Dose and type of estrogen in combined oral contraceptives

Formulations of COCs available in Australia contain estrogen (estetrol, estradiol [or its prodrug estradiol valerate], ethinylestradiol or mestranol); see Formulations of combined hormonal contraception available in Australia. COCs containing high-dose estrogen (50 micrograms of ethinylestradiol or mestranol) are not recommended for contraception in any situation because they pose an unacceptable risk of venous thromboembolism (VTE); their role is limited to short-term use for acute severe heavy uterine bleeding.

Note: Do not use COCs containing 50 micrograms of ethinylestradiol or mestranol for contraception because they pose an unacceptable VTE risk.

The first-line choice of COC is a monophasic formulation containing ethinylestradiol (20 or 30 micrograms) and levonorgestrel. These COCs have similar discontinuation rates to other combined hormonal contraception, and are generally inexpensive (they are available on the Pharmaceutical Benefits Scheme [PBS]). Although COCs containing 20 micrograms of ethinylestradiol are more likely to cause breakthrough bleeding than those containing 30 or 35 micrograms of ethinylestradiol, they appear to have a slightly decreased risk of VTE and cardiovascular disease, compared to COCs containing a higher dose of ethinylestradiol.

Unlike ethinylestradiol, estradiol and estradiol valerate are identical to (or metabolised to) estrogen produced by the ovaries. COCs containing these 2 forms of estrogen have a reduced effect on laboratory markers for VTE and cardiovascular disease compared to those containing ethinylestradiol; however, cohort studies have not demonstrated a significantly reduced risk of VTE or cardiovascular disease. Amenorrhoea in the hormone-free interval occurs in 20% of users of a COC containing estradiol valerate and 30% of users of a COC containing estradiol.

Estetrol is a synthetic version of estrogen naturally produced in fetal liver. It is combined with drospirenone in a COC. Like estradiol and estradiol valerate, estetrol has less effect on laboratory markers for VTE and cardiovascular disease than ethinylestradiol; however, data are awaited on whether the risk of these conditions is reduced. Estetrol has much lower affinity for estrogen receptors in breast tissue than ethinylestradiol and estradiol; it is yet to be seen if the effect on breast cancer risk is less with estetrol than other estrogens. Amenorrhoea in the hormone-free interval occurs in 6 to 8% of users of the COC containing estetrol and drospirenone.