Index

A

Abortion, 2, 72, 92, 106

animal studies, 58-59, 265-266

cervical ripening for, 32, 96-97, 175, 177-179

dosages, 26-27, 28, 31, 94, 166, 168-170, 185-186

enzymatic inhibitor use, 73, 258

first trimester, 6-7, 26-29, 92-96, 149, 164-172, 174

protocols, 27, 29-30, 166

research needs, 6, 7, 29, 30, 31-32

second trimester, 7, 30-32, 97, 175, 186-187

service delivery and access, 6, 29-30, 95-96, 106, 168, 183-185

side effects, 27-28, 78, 94, 167, 175, 186

success rates, 27, 28, 94, 165, 166, 167

Acceptability (to patients), 6-7, 30

Adenocorticotropic hormone (ACTH), 38, 43, 45, 52-54, 102, 104, 192 -193, 229-231, 234-235, 244

Adjuvant therapy, for breast cancer, 11, 45-46

Adrenal insufficiency, 53, 55

AIDs, 105

Alzheimer's disease, 105

Amenorrhea, 4, 21

Animal models and studies, 15, 57-61, 262-266

abortifacient use, 58-59, 265-266

antiestrogenic effects, 247-249

breast cancer, 11, 43-44, 47, 60, 217-219

endometriosis therapy, 37-39

and labor induction, 8, 33, 34, 59-60

Antiandrogen effects, 235, 239, 240

Antiestrogenic effects, 9, 10, 153-154, 244-245, 247-249, 269-270



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Clinical Applications of Mifepristone (RU 486) and other Antiprogestins: Assessing the Science and Recommending a Research Agenda Index A Abortion, 2, 72, 92, 106 animal studies, 58-59, 265-266 cervical ripening for, 32, 96-97, 175, 177-179 dosages, 26-27, 28, 31, 94, 166, 168-170, 185-186 enzymatic inhibitor use, 73, 258 first trimester, 6-7, 26-29, 92-96, 149, 164-172, 174 protocols, 27, 29-30, 166 research needs, 6, 7, 29, 30, 31-32 second trimester, 7, 30-32, 97, 175, 186-187 service delivery and access, 6, 29-30, 95-96, 106, 168, 183-185 side effects, 27-28, 78, 94, 167, 175, 186 success rates, 27, 28, 94, 165, 166, 167 Acceptability (to patients), 6-7, 30 Adenocorticotropic hormone (ACTH), 38, 43, 45, 52-54, 102, 104, 192 -193, 229-231, 234-235, 244 Adjuvant therapy, for breast cancer, 11, 45-46 Adrenal insufficiency, 53, 55 AIDs, 105 Alzheimer's disease, 105 Amenorrhea, 4, 21 Animal models and studies, 15, 57-61, 262-266 abortifacient use, 58-59, 265-266 antiestrogenic effects, 247-249 breast cancer, 11, 43-44, 47, 60, 217-219 endometriosis therapy, 37-39 and labor induction, 8, 33, 34, 59-60 Antiandrogen effects, 235, 239, 240 Antiestrogenic effects, 9, 10, 153-154, 244-245, 247-249, 269-270

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Clinical Applications of Mifepristone (RU 486) and other Antiprogestins: Assessing the Science and Recommending a Research Agenda Antiglucocorticoid effects, 1, 13, 16, 52, 55, 76, 78, 104-105, 140 -141, 234-239, 244 of cancer therapy, 10, 21, 40, 41, 236 of endometriosis therapy, 9, 38, 39 of low dosages, 4, 9, 21 research needs, 13, 55, 239-240 therapeutic, 13, 53-55, 170, 234-235, 239-240, 271 Antihormone antibodies, 73 Antitumor effects, 11, 43-44, 47, 103-104, 106, 217-219, 235-236 Apoptosis, and breast cancer therapy, 12, 43, 103 Arthritis, 55, 236 Azastene, 258 B Biosynthesis inhibition, 73, 257-259 Bone retention and loss, 4, 10, 21, 22, 38, 40 Brain, see Meningiomas; Mood effects Breast cancer, 11, 41-47, 91, 103-104, 105, 210, 271 animal studies, 11, 43-44, 47, 60, 217-219 dosages, 12, 46, 48 and oral contraceptives, 20 progesterone receptors, 11, 12, 42-43, 48, 123-124, 133, 213-217, 220-222 research needs, 11-12, 47-48, 222-224 and side effects, 12, 45 C Cancer and tumors, see Antitumor effects; Breast cancer; Meningiomas; Uterine leiomyomas Cardiovascular effects, of prostaglandin, 27-28, 94, 167 Cataracts, 55, 236 Cervical mucus, 139-140, 141 Cervical ripening, 7-8, 32-33, 96-97, 165, 270 for abortion, 32, 96-97, 175, 177-179, 270 dosages, 32, 177-178 side effects, 32 Cesarean section, 34 Chemoprevention, for breast cancer, 11, 45-46 China, abortifacient use and licensing, 149, 271 trials, 265 Cholesterol, 140 Chromatin modification, 88 Clinical trials, 2-3, 18 abortifacient use, 6, 7, 29, 31-32, 165, 166-167, 168-170, 176 breast cancer therapy, 11-12, 44-45, 47-48, 60, 103, 219-220, 223 cervical ripening, 177-179 contraceptive use, 4, 22, 160 endometriosis therapy, 10, 38-39, 189, 190, 192-197 leiomyoma therapy, 10, 189-190, 198-207 meningioma therapy, 13, 49, 50 post-coital contraception, 5, 23, 160 Complications, see Antiglucocorticoid effects; Side effects and toxicity Conception, 19 Contraception, definition, 72, 98. See also Contraceptive use; Menses induction; Oral

