This article has been updated since its original release. [Details]

The low-oestrogen-dose combined oral contraceptive (COC) levonorgestrel with ethinyloestradiol (Femme-Tab ED 20/100) was listed on the Pharmaceutical Benefits Scheme on 1 July 2013.1


Efficacy similar to that of standard-dose formulations

In a recent meta-analysis, levels of ovulation in women taking low-oestrogen (20 microgram) formulations of levonorgestrel COCs were shown to be similar to those in women taking standard-dose (30 microgram) formulations (Table 1).2

Table 1
Incidence of ovulation in women taking levonorgestrel COCs2

Oestrogen dose
% ovulation rate 95% confidence interval
20 micrograms 8.6 4.0 to 15.6
30 micrograms 2.2 0.8 to 4.7

Therapeutic considerations

Low-dose ethinyloestradiol preparations have been shown to elicit fewer of the oestrogen-related side effects such as bloating, breast tenderness and nausea compared with standard-ethinyloestradiol-dose (30–35 microgram) formulations,3,4 but these side effects have still been commonly reported in clinical studies and from postmarketing data of low-oestrogen formulations of levonorgestrel COCs.5 Headache is reported to be a very common side effect associated with use of low-oestrogen formulations of levonorgestrel COCs.5 Some women who are particularly sensitive to oestrogen levels may therefore find the lower ethinyloestradiol dose beneficial.

Break-through bleeding is also a common side effect associated with low-ethinyloestradiol-dose COC formulations such as Femme-Tab ED 20/100.5 Such formulations are associated with an increased risk of bleeding disturbances (amenorrhoea or infrequent bleeding, break-through bleeding or spotting, or irregular, prolonged frequent bleeding) compared with higher-ethinyloestradiol-dose COC formulations.6 While this bleeding is not a threat to a woman's health it can reduce acceptance and adherence to the contraceptive.6


Safety issues

Venous thromboembolism (VTE) is a rare side affect associated with use of all COCs. The risk is dependent on the dose of oestrogen, the progestogen used and the presence of other risk factors.7 Using a COC with an oestrogen dose of <50 micrograms reduces the risk of adverse events, including VTE, compared with formulations containing ≥ 50 micrograms of oestrogen.8-10

Reducing the oestrogen dose of COCs from 30 micrograms or 30–40 micrograms to 20 micrograms reduced the risk of VTE in three recent studies.9-11 In the only study to consider levonorgestrel / low-oestrogen-dose (20 microgram) COCs, risk of VTE was similar to that with levonorgestrel / standard-dose oestrogen (30 microgram) COCs.10 The authors suggested that the study was underpowered to determine a difference in VTE risk between these doses.10 The risk of VTE with levonorgestrel / low-oestrogen-dose COCs such as Femme-Tab ED 20/100 may therefore be lower than with levonorgestrel / high-oestrogen-dose (≥ 50 microgram) COC formulations and similar to that with standard doses (30 microgram).8,10

The risk of cardiovascular complications from COCs is well established. Take a thorough medical history before prescribing any COC to identify contraindications.12 Do not prescribe COCs for women with cardiovascular risk factors, including prior VTE.5,12 When choosing a COC, select one that has the lowest effective dose of oestrogen and progestin, is well tolerated and provides acceptable cycle control with the least known effect on carbohydrate or lipid metabolism and haemostatic parameters.12

As reducing the oestrogen dose of COCs can reduce risk of VTE,8-11 levonorgestrel COCs with standard oestrogen dose (30–35 micrograms) or low oestrogen dose (20 micrograms) may be suitable for women requiring contraception but who have other risk factors for VTE but not contraindications. Refer women with a family history of VTE to a specialist.5


Revision history

Updated May 2013 to reflect delisting from the PBS.
Updated July 2013 to reflect relisting on the PBS.



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