Combined hormonal contraceptives contain an oestrogen and progestogen, and their main mode of action is inhibition of hypothalamic and pituitary function leading to anovulation. They are available as a combined oral contraceptive pill (COC) and the vaginal ring. COCs and vaginal rings work in the same way and are treated similarly in terms of contraindications, complications, side effects and drug interactions.
Combined oral contraception (COC)
COCs in Australia contain ethinyloestradiol (EE), oestradiol valerate (EV), oestradiol (E2) or mestranol and one of a range of progestogens. Efficacy is 99.7% with perfect use, 91% with typical use.
EE is the most commonly used oestrogen. The active oestrogen in the newer E2 and EV pills is structurally identical to the E2 produced by the ovaries. They have a theoretical but unproven benefit in terms of venous thromboembolism (VTE) risk, and it will be some years before there is any evidence of VTE rates in women using these pill preparations. Both E2 and EV are associated with a moderately high rate of amenorrhoea during the hormone-free break.
It is recommended to use a dose of 35 mcg EE or less. There is some association between increasing EE dose and risk of venous thromboembolism (VTE). Formulations containing 50 mcg EE are no longer recommended because there is no known additional benefit from their use and they are associated with an increased risk of VTE. Women starting on a 20 mcg EE pill are likely to have fewer hormonally related side effects such as headaches or mood swings, but have a higher chance of discontinuation due to breakthrough bleeding.
Which progestogen to use7
The early progestogens include levonorgestrel and norethisterone. Newer progestogens have been developed over recent decades to reduce androgenic side effects and to minimise the effect EE has on lipids. Nomogestrol acetate, gestodene, desogestrel and etonogestrel are less androgenic, while cyproterone acetate, drospirenone and dienogest are anti-androgenic. Drospirenone is an analogue of spironolactone and has a mild diuretic effect. There is insufficient data to initially prescribe newer progestogens in preference to older versions.
Various COC preparations available in Australia are listed in TABLE 99.2.
Table 99.2Combined oral contraceptive pill formulations available in Australia7 |Favorite Table|Download (.pdf) Table 99.2 Combined oral contraceptive pill formulations available in Australia7
|Oestrogen ||Dose (mcg) ||Progestogen ||Dose (mcg) ||Trade name |
|Monophasic || || || || |
|Ethinyloestradiol ||20 ||Drospirenone ||3000 ||YAZ, YAZ Flex |
|Ethinyloestradiol ||20 ||Levonorgestrel ||100 ||Femme-Tab ED 20/100, Lenest 20, Loette, Microgynon 20, Microlevlen, Micronelle 20 |
|Ethinyloestradiol ||30 ||Levonorgestrel ||150 ||Eleanor 150/30, Evelyn 150/30, Femme-Tab 30/150, Lenest 30, Levlen, Microgynon 30, Micronelle 30, Monofeme, Nordette, |
|Ethinyloestradiol ||10, 30 ||Levonorgestrel ||150 ||Seasonique* |
|Ethinyloestradiol ||30 ||Dienogest ||2000 ||Valette |
|Ethinyloestradiol ||30 ||Gestodene ||75 ||Minulet |
|Ethinyloestradiol ||30 ||Desogestrel ||150 ||Marvelon |
|Ethinyloestradiol ||35 ||Cyproterone acetate ||2000 ||Brenda-35, Carolyn-35, Chelsea-35, Diane-35, Estelle-35, Juliet-35, Laila-35, Jene-35 |
|Ethinyloestradiol ||35 ||Norethisterone ||500 ||Brevinor, Norimin |
|Ethinyloestradiol ||35 ||Norethisterone ||1000 ||Brevinor-1, Norimin-1 |
|Ethinyloestradiol ||30 ||Drospirenone ||3000 ||Yasmin, Petibelle |
|Ethinyloestradiol ||50 ||Levonorgestrel ||125 ||Microgynon 50 |
|Mestranol ||50 ||Norethisterone ||1000 ||Norinyl-1 |
|Oestradiol ||1500 ||Nomegestrol acetate ||2500 ||Zoely |
|Triphasic || || || || |
|Ethinyloestradiol ||30, 40 ||Levonorgestrel ||50, 75, 125 ||Logynon, Trifeme, Triphasil, Triquilar |
|Ethinyloestradiol ||35 ||Norethisterone ||500, 1000 ||Improvil |
|Quadraphasic oestradiol valerate ||1000–3000 ||Dienogest ||2000, 3000 ||Qlaira |
Starting the pill: which COC to use7
The past menstrual and medical history of the woman should be documented and contraindications excluded.