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Clinical Applications of Mifepristone (RU 486) and other Antiprogestins: Assessing the Science and Recommending a Research Agenda contraceptives Contraceptive use, 3-4, 20-21, 22, 99-102, 106, 187 dosages, 3, 4, 20-21, 141-142, 159 endometrial, 100-101, 148, 157 follicular phase administration, 3, 20, 141-142, 144, 145, 148, 150, 153, 156 luteal phase administration, 3, 20-21, 99-100, 143, 148, 157-158 for males, 101-102 post-coital, 4-5, 22-23, 98, 99, 143, 148, 157-158, 187 research needs, 4, 22, 106, 144, 160 side effects, 4, 21, 22 Contragestion, 72, 98-99. See also Menses induction Contraindications, abortifacient use, 6, 28, 29, 167 Corpus luteum, 3, 14, 19, 21, 150, 253-254 progesterone production, 6, 15, 26, 164 Cortisol antagonism, 54, 76, 104, 141 Cushing's syndrome, 1, 13, 53-54, 105, 234-235, 236, 271 D Danazol in endometriosis therapy, 9, 37, 191 as post-coital contraceptive, 22-23 Depression, 238, 270 Developing countries, abortifacient access, 96, 106 Development of antiprogestins, 1, 71-72, 76, 149, 259-260 Dexamethasone, 54, 55 Dilapan, 31, 97, 175, 187 Dilation and evacuation (D&E), 7, 31, 187 Dimerization, 87, 122, 129-130 DNA binding, 87-88, 120-125 passim, 127, 129-130 Dosages, 140 abortifacient use, 26-27, 28, 31, 94, 166, 168-170, 185-186 breast cancer therapy, 12, 46, 48 cervical ripening, 32, 177-178 contraceptive use, 3, 4, 20-21, 141-142, 159 Cushing's syndrome, 54 endometriosis therapy, 9 labor induction, 8, 33-34 leiomyoma therapy, 10, 40-41, 102 menses induction, 5 ovulation inhibition, 154-156 post-coital contraception, 22-23, 156-157 E Ectopic tissue, see Endometriosis Endometrial contraception, 100-101, 148, 157 Endometriosis, 8-9, 10, 36-39, 92, 102, 189, 190-197, 271 Endometrium, 3, 19, 21, 90-91, 150, 152-153 effects of contraceptive use, 4, 21, 22 End points, 140-141 Enzymatic inhibitors, 73, 257-259 Epidermal growth factor, 12, 48 Epostane, 73, 258-259 Estradiol, 9, 15, 22, 39, 73-74, 144 Estrogen, 14, 19, 139-140 and breast cancer, 42 and long-term use, 10, 144

