CONTRIBUTORS Yasmin H. Ahmed Bangladesh Institute of Research for Promotion of Essential and Reproductive Health and Technologies (BIRPERHT) 25 Shyamoli, Mirpur Road Dhaka 1207 Bangladesh David Back Ph.D. The University of Liverpool Department of Pharmacology and Therapeutics New Medical Building Ashton Street Liverpool L69 3BX, United Kingdom Elizabeth Belsey Ph.D. Global Program on AIDS World Health Organization 1211 Geneva 27, Switzerland Leon Bradlow Ph.D. Strang Cornell Cancer Research Laboratory 510 East 73rd Street New York, New York 10021-4004 Judith Bruce Population Council 1 Dag Hammarskjold Plaza New York, New York 10017 257
258 Contributors Lincoln Chen M.D., M.P.H. Department of Population and International Health School of Public Health 665 Huntington Avenue Boston, Massachusetts 02115 Soledad Diaz M.D. Instituto Chileno Midicina Reproductiva Jose Victorino Lastarria 29 Depto. 101 Casilla 6006, Santiago, Chile Laneta Dorflinger Ph.D. Family Health International P.O. Box 13950 Research Triangle Park, North Carolina 27709 Kenneth Fotherby Ph.D. Royal Postgraduate Medical School University of London London WI2 ONN, United Kingdom Josue Garza-Flores M.D. Instituto Nacional de la Nutricion Salvador Zubiran Departamento de Biologia de la Reproduccion Col. Tlalpan Vasco de Quiroga 14000 Mexico, D.F. Barry Goldin Ph.D. Tufts University School of Medicine 136 Harrison Avenue Boston, Massachusetts 02111 Joseph Goldzieher M.D. Texas Tech University 1400 Wallace Boulevard Amarillo, Texas 79106 Gary S. Grubb M.D., M.P.H. Family Health International P.O. Box 13950 Research Triangle Park, North Carolina 27709
Contributors 259 Peter Hall World Health Oganization 1211 Geneva 27, Switzerland Siobhan Harlow Ph.D. Departamento de Epidemiologia Escuela de Salud Publica de Mexico Instituto Nacional de Salud Publica Cuernavaca, Morelos, Mexico Michael Humpel Ph.D. Schering AG Muellerstrasse 178 13342 Berlin Federal Republic of Germany Joan Kaufman Sc.D. Department of Population and International Health Harvard School of Public Health 665 Huntington Avenue Boston, Massachusetts 02115 Christopher Longcope M.D. Department of OB/GYN UMASS Medical School Worcester, Massachusetts 01655 Harold Nash Ph.D. The Population Council Center for Biomedical Research 1230 York Avenue New York, New York 10021 Carla Obermeyer Sc.D. Department of Population and International Health Harvard School of Public Health 665 Huntington Avenue Boston, Massachusetts 02115 Michael Orme M.D. The University of Liverpool
260 Contributors Department of Pharmacology and Therapeutics New Medical Building Ashton Street Liverpool L69 3BX, United Kingdom Dale Robertson M.D. The Population Council Center for Biomedical Research 1230 York Avenue New York, New York 10021 Guo-wei Sang M.D. Family Planning Research Institute of Zhejiang Zhejiang Academy of Medical Sciences Hangzhou, Zhejiang 310013, People's Republic of China Pramilla Senanyake Ph.D. International Planned Parenthood Federation Regent's College Inner Circle, Regent's Park London NW1 4NS, United Kingdom Rachel Snow Sc.D. Department of Population and International Health Harvard School of Public Health Boston, Massachusetts 02115 James Trussell Ph.D. Office of Population Research Princeton University Princeton, New Jersey 08544 Lucy E. Wilson M.S. University of Maryland School of Medicine 700 Portland Street Baltimore, Maryland 21230