A suitable first choice is a monophasic pill containing 30 mcg or 35 mcg ethinyloestradiol (EE) with levonorgestrel or norethisterone (e.g. Nordette, Microgynon 30, Monofeme, Levlen ED, Brevinor).
Education and counselling are very important for the woman starting the pill. Suitable patient education should be given. Pill swatches produced by manufacturers are a useful aid. Cover starts immediately if a hormone (active) pill is commenced on day 1–5 of the menstrual cycle (except the quadriphasic pill Qlaira—refer to product information).
Note: A ‘quick-start’ technique, described by Westhoff, can be used to start the COC on the day of the consultation. If commenced at any time other than day 1–5 of the menstrual cycle, abstinence/condoms are required for the first 7 days after the start.9
Specific patient groups4,7
Adolescents. There is no lower age limit if the young woman has started menstruating.
Acne and hirsuitism. The oestrogen in any CHC may improve acne and hirsuitism via increased sex hormone binding globulin (SHBG) levels and reduction of free testosterone. COCs containing an anti-androgenic progestogen have a theoretical advantage for women who request management of androgenic symptoms. Any beneficial effect may take up to 6 months.
Women over 35 years. CHC use is safe for healthy non-smoking women until 50 years (MEC 2 for women over 40). CHC is not recommended if a woman is over 35 years and has multiple cardiovascular risk factors, including obesity, smoking, diabetes and hypertension (MEC 3/4).
Women taking liver enzyme-inducing drugs. Alternative contraception is strongly advised. The only hormonal contraceptives not affected by liver enzyme-inducing drugs are DMPA and IUDs. Current evidence suggests that most antibiotics do not interact with combined hormonal contraceptives. The only exceptions are liver enzyme-inducing rifabutin and rifampicin. Other liver enzyme-inducing drugs include many of the older anti-epileptics (e.g. phenytoin, carbamazapine), St John’s wort and protease inhibitors. For women who still request the use of COC, an extended or tricycling regime of a higher dose pill (e.g. containing at least 50 mcg EE) may be effective. Further guidance on drug interactions is provided by the UK Faculty of Sexual Health & Reproductive Healthcare at <https://www.fsrh.org/standards-and-guidance/documents/ceu-clinical-guidance-drug-interactions-with-hormonal/>.
Contraindications to CHC usage are shown in TABLE 99.3.
Table 99.3Contraindications for the use of COC7 |Favorite Table|Download (.pdf) Table 99.3 Contraindications for the use of COC7
Absolute (MEC 4)
First 2 weeks postpartum, 6 weeks if breastfeeding
≥35 years and smoking ≥15 cigarettes/day
History of thomboembolic disease, including known thrombophilia
Ischaemic heart disease
Complicated valvular heart disease
Migraine with aura
Malignancy of the breast or genital tract
Severely impaired liver function
Major surgery with prolonged immobilisation
Positive antiphospholipid antibodies
Relative (MEC 3)
BMI >35 kg/m2
Multiple risk factors for cardiovascular disease
First-degree relative who had a VTE <45 years
Undiagnosed abnormal vaginal bleeding
Past history of migraine with aura, none for 5 years
Known gene mutation associated with breast cancer
Gall bladder disease
Non-contraceptive advantages of CHCs7
A number of significant beneficial effects arising from the use of COCs have now been documented:
Reduction in most menstrual cycle disorders, including dysmenorrhoea, symptoms of endometriosis and heavy menstrual bleeding
Reduction in the incidence of functional ovarian cysts and benign ovarian tumours
Reduced incidence of ovarian and endometrial cancer
Can reduce acne
Can be useful in managing symptoms of polycystic ovarian syndrome
Can assist with perimenopausal symptoms
Can be used to manage premenstrual syndrome (PMS) and its more severe form (PMDD) in some women
Can reduce the risk of bowel cancer
Serious side effects of CHCs
The most serious side effects to be considered are the effects of COCs on the circulatory system and the incidence of cancer.
The following circulatory disorders have been linked with pill usage.
Venous deep vein thrombosis, pulmonary embolism, rarely: mesenteric, hepatic and kidney thrombosis
Arterial myocardial infarction, thrombotic stroke, haemorrhagic stroke, rarely: retinal and mesenteric thrombosis
The risk of circulatory disease has not been related to duration of use and there is no increased risk in perpetual users.
The oestrogen content of the pill is considered to be the aetiological factor and the problem is increased in women taking high oestrogen-content COCs, but now that the oestrogen content of each pill has been reduced to 35 mcg EE or less, these risks of morbidity and mortality have been reduced.
