As the biological effects of progestins vary according to their molecular structure, it becomes essential to differentiate the various types of progestins, particularly with regard to the breast. Objective. The purpose of this review was to gather published data on the effects of a 19- norprogesterone derivative, nomegestrol acetate, on the breast. Materials and methods. All experimental and clinical published studies reporting data in the literature on nomegestrol acetate and breast were reviewed. Results. In experiments on steroid receptors, it was shown that nomegestrol acetate presents a high binding specificity and affinity for progesterone receptors, notably in normal and cancerous human breast tissues. It sharply inhibits synthesis of progesterone receptors in hormone- dependent T- 47D human breast cancer cells grown in an estrogenic culture medium, thereby demonstrating its strong progestational activity. On the other hand, it does not bind to estrogen receptors and lacks any estrogenic potential, confirmed by the lack of induction of alkaline phosphatase activity of endometrial Ishikawa cells. Estrogen- induced synthesis of estrogen receptors is also inhibited by nomegestrol acetate, a major determinant of its strong intrinsic anti- estrogenic activity. Unlike androgenic progestins (e.g. 19- nortestosterone derivatives and medroxyprogesterone acetate) which may act indirectly on the breast by inducing modifications of sex hormone binding globulin (SHBG) and insulin- like growth factor- I (IGF- I), nomegestrol acetate is devoid of any androgenic activity. In studies carried out on the effects of progestins on enzyme activities involved in estradiol (E2) formation in breast tissue, nomegestrol acetate can control E2 levels in breast cancer tissue in vitro: it inhibits estrone sulfatase activity that converts estrone sulfate (E1S)- to estrone (E1) and inhibits 17β - hydroxysteroid dehydrogenase type 1 activity that converts E1 to E2, resulting in blockade of E2 bioformation in MCF- 7 and T- 47D human breast cancer cells. It also stimulates sulfotransferase activity and subsequently the transformation of non conjugated estrogens E1 and E2 into biologically inactive estrogen sulfates. In vitro studies on cell proliferation have demonstrated that nomegestrol acetate, on the one hand, is unable to stimulate proliferation of MCF- 7 cells cultured in a medium devoid of estrogens and, on the other hand, can exert antiproliferative effects on T- 47D cells grown in an estrogenic environment. Furthermore, studies on mammary apoptosis have shown that the withdrawal of nomegestrol acetate induces apoptosis peak of normal human breast epithelial cells in vitro and in vivo. In clinical trials carried out with premenopausal women, nomegestrol acetate administered in antigonadotropic sequence has demonstrated its efficacy in the treatment of cyclical mastodynia and early onset benign breast diseases. With post- menopausal hormone replacement therapy (HRT) combining estrogen and nomegestrol acetate, clinical trial results showed low incidence of mastodynia while under treatment as well as moderate increase in mammographic density, particularly with continuous combined regimens, however rapidly reversed by a short- term suspension of HRT. No clinical data with this progestagen is available on breast cancer risk. Conclusion. In addition to efficacy on mastodynia, in vitro and in vivo study results support the good tolerance of nomegestrol acetate on breast, in the short and medium term. As the biological effects of progestins vary according to their molecular structure, it becomes essential to differentiate the various types of progestins, particularly with regard to the breast. Objective. The purpose of this review was to gather published data on the effects of a 19- norprogesterone derivative, nomegestrol acetate, on the breast. Materials and methods. All experimental and clinical published studies reporting data in the literature on nomegestrol acetate and breast were reviewed. Results Experiments in steroid receptors, it was shown that nomegestrol acetate presents a high binding specificity and affinity for progesterone receptors, notably in normal and cancerous human breast tissues. It sharply inhibits synthesis of progesterone receptors in hormone- dependent T- 47D human breast cancer cells grown in an estrogenic culture medium, thereby demonstrating its strong progestational activity. On the other hand, it does not bind to estrogen receptors and lacks any e strogenic potential, confirmed by the lack of induction of alkaline phosphatase activity of endometrial Ishikawa cells. Estrogen-induced synthesis of estrogen receptors is also inhibited by nomegestrol acetate, a major determinant of its strong intrinsic anti- estrogenic activity. - nortestosterone derivatives and medroxyprogesterone acetate) which may act indirectly on the breast by inducing modifications of sex hormone binding globulin (SHBG) and insulin-like growth factor- I (IGF- I), nomegestrol acetate is devoid of any androgenic activity. carried out on the effects of progestins on enzyme activities involved in estradiol (E2) formation in breast tissue, nomegestrol acetate can control E2 levels in breast cancer tissue in vitro: it inhibits estrone sulfatase activity that converts estrone sulfate (E1S) -to estrone ( E1) and inhibits 17β - hydroxysteroid dehydrogenase type 1 activity that converts E1 to E2, resulting in blockade of E2 also bioformation in MCF-7 and T-47D human breast cancer cells. It also stimulates sulfotransferase activity and subsequently the transformation of non-conjugated estrogens E1 and E2 into biologically inactive estrogen sulfates. On vitro studies on cell proliferation have demonstrated that nomegestrol acetate, on the one hand, is unable to stimulate proliferation of MCF-7 cells cultured in a medium devoid of estrogens and, on the other hand, can exert antiproliferative effects on T- 47D cells grown in an estrogenic environment. shown that the withdrawal of nomegestrol acetate induces apoptosis peak of normal human breast epithelial cells in vitro and in vivo. In clinical trials carried out with premenopausal women, nomegestrol acetate administered in antigonadotropic sequence has demonstrated its efficacy in the treatment of cyclical mastodynia and early onset benign breast diseases. With post-menopausal hormone replacement therapy (HRT) combining clinical estrogen and nomegestrol acetate, clinical trial results showed low incidence of mastodynia while under treatment as well as moderate increase in mammographic density, particularly with continuously combined regimens, but but notably shortening of HRT. No clinical data with this progestagen In addition to efficacy on mastodynia, in vitro and in vivo study results support the good tolerance of nomegestrol acetate on breast, in the short and medium term.