• CHC is available in a range of delivery systems.
• The main action of CHC is to suppress ovulation.
• The length of the hormone-fnt free interval is crucial to efficacy.
• The COC reduces the risk of ovarian and endometrial cancer by 50%.
• CHC is contraindicated in women with arterial and venous disease.
• Third generation progestogens may increase the risk of venous thromboembolism.
• Current users of the COC have an increased risk of breast cancer (RR 1.24).
• The perfect-use failure rate for the COC is 0.1/HWY, the typical-use failure rate is 8 per 100.
Progestogen-only contraception (POC) avoids the side effects of oestrogen. It is available in a wide variety of delivery systems including oral, injectables, implants and intrauterine systems (IUS). Implants and the IUS last for 3 and 5 years respectively. POC is much less commonly used than combined hormonal contraception and there are fewer data, particularly on the risks associated with long-term use.
A number of types of progeotogen only pills (POP) (often called mini-pills) are available in the UK. The older formulations of POP contain a very low dose of second generation progestogen which inconsistently inhibits ovulation. The newest POP (Cerazette®) contains the third generation progestogen desogestrel at a dose sufficient to inhibit ovulation in almost every cycle .
Long-acting injections of norethisterone-enanthate (NET-En) and depot medroxyprogesterone acetate (DMPA, Depo-Provera® )are both highly effective. Depo-Provera® is given by deep intramuscular injection, 150 mg every 12 weeks. NET-En is administered every 8 weeks (at least initially). It is not licensed for long-term use in the UK and has to be warmed before it can be drawn up into the syringe. A new micronized preparation of DMPA is likely to become available in 2007. Since it is a lower dose (104 mg DMPA), it is administered subcutaneously and can be self-administered.
The first contraceptive implant to become available was Norplant® but this has not been marketed in the UK for over 5 years. Implanon® is a single rod, containing 68 mg 3-keto-desogestrel (a metabolite of desogestrel) providing contraception for 3 years. The initial release rate of 6070 ^g/day falls gradually to around 25-30 ^g/day at the end of 3 years. Implanon® is preloaded into a sterile disposable inserter and is inserted subdermally on the inner aspect of the non-dominant arm above the elbow. It is inserted and removed using local anaesthetic.
The IUS (Mirena®) has a T-shaped plastic frame with a reservoir on the vertical stem containing 52 mg lev-onorgestrel (LNG) releasing 20 p,g LNG/day for at least 5 years . The IUS is inserted and removed using the same procedures as for copper IUD insertion (see Intrauterspine device, p.310) although the stem of the IUS is bigger and difficulties with insertion may be experienced particularly in women with a small uterus (such as following prolonged use of DMPA). Mirena® is licensed for the management of menorrhagia and is increasingly being used to deliver the progestogen component of hormone replacement therapy.
All methods of POC have a number of mechanisms of action. Depo-Provera® Implanon® and Cerazette® inhibit ovulation. Lower-dose methods (older pill formulations and Norplant®) inhibit ovulation only inconsistently. All POC, regardless of the route of administration, affect cervical mucus reducing sperm penetrability and transport, and all (but particularly the LNG-IUS which has little effect on ovarian activity but causes marked endometrial atrophy) have an effect on the endometrium compromising implantation if ovulation and fertilization occur.
Failure rates for the progestogen-only methods are shown in Table 32.2. The older POPs (containing low doses of second generation gestogens) have higher failure rates than the combined pill. The reduced efficacy is due partly to the fact that many women continue to ovulate, and partly because the POP has a shorter half-life in the circulation so that missing even just one pill may interfere with contraceptive efficacy. The desogestrel-containing POP is believed to have failure rates equivalent to those of the COCP as ovulation is consistently inhibited. The LNG-IUS lasts for 5 years but there are data demonstrating continued effectiveness for up to 7 years. Although not licensed beyond 5 years, extended use for up to 7 years may be discussed with older women who have amenorrhoea since the risks of perforation, expulsion and infection are all highest during the first few weeks after insertion (and re-insertion). Implanon® is effective (and licensed) for 3 years; there are no data on use beyond this time.
POC is commonly prescribed for women in whom estrogen is absolutely or relatively contraindicated, for example women with cardiovascular disease, migraine, diabetes or mild hypertension. In the UK, breastfeeding women are advised to use POC since estrogen impairs milk production. Contraindications (MEC conditions 3) which apply to all progestogen-only methods are shown in Table 32.6. In many countries regulatory authorities still insist on a long list of contraindications which apply to the combined pill.
