Based on the ability to bind to the androgen receptor, bind to SHBG (Sex Hormone Binding Globulin) and studies on fish, drospirenone is a lower environmental risk than levonorgestrel, etongestrel and norethisterone. Binding to SHBG is believed to contribute to increased bioconcentration (and thus potency) in fish. Drosperionone binds less to SHBG than, for example, levonorgestrel, norethisterone and etonogestrel.
A substance's ability to activate the androgen receptor in fish is believed to also contribute to increased risk of environmental impact. Levonogestrel, norethisterone and etonogestrel activate all the androgen receptor in fish at very low concentrations, whereas, for example, drosperionone is a much less potent androgen receptor agonist.
In a study by Zeilinger at al where levonorgestrel was compared with drospirenone, levonogestrel was shown to inhibit egg production in fish at 0.8 ng/L while requiring 6 500 ng/L of drosperionone to effect.
Studies show that levonogestrel and etonogestrel are the most environmental hazard of the progestogen component. Drosperinone is significantly less environment-affecting based on ecotoxicological studies, partly due to its low affinity for the androgen receptor and SHBG. For nomegestrel, both exposure data and effect data are missing in fish. However, nomegestrel binds poorly to both the androgen receptor and SHBG, which makes a low risk profile.
Of the oestrogens ethinyl estradiol causes high environmental risk while estradiol is less dangerous. At the same time, the amount of estradiol in pharmaceuticals is often higher, but estradiol is degraded more easily than ethinyl estradiol in the body, in the wastewater treatment plant and in the environment, and is less potent in fish. An oral dose of 1.5 mg estradiol gives an excreeted dose in the urine of only 100 micrograms. Therefore, the risk is probably lower with estradiol despite the higher dosage.
In total, levonorgestrel + ethinyl estradiol and ethonogestrel + ethinyl estradiol are considered to be of the highest environmental risk, drosperinone + ethinyl estradiol of lower risk (based on the gestagen component) and nomegestrol and estradiol of the lowest risk (based on the primary gestagen component but also the estrogen component).
Author: Department of Strategic Careers, Stockholm County Council.