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Norethisterone

Contraceptives, Oral, Synthetic
CATEGORIES

Contraceptives, Oral, Synthetic


ALIASES

Activelle, Activelle®, Cliovelle, Estalis, Estalis Sekvens, Estalis®, Estalis® Sekvens, Eviana, Evorel® Micronor, Femanor®, Femasekvens®, Kliogest®, Mini-Pe®, Noresmea, Noriday, Novofem®, Orthonett® Novum, Primolut®-Nor, Sequidot®, Synfase®, Synfase® 28, Synphase, Triella, Trinovum, Trinovum®, Trinovum® 28, Trisekvens, Trisekvens®


SUBSTANCES

norethisterone, norethisterone acetate


ENVIRONMENTAL CONCERN: HIGH
A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. [PubChem]

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HIGH
In various international studies, reported levels of norethisterone in purified wastewater vary from not detectable to 188 ng/L (the latter appears to be unreasonably high) and in surface water from 1 to 7.5 ng/L.

Impact on fish has been demonstrated in various studies at levels of 1 ng/L. Based on prescription data, expected levels downstream Swedish watewater treatment plants could be around 2.6 ng/L.

Comparisons with other substances
A substance's ability to activate the androgen receptor in fish is believed to also contribute to increased risk of environmental impact. Norethisterone, levonogestrel and etonogestrel activate the androgen receptor in fish at very low concentrations, whereas, for example, drospirenone is a much less potent androgen receptor agonist. The risk is likely to be lower for norethisterone than for levonorgestrel seen from the risk of affecting fish via the androgen receptor.

Based on binding to the androgen receptor, binding to SHBG (Sex Hormone Binding Globulin) and studies on fish, norethisterone and levonogestrel are a higher environmental risk than medroxyprogesterone. Binding to SHBG is believed to contribute to increased bioconcentration (and thus potency) in fish.

REFERENCES

  1. Fent K. Progestins as endocrine disrupters in aquatic ecosystems: Concentrations, effects and risk assessment. Environ Int. 2015;84:115-30.
  2. Ellestad LE, Cardon M, Chambers IG, Farmer JL, Hartig P, Stevens K et al. Environmental gestagens activate fathead minnow (Pimephales promelas) nuclear progesterone and androgen receptors in vitro. Environ Sci Technol. 2014;48:8179-87.
  3. Bain PA, Kumar A, Ogino Y, Iguchi T. Nortestosterone-derived synthetic progestogens do not activate the progestogen receptor of Murray-Darling rainbowfish (Melanotaenia fluviatilis) but are potent agonists of androgen receptors alpha and beta. Aquat Toxicol. 2015;163:97-101.
  4. Paulos P, Runnalls TJ, Nallani G, La Point T, Scott AP, Sumpter JP et al. Reproductive responses in fathead minnow and Japanese medaka following exposure to a synthetic progestin, Norethindrone. Aquat Toxicol. 2010;99:256-62.