Project Details
Projekt
Anti-thyroidal effects of hormonal contraceptives
Applicant
Dr. Claudia Lorenz
Subject Area
Endocrinology, Diabetology, Metabolism
Animal Physiology and Biochemistry
Ecology and Biodiversity of Animals and Ecosystems, Organismic Interactions
Animal Physiology and Biochemistry
Ecology and Biodiversity of Animals and Ecosystems, Organismic Interactions
Term
from 2013 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 235011938
Levonorgestrel (LNG) is a synthetic gestagen and a widely used component of several hormonal contraceptives. In terms of pharmaceutical drug safety, LNG is generally regarded as safe compound having no side-effects of clinical significance. An ecotoxicological relevance of LNG arises from its occurrence in surface waters and the consequential exposure of aquatic organisms. So far, data on physiological LNG effects on aquatic non-target organisms are scarce and limited to reproductive function.Recently, in the context of the applicant´s dissertation, LNG was found to affect the thyroid system of amphibians. The mechanisms underlying LNG´s actions have been clarified only to some extend, however, three independent modes of LNG action could be identified. Amongst others and demonstrated by ex vivo tissue cultures, LNG was found to directly affect thyroidal gene expression.The aim of the applied project is to identify further modes of LNG action. Moreover, it is of interest whether the effects of LNG are applicable for other (all) synthetic gestagens that are used for hormonal contraception. As a third point, it is intended to investigate, whether LNG has also an impact on the thyroid system of mammalians. So far, LNG is generally regarded as a safe compound having no side-effects of clinical significance. However, the amphibian metamorphosis assay is well-accepted to be a very sensitive tool for the detection of (anti)thyroidal chemicals, which can be extrapolated for all vertebrates including humans. Hence, the present results may also be considered in respect of human exposure to synthetic gestagens. Pharmaceutical LNG-plasma level of women using LNG for contraception are in the range of the test concentrations being effective in the amphibian assay. Since thyroid hormones are crucial factors for diverse processes in the vertebrate organism, the knowledge of a gestagen action on the mammalian thyroid system is of considerable interest.Of particular concern seems to be the use of hormonal contraceptives during the period of lactation, since TH are essential for normal brain development. Although LNG has been shown to be transferred to the infants circulation via breast milk and even to affect the infant´s TSH serum concentration, it is generally regarded as a pharmaceutical compatible with breastfeeding.
DFG Programme
Research Grants
