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Effect of long-term continuous combined hormone replacement therapy with estradiol valerate and either dienogest or norethisterone acetate on mammographic density in postmenopausal women.

INTRODUCTION: The potential effect of hormone replacement therapy (HRT) on the appearance of the breast on screening mammography is of considerable interest and may have important practical implications. OBJECTIVE: The aim of this study was to evaluate the changes in the mammographic breast density during long-term continuous combined HRT with 2 different preparations. MATERIAL AND METHODS: Nineteen patients were studied. Fifteen were treated with Climodien (Schering, 2 mg estradiol and 2 mg dienogest [E2/dienogest]), and 4 patients were treated with Kliogest (Novo Nordisk, 2 mg estradiol and 1 mg norethisterone acetate [E2/NETA]). All were followed with yearly mammography for 4 years. RESULTS: Increase in the mammographic density was noted in 3 patients (15.8%). The change was evident after the first year of treatment with no further change during the rest of the study period. CONCLUSIONS: Long-term therapy with continuous combined HRT (E2/dienogest or E2/NETA) increased breast density in 3/19 (15.8%) of the patients. Our results suggest that the effect of these HRT preparations on mammographic density may be less significant than suggested by the results of similarly designed trials evaluating different HRT preparations.

Aged↗

Mechanistic studies on N-benzyladriamycin-14-valerate (AD 198), a highly lipophilic alkyl adriamycin analog.

AD 198, a novel lipophilic N-alkyl derivative of adriamycin (ADR) and a potential anticancer agent for preclinical development, was studied for its effects on the activities of DNA and RNA polymerases in vitro and its ability to bind DNA. AD 198, which contains a benzyl substituent on the glycosidic amine, was found to interact with DNA through drug-DNA binding to an extent less than its parent compound ADR as shown by fluorescent emission spectra studies. It had a preferential inhibitory effect against RNA vs. DNA synthesis in vitro by RNA or DNA polymerases from both E. coli and chicken leukemia cells. Preincubation studies indicated that AD 198 may inhibit the activity of E. coli RNA polymerase through drug-template interaction and that of leukemic RNA polymerase, which uses single stranded DNA as template, through enzyme inactivation.

Animals↗