Bleeding disturbances. The commonest side effect and cause for discontinuation of POC is an unacceptable bleeding pattern. This includes amenorrhoea if women have
Table 32.6 WHO Medical Eligibility Criteria category 3 conditions (relative contraindications) for use of progestogen-only methods
Breastfeeding at less than 6 weeks post-partum (all methods) Current deep-vein thrombosis (DVT) pulmonary embolism (all methods)
Previous breast cancer with no evidence of disease for 5 years
(all methods) Active viral hepatitis (all methods) Benign hepatic adenoma (all methods) Severe decompensated cirrhosis (all methods) Benign hepatic adenoma (all methods) Malignant hepatoma (all methods) Current or history of ischaemic heart disease or stroke (injections, starting or continuing; continuation of progestogen-only pills or implants) Migraine with aura (continuation of all progestogen-only methods)
Unexplained vaginal bleeding (injections and implants) Use of certain drugs: rifampicin (rifampin), griseofulvin, phenytoin, carbamazine, barbiturates, primidone (progestogen-only pills; implants) Multiple risk factors for arterial cardiovascular disease
(injections only) Systolic blood pressure >160 or diastolic >100 mmHg
(injections only) Vascular disease (injections only)
Diabetes with nephropathy, other vascular disease or disease duration of >20 years (injections only)
not been forewarned that it may happen or find that they do not like it. Low-dose progestogen-only methods (pills and implants) are associated with a high incidence of irregular vaginal bleeding. This is due partly to their effect on ovarian function. In the normal cycle ovulation determines regular menstruation. Inconsistent ovulation and fluctuating endogenous oestrogen production from irregular follicle growth provide a recipe for irregular bleeding. However, there is also evidence to suggest that progestogen-only methods directly affect the vas-culature of the endometrium increasing the chance of bleeding. Bleeding patterns differ according to the dose of progestogen and the route of administration.
Oral: Around 50% of women using the classical POPs continue to ovulate and therefore they menstruate regularly. Ten percent will experience complete suppression of fol-licular development and will have amenorrhoea. The rest will have inconsistent ovulation (often with a short luteal phase), or follicular development only and will bleed irregularly. Up to 20% of women using the desogestrel-containing POP will experience amenorrhoea while the rest are likely to have irregular bleeding since ovulation is inhibited.
Injectable: The high dose of progestogen in Depo-Provera® inhibits ovulation and by the end of 1 year of use, 70% of women have either infrequent scanty vaginal bleeding or amenorrhoea. Heavy prolonged bleeding may be a problem in around 2% of women. The cause is unknown and often leads to discontinuation of the method.
Subdermal: Menstrual disturbance is the norm; up to 20% of users experience amenorrhoea and almost all the rest will have irregular, unpredictable bleeding. Heavy bleeding is uncommon and measured blood loss is much less than that experienced during a normal menstrual cycle. Many women do not like the unpredictability of the bleeding; even very light bleeding is unacceptable if it lasts for days on end. Patterns do not become more regular with time as the dose of progestogen remains sufficient to inhibit ovulation for the full 3 years (unlike Norplant®).
Intrauterine: While women using the LNG-IUS continue to develop ovarian follicles and ovulate, most have amen-orrhoea or only very light occasional bleeding because the presence of high concentrations of LNG in the uterine cavity induces endometrial atrophy. However, it takes time for atrophy to occur and most women experience frequent and often persistent spotting for 3 to 6 months after IUS insertion. LNG-IUS users can be reassured that bleeding patterns will improve with time.
Long-term use of both implants and the IUS (for which upfront costs are high) is essential for cost-effectiveness, and careful counselling about menstrual irregularities is vital to avoid premature discontinuation.
Irregular bleeding in association with both Depo-Provera® and Implanon® can be temporarily alleviated by the administration of oestrogens (simply by adding the combined pill) but this is only suitable as a short-term solution. Aspirin and vitamin E have both been shown to be ineffective for this purpose.
Persistent follicles/follicular cysts. The effect of the low-dose POCs on ovarian activity also results in a relatively high incidence of functional ovarian cysts or, more accurately, persistent follicles. It has been estimated that one in five women using the POP will have a 'cyst' demonstrable by ultrasound, and they are common among IUS users. Usually asymptomatic, persistent follicles can cause abdominal pain or dyspareunia. Most will disappear with menstruation and so treatment should be conservative.
Other 'hormonal' side effects. These include headache, nausea, bloating, breast tenderness and weight and mood change - all common in women not using hormonal contraception. They often settle with time but if not may be alleviated by changing to a different progestogen. Depo-Provera®, however, is associated with weight gain and women may gain as much as 16 kg after 2 years of use. Oily skinand acne can be a problem particularly with the more androgenic progestogens - LNG and NET. Some studies have suggested an increased risk of ectopic pregnancy. This has not been confirmed although methods of contraception which do not prevent ovulation are more likely to be associated with ectopic pregnancies than those which prevent ovulation.
