Disease relevance of Nomegestrol

• Inhibition by nomegestrol acetate and other synthetic progestins on proliferation and progesterone receptor content of T47-D human breast cancer cells [1].
• No significant increase in androgen levels and in the development of acne vulgaris was observed in these women using nomegestrol acetate implant during two years [2].
• Nomegestrol (NOM) belongs to a new derivation of progestogens and shows very low toxicity [3].

High impact information on Nomegestrol

• We have previously shown in postmenopausal women that a 19-nor-progesterone derivative, nomegestrol acetate (NOMA) had a strong antigonadotropic activity and that this effect was not mediated via the androgen receptor [4].
• In vitro and in premenopausal women, stopping the administration of nomegestrol acetate triggers a peak of apoptosis [5].
• The regulatory effects of nomegestrol acetate (NOM-Ac: 17 alpha-acetoxy-6 alpha-methyl-19-nor-pregna-4,6-diene-3,20-dione), a new 19-nor-progesterone derivative, active p.o. progestin, were studied on rat uterine estrogen (ER) and progestogen receptor (PgR) levels [6].
• Binding was almost abolished completely (0.23%) by acetylation of the 17 alpha-OH group (nomegestrol-acetate) [7].
• METHODS: We used human endothelial cells to study the action of nomegestrol acetate (either alone or in the presence of estradiol [E2]) on the synthesis of nitric oxide (NO) and on the activity or expression of endothelial nitric oxide synthase (eNOS) [8].

Biological context of Nomegestrol

• The present study assesses the endocrinological, endometrial histology and vaginal ultrasound profiles of nomegestrol acetate subdermal implant users at varying times after insertion [9].
• Spontaneous and sulprostone-induced uterine contractions were compared between nomegestrol acetate- and vehicle-treated animals [10].
• Currently available chromatographic assays of the progestative drug nomegestrol acetate in human plasma are not suitable for monitoring drug kinetics more than 24 h after clinical dosage [11].
• Neuroendocrine mechanism of anovulation in users of contraceptive subdermal implant of nomegestrol acetate (Uniplant) [12].
• In conclusion, these findings suggest that the contraceptive mechanisms of a single nomegestrol acetate subdermal implant involve prevention of follicular growth, development of a persistent non-luteinized follicle, inadequate luteal phase and disruption of the endometrial architecture [9].

Anatomical context of Nomegestrol

• Activation of nitric oxide synthesis in human endothelial cells using nomegestrol acetate [8].
• Effects of a single contraceptive Silastic implant containing nomegestrol acetate on ovarian function and cervical mucus production during 2 years [13].
• In the present review, we summarized the action of the 19-nor-progestin nomegestrol acetate (NOMAC) on the sulfatase, 17beta-HSD1 and sulfotransferase activities in the hormone-dependent MCF-7 and T47-D human breast cancer cell lines [14].
• A study was carried out in order to determine the impact of Nomegestrol acetate on the human cervix and to evaluate the ability of changes induced in cervical mucus to render the cervical canal hostile to spermatozoa at midcycle [15].
• CONCLUSION: Nomegestrol acetate directly inhibited the steroidogenesis of granulosa cells [16].

Associations of Nomegestrol with other chemical compounds

• The aim of this study was to establish whether nomegestrol acetate induces signaling events in human endothelial cells that differ from those of other progestins, such as natural progesterone or medroxyprogesterone acetate [8].
• The effectiveness of a sequential regimen consisting of mifepristone, 10 mg/day for 15 days, followed by nomegestrol acetate (NOMA), 5 mg/day for the next 13 days, for inhibiting ovulation and maintaining regular bleeding cycles was assessed in 10 surgically sterilized volunteers who were followed for one pretreatment and three treated cycles [17].
• In the same animal model, the addition of cyclic or continuous medroxyprogesterone acetate (MPA) to E inhibited vasodilatation by 50%, while nomegestrol acetate did not diminish the E-induced vasodilatation [18].
• OBJECTIVE: To assess the effects of oral E2 replacement therapy combined with nomegestrol acetate, a 19-norprogesterone derivative, on cardiovascular risk factors [19].
• These include dienogest, drospirenone, Nestorone (Population Council, New York, NY, USA), nomegestrol acetate and trimegestone [20].

Gene context of Nomegestrol

• INTERVENTION(S): Twenty-six women received no HRT and 24 received continuous transdermal 17 beta-estradiol, 0.05 mg/d, plus oral acetate nomegestrol, 5 mg/d. MAIN OUTCOME MEASURE(S): Levels of the soluble forms of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin [21].
• Effect of nomegestrol acetate on human estrogen sulfotransferase activity in the hormone-dependent MCF-7 and T-47D breast cancer cell lines [22].
• OBJECTIVE: To study the mechanism of action of Uniplant (South to South Corporation in Reproductive Health, Salvador, Brazil), a single Silastic capsule containing nomegestrol acetate (Lutenyl, Theramex, France) in women during 2 years [13].
• Using intact hormone-dependent cells it was observed that Nomegestrol acetate can block the conversion of E1 to E2 [23].
• At a high concentration (5 x 10(-5) mol/l) the stimulatory effect of nomegestrol acetate on the sulfotransferase activity was only 5.4% and 6.1%, respectively, in MCF-7 and T-47D cells [22].

Analytical, diagnostic and therapeutic context of Nomegestrol

• RESULTS: After use of nomegestrol acetate for 1 to 9 months, the women in the test group had symptomatic improvement, with no crisis that required hospitalization and no deaths [24].
• Enzyme immunoassay for nomegestrol acetate in human plasma [11].
• CONCLUSIONS: Sequentially combined with oral E2 in hormone replacement therapy, nomegestrol acetate had favorable effects on plasma lipids and lipoproteins [19].
• This was carried out in Assiut, Egypt. Two-hundred-forty fully breastfeeding mothers asking for initiation of contraception early postpartum were assigned according to their choices into either nomegestrol subdermal contraceptive implant (Uniplant) (120 women) or intrauterine contraceptive device (CuT 380A) (120 women) [25].
• A 12 months longitudinal study was carried out in 214 consecutive Nigerian women using Nomegestrol acetate subdermal contraceptive implant (Uniplant) for the first time to establish the rates of different vaginal bleeding patterns according to WHO bleeding/spotting classification, and to assess their relationship with Uniplant discontinuation [26].

References