Disease relevance of CENTCHROMAN

• Efficacy of levormeloxifene in the prevention of postmenopausal bone loss and on the lipid profile compared to low dose hormone replacement therapy [1].
• Treatment with Centchroman (3,4-trans-2,2-dimethyl-3-phenyl-4-p-(beta-pyrrolidinoethoxy) phenyl-7-methoxy chroman) has been evaluated in 4 male and 75 female patients with advanced breast cancer [2].
• The most frequent adverse events after multiple dosing were headache, abdominal pain and leukorrhea with the highest frequency reported after the highest daily dose of 160 mg levormeloxifene [3].
• Hysteroscopic examinations showed that levormeloxifene was related to increased incidence of edema, vascularization and cysticity [4].
• In the levormeloxifene groups, a total of eight women had utero-vaginal prolapse and five women reported urinary incontinence (including worsening of a previously existing condition) [4].

High impact information on CENTCHROMAN

• Centchroman, a selective estrogen receptor modulator, as a contraceptive and for the management of hormone-related clinical disorders [5].
• Spinal bone mineral density (BMD) decreased by less than 1% in the placebo group and increased by about 2% in the levormeloxifene groups and by almost 5% in the HRT group (P < 0.001 for the difference between levormeloxifene and HRT vs. placebo) [1].
• In conclusion, the study shows that levormeloxifene, a new selective estrogen receptor modulator, has positive effects on BMD and bone turnover and apparently strong estrogenic effects on the serum concentrations of different cholesterol subfractions [1].
• Both E and lasofoxifene stimulated uterine MMP2 activity to a level twofold that of Ral, whereas levormeloxifene elevated MMP2 activity to a level 12-fold that of Ral [6].
• Ovariectomy resulted in an increase in these markers; the increase was prevented by estradiol or levormeloxifene [7].

Chemical compound and disease context of CENTCHROMAN

• In fact, compounds that are more estrogenic on the uterus such as levormeloxifene and idoxifene also increase the risk of prolapse and incontinence [8].

Biological context of CENTCHROMAN

• Effect of centchroman on preimplantation embryonic development and tubal transport in mice [9].
• AIMS: The safety, pharmacodynamics and pharmacokinetics of levormeloxifene, a selective oestrogen receptor modulator (SERM), were investigated in postmenopausal women following single doses and multiple dosing once daily up to 56 days [3].
• Induction of ovulation in the human with centchroman: a preliminary report [10].
• This study reports assay methodology, tissue distribution, and the basic pharmacokinetic behavior of centchroman and its 7-desmethyl metabolite [7-desmethyl centchroman (DMC)] after a single 12.5 mg/kg po dose in young female rats [11].
• One of these, viz., the cis isomer of centchroman, has however emerged as a selective ligand for the antiestrogen binding site since its estrogen receptor affinity is nearly 50,000 times lower on a relative scale [12].

Anatomical context of CENTCHROMAN

• Additional experiments were conducted to determine the levels of MMP2 activity in uterus explants from ovariectomized rats following 2 wk of treatment with E, Ral, or one of two additional SERMs: lasofoxifene, and levormeloxifene [6].
• Excretion of centchroman in breast milk [13].
• Recovery of normal blastocysts from rats treated continuously with this dose of centchroman at these intervals suggests lack of significant effect on follicular maturation, ovulation, fertilization, preimplantation development or mating behaviour.(ABSTRACT TRUNCATED AT 250 WORDS)[14]
• A single oral administration of centchroman (1.25 mg/kg) to adult female rats within 24 h of mating induced slight acceleration in the rate of transport of embryos through the oviducts [15].
• The mean residence time of centchroman was highest in the liver (78.4 hr), followed by the uterus (72.7 hr), adipose tissue (47.5 hr), lung (46 hr), spleen (44.1 hr), and plasma (37.7 hr) [11].

Associations of CENTCHROMAN with other chemical compounds

• Preparation and characterization of sodium hexameta phosphate cross-linked chitosan microspheres for controlled and sustained delivery of centchroman [16].
• The effect of three compounds (clomiphene citrate, centchroman, embelin) and plant-derived methanolic extracts (Abutilon indicum and Butea monosperma) was studied on uterotropic and uterine peroxidase activities in ovariectomized rats [17].
• Effect of long-term centchroman treatment on plasma steroid and peptide hormones in female rhesus monkeys (Macaca mulatta) [18].
• To assess the alleged estrogenic and antiestrogenic profile of centchroman, a phenotypical response was studied in native uterine cells or migrant blood cells in adult ovariectomized rats under the influence of estradiol-dipropionate (EDP) and centchroman (CC) given per se and together [19].
• Failure of Centchroman to counteract progesterone-induced changes in the uterus of delayed implantation rats [20].

Gene context of CENTCHROMAN

• Animals in the remaining five groups were ovariectomized and received either vehicle (ovx); 17beta-estradiol at 0.016 mg/kg (est); or levormeloxifene at 0.5 (L1), 1 (L2), or 5 (L3) mg/kg [7].
• The tissue distribution, pharmacokinetics, metabolism, and excretion of the selective estrogen receptor modulator levormeloxifene have been investigated after oral administration of [(14)C]-levormeloxifene to male and female Sprague-Dawley rats [21].
• Effect of Centchroman on serum gonadotropins & prolactin in rats [22].
• Centchroman did not compete either with sex hormone binding globulin or corticosteroid binding globulin [23].
• Anti-tumor efficacy of Centchroman formulated as niosomes and gel implant was evaluated in Swiss albino mice bearing Ehrlich ascites carcinoma at 10 mg/kg body weight dose given subcutaneously [24].

Analytical, diagnostic and therapeutic context of CENTCHROMAN

• Levormeloxifene prevents increased bone turnover and vertebral bone loss following ovariectomy in cynomolgus monkeys [7].
• High performance liquid chromatographic (HPLC) determination of centchroman in human serum and application to single-dose pharmacokinetics [25].
• The quantitative distribution of radiolabeled levormeloxifene and/or metabolites was confirmed by whole body autoradiography [21].
• The marked uterine effects of levormeloxifene detected by this model are probably highly predictive of the adverse events that would be encountered in clinical trials [26].
• The effect of MW, DDA, and degree of cross-linking in microspheres was studied on the degree of swelling, as well as by the loading and release of centchroman [27].

References