{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:03:16Z","timestamp":1791104596413,"version":"4.1.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T00:00:00Z","timestamp":1259625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2010,1,6]],"date-time":"2010-01-06T00:00:00Z","timestamp":1262736000000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["setac.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although it is well known that estrogenic steroidal hormones are able to affect the sexual development and reproduction of fish at low concentrations, no data on environmental effects of the class of progestogenic hormones are available yet. Synthetic gestagens (progestins) are a component in oral contraceptives. Upon their use, a fraction of the progestins will be excreted via urine into the aquatic environment. On the basis of their pharmacological action in mammals, it is supposed that fish reproduction is the most sensitive endpoint for the progestin treatment. In order to test this assumption, the effects of two progestins currently marketed in contraceptive formulations, levonorgestrel (LNG) and drospirenone (DRSP), were investigated in adult fathead minnows (Pimephales promelas) following an Organization for Economic Cooperation and Development 21-d fish reproduction screening assay draft protocol with additional end points. Levonorgestrel was tested at measured concentrations of 0.8, 3.3, and 29.6 ng\/L, and DRSP at concentrations of 0.66, 6.5, and 70 \u03bcL. Both tested progestins caused an inhibition of reproduction. For LNG, this occurred at concentrations of 2:0.8 ng\/L, no no-observed-effect concentration (NOEC) could be defined. Higher concentrations resulted in masculinization of females with de novo synthesis of nuptial tubercles. Drospirenone treatment, however, affected the reproductive success of fathead minnow at concentrations of 6.5 \u03bcL and higher with a clear dose-response relationship and a NOEC of 0.66 \u03bcL, which is above environmentally relevant concentrations.<\/jats:p>","DOI":"10.1897\/08-485.1","type":"journal-article","created":{"date-parts":[[2009,5,26]],"date-time":"2009-05-26T16:00:48Z","timestamp":1243353648000},"page":"2663-2670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":253,"title":["Effects of synthetic gestagens on fish reproduction"],"prefix":"10.1093","volume":"28","author":[{"given":"Jana","family":"Zeilinger","sequence":"first","affiliation":[{"name":"Bayer Schering Pharma AG, M\u00fcllerstrasse 178, 13342 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Steger-Hartmann","sequence":"additional","affiliation":[{"name":"Bayer Schering Pharma AG, M\u00fcllerstrasse 178, 13342 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund","family":"Maser","sequence":"additional","affiliation":[{"name":"Institute for Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Campus Kiel, Brunswiker Strasse 10, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Goller","sequence":"additional","affiliation":[{"name":"Dr. U. Noack Laboratories, K\u00e4the-Paulus-Strasse 1, 31157 Sarstedt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richardus","family":"Vonk","sequence":"additional","affiliation":[{"name":"Bayer Schering Pharma AG, M\u00fcllerstrasse 178, 13342 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"L\u00e4nge","sequence":"additional","affiliation":[{"name":"Bayer Schering Pharma AG, M\u00fcllerstrasse 178, 13342 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,1]]},"reference":[{"key":"2025010317062179900_bib1","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1002\/etc.5620200610","article-title":"Effects of the synthetic estrogen 17\u03b1-ethinylestradiol on the life-cycle of the fathead minnow (Pimephales promelas)","volume":"20","author":"L\u00e4nge","year":"2001","journal-title":"Environ Toxicol Chem"},{"key":"2025010317062179900_bib2","first-page":"469","article-title":"Small fish models for identifying and assessing the effects of endocrine-disrupting chemicals","volume":"45","author":"Ankley","year":"2004","journal-title":"Institute for Laboratory Animal Research Journal"},{"key":"2025010317062179900_bib3","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.steroids.2003.08.008","article-title":"Conception and pharmacodynamic profile of drospirenone","volume":"68","author":"Elger","year":"2003","journal-title":"Steroids"},{"key":"2025010317062179900_bib4","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0010-7824(96)00195-3","article-title":"The novel progestin drospirenone and its natural counterpart progesterone: Biochemical profile and antiandrogenic potential","volume":"54","author":"Fuhrmann","year":"1996","journal-title":"Contraception"},{"key":"2025010317062179900_bib5","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.maturitas.2004.01.001","article-title":"Pharmacological profile of progestins","volume":"47","author":"Sitruk-Ware","year":"2004","journal-title":"Maturitas"},{"key":"2025010317062179900_bib6","first-page":"217","article-title":"Endocrine regulation of gametogenesis in fish","volume":"38","author":"Nagahama","year":"1994","journal-title":"Int J Dev Biol"},{"key":"2025010317062179900_bib7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0048-9697(98)00328-3","article-title":"A strategy for assessing the effects of xenobiotics on fish reproduction","volume":"225","author":"Kime","year":"1999","journal-title":"Sci Total Environ"},{"key":"2025010317062179900_bib8","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1897\/03-42","article-title":"Quantification of steroid hormones with pheromonal properties in municipal wastewater effluent","volume":"22","author":"Kolodziej","year":"2003","journal-title":"Environ Toxicol Chem"},{"key":"2025010317062179900_bib9","doi-asserted-by":"crossref","first-page":"6377","DOI":"10.1021\/es049585d","article-title":"Dairy wastewater, aquaculture, and spawning fish as sources of steroid hormones in the aquatic environment","volume":"38","author":"Kolodziej","year":"2004","journal-title":"Environ Sci Technol"},{"key":"2025010317062179900_bib10","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1358\/dot.2008.44.2.1191057","article-title":"Drospirenone\/ethinyl estradiol","volume":"44","author":"Rapkin","year":"2008","journal-title":"Drugs Today"},{"key":"2025010317062179900_bib11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0010-7824(00)00133-5","article-title":"Drospirenone: Pharmacology and pharmacokinetics of a unique progestogen","volume":"62","author":"Krattenmacher","year":"2000","journal-title":"Contraception"},{"issue":"Suppl. 