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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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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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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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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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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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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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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
Representative terms from entire chapter:
cervical ripening