INDEX Acceptability of steroid contraceptives, 187-196 Access to information on contraceptives, 191-192, 199,203,205 Acetylsalicylic acid, 116 Activated charcoal, 114 Acetylenic steroids, 115 Adsorbents interaction with oral contraceptives, 114 Africa contraception, 33-34, 38 regional trends in contraceptive side-effects, 2, 30 use of hormonal contraceptives, 1 African women, 30 Aluminum hydroxide, 114 Amenorrhea, 180 American women, 4, 88, 175, 201, 256 Americas use of hormonal contraceptives, 1 Ampicillin, 110-111 Analgesic drugs, 116 Androgens, 241 Androstenedione, 153, 162, 171-172 Anorexia nervosa, 180 Antacids, 114 Anticonvulsant drugs, 103, 105-107, 119 Antibiotics interactions with oral contraceptives, 109-111, 119 Arachidonic acids, 176 Asia and the Pacific contraception, 29 side-effects from hormonal use of sterilization and the IUD, 1 Asian women, 157, 162, 175,210 Australia Australian women, 88 Bangladesh family planning, 65 Bengali women, 65, 193-195,201 Benzpyrene, 175 Benzodiazepines, 115-116 Bioavailability studies, 248-249 Biological issues in acceptability of steroid contraceptives, 188-189 Bleeding, see Menstrual bleeding Bleeding patterns, and oral contraceptives, 29, 31-32 Body composition, 179-182, 214; see also Fatness Body fat, 70-72, 179-184, 214; see also Fat topography Body mass index (Quetelet index), 42, 45, 72, 176, 180 definition of, 49 Body weight, 19-20 body composition and, 180, estrogen metabolism and, 175,214-215 Brazil study of side-effects of Norplant, 29 Brazilian women, 29, 88, 193, 195 British women, 4, 29, 78, 220, 223 Canada Canadian women, 88 Cancer breast, 173-176 endometrial, 176 Carbamazepine, 103, 105-106 Caribbean side-effects from hormonal Caucasian women, 157, 162 CEE, see Quinestrol Chile post-marketing survey of use of Norplant, 16-20 side-effects from use of Norplant, 29-30 261
262 Chilean women, 19-20, 29-30, 215, 217 China contraception, 29, 37 post-marketing survey of use of Norplant, 16-20 Chinese women, 4, 19-20,24, 30, 61, 78, 81, 189,220 serum levonorgestrel levels after three doses, 227 serum norethisterone levels after long-term use, 226 side-effects from use of levonorgestrel, 223 variation between dose and serum norethisterone levels in, 223-224 Choice of contraceptives, 249-250 convenience vs. control, 207-208 diet and, 213-214 effectiveness, 209 ensuring method switching instead of discontinuation, 190-191,210-211 irregular bleeding and, 210 lactational amenohorrea and, 215-217 risk and effectiveness implications, 200-205 for policy makers, 202 for program managers, 202-203 for providers, 204-205 for scientists, 200-201 service approaches to, 191 side-effects, 209, 214-217 Clarithromycin, 110 Clinical trials, 247-249, 255 Condoms, 12 Corticosteroids, 117 Cotrimoxazole, 110 CycIosporin, 116 Cytochrome, 103 Danish women, 29 De-ethinylation, 145 Denmark study of side-effects of Norplant, 29 Depot medroxyprogesterone acetate, 70-72, 27, 30-32, 35, 45, 47-48 body weight and, 226 effect of dose reduction, 72, 211 effect of particle size, 76 pharmacokinetics of, 78, 179, 224 ovulation and, 241-243 recent research on, 45 regional studies of, 35 side-effects, 4, 188-189 Depo-Provera, see Depot medroxyprogesterone acetate Desogestrel, I 17-1l8 Snow. Hall. eds. Developing countries, 187-196 Diabetes, 182 Diarrhoea, I I Diet American, 175 Asian, 175 body composition and, 180 carbohydrate, 174 contraceptive steroid metabolism and, 128, 179,214 cruciferous vegetables in, 176 endogenous steroids and, 179,214 estrogen metabolism and, 143-149, 153-168, 171-177,213-215,239 high fat, 146-147, 156, 168 high protein, 148-149, 174 high fiber, 156, 168, 175 indoles, 148-149, 176-177 lacto-ovo, 162 low carbohydrate, 148-149 low fat, 146-147, 149, 155-156, 168 low fiber, 168, 175 omnivorous, 156-157, 162 vegan, 162 vegetarian, 155-157 Dimethylbenzan-thracene, 175 Discontinuation of contraceptives, 3, 41, 61-67, 210 DMPA, see