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Abstract

Non-oral contraception is increasingly being promoted by contraceptive experts as a more convenient and, in many cases, safer and more efficacious alternative to short as acting methods such as oral contraception. Injectables, implants and intrauterine methods offer the advantage of being long-acting and less user dependent, factors which may potentially improve contraceptive compliance. Implants and intrauterine methods are also recognised to be more cost-effective, largely through the prevention of unintended pregnancy. Combined contraceptive methods in non-oral delivery forms [patches, gels and vaginal rings] offer a choice for women who find it difficult to adhere to daily use. The barrier methods, particularly the male and female condoms have the advantage of being user-controlled but they are vulnerable to misuse and can fail to protect against pregnancy and more importantly in the case of condoms, sexually transmitted infections. Male and female sterilisation offer irreversible contraception.

 

Keywords

condoms; contraceptive implants; contraceptive patch; depot medroxyprogesterone acetate; intrauterine device; non-oral contraception; vaginal contraceptive ring
 

In the United Kingdom (UK), as in much of the developed world, the combined oral contraceptive pill is the most popular reversible method of contraception. Despite a variety of non-oral methods entering the market in the last decade, the reported use of the contraceptive pill has remained constant in the UK during this time. A proportion of women possibly remain unaware of all the contraceptive options available and may be uninformed of the benefits many of the non-oral methods offer. Most non-oral methods do not rely on daily compliance and indeed increased uptake of the longer-acting, reversible methods (such as intrauterine devices and subdermal implants), may enhance other public health measures to reduce unplanned pregnancies. The other group of non-oral methods are the male and female barrier methods, which rely on reliable self directed use, and in the case of condoms, offer the advantage of protection against sexually transmitted infections. This discussion will highlight some of the new developments in the field of contraception with respect to non-oral methods.

 

Researchers into alternative methods of contraception that avoid dependence on daily adherence have developed a number of new products. These include the EVRA patch and the combined contraceptive vaginal ring (NuvaRing). Long-acting progestogen methods too have increased in popularity with a variety of delivery mechanisms including intrauterine and subdermal. Apart from avoiding the necessity of daily compliance, some of the non-oral hormonal methods offer the advantage of direct absorption into the circulation and therefore have consistent bioavailability, thereby providing lower or comparable doses of circulating hormone, but with a more steady state of release.

 

Although most women using contraceptive methods are medically fit, co-morbidities may lead to unacceptable health risks with particular contraceptives. An essential resource to indicate which women are eligible for a particular method is the UK version of the WHO Medical Eligibility Criteria for Contraceptive Use (UKMEC), published in 2009 (Table 1). The efficacy of each of the methods to be discussed is listed in Table 2 which documents rates of both perfect use (failure rates for women when contraception is used every time they have sexual intercourse and it is used according to instructions every time), and typical use (failure rates for women when contraception is not used every time they have sexual intercourse and/or it is not used according to instructions every time).

 

Combined hormonal contraceptives

The vaginal contraceptive ring

The combined vaginal contraceptive ring (VCR) is a flexible 54 mm silicone vaginal ring. Most of the published trials have examined the one ring available on the market, the NuvaRing® (NV Organon Oss. The Netherlands) which releases 15 ug of ethinyl oestradiol (EE) and 120 ug of etonogestrel per day in a sustained release fashion.

 

The ring is inserted high in the vagina and left in situ for three weeks. After three weeks the ring is removed to allow for a hormone-free interval of 7 days during which the user experiences a withdrawal bleed. A new ring is then inserted. The ring's hormone reservoir has enough hormone for a 4th week to allow for users forgetting to change it on time. The ring can be removed up to 3 hours without loss of efficacy. However, if removed for longer than 3 hours the ring should then be re-inserted and extra precautions used for 7 days. Several studies found the VCR to be comparable in efficacy to the COC and to have similar tolerability.

