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
Incidence of ovulation in women taking levonorgestrel COCs2
||% ovulation rate||95% confidence interval|
|20 micrograms||8.6||4.0 to 15.6|
|30 micrograms||2.2||0.8 to 4.7|
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
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
Updated May 2013 to reflect delisting from the PBS.
Updated July 2013 to reflect relisting on the PBS.
- Australian Government Department of Health and Ageing. November 2012 PBAC Outcomes – Positive Recommendations. 2012. http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/pbac-outcomes/2012-11/positive-recommendations (accessed 22 February 2013).
- Milsom I, Korver T. Ovulation incidence with oral contraceptives: a literature review. J Fam Plann Reprod Health Care 2008;34:237–46. [PubMed]
- Reid R, Leyland N, Wolfman W, et al. SOGC clinical practice guidelines: oral contraceptives and the risk of venous thromboembolism: an update: no. 252, December 2010. Int J Gynaecol Obstet 2011;112:252–6. [PubMed]
- Rosenberg MJ, Meyers A, Roy V. Efficacy, cycle control, and side effects of low- and lower-dose oral contraceptives: a randomized trial of 20 micrograms and 35 micrograms estrogen preparations. Contraception 1999;60:321–9. [PubMed]
- AFT Pharmaceuticals Pty. Ltd. Femme-Tab ED 20/100 (levonorgestrel/ethinyloestradiol film-coated tablets) Product Information. 3 December 2012.
- Gallo MF, Nanda K, Grimes DA, et al. 20 microg versus >20 microg estrogen combined oral contraceptives for contraception. Cochrane Database Syst Rev 2011:CD003989. [PubMed]
- Rossi S (ed). Australian Medicines Handbook, 2012. Adelaide: Australian Medicines Handbook Pty Ltd, July 2012.
- Manzoli L, De Vito C, Marzuillo C, et al. Oral contraceptives and venous thromboembolism: a systematic review and meta-analysis. Drug Saf 2012;35:191–205. [PubMed]
- Lidegaard O, Nielsen LH, Skovlund CW, et al. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001–9. BMJ 2011;343:d6423. [PubMed]
- van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, et al. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ 2009;339:b2921. [PubMed]
- Lidegaard O, Lokkegaard E, Svendsen AL, et al. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 2009;339:b2890. [PubMed]
- Endocrinology Expert Group. Therapeutic Guidelines: Endocrinology. In: eTG complete 13. Therapeutic Guidelines Limited. http://etg.hcn.com.au (accessed 22 February 2013).