The progestogen effect on lipid metabolism is not considered significant in the aetiology of circulatory disease. Circulatory diseases have now been recognised as occurring predominantly in certain high-risk groups—the ‘at-risk female’, particularly the smoker over 35 years of age.
Other at-risk groups include those with thrombophilia, hyperlipidaemia, diabetes, hyper-stension and a family history of cardiovascular disease or immobilisation.
Venous thromboembolism (VTE) risk is increased 2–3 times in users of CHCs compared to non-users, with an increase of between one and three extra cases per 10 000 women in a year. The risk is highest in the first 4 months of use and gradually decreases with duration of use. Studies have shown that COCs containing cyproterone, desogestrel, drospirenone or gestodene have a higher risk of VTE than COCs containing levonorgestrel or other progestogens. However, the absolute risk of VTE in users of any CHC is very low and much lower than the risk associated with pregnancy and the postpartum period. Women who are eligible for an oestrogen-containing method of contraception can safely use any pill on the market with 35 mcg EE or less.
Women who have used CHC have an overall lower risk of cancer compared to women who have not.
The relatively minor side effects listed in TABLE 99.4 may discourage women from persisting with oral contraception in the absence of appropriate explanation and reassurance. Management of these side effects is listed in the same table. It is useful in practice to have this list available as a ready reference for manipulating the COC if necessary. A common nuisance side effect is breakthrough bleeding in the first 2 months.
Table 99.4Management of common side effects of COC4,8 |Favorite Table|Download (.pdf) Table 99.4 Management of common side effects of COC4,8
Change to a pill containing an anti-androgenic (drospirenone, dienogest or cyproterone acetate) or less androgenic (gestodene, desogestrel or etonogestrel) progestogen
Exclude underlying causes (e.g. chlamydia, pregnancy, missed pills, malabsorption, diarrhoea or vomiting, concurrent medications)
Increase oestrogen if taking a pill with 20 mcg EE to a maximum of 35 mcg EE
Change progestogen if already taking a pill with 30 or 35 mcg EE
Consider vaginal ring
Decrease oestrogen and/or progestogen dose
Consider change of formulation
Consider using pill containing drospirenone
Change to non-oestrogen-containing contraception
Avoid direct sun (use blockout)
Absence of withdrawal bleed is not harmful and occurs in 6% of cycles with EE and 20–30% of EV or E2 pills
Switch to a pill with a more predictable bleeding pattern
Lowered libido, mood changes
No evidence of a difference between COCs
Trial a change of formulation
Any new headache or marked changes in headache should be evaluated
Reduce oestrogen dose
If occurs in pill-free week, consider a pill with a reduced number of placebo pills, an extended regimen, running packs together or giving an oestrogen supplement in the pill-free weeks (100 mcg oestrogen patch or 2 mg or 4 mg oestradiol)
Take the pills at night
Evidence does not support an increase in weight related to COCs
Drospirenone pills are associated with a small, unsustained average weight loss of 0.5 kg in the first year and may be useful for some women
Important advice for the patient
Diarrhoea and vomiting may reduce the effectiveness of the pill. If a woman vomits within 2 hours of taking an active pill, she should take an additional active pill.
Withdrawal bleeds can be skipped for a woman’s convenience, by going straight from the last active pill in the cycle to the first active pill in the next cycle. Running packs of multiphasic pills together can result in unpredictable bleeding as a result of the fluctuating dose of hormones.10 A Cochrane Review did not demonstrate any additional safety concerns for women taking CHCs continuously without placebo breaks for up to 12 months.11 An extended-regimen pill with 84 active pills plus 7 inactive pills is now available.
A missed pill is defined as one that is taken more than 24 hours late (>48 hours since last pill was taken). The advice is to take the missed pill as soon as possible, even if it means taking two pills in one day. Any previously missed pills should be discarded and the usual pill-taking schedule resumed. Condoms or abstinence should be used for 7 days (the ‘Seven-day rule’). This advice does not apply to the quadriphasic pill Qlaira and the product information should be consulted. Refer to FIGURE 99.1.
Missed combined oral contraceptive pill7
Source: Adapted from Contraception: An Australian Clinical Practice Handbook and reproduced with permission © 2012: Family Planning NSW, Family Planning Victoria and Family Planning Queensland
Note: These instructions do not apply to the quadriphasic pill Qlaira. See product information for advice
If the pill is missed with <7 pills left before the next placebo break, skip placebos and continue active pills.
If <7 active pills were taken before the missed pill, consider emergency contraception if unprotected sex took place in the past 5 days. If ulipristal acetate emergency contraception is used, the woman needs to wait 5 days before restarting the pill.