Disease relevance of Trimegestone

• OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg 17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal osteoporosis [1].
• Acceptability and patterns of uterine bleeding in sequential trimegestone-based hormone replacement therapy: a dose-ranging study [2].
• RU-27987, a synthetic progestin, which was recently developed by Roussel Uclaf, Paris, was tested for its validity as a ligand to determine the progesterone receptor in breast cancer [3].
• 17 beta-Estradiol induced uterine hypertrophy on all these protocols and this was blocked completely by trimegestone [4].
• The effect of submucous fibroids on the dose-dependent modulation of uterine bleeding by trimegestone in postmenopausal women treated with hormone replacement therapy [5].

High impact information on Trimegestone

• Moreover, GP3 is not able to mediate RU 27987-induced transactivation [6].
• Natural progesterone (P) and some of its derivatives, such as the 19-norprogesterones (Nestorone, nomegestrol acetate, trimegestone), do not bind to the androgen receptor and, hence, do not exert androgenic side effects [7].
• However, TFPI activity was reduced by EE alone (10-100 microg/kg/day) in a dose-dependent manner; NETA (3 or 10 mg/kg/day) reduced TFPI by approximately 40 or approximately 80%, respectively, while TMG and DSP had no effect [8].
• We studied the effect of short-term oral hormone replacement therapy (unopposed oestradiol or sequentially combined oestradiol and trimegestone or dydrogesterone) on platelet activation parameters in healthy postmenopausal women [9].
• Oral oestradiol/trimegestone replacement reduces procarboxypeptidase U (TAFI): a randomized, placebo- controlled, 12-week study in early postmenopausal women [10].

Biological context of Trimegestone

• In this multicentre dose-ranging study using randomized parallel groups, four doses of trimegestone were used to compare data on the patterns of uterine bleeding, the endometrial histology, and the control of menopausal symptoms in 203 women who completed treatment for 6 months [2].
• Screening microorganisms for the biotransformation of the 3-keto-delta(4,9(10))-19-norsteroid RU27987 (Trimegestone) resulted in the isolation of nine identified metabolites, some of them being selectively produced by different strains [11].
• Trimegestone: expanding therapeutic choices for the treatment of the menopause [12].
• In cytosols, the binding affinity of RU 27987 was higher than that of R 5020, and the number of maximum binding sites for RU 27987 seemed to be large but correlated well with those of R 5020 [13].

Anatomical context of Trimegestone

• NET-based HRT was associated with a higher number of smaller vascular spaces compared with the trimegestone-treated endometrium or that of the natural cycle [14].
• The distribution of endometrial leukocytes and their proliferation markers in trimegestone-treated postmenopausal women compared to the endometrium of the natural cycle: a dose-ranging study [15].
• The binder for RU 27987 sedimented at 8.6 S, and the binding was specific to progestational steroids, indicating that binding properties of this binder in the cytosols are identical to those for R 5020 [13].
• Effects of 17 beta-estradiol and trimegestone alone, and in combination, on the bone and uterus of ovariectomized rats [4].

Associations of Trimegestone with other chemical compounds

• The model was also used to evaluate trimegestone (TMG), a new steroidal progestin, that has been shown to be a potent and selective progesterone receptor agonist [16].
• The effect of trimegestone-based and norethisterone-based hormone replacement therapy (HRT) regimens on the endometrial vascularity compared with that of the endometrium of the natural cycle were evaluated using immunohistochemical techniques [14].
• Rat uterine complement C3 expression as a model for progesterone receptor modulators: characterization of the new progestin trimegestone [16].
• The new molecules trimegestone, drospirenone and dienogest also have antiandrogenic activity.Following the publication of the results of the Women's Health Initiative study, the role of progestins in HRT became controversial [17].
• When apoB was added in AMORIS model 4, the difference between treatments (5% reduction in the two doses of TMG, compared to NETA) decreased over time, probably due to the effect of dropouts in the NETA group [18].

Gene context of Trimegestone

• Evaluation of RU-27987 as a ligand to determine the progesterone receptor [3].

Analytical, diagnostic and therapeutic context of Trimegestone

• Trimegestone has been developed for use in conjunction with oestrogen for postmenopausal hormone replacement therapy (HRT) [12].
• However, the cytosol bound with RU 27987 was not retained in DNA Sepharose and no specific binder for RU 27987 in the nuclear extract was observed in a sucrose density gradient centrifugation [13].
• The concentration of triglycerides was elevated after treatment with the estradiol/trimegestone combinations but was unchanged after treatment with the estradiol/norethisterone acetate combination [19].

References