Depot medroxyprogesterone acetate Dominican Republic study of side effects of Norplant, 29 Dominican women, 29 Drug interactions, see Pharmacological interactions East African women, 204 East Asian women, 157, 162 Ecuadorian women, 193 EE, see Ethinyl estradiol Effectiveness of contraceptives, 199-200, 202 Egypt contraception, 29-30 Egyptian women, 29-30, 203 Enterohepatic recirculation, 134, 153-156, 214, 252 Estradiol estrogen metabolism and, 143-149, 153-155,162,171-172,175-176,181 increased dietary cholesterol and, 167 low concentration in women of low fatness, 180 low fat diet and, 155 levels in lactating women, 216 omnivorous diet and, 156 ovarian function and, 183 vegetarian diet and, 157 Estradiol cypionate, 31, 241
Steroid Contraceptives and Women's Response 263 Estradiol valerate, 31, 223, 241 Estriol, 155, 162, 172, 181 Estrogen body weight and production of, 172 honnone ratios for, 243 variability in response to steroid contraceptives, 239, 240-242 Estrogen metabolism biological variability of, 252 body weight and, 181 diet and, 143-149, 153-168, 171-177, 239 fat topography and, 239 low fatness and, 181-182 Estrogen sulfates, 153 Estrogens, 34, ll7-ll8, 127, 130; see also individual compounds Estrone, 144-145, 153-157, 162, 171-172, 180-181 Estrone sulfate, 144-145 Ethanol, 117 Ethinyl estradiol, 3-4, 85-89 bioavailability as free honnone, 243-244 effect on serum sex honnone-binding levels, 138 interaction between progestogen and estrogen, 117-118 interaction with anticonvulsant drugs, 105 interaction with paracetamol, ll3 interaction with rifampicin, 103, 112 interference from troleandomycin, 119 interference with the metabolism of other drugs, ll5 intersubject variability, 219 metabolism of, 145-146, 149 pharmacokinetic parameters, 129 physiological factors affecting serum concentrations, 126-127 serum concentrations following administration, 241 variability between individuals in absorbing a dose, 131, 133-134 Ethosuximide, 105 Europe contraception, 29, 33, 36 contraception, 2 side-effects from honnonal trials of steroid contraceptives, 34-35 European women, 29-30, 56, 78 Family planning services choice of methods, 190-191,200-205, 207-2ll,213-214 providers, 192-194, 204-205 Family planning services (con't) quality of care, 187-196 Fat topography, 179-184, 239; see also Body fat android obesity, 182 gynoid obesity, 182 Fatness, low, 180-181 Fecal excretion of steroids, 154, 156 Femodene, 138 Filipino women, 200 Finland study of the side effects of Norplant, 29 Finnish women, 29 Free vs. bound steroids, 243-244 Gestagens, 127, 130 Gestodene, 117 -ll8, 137 Glucuronides, 144-145, 147-148, 153-154 GnRH, see Gonadotropic releasing honnone Gonadotropic releasing honnone, 180-181 Griseofulvin, ll2 Guatemala contraception, 2 Gynecomastia, 176 Health risks, 189, 192-193 Hepatic cholestasis, 115 Herpes virus, 176 Honduran women, 194 Honnonal contraceptives bleeding patterns, 27-30 health risks from, 189 ovulation and, 243 variation in absorption of, 239 Honnones environmental effects on, 58 free, 243-244 ovarian, 181 bleeding patterns associated with, 56 Hyper-insulinemia, 182-183 Hyperlipidemia, 182 Hypertension, 182 India contraception, 29, 34, 37 contraception, 3-4, 30 trials of steroid contraceptives, 34-35 Indian women, 3-4, 29-30 Indonesia side-effects from honnonal Indonesian women, 30, 81, 190-191, 194,222 Infonnation, see Access to infonnation on contraceptives