3","key":"2025010317062179900_bib12","first-page":"49","article-title":"Drospirenone: A new cardiovascular-active progestin with antialdosterone and antiandrogenic properties","volume":"6","author":"Rubig","year":"2003","journal-title":"Climacteric"},{"key":"2025010317062179900_bib13","author":"Organization for Economic Cooperation and Development","year":"2008"},{"key":"2025010317062179900_bib14","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1021\/es991292a","article-title":"Development of a reproductive test for endocrine disrupting chemicals using pair-breeding fathead minnow (Pimephales promelas)","volume":"34","author":"Harries","year":"2000","journal-title":"Environ Sci Technol"},{"key":"2025010317062179900_bib15","author":"European Medicines Agency","year":"2006"},{"key":"2025010317062179900_bib16","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.etap.2004.05.010","article-title":"Gonadal histology and characteristic histopathology associated with endocrine disruption in the adult fathead minnow (Pimephales promelas)","volume":"19","author":"Leino","year":"2005","journal-title":"Environ Toxicol Pharmacol"},{"key":"2025010317062179900_bib17","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1897\/1551-5028(2003)022<0908:HAATFT>2.0.CO;2","article-title":"Histopathology as a tool for the evaluation of endocrine disruption in zebrafish (Danio rerio)","volume":"22","author":"Van der Ven","year":"2003","journal-title":"Environ Toxicol Chem"},{"key":"2025010317062179900_bib18","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1002\/etc.5620220623","article-title":"Effects of the androgenic growth promoter 17-\u03b2-trenbolone on fecundity and reproductive endocrinology of the fathead minnow","volume":"22","author":"Ankley","year":"2003","journal-title":"Environ Toxicol Chem"},{"key":"2025010317062179900_bib19","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S1532-0456(00)00185-X","article-title":"Aspects of basic reproductive biology and endocrinology in the fathead minnow (Pimephales promelas)","volume":"128","author":"Jensen","year":"2001","journal-title":"Comp Biochem Physiol C Toxicol Pharmacol"},{"key":"2025010317062179900_bib20","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1080\/13697130500330382","article-title":"Pharmacology of different progestogens: The special case of drospirenone","volume":"8","author":"Sitruk-Ware","year":"2005","journal-title":"Climacteric"},{"issue":"Suppl. 1","key":"2025010317062179900_bib21","first-page":"195","article-title":"Regulation of oocyte maturation in fish","volume":"50","author":"Nagahama","year":"2008","journal-title":"Dev Growth Differ"},{"key":"2025010317062179900_bib22","volume-title":"Fish Pathology","author":"Roberts","year":"2001","edition":"3rd ed."},{"key":"2025010317062179900_bib23","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/BF00122584","article-title":"Oocyte growth and development in teleosts","volume":"6","author":"Tyler","year":"1996","journal-title":"Rev Fish Biol Fish"},{"key":"2025010317062179900_bib24","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1897\/06-092R1.1","article-title":"Effects of the estrogen agonist 17\u03b2-estradiol and the antagonist tamoxifen in a partial life-cycle assay with zebrafish (Danio rerio)","volume":"26","author":"Van der Ven","year":"2007","journal-title":"Environ Toxicol Chem"},{"key":"2025010317062179900_bib25","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0044-8486(94)00229-H","article-title":"Endocrine control of gametogenesis and spawning induction in the carp","volume":"129","author":"Yaron","year":"1995","journal-title":"Aquaculture"},{"key":"2025010317062179900_bib26","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0010-7824(94)00015-O","article-title":"Drospirenone: A novel progestogen with antimineralocorticoid and antiandrogenic activity: Pharmacological characterization in animal models","volume":"51","author":"Muhn","year":"1995","journal-title":"Contraception"},{"key":"2025010317062179900_bib27","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1210\/en.2008-0384","article-title":"Sex hormone-binding globulin in fish gills is a portal for sex steroids breached by xenobiotics","volume":"149","author":"Miguel-Queralt","year":"2008","journal-title":"Endocrinology"}],"container-title":["Environmental Toxicology and Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1897%2F08-485.1","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/etc\/article-pdf\/28\/12\/2663\/59853949\/5620281222.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/etc\/article-pdf\/28\/12\/2663\/59853949\/5620281222.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T13:21:42Z","timestamp":1739107302000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/etc\/article\/28\/12\/2663\/7763927"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12,1]]},"references-count":27,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2009,12,1]]},"published-print":{"date-parts":[[2009,12,1]]}},"URL":"https:\/\/doi.org\/10.1897\/08-485.1","relation":{},"ISSN":["0730-7268","1552-8618"],"issn-type":[{"value":"0730-7268","type":"print"},{"value":"1552-8618","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2009,12,1]]},"published":{"date-parts":[[2009,12,1]]},"assertion":[{"value":"2008-09-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-02-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-01-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}