Delay in the resumption of fertility. Fertility returns rapidly after stopping low-dose POC. It may take up to 1 year, however, for normal fertility to return following cessation of Depo-Provera®. Women often complain of' feeling premenstrual' despite continuing amenorrhoea. They can be assured that there is no permanent impairment of fertility but this delay makes Depo-Provera® an inappropriate method for women wishing short-term contraception.
Sexually transmitted infection. Anumber of studies undertaken in the late 1980s and early 1990s suggested that the use of hormonal contraception may be associated with an increased risk of chlamydia and gonorrhoea. Hormonal contraceptive use is common and so are sexually transmitted infections (STI). Most of the studies have been cross-sectional in design, have used insensitive tests for chlamydia infection and most have failed to control for potential confounding factors such as sexual behaviour. A study involving over 800 women in the USA  suggested that the use of Depo-Provera® but not of oral contraception was significantly associated with an increased risk of chlamydia and gonorrhoea after adjusting for other risk factors (HR for Depo-Provera 3.6; 1.6-8.5: HR for the OC 1.5; 0.6-3.5). It has been suggested that since Depo-Provera® causes hypo-oestrogenism, thinning of the vaginal epithelium may increase the risk of infection. Further studies need to be done to determine whether the link between and STIs is causal or merely related to sexual behaviour.
Because progestogen-only methods are much less widely used than the combined pill, data on long-term risks are sparse. Long-term (5 years) follow-up of over 16,000 women using Norplant reported no significant excess of any health problems including cardiovascular disease and neoplasia.
Cardiovascular disease. There is no evidence for an increase in the risk of stroke, myocardial infarction or VTE in association with POC. Any association between VTE
and progestogen used for the treatment of gynaecological conditions such as anovulatory dysfunctional uterine bleeding may be due to prescriber bias since the COC -often the method of choice - is contraindicated in women with known risk factors for VTE.
Malignant disease. Depo-Provera® confers a high degree of protection against endometrial carcinoma but although it should theoretically also protect against ovarian cancer thereareas yet no data to support this. Thereareno data on risks of cervical cancer although it is thought that all hormonal contraception may play a promoting role. Recent concern that the progestogen component of HRT may contribute to the increased risk of breast cancer has raised concerns about POC. The large meta-analysis on breast cancer and hormonal contraception included a small percentage of POP (0.8%) and injectable (1.5%) users . Use of the POP within the last 5 years was associated with a very small but statistically significant increase in relative risk of breast cancer (1.17%). The same increase among injectable-users was not, however, significant. For both methods the relative risk had returned to normal 5 years after stopping.
Bone mineral density. Complete inhibition of ovulation by Depo-Provera® causes hypo-oestrogenism and amenor-rhoea. Hypo-oestrogenism is associated with a reduction in bone mineral density (BMD). It has been recognized for some time that current use of Depo-Provera® is associated with a loss of BMD when compared with non-users. This may be more of an issue with very young women who have not yet achieved peak bone mass. Results of cross-sectional studies are limited and inconsistent; however, two prospective studies have reported statistically significant decreases in BMD over two years among Depo-Provera® users aged between 12 and 21 compared with users of non-hormonal contraception [23,24]. While current DMPA users in older age groups do seem to have a decreased BMD compared with non-users, limited evidence suggest that women who stop using DMPA before the menopause can regain lost bone mass. There is, however, some concern about women over 40, who may not recover normal BMD after stopping Depo-Provera® before they inevitably lose more bone when they reach the menopause. While the data on BMD across all age groups is consistent, only one study has examined fracture risk and this was among women of a mean age of 21. There was no significant association between use of Depo-Provera® and the risk of stress fractures after adjusting for baseline BMD. In the UK the Committe on Safety of Medicines (CSM) has very recently advised that • In adolescents, Depo-Provera® may be used as firstline contraception but only after other methods have been discussed with the patient and considered to be unsuitable or unacceptable.
• In women of all ages, careful re-evaluation of the risks and benefits of treatment should be carried out in those who wish to continue use for more than 2 years.
• In women with significant lifestyle and or medical risk factors for osteoporosis, other methods of contraception should be considered.
The CSM does not advise how women who wish to continue Depo-Provera® should be evaluated after 2 years of use. However, the Faculty of Family Planning and Reproductive Healthcare in the UK cautions against using BMD scans which are unlikely to help in the decision-making process.
There are no sound data which demonstrate an effect of low-dose progestogen-only methods on BMD. Whether women who experience amenorrhoea while using Implanon® or the POP are at any risk is unknown.
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Once your pregnancy is over and done with, your baby is happily in your arms, and youre headed back home from the hospital, youll begin to realize that things have only just begun. Over the next few days, weeks, and months, youre going to increasingly notice that your entire life has changed in more ways than you could ever imagine.