An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells

Effects of nomegestrol acetate administration on central and peripheral beta-endorphin and allopregnanolone in ovx rats

“…Nomegestrol acetate (NOMAc, 17a-acetoxy-6-methyl-19-nor-4,6-pregnadiene-3,20-dione) is a 19-nor-progesterone derivative, used alone, or in combination with 17␤-estradiol (E2) for hormone replacement therapy (HRT), and it is under current development for oral contraception [1]. It is formed by the addition of a double bond between C-6 and C-7 of the 17-hydroxyprogesterone skeleton, and has a deletion of the angular methyl group at C-19.…”

“…The relative binding affinity of NOMAc for the rat's progesterone receptor (PR) changes according to the diverse ligand used in different studies and varies from 67 to 250% in comparison to the full affinity (100%) of progesterone. However, it has been demonstrated that there is no correlation between the degree of affinity for the PR and the related pseudogestagenic potency [1]. NOMAc does not bind to the estrogen receptor, the glucocorticoid receptor or the aldosterone receptor [1,3] while it binds to the androgen receptor, resulting in an anti-androgenic activity.…”

“…However, it has been demonstrated that there is no correlation between the degree of affinity for the PR and the related pseudogestagenic potency [1]. NOMAc does not bind to the estrogen receptor, the glucocorticoid receptor or the aldosterone receptor [1,3] while it binds to the androgen receptor, resulting in an anti-androgenic activity. Therefore, the compound is devoid of estrogenic, mineralocorticoid, and androgenic effects [1].…”

Effect of nomegestrol acetate on estrogen biosynthesis and transformation in MCF-7 and T47-D breast cancer cells

“…It was previously shown that NOMAC as a 19-norprogesterone derivative had no estrogenic or estrogeniclike activity in different in vitro models: as opposed to 19-nor-testosterone derivatives it was exclusively antiproliferative in MCF-7 or T47-D cells [24,109]; it did not stimulate transcription of estrogen response element in the same cells [110]; it inhibited estrogen induced-PgR in T47-cells [109]; it did not induced phosphatase alkaline activity in endometrial Ishikawa cells [111].…”

“…This potent and clinically useful progestin is used in France and some other countries alone (Lutenyl ® ) or in combination with E 2 (Naemis ® ) for the treatment of menopausal complaints. NOMAC has been shown to lack any estrogenic activity and to display antiestrogenic activity in vitro and in vivo (for a review see [24]). …”