 

The key advantages are that the ring does not require daily administration, it uses lower doses of contraceptive hormones and its controlled release delivery avoids daily fluctuations in hormone levels. Maximum serum concentrations of EE and etonogestrel are achieved one week after insertion and are 60–70% lower than peak concentrations which occur if taking a COC with 150 μg desogestrel and 30 μg of ethinyl oestradiol. The theoretical advantage of better compliance has not been substantiated in the published trials, but is cited by users as a major advantage. Discontinuation rates have been similar to COC. Cycle control has generally been found to be good or superior.

 

Women experience the hormonal side effects of nausea, breast tenderness and headache as with other combined oral contraceptive methods, but these are less than COCPs. However vaginal irritation and discharge are increased with ring use compared to women using the COC and are reported in around 10% of women. The VCR has the same contraindications as all combined oral contraception. The UKMEC categories for Category 4 restricted use are documented in Table 1. Evidence suggests no detrimental effect on cervical or vaginal epithelium. There is limited data about the risk of VTE in ring users which currently equates with other combined methods.

 

Future developments: extended use rings left in situ for 3 or 6 months would further boost compliance and are being evaluated. A ring that lasts for one year is close to market release. Progestogen only vaginal rings have been developed on a small scale in some regions such as South America but are unlikely to become widely available.

 

Contraceptive patch

The contraceptive patch currently available on the market is the Ortho Evra® transdermal patch which delivers 20 μg of ethinyl oestradiol and 150 ug of norelegestromin per day. The patch produces plasma levels higher than comparable oral preparations but without the peaks and troughs of the oral regimen. The patch is licensed for 2 cycle continuous use.

 

A patch is applied weekly for 3 weeks followed by a patch free week. It exerts its contraceptive effect through suppression of ovulation and the secondary effects of cervical mucus and endometrial suppression. If the first patch is applied on days 1–5 of the cycle, no extra precautions are required. Detachment is uncommon, but where this does occur, extra precautions are only required if this is for greater than 24 hours. Extending the patch free interval for more than 7 day risks pregnancy. The contraindications to the Patch are the same as for the combined oral contraceptive pill (Table 3).

   

The continuation rates with the patch have been found to be lower compared to the COC, although in those who continue to use it, there is good compliance. Around 10% of women may develop application site reactions. Breast tenderness and nausea occur more in patch users compared to COC users but resolve by the 3rd cycle of use. Pharmacokinetic studies have found higher mean oestradiol level in women using the patch compared to COCs and VCR and some evidence has found that the risk of VTE is indeed increased in patch users compared to women taking a levonorgestrel pill. Using them in the presence of history of thromboembolic, cardiovascular or cerebrovascular disease is regarded as posing an unacceptable health risk (Category 4) which is the same classifications as oral contraception (Table 3).

 

Progestogen only methods – implants and injectables

Contraceptive implant

Implanon NXT® (MSD) has replaced the previous version of Implanon with an updated inserting system that ensures subdermal placement of the implant, protects against needle stick injury and has rendered the implant radio-opaque. The implant is a progestogen only method that comprises a non-biodegradable single rod, about the size and shape of a match stick, which is inserted subdermally into the non-dominant upper arm. The rod contains 68 mg of etonogestrel which releases 30–40 μg daily over the three years for which it is licensed. The implant is a long-acting method that is easily reversible. Its primary mode of action is ovulation inhibition with the secondary effects being on cervical mucus making it impenetrable to sperm and endometrial thinning. Training is required to ensure it is correctly inserted and removed.

 

Whilst Implanon NXT is a very effective method (Table 2) altered bleeding patterns are common and around 20% of women will experience amenorrhoea, and almost 50% will have infrequent, frequent or prolonged menstruation. Changes in bleeding patterns are largely responsible for method discontinuation, with up to a quarter of women requesting removal within one year. Women considering the method should be advised that, although there is no evidence of a causal relationship between use of a progestogen only implant and weight change, mood change, headaches, acne and loss of libido, these side effect have all been reported in retrospective and non-comparative studies. There is no increased risk of venous thromboembolism and no clinically significant effect on bone mineral density with the use of a progestogen only implant as follicular activity is spared while the inhibition of ovulation is achieved through suppression of LH.