264 Injectable contraceptives access to, 191, 31, 34-35, 37-38, 42 body weight and bleeding patterns, 45 body weight and the pharmacokinetics of contraceptive steroids, 127-128 factors influencing serum concentrations, 126 ovulation and, 241-243 prevalence of use, 69-70 side-effects from, 1, 239 Insulin, 182-183 Intra-uterine devices effectiveness of, 209 prevalence of use, 1 side-effects, 17, 19,22-24, 61 variable dosing, 211 IUDs, see Intra-uterine devices Iran women's perception of contraceptives, 64 Iranian women, 64 Islamic women, 189 Jamaica contraception, 29 women's perceptions of the effects of contraceptives, 64 Jamaican women, 29, 64 Jewish women, 189 Kaolin,114 Kenya contraception, 2 Kuwait family planning, 65 Kuwaiti women, 65 Lactational amenorrhea, 214-217 Latin America contraception, 29, 33, 37 contraception, 2 side-effects from hormonal trials of steroid contraceptives, 34-35 Latin American women, 29-30 Levonorgestrel, 30, 91, 95-96, 98 access to, 191 body weight and, 4 comparison of bleeding patterns, 29-30 factors influencing senim concentrations, 126-127 free hormones and, 244 Snow, Hall, eds. Levonorgestrel (con't) interaction with anticonvulsant drugs, 105 interaction with paracetamol, 113 intersubject variability, 130-131,219 pharmacokinetics, 5, 130 potential for widespread use, 61-62 results of post-marketing survey, 26 serum concentrations after insertion, 220-223 side-effects complaints of users, 16-19, 25-26 discontinuation due to, 210 linked to variability in steroid metabolism, 188-189,239-240 ovarian activity, 214-215 social science perspective, 62-64 symbolic aspects, 64-68 Levonorgestrel butanoate, 81 Levonorgestrel implants, 91-10 1, 100 side-effects associated with, amenorrhea, 101 anxiety, 101 breast discharge, 101 headaches, 101 nervousness, 10 1 weight gain, 101 Linoleic acids, 176 Liver metabolism, 116,153-154,180,214,217, 252 LNG, see Levonorgestrel Lorazepam, 116 Low income women, 193 Lower-weight women, 210 Magnesium trisilicate, 114 Marvelon, 138 Men's roles in contraception, 205 Menstrual bleeding, 27-49 Amenorrhea, 175, 180,216 Defmition of, 28 Menarche and, 47 Irregular, 210 Parity and, 47 Social aspects of, 64 Variability of, 27-49, 55-59 Menstrual dysfunction, 180-181, 189 Mestranol, 86-87 Metabolism, estrogen, see Estrogen metabolism Methylphenobarbitone, 105 Mexican women, 4, 29,76,74,78, 81, 179 relationship between dose and serum concentration of Depot medroxyprogesterone acetate, 224
Steroid Contraceptives and Women's Response Mexico contraception, 29 effect of contraceptive dose reduction, 72 effect of particle size of Depot medroxyprogesterone acetate, 76 MPA, see Depot medroxyprogesterone acetate Moslem women, 192 Myocardial infarction, 182 Nepal contraception, 2 NET, see Norethisterone NET-EN, see Norethisterone enanthate Nigeria contraception, 3-4 Nigerian women, 3, 88 Norethindrone, 86, 241 Norethindrone enanthate, 242 Norethisterone, 105, 112, 126, 224 Norethisterone acetate, 30, 70-72, 211, 224, 226 Norethisterone enanthate, 3-4, 31, 41, 78, 127, 179,220 Norplant, 30, 91, 95-96, 98 access to, 191 body weight and, 4 comparison of bleeding patterns, 29-30 dosage, 210 factors influencing serum concentrations, 126-127 free hormones and, 244 interaction with anticonvulsant drugs, 105 interaction with paracetamol, 113 intersubject variability, 130-131,219 pharmacokinetics, 5, 130 potential for widespread use, 61-62 results of post-marketing survey, 26 serum concentrations after insertion, 220-223 side-effects complaints of users, 16-19, 25-26 discontinuation due to, 210 linked to variability in steroid metabolism, 188-189,239-240 ovarian activity, 214-215 social science perspective, 62-64 symbolic aspects, 64-68 North Africa contraception, 38 trials of steroid contraceptives, 34-35 North African women, 30 Obesity, see Body fat Oestradiol, 127 Oral contraceptives, 255-256 1-2, 12, 