro, professor of cardiovascular clinical pharmacology, King’s College London. To suggest a topic for this series, please email us at practice{at}

  • Contributors: DB wrote the first draft; KMcN and PB revised subsequent versions of the manuscript. All authors agreed the final version. DB is the guarantor.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: (1) DB’s institution has received consultancy fees, research funding, payments for lectures and educational material, and sponsorship for courses and conferences from Bayer Healthcare and MSD, and consultancy fees from Pfizer; DB has received travel, accommodation, and registration costs from by Bayer Healthcare and MSD to attend conferences. (2) KM’s institution has received consultancy fees and payments for lectures and development of educational material from Bayer Healthcare and MSD; sponsorship for courses and conferences from, Bayer Healthcare and MSD. (3) PB and PB’s institution have received consultancy fees from Bayer Healthcare, MSD, HRA Pharma, Astellas, and GSK; PB’s institution has received funding for research from Bayer Healthcare and HRA Pharma; PB and PB’s institution have received payments for lectures by Bayer Healthcare, MSD, HRA Pharma and Astellas; PB has received payment from MSD for data analysis; PB has received payment from HRA Pharma and Bayer Healthcare for the development of educational material; PB has received travel, accommodation, and registration costs from Bayer Healthcare, MSD, HRA Pharma, PregLem, Quintiles, and GSK to attend conferences. (4) None of the authors has other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Commissioned; externally peer reviewed.