 

Women should be adequately counselled about the potential side effects before insertion, after which routine follow-up is not required. In women who experience problematic bleeding, sexually transmitted infections and gynaecological pathology should first be excluded. There are several management options for the irregular bleeding (Table 4).

 

  

 

There are very few conditions that represent an unacceptable health risk if the implant is used and these are documented in Table 4. Enzyme-inducing drugs make Implanon NXT less effective and it is not suitable for a patient on such long-term therapy. However those on shorter courses should use condoms during therapy and for a month after.

 

Injectable hormonal options

Injectable contraceptive methods are safe and effective. The progestogen only injectable is the most popular. Depo-Provera (150 mg dose of medroxyprogesterone acetate) is widely available as a 12 week injection. Other formulations include Noristerat which contains Norethisterone enantate 200 mg as an 8 week injection. These injectable methods offer discrete long-acting, reversible contraception with many non-contraceptive benefits such as a reduction in endometrial cancer, and theoretically reduced risk of pelvic inflammatory disease, fibroids and endometriosis. They offer an alternative for women in whom oestrogen is contraindicated. Combined injectables were available in the USA but have been withdrawn from the market for manufacturing reasons.

 

Depo medroxyprogesterone acetate (DMPA or Depo-Provera): medroxyprogesterone acetate 150 mg (DMPA) is given by deep intramuscular injection into the gluteal, thigh or deltoid muscle every 12–14 weeks. Its primary mode of action is ovulation suppression, with a secondary effect on cervical mucus and the endometrium. It is highly effective and as it does not require daily compliance, it is a good choice for women who struggle to remember to use a contraceptive method regularly. It has been found to have a stabilising effect in women with epilepsy and sickle cell disease and can be used with unaltered routine in women taking liver enzyme-inducing drugs, as the dose is high enough that the contraceptive effect is not compromised.

 

Menstrual disturbance is common especially in the first year of use and up to 25% of women will discontinue it within this time. The irregular bleeding tends to diminish with each injection and by 12 months half of users become amenorrhoeic. The bleeding can be managed with a variety of medical treatments (Table 4). The return to fertility may be delayed following even one injection of DMPA and only half of women who discontinue the method will have return to fertility at 6–8 months. Apart from irregular bleeding women cease using the method because of headaches, weight gain, acne, and mood swings; the classic progestogen side effects. The studies examining weight gain seem to indicate that women of normal weight do not gain significant weight on DMPA, but those that are obese prior to starting show increasing rates of weight gain.

 

DMPA results in decrease in circulating endogenous oestradiol and there is data to indicate that, in long term users, bone density is reduced. This change is reversible, but may be significant to women at the extremes of reproductive age; in those who are very young (under 18) and have not yet achieved peak bone mass, and women entering the menopause. The UKMEC suggest that DMPA may be used in very young women in situations where other methods are unacceptable and this statement also applies to women over 45 years of age. Counselling women about life style factors impacting on bone density such as exercise (positive effect) and smoking (negative effect) is a must.

 

DMPA is a reversible method in that fertility returns after cessation. Nevertheless, if adverse effects occur they have to be tolerated until the effects wear off. Injections can be given up to 14 weeks after the last one, but beyond that additional contraception is required for 7 days. Noristerat is an 8 week oily injectable associated with less menstrual irregularities than DMPA but usage has not been as wide.

 

A subcutaneous DMPA has now been marketed in a preloaded unijet injector for injection in the thigh under the trade name of Sayana Press®. This makes self administration more possible. The dose is 104 mg regardless of BMI and the injection cycle is the same as the IM version. As the volume is 0.65 ml, the injection is less painful.

 

Intrauterine contraception copper intrauterine device (CU-IUD)

The copper intrauterine device (Cu-IUD) is a long term contraceptive which is highly effective. Indeed the failure rates of Cu-IUD, particularly those with high levels of copper, are similar to rates for sterilisation. The method is rapidly reversible and is therefore suitable for young women who want a method lasting 5–10 years yet retains the chance of fertility.