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Clinical Applications of Mifepristone (RU 486) and other Antiprogestins: Assessing the Science and Recommending a Research Agenda and low dosages, 21, 39, 142 see also Antiestrogenic effects Estrogen receptors, 10, 15, 74-75, 153-154, 268-270 and breast cancer, 11, 42 F Fertility effects, 10 of mother's use, 8, 34 Fetal demise and cervical ripening, 7-8, 32, 33 labor induction, 33, 175 Fibroids, see Uterine leiomyomas Follicle-stimulating hormone (FSH), 14, 91, 102, 150 Follicular phase, 9, 14, 19, 20, 140 contraceptive administration over, 3, 20, 141-142, 144, 145, 148, 150, 153, 156 Food and Drug Administration, 6, 29, 30, 32 France, abortifacient use and licensing, 2, 6, 27, 29, 93, 149, 166 G Gemeprost, 27, 28, 31, 94, 166, 167, 169 Glaucoma, 92, 105, 236, 238, 271 Glucocorticoids, 1, 13, 52-53, 229-234. See also Antiglucocorticoid effects Gonadotropin-releasing hormone (GnRH) and agonists, 14, 91 and endometriosis therapy, 37, 39, 191 and leiomyoma therapy, 9, 40, 198 Gynecomastia, 235, 239 H Half-life, of mifepristone, 77-78, 140 Heat shock protein binding, 86-87, 123, 127, 128 Heterodimerization, 87 Hospitalization, second-trimester abortion, 7, 31, 175, 187 Human chorionic gonadotropin, 91, 93, 99, 100, 150, 158, 170, 247-249 Human papillomavirus, 102-103 Hypercortisolism, 235, 271 Hypertension, 27, 55, 105, 236-237, 239, 270 I Immune suppression (protection against), 105, 237 infertility, and endometriosis, 8, 9, 36, 37 Inflammation, 55, 236, 237 Insulin-like growth factor, 12, 48 Intrauterine devices, 98 Intraocular pressure, 54, 236 L Labor induction, 8, 33-34, 97, 179-180, 186-187 animal studies, 8, 33, 34, 59-60 cervical ripening for, 7, 32, 270 Lactation, 8, 33, 34, 139 Lamicel dilator, 97, 187 Laminaria tents, 31, 97, 175, 187 Leiomyomas, see Uterine leiomyomas Licensing, see Regulatory approval Ligand binding, 81-82, 84-85, 121, 122 Lilopristone, 16, 77, 78, 260

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Clinical Applications of Mifepristone (RU 486) and other Antiprogestins: Assessing the Science and Recommending a Research Agenda Lipid profiles, 140 and contraceptive use, 4, 21, 22 Local administration, 54, 236, 238, 239 Long-term administration, 3-4, 18, 21, 105, 195-197 side effects, 3, 18, 143-144, 196 Low-dosage administration, 4, 21, 22 Luteal phase, 6, 15, 19, 38, 140, 150, 152-153 and breast cancer, 42 contraceptive administration over, 3, 20-21, 99-100, 143, 148, 157 -158 and menses induction, 5, 23 and post-coital administration, 156-158 Luteinizing hormone (LH), 14, 40, 91, 102, 140, 141-142, 150 M Male contraception, 101-102 Mechanisms of action, 2, 18, 76-78 cervical ripening, 175, 177 myometrial gap junctions, 268 ovulation inhibition, 154-156 prostaglandin metabolism, 266-268 receptor mediation, 78-89, 120-130, 268-270 reproductive effects, 89-92, 141, 149-154, 164-165 research needs, 2, 18, 134-135, 144, 159-160 transcription activity, 75, 84, 88-89, 121-123, 127-128, 130-135 Meningiomas, 12-13, 48-50, 104 and side effects, 13, 21, 49 Menses induction, 5, 23-24, 98, 171 Menstrual cycle, 3, 19 contraceptive administration over, 3-4, 141-143 and endometriosis, 8 progesterone production, 3, 4-5, 19, 140 see also Follicular phase; Luteal phase; Menses induction Metabolism, 76-77, 237, 240 of prostaglandin, 266-268 Miscarriage, see Abortion; Fetal demise Misoprostol, 28, 30, 94, 95, 99, 100, 169-171 Mood effects of contraceptive use, 4, 21, 22 of progesterone, 140 Morning-after pill, 4, 22 Muscular deterioration, 54 Myocardial infarction, from abortifacient use, 27-28, 94 Myometrium, 31, 32, 40, 90, 139, 164, 268 Myopathy, 54 N Neonatal effects, 8 of labor induction, 33, 34, 97, 180 of unsuccessful abortion, 28, 167 New Drug Application, for abortifacient use, 6, 30 Norethisterone, 142 Novel antiprogestins, research needs, 106, 107 O Obesity, 105 Older women, and abortifacient use, 6, 28, 29, 167

