Lack of estrogenic potential of progesterone- or 19-nor-progesterone-derived progestins as opposed to testosterone or 19-nor-testosterone derivatives on endometrial Ishikawa cells

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

“…Intrinsic estrogenicity was confirmed for compounds derived from T and 19-norT (Table 9); EC 50 of 0.5, 3.6 and 64 nM were found for E 2 , norethynodrel (NEL, 17␣-ethynyl,17␤-hydroxy-5(10)-estren-3-one) and NET, respectively. The effect of NET was partially blocked by the anti-estrogen 4OHTAM, which was also partially agonistic in this model, but neither by the anti-progestin mifepristone (RU486) nor by the aromatase inhibitor aminogluthetimide or by an antiandrogen like hydroxyflutamide ( [26] and Théramex unpublished results). In contrast, all P and 19-norP derivatives remained totally inactive.…”

“…As a 19-norP derivative, nomegestrol acetate (NOMAC, 17␣-acetoxy-6-methyl-19-nor-4,6-pregnadiene-3,20-dione) is a potent and clinically useful progestin devoid of androgenic, mineralocorticoid and estrogenic effects [25][26][27][28][29][30] that is used alone in France and some countries (Lutenyl ® ), or in combination with 17␤-estradiol (E 2 ) for HRT (Naemis ® ); It is under current development for OC. The main objective of the present review is to gather data already available and to concentrate on interaction with sex steroid receptors and the lack of estrogenic effects on breast cancer cells in vitro.…”

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].…”

Nomegestrol acetate is an anti-aromatase agent in human MCF-7aro breast cancer cells

“…It was demonstrated that NOMAC as 19-nor-progesterone derivative lacks any estrogenic activity in different 'in vitro' models (37) as opposed to 19-nor-testosterone derivatives, it was exclusively antiproliferative in MCF-7 or T-47D cells and displayed other anti-estrogenic activity 'in vitro' and 'in vivo' (38)(39)(40). NOMAC is referred to as a pure progestational molecule because it binds almost exclusively to the progesterone receptor (PR) and does not interfere with androgen or mineralo-and glucocorticoid receptors; however, NOMAC also has partial anti-androgenic activity (41).…”