 

Advantages: the Cu-IUD is hormone-free, independent of intercourse and its use does not affect weight. Any changes in mood and libido are minimal and comparable to other methods. The device can also be used as emergency contraception up to 5 days after unprotected sexual intercourse and will prevent 99% of expected pregnancies. There is evidence that the Cu-IUD may offer protection against endometrial cancer.

 

Clinical assessment: prior to the insertion of a Cu-IUD a clinical history should be taken which includes a sexual history. The sexual history should identify women at risk of sexually transmitted infections who require screening. Factors associated with high STI risk are age <25 years, or age >25 years with a history of a new sexual partner or a history of two or more sexual partners in the last year. Women are also at increased risk if their regular partner has other partners. The Faculty of Sexual and Reproductive Healthcare in the UK recommends screening for Chlamydia trachomatis and Neisseria gonorrhoea prior in to Cu-IUD insertion for those women at risk and in all women who request screening. There is no indication to test for other lower genital tract infections such as bacterial vaginosis.

 

Mode of action: the primary mode of action of Cu-IUDs is prevention of fertilisation. The copper they contain has been found to be toxic to sperm and ovum and acts on cervical mucus to reduce sperm penetrability. The IUD also sets up an inflammatory reaction within the endometrium which inhibits implantation in the rare situation where this mechanism operates. The Cu-IUD does not cause miscarriage.

 

Efficacy and duration of use: efficacy is extremely high for Cu-IUD, especially for those devices with surface area of copper higher than 300 mm Cu like the TCu380S and the TCu380S which have copper on the sleeves as well as the stem. Duration of use varies from 5 to 10 years and depends on the size of the device and the copper content. The duration of use can be extended to the time of the menopause in women who have a Cu-IUD inserted at or after the age of 40. The device will provide protection against pregnancy provided it is left in situ a year after the last menstrual period if menopause occurs after 50, or 2 years if menopause occurs before 50.

 

Risks and side effects: the risk of pelvic infection is greatest around the time of insertion and is related to the presence of sexually transmitted infections in the cervix. In low risk women the chance of developing pelvic inflammatory disease (PID) is less than 1 in 100. Thereafter the risk is the same as the non-using IUD population and is estimated at around 1.6 per 100 woman-years. Prophylactic antibiotics are not routinely recommended. Women should be advised that there is a small risk of perforation at the time of insertion of around 1–2 per 1000. In around 1 in 20 women the Cu-IUD may be expelled or displaced. This occurs most commonly in the first 12 months, and largely in the first 3 months after insertion. Frameless devices (Gynae-fix) which were developed to reduce this risk and the risk of heavy bleeding, do not seem to confer an advantage. The risk of ectopic pregnancy when using IUCD is lower than if no contraception is being used and occurs about 1 in 1000 over 5 years. A recent review concluded that post IUD fertility is no different from that in the general population.

 

IUD use may be associated with heavier or prolonged bleeding and/or dysmenorrhoea. Indeed up to 50% of women discontinue use within 5 years with the most common reason being unacceptable vaginal bleeding. Women therefore require careful counselling prior to insertion. Tranexamic acid and Mefenamic acid prn reduce bleeding individually but can be used together. Lower doses seem to work as well as standard doses.

 

Levonorgestrel intrauterine system (LNG-IUS)

The levonorgestrel intrauterine system (LNG-IUS) is a T shaped plastic device with a reservoir on the stem that releases 20 μg levonorgestrel per day and is licensed for use for 5 years. It is extremely efficacious with failure occurring in 2 per 1000 women in the first year of use (Table 2). It is marketed under the name of Mirena (Bayer Healthcare).

 

Advantages: the LNG-IUS offers excellent contraception and a range of non-contraceptive benefits. It results in significant reduction in mean menstrual blood loss and is licensed for treatment of heavy menstrual bleeding. In limited studies it has been found to reduce endometriosis associated pain and fibroid associated blood loss.