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Clinical Applications of Mifepristone (RU 486) and other Antiprogestins: Assessing the Science and Recommending a Research Agenda Onapristone, 16, 78, 153, 260 breast cancer therapy, 42, 43, 44, 46 Oral contraceptives, 14, 20, 71, 187 in endometriosis therapy, 37 post-coital use, 4, 5, 22, 23, 156 side effects, 20, 156 Organon, 16-17, 260 Orosomucoid binding, 77, 264-265 Osteoporosis, 4, 10, 21, 22, 38, 40 Ovarian cysts, 4, 21, 36-37 Ovulation, 14, 58 Ovulation inhibition, 3, 16, 91, 148, 154-156 contraceptive application, 4, 21, 101, 142, 156-157 Oxytocin, 8, 34, 97, 179 P Pain and pain relief abortion, 94, 169, 170, 171 breast cancer therapy, 44 endometriosis therapy, 38, 102, 193 Phosphorylation, 123-124, 133 Pituitary gland, 14, 16 Placenta, progesterone production, 3, 19, 164 Post-coital contraception, 4-5, 22-23, 98, 99, 143, 148, 157-158, 187 failure rates, 157-158 research needs, 160 side effects, 22-23, 156 Pregnancy, 1, 72 animal models, 58-60 progesterone role, 1, 3, 72, 139, 149, 164 see also Abortion; Cervical ripening; Fetal demise; Labor induction Premenstrual syndrome, progesterone effects, 140 Progesterone, 1, 4-5, 14, 16, 72, 254 and breast cancer, 42, 212-213 menstrual cycle production, 3, 4-5, 19, 140 and normal breast function, 211-212 ovarian production of, 3, 6, 15, 26 placental production, 3, 19, 164 pregnancy role, 1, 3, 72, 139, 149, 164 Progesterone receptors, 72, 254, 263-264 animal models, 57-58 of breast tumors, 11, 12, 42-43, 48, 123-124, 133, 213-217, 220-222 of leiomyomas, 9, 40 mechanisms of action, 81-89, 120-135, 149, 268, 269 membrane-bound, 134 of meningiomas, 12, 48-49 Programmed cell death, see Apoptosis Prostaglandin abortifacient use, 6, 7, 26-29, 31, 93-96, 165-171 passim, 175, 255, 258 and cervical ripening, 8, 32-33, 165 contraceptive use, 3, 158 and menses induction, 5, 24 metabolism, 266-268 side effects, 27-28, 94, 167, 175, 186 see also Gemeprost, Misoprostol, Sulprostone

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Clinical Applications of Mifepristone (RU 486) and other Antiprogestins: Assessing the Science and Recommending a Research Agenda Protocols, abortion, 27, 29-30, 166 Psychosis, 105 R Receptors, see Estrogen receptors; Progesterone receptors Regulatory approval, 6, 30 France, 2, 27, 93 Sweden, 2, 27 United Kingdom, 2, 27 Research Triangle Institute, 16-17, 245-246 Resistance to antiprogestins, of tumors, 12, 46, 220-222 Risk assessment, 4, 6, 29 Roussel-Uclaf, 16-17, 75-76, 149, 259 abortion protocol, 29-30, 166 S Saline injection, 7, 31 Schering AG, 16-17, 78 Septic shock, 105 Sexual behavior effects, 91 Side effects and toxicity abortifacient use, 27-28, 94, 167, 175, 186 breast cancer therapy, 12, 45 cervical ripening, 32 contraceptive use, 4, 21, 22 endometriosis therapy, 9, 10, 38, 191, 193-194, 196 leiomyoma therapy, 21, 40-41, 201 long-term use, 3, 18, 143-144, 196 meningioma therapy, 13, 21, 49 of oral contraceptives, 20, 156 post-coital contraception, 22-23, 156 of prostaglandin, 27-28, 94, 167, 175, 186 see also Antiglucocorticoid effects Smoking, and abortifacient use, 6, 28, 29, 167 Southwest Oncology Group, 13, 50 Special Programme of Research, Development and Research Training in Human Reproduction, 254-255, 257 Steroid-induced myopathy, 54 Sulprostone, 27, 28, 93-94, 166, 167 Surgical abortion, 6, 7, 31, 187 after mifepristone failure, 28, 94, 167 cervical ripening for, 175, 177-179 Sweden, abortifacient use and licensing, 2, 6, 27, 94, 149, 166 T Tamoxifen, 42, 44-45, 46, 74-75, 217-218, 223 Tenascin, 43 Teratogenicity, 28, 167 Testosterone, 37 Topical administration, 54, 236, 238, 239 Toxicity, see Antiglucocorticoid effects; Side effects and toxicity Transconformation, 85-86 Transcription activity, 75, 84, 88-89, 121-123, 127-128, 130-135 Transforming growth factor, 12, 48

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Clinical Applications of Mifepristone (RU 486) and other Antiprogestins: Assessing the Science and Recommending a Research Agenda Triphenylethylene derivatives, 73-74 Tumors, see Antitumor effects; Breast cancer; Meningiomas; Uterine leiomyomas U United Kingdom, abortifacient use and licensing, 2, 6, 27, 94, 149, 166 Uterine contractility, 164-165 Uterine leiomyomas, 9-10, 39-41, 92, 102-103, 189-190, 197-207, 271 dosages for, 10, 40-41, 102 research needs, 10 and side effects, 21, 40-41, 201 Uterine perforation, 7, 32 V Viral disease, 54 W Wound healing, 55, 92, 105, 236, 270, 271 Y Yuzpe regimen, 156 Z ZK 98 299 antiprogestin, 125, 130, 133, 219 ZK 112 993 antiprogestin, 43, 78