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International Journal of Pharmacology
Year: 2008  |  Volume: 4  |  Issue: 6  |  Page No.: 410 - 430

A Review on the Genotoxic Effects of Some Synthetic Progestins

Y.H. Siddique and M. Afzal    

Abstract: The present review gives the details of the genotoxic studies carried out till date for some selected synthetic progestins. Mutagenicity is defined as a permanent change in content or structure of the genetic material of an organism. A mutagenic hazard can be manifested as a heritable change resulting from germ-line mutations and/or somatic mutations leading to cancer or other chronic degenerative processes such as aging. Reactive Oxygen Species (ROS) generated through normal metabolic processes or from toxic products, can lead to a state of oxidative stress that contributes to the pathogenesis of a number of human disease by damaging lipids, protein and DNA. Oral contraceptives have been used since the early 1960s and are now used by about 90 million women world wide. The pill is given as a combination of an estrogen and a progestogen. The estrogen component of combined oral contraceptives is either ethinylestradiol or mestranol and the progestogens used are cyproterone acetate, desogestrol, ethynodiol diacetate, levonorgestrel, lynestrenol, megestrol acetate, norethisterone, norethisterone acetate, norethynodrel, norgestimate and norgestrel. Little is known about the long term health risks and potential protective effects of these individual components. Synthetic progestins induced the genotoxic damage and also various types of cancers, both singly as well as in combination with estrogens. Various synthetic progestins have been tested for their genotoxic effects in different experimental models, using different genotoxic end points. Ethynodioldiacetate, norethynodrel, norgestrel, lynestrenol and medroxyprogesterone acetate were found to be genotoxic only in the presence of metabolic activation supplemented with NADP. Megestrol acetate, cyproterone acetate and chlormadinone acetate were found to be genotoxic in the absence of metabolic activation. On the basis of reports available it is suggested that the progestins in which double bond between carbon-6 and carbon-7 is present, they undergo nucleophilic reaction and generates free radical in the system to show the genotoxic effects and the progestins in which double bond between carbon-6 and carbon-7 is absent, they need metabolic activation like estrogens, such as estradiol-17β and ethinylestradiol to show the genotoxic effects.

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