Differential metabolism of clinically-relevant progestogens in cell lines and tissue: Implications for biological mechanisms

Abstract

Steroid hormones regulate a variety of physiological processes, including reproductive function, and are widely used in hormonal therapy. Synthetic progestogens, or progestins, were designed to mimic progesterone (P4) for use in contraception and hormonal replacement therapy in women. Medroxyprogesterone acetate (MPA) and norethisterone (NET) are the most widely used injectable contraceptives in the developing world, while other progestins such as levonorgestrel (LNG), etonogestrel (ETG) and nestorone (NES) are used in or being developed for other forms of contraception. As concerns remain about the most appropriate choice of progestin and dosage, and the associated side-effects, the mechanisms and biological effects of progestins are frequently investigated in various in vitro mammalian cell line and tissue models. However, whether progestogens are differentially metabolised in different cell types in vivo or in vitro is unknown.

Effects of prenatal exposure to synthetic sex hormones on neurodevelopment: a biological mechanism.

“…The hypermethylation of the estrogen and progestogen receptor promoters upon in utero exposure to LNG (Zou et al, 2017) suggests that the molecular machinery and its effects on offspring might be the same as with synthetic estrogens, although no study on progestin effects on the third generation has been published yet. Only recently Skosana et al (2019), showed for the first time that progestins are very rapidly degraded (less than 24 h) in mammalian cell lines and are significantly metabolized in human cervical tissue. This could explain why the toxic effect of these xenohormones is more quickly harmful.…”