ABSTRACT
A Phase II multicentric study was carried out to compare the different contraceptive treatment schedules of the monthly injectable consisting of norethisterone oenanthate (NET OEN) 50 mg either given alone or in combination with estrogen esters, 2.5 or 5 mg of estradiol valerate (E2 Val.) or estradiol cypionate (E2 Cyp.). A total of 364 women were observed for 1686 months of use. Analysis of the bleeding pattern data indicated that NET OEN 50 mg when given alone gave rise to delayed cycles and/or amenorrhoea. However, the addition of estrogen esters in a dose of either 2.5 or 5 mg provided significantly better bleeding patterns. Of the different treatment schedules investigated, the combination of NET OEN 50 mg with E2 Val. 5 mg provided more consistent and better cycle control. These findings however need further validation on a larger study sample.
Subject(s)
Contraceptive Agents, Female/adverse effects , Estradiol/analogs & derivatives , Norethindrone/analogs & derivatives , Adult , Amenorrhea/chemically induced , Blood Pressure/drug effects , Body Weight/drug effects , Clinical Trials as Topic , Contraceptive Agents, Female/administration & dosage , Contraceptive Agents, Female/pharmacology , Estradiol/administration & dosage , Estradiol/adverse effects , Estradiol/pharmacology , Female , Humans , Injections , Menstruation/drug effects , Menstruation Disturbances/chemically induced , Norethindrone/administration & dosage , Norethindrone/adverse effects , Norethindrone/pharmacology , Oligomenorrhea/chemically induced , Random Allocation , Time FactorsSubject(s)
Cytarabine/analogs & derivatives , Cytarabine/metabolism , Leukemia, Lymphoid/metabolism , Leukemia, Myeloid/metabolism , Bone Marrow/metabolism , Cytarabine/therapeutic use , DNA, Neoplasm/biosynthesis , Drug Therapy, Combination , Female , Humans , In Vitro Techniques , Leukemia/drug therapy , Male , RNA, Neoplasm/biosynthesis , Tetrahydrouridine/pharmacology , Tetrahydrouridine/therapeutic use , Thymidine/metabolismABSTRACT
Antitumor agents cause selective lethal injury in tissues in which there is high proliferative activity. It is a reasonable postulate that the selective pathology is the consequence of interference with the replication of DNA in mitotically active cells. The crypt epithelium of the small intestine of rodents, which is highly susceptible to injury by antitumor agents, has served as a useful object for in vivo study of the relationship between inhibition of DNA synthesis and cell death in proliferating tissues. The lethal effects of highly selective inhibitors of DNA synthesis, such as hydroxyurea and 1-beta-D-arabinofuranosylcytosine, develop rapidly and are restricted to those crypt cells which are committed to DNA synthetic activity. Agents like methotrexate, which concurrently suppress DNA, RNA, and protein synthesis, induce more slowly developing and more persistent alterations. As illustrated in mice treated with 1-beta-D-arabinofuranosylcytosine and polyinosinic-polycytidylic acid, the necrotic process in intestinal epithelial cells involves rapid envelopment of degenerating organelles in cytolysomal vacuoles.