29, 31, 47 access to, 191, 29, 31, 33-34, 37-38, 45, 47-48 convenience factor, 208 effectiveness of, 200, 209 interference with the metabolism of other drugs, 115-117 minimizing steroid exposure, 211 pharmacological interactions with, 103-118 sexual relationships and, 12 side-effects from, 1-2, 188-189, 239-240 Ovarian function, 183 Ovulation, 241-243 265 P450 isoenzymes, 103, 109-110, 112, 114-115, 118, 177; see also Liver metabolism Pakistan contraception, 29, 34, 37 side-effects from hormonal trials of steroid contraceptives, 34-35 Pakistani women, 29-30 Paracetamol, 113, 119 Penicillin, 109 Pharmacokinetic parameters, 133-140 description of, 85 use in population studies, 219-236 Pharmacological interactions, 103-119, 176-177, 188, 214 Phenobarbitone, 103, 105-106 Phenytoin, 103, 105-106 Pill, the, see Oral contraceptives Polycystic ovaries, 182 Population pharmacokinetics, 219-236 Population policy, 202-203 Population surveys, 249-250 Post-menopausal women, 173 Primidone, 105 Progesterone, 180, 216, 241-242 Progestin, 215, 239, 240-244 Progestogen, 2, 30, 34, 115, 118, 134-137 Prolactins, 167, 216 Quetelet index, see Body mass index Quinestrol, 227 Research methods, 49, 233-236, 249-250, 255 Research needs, 183-184,227-233,244-245, 247-256 Rifampicin interaction with oral contraceptives, 103, 111-112,119
266 Salicylic acid, 116 Sex hormone-binding globulin anticonvulsant drugs and, 105 biological variability in metabolizing, 252 body weight and, 4, 128 diet and, 128, 167, 214 distribution of serum levels after oral contraceptive treatment, 13 7-138, 226-227 fat typography and, 180, 182 insulin and, 183 level decreased by androgens, 241 low fatness and, 181 obesity and, 182 pharmacokinetics, 4-5 physiological factors affecting serum concentrations, 126-127 Scottish women, 215 Sex steroids, 180-181, 183 SHBG, see Sex hormone-binding globulin Side-effects of contraceptives acceptability of contraceptives and, 187-190 bleeding problems, 27-49 cultural and personal issues, 189-190 fear of, 2 health risks from, 194-195, 199-202, 204, 209 implications, 5 regional trends, 1-3 relation to estrogen to progestin ratio, 243 social and cultural factors, 62-66 spotting, 28, 31 Smoking, 114, 128-129, 176, 193 Sodium valproate, 103, 106 South East Asia, 33, 34-35 contraception, 36-37 South East Asian women, 29-30 Sri Lanka post-marketing survey of use of Norp1ant, 16-20 Sri Lankan women, 19-21, 88, 192 Sterilization, 1, 17,207,210 contraception, 3-4 Swedish women, 3-4, 226 Tagamet, 176 Temazepam, 116 Temafloxacin, 110 Testosterone, 171 Tetracycline, 109-110 Thai women comparison of response to steroid contraceptives by region, 3-4 Snow. Hall. eds. Thai women (con't) pharmacokinetic studies in obese and thin women, 72-76 relationship between dose and serum concentration of Depot medroxyprogesterone acetate, 78, 81, 179,224 study of side-effects among Norplant users, 19-21, 30 Thailand effect of contraceptive dose reduction, 72 effect of particle size of Depot medroxyprogesterone acetate, 76, 81 post-marketing survey of use of Norplant, 16-20 contraception, 3-4 side-effects from hormonal side-effects from injectable steroids and oral contraceptives, I Troleandomycin, 115, 119 United Kingdom; see also British contraception, 29 contraception, 4 United States; see also American contraception, 3-4 Vaginal rings, 35, 37-38, 45, 47 comparison of bleeding patterns, 30-32 factors influencing serum concentrations, 126 variable dosing, 211 Variability of response to steroid contraceptives, 187-196,239-240 Vietnamese women, 157 Vitamin C, 112 Weight, see Body weight Yugoslavia contraception, 29 Yugoslavian women, 29 Zantac, 176