Disease relevance of Premarin

• A follow-up survey of 908 women who had received 'Premarin' (conjugated equine oestrogen) for menopausal symptoms revealed 8 cases of ovarian cancer [1].
• These data seem to indicate that in patients with hyperprolactinemia, tonic secretion of gonadotropin is maintained fairly well, while of the positive feedback effect of Premarin on the release of LH is impaired [2].
• In 10 normal cyclic women at the mid-follicular phase (D7-9) and 10 hypothalamic amenorrhea patients without galactorrhea, LH release was found 48 to 72 h after the iv injection of 20 mg conjugated estrogens (Premarin) [2].
• However, long-term exposure to estrogens from the Premarin drug increases the risk of breast cancer [3].
• Estrogen replacement therapies, such as conjugated equine estrogen (CEE, Premarin), reduce the risk of coronary heart disease among postmenopausal women [4].

Psychiatry related information on Premarin

• CONCLUSION: A 1.25-mg/day dose of Premarin administered for 12 consecutive weeks does not produce a meaningful effect on cognitive performance, dementia severity, behavior, mood, and cerebral perfusion in female AD patients [5].
• Three recent controlled experimental studies using Premarin showed no effects of HRT in preventing further cognitive decline in women who already have Alzheimer's disease [6].

High impact information on Premarin

• To investigate whether these perturbations have metabolic consequences, we compared the effects of 24 wk each of oral (Premarin 1.25 mg) and transdermal (Estraderm 100TTS) estrogen on energy metabolism and body composition in 18 postmenopausal women in an open-label randomized crossover study [7].
• Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism [8].
• OATP-B also transported estrone-3-sulfate but not bile salts [9].
• In 4 patients the bleeding time became normal after 2 to 5 days of premarin therapy [10].
• There was no consistent improvement in platelet aggregation nor increase in plasma factor-VIII-ristocetin cofactor activity during premarin therapy [10].

Chemical compound and disease context of Premarin

• The five endometrial cancers occurred in postmenopausal patients 57 to 69 years of age; two of them were receiving, or had been receiving, premarin and provera and two were receiving only premarin [11].
• Alterations in the production rate and the metabolism of oestrone and oestrone sulphate in breast cancer patients treated with aminoglutethimide [12].
• OBJECTIVE: We evaluated bleeding as a predictor of endometrial hyperplasia in postmenopausal women receiving conjugated estrogens (Premarin) alone or with medroxyprogesterone acetate [13].
• Steroid sulphates such as oestrone sulphate (OE1S) and dehydroepiandrosterone sulphate (DHEAS) have been suggested to be of biological importance in different disease states such as breast cancer and atherosclerosis [14].
• Effect of experimental infection with Listeria monocytogenes on the development of pregnancy and on concentrations of progesterone, oestrone sulphate and 15-ketodihydro-PGF2 alpha in the goat [15].

Biological context of Premarin

• A favorable advance of bone maturation in relation to chronological age was achieved by the administration of 0.15 mg Premarin daily, a dose which caused a satisfactory onset of secondary sex characteristics [16].
• Many tumours in endocrine-sensitive tissues, such as the breast and endometrium, are hormone-dependent and the hydrolysis of oestrone sulphate (EIS) to oestrone by oestrone sulphatase (EI-STS) is a major source of oestrogen in such tumours [17].
• The porphyrins can be displaced from their binding site on ligandin by bromosulphophthalein and oestrone sulphate [18].
• Our results, although preliminary, suggest that aminoglutethimide is a potent inducer of aminoglutethimide metabolism, thereby producing a significant reduction in plasma bioavailability of oestrone sulphate [19].
• Eleven patients with moderate to severe premenstrual syndrome were given Premarin during the latter half of the menstrual cycle for at least two cycles, and a placebo for at least two cycles [20].