 

Mode of action: it exerts its contraceptive effect mainly via the release of progestogen into the endometrium which produces endometrial changes that disrupt sperm transfer and impede fertilisation and implantation. The local progestogen effect on the cervical mucous results in a reduction in sperm penetration. The system does not generally inhibit ovulation.

 

Clinical assessment and use: insertion of an IUS should take place within the first 7 days of the menstrual cycle or at any time if there is no risk of pregnancy. It must not be used for postcoital contraception as its effects on the endometrium are not immediate. The device is slightly wider than the Cu-IUDs but use in nulliparous women with or without local anaesthetic is feasible.

 

Side effects: the LNG-IUS has the same risks as the Cu-IUD; that is the risk of uterine perforation (approx 2 per 1000), expulsion (1 in 20) and infection. The most common cause of complaint with IUS use is early irregular bleeding as almost a fifth of women experience prolonged bleeding in the first month of use. The irregular bleeding often continues for the first 6 months after insertion. At one year of use the most common pattern is amenorrhoea or oligomenorrhoea. Although there is very little systemic release of levonorgestrel, some women experience transient progestogenic side effects such as mood changes, headache, bloating, and breast tenderness. In a few women, these symptoms will be the reason for removal. Table 5 documents some of the key management issues.

    
     

 

Low dose LNG-IUS

A low dose LNG-IUS has now been approved in Europe. This device was designed to suit nulliparous women as it is narrower and shorter that the LNG-IUS. The low dose system measures 28 mm × 28 mm compared to the Mirena (32 mm × 32 mm). The inserting tube is also narrower (3.80 mm) compared to that of the Mirena inserter (4.75 mm). The low dose LNG-IUS releases 12 ug of levonorgestrel and lasts for three years. In a comparative trial the number of bleeding and spotting days in the first 180 days was significantly less with the higher dose LNG-IUS.

 

Barrier methods

Throughout history barrier methods, in various forms, have been a mainstay of contraception. These methods have regained their preeminent place as sexual health interventions in recent decades with the rise in sexually transmitted infections. Both male and female condoms offer protection against infections caused by Chlamydia trachomatis and Neisseria gonorrhoea, but only male condoms have been demonstrated to protect against HIV. Unfortunately there is limited evidence to support the notion that diaphragms and caps confer a similar advantage. Barrier methods work by preventing the sperm meeting and fertilising the ovum and offer contraception free from systemic side effects that will not alter the menstrual cycle.

 

Male condoms

Male condoms provide an effective barrier against semen and sexually transmitted bacteria and viruses. They are available in latex and polyurethane in a range of sizes, shapes, flavours and colours. With correct usage condoms are up to 98% effective, although slippage and breakage rates up to 6–7% have been reported. Condoms lubricated with spermicide are no longer recommended because they do not enhance efficacy and because of evidence that the spermicide nonoxinol-9 can cause vaginal epithelial disruption and potentially therefore increase the chance of HIV transmission. In addition to preventing STI transmission, consistent and correct use can lead to more rapid clearance of Human Papillomavirus and resolution of low grade cervical intraepithelial neoplasia. The disadvantages of condoms include that they are intercourse related and may reduce spontaneity and sensitivity, and they have variable, user-dependant efficacy. Latex condoms cannot be used in men or women with latex sensitivity.

 

Female condoms

Female condoms are made of polyurethane and consist of an inner ring that fits into the vagina, and an outer ring that sits on the vulva. With consistent and correct use the failure may be as low as 5%, but typical use results in a 21% failure rate. Female condoms protect against STIs. Breakage rates for female condoms are lower than for male condoms (<1 in 100) but slippage rates (slipping out of the vagina or into the vagina), at over 5% are higher than male condoms.

 

Diaphragms and caps

The diaphragm prevents sperm reaching the cervix by covering the cervix and by sitting snugly between the symphysis pubis and the posterior fornix and creating a seal. The method is manufactured in both latex and silicon and in a variety of forms. Women need to be assessed by a health professional who can advise on the correct size and fitting of these methods. Women are advised to present for review if they have had a change in weight of more than 3 kg or a pregnancy. Cervical caps are made of latex or silicone and fit over the cervix. They are manufactured in different sizes and must be correctly fitted.