Anatomical context of Premarin

• In vitro study of the functional expression of organic anion transporting polypeptide 3 at rat choroid plexus epithelial cells and its involvement in the cerebrospinal fluid-to-blood transport of estrone-3-sulfate [21].
• Taurocholate inhibited the uptake of T4 by the cerebral cortex completely, but the inhibition by estrone-3-sulfate was partial (50%) [22].
• In contrast to the reduced LTC4 and oestrone sulphate transport, stably transfected HeLa cells expressing Arg433Ser mutant MRP1 were 2.1-fold more resistant to doxorubicin than cells expressing wild-type MRP1, while resistance to VP-16 and vincristine was unchanged [23].
• Compared to LLC-PK1 cells and cells which expressed only OATP1B1, the cell line that co-expressed MRP2 and OATP1B1 displayed high directional basolateral-to-apical transport of 17 beta-estradiol-17 beta-glucuronide and estrone-3-sulfate [24].
• In Xenopus laevis oocytes expressing OATP1A2, the uptake of the model substrate, estrone-3-sulfate (ES), was enhanced 30-fold compared with uninjected oocytes [25].

Associations of Premarin with other chemical compounds

• Whereas an additive effect of hormones plus chemotherapy cannot be entirely excluded as the explanation for the improved results with the addition of tamoxifen for four days plus one day of premarin, results suggest that further efforts to increase the efficacy of chemotherapy by perturbing tumor growth rates may be worthwhile [26].
• Among postmenopausal women, hormone replacement therapy (both premarin only and combined premarin and provera) appears to be associated with favorable effects on the lipid profile [27].
• A total of 8 patients were treated with 0.6256 mg Premarin daily for 25 days and 5 mg/day of medroxyprogesterone on days 15-25 (ERT, group 2); 7 were followed without ERT (group 1) [28].
• Radioimmunoassay of plasma equilin and estrone in postmenopausal women after the administration of premarin [29].
• In addition, OAT3 interacted with sulfated steroid hormones such as estrone-3-sulfate [30].

Gene context of Premarin

• The Km value for estrone-3-sulfate uptake by OATP-B (1.56 microM) was close to that for the high-affinity component observed in Caco-2 cells [31].
• Human organic anion transporter OAT4 is expressed in the kidney and placenta and mediates high-affinity transport of estrone-3-sulfate (E1S) [32].
• However, in the ER expressing cells the ability of IL-1beta to increase PAI-1 mRNA and protein levels was attenuated by 17beta-estradiol, tamoxifen and twelve estrogen components of Premarin [33].
• Additionally, comparisons were made of animals treated with PTH alone, 17alpha-ethynyl estradiol alone, equine estrogens (Premarin) alone, raloxifene alone, or combinations of PTH and equine estrogens or raloxifene [34].
• When initial uptake of estrone-3-sulfate, a typical substrate of OATP, was studied kinetically, we observed an increase in V(max) with decrease of pH from 7.4 to 5.0, whereas the change in K(m) was negligible [35].

Analytical, diagnostic and therapeutic context of Premarin

• After ovariectomy, the moderately atherogenic diet was continued, and they were treated (36 months) with a control diet (soy protein depleted of SPEs), a diet containing SPEs in soy protein isolate, or a diet containing SPE-depleted soy protein with conjugated equine estrogens (CEE; Premarin) added [36].
• The putative skeletal effects of dietary soy phytoestrogens (SPE) were examined in comparison with those of conjugated equine estrogens (CEE; Premarin) in a 3-yr longitudinal study in ovariectomized female monkeys [37].
• METHODS: We studied 120 postmenopausal women who underwent hysterectomy and who had AD treated with Premarin for 1 year [38].
• The effects of intracortical injections of penicillin, bicuculline, and conjugated estrogens (Premarin) were determined on EEG activity and motor performance [39].
• Quantitative in situ hybridization with an RNA probe for the 68-kDa neurofilament mRNA revealed a significant dose-dependent effect of Premarin on DRG neurofilament gene expression [40].

References