 

Spermicide should be used with both caps and diaphragms. They can be inserted any time before intercourse and should be left in situ for 6 hours after sex. Latex diaphragms can remain in situ for a maximum of 30 hours. The silicone cervical cap can remain in situ up to 48 hours. With consistent and correct use, latex diaphragms and cervical caps when used with spermicide are estimated to be between 92% and 96% effective. There is no evidence on the effectiveness of these methods without spermicide, and hence their use is not recommended in women living with or at high risk of HIV/AIDS because of the detrimental effects of spermicide on vaginal mucosa as previously outlined. A history of toxic shock syndrome also precludes use, as does sensitivity to latex.

 

Spermicides

Nonoxinol-9 is the only spermicide available in the UK, and is available as a cream and pessaries. The method is not recommended for use alone as the failure rates are high with 28% of typical users falling pregnant in the first year of use. Recent evidence links it with an almost doubled increased risk of HIV transmission when used repeatedly; its use is still recommended, however, with caps and diaphragms but not with condoms.

 

Future developments: future developments for barrier methods are mainly in the field of spermicidal microbicides that are safe for the vaginal epithelium by lacking a detergent effect. Acid Buffer preparations lead the research priorities. Progestogen ‘laced’ vaginal gels are also under assessment.

 

Sterilisation: male sterilisation involves interruption of the vas deferens. Failures are rare with only one in 700 to one in 1000 pregnancies occurring in the first year. The procedure is usually done under a local anaesthetic through a small incision in the scrotum [Use of a non-scalpel procedure is increasing]. The vas deferens is identified and divided and the two ends are sealed. The procedure is not considered complete until clearance of semen from sperms is confirmed by examining the man's semen during the three months post vasectomy. Apart from local bruising, serious side effects are rare. Some men form antibodies which leave them infertile should they seek a reversal down the track.

 

Female sterilisation is a permanent form of contraception that involves blocking of the fallopian tubes that is more that 99.5% effective. It is most commonly done through a laparoscopic procedure, although in low resources setting a mini laparotomy is often undertaken. The tubes are divided by the use of clips, rings or cutting and tying. The risks of the procedure are the same as for other abdominal procedures and include the risk of damage to bowel, bladder and blood vessels, as well as the risk of infection. A newer alternative is Hysteroscopic sterilisation by tubal cannulation and placement of small flexible intrafallopian implants; a method called Essure®. Once the implants are placed the procedure takes about three months to become effective and confirmation by ultrasound or hysterosalpingogram is required before tubal blockage is confirmed.

   

 

Further reading

 

1        National Collaborating Centre for Women's and Children's Health

          Long-acting reversible contraception: the effective and appropriate use of long-acting reversible contraception

          Commissioned by the National Institute for Health and Clinical Excellence RCOG Press, London (2005)

 

2        Faculty of Sexual and Reproductive Healthcare. UK Medical eligibility criteria for contraceptive use (UKMEC 2005/2006). Retrieved 10/06/2008           from www.ffprhc.org.uk.

 

3        Faculty of Sexual and Reproductive Healthcare

          FSRH guidance (November 2007). Intrauterine contraception

          (2007) Retrieved 15/05/2008 from www.ffprhc.org.uk

 

4        Faculty of Sexual and Reproductive Healthcare

          FSRH guidance (April 2008). Progestogen-only implants

          (2008) Retrieved 15/05/2008 from www.ffprhc.org.uk

 

5        Faculty of Sexual and Reproductive Healthcare

          "FFPRHC guidance (January 2007). Male and female condoms

          (2008) Retrieved 01/06/2008 from www.ffprhc.org.uk

 

6        Faculty of Sexual and Reproductive Healthcare

          FFPRHC guidance (June 2007). Female barrier methods

          (2007) Retrieved 01/06/2008 from www.ffprhc.org.uk

 

7        A.M. Kaunitz, R. Arias, M. K McClung

          Bone density recovery after de