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48 Health Effects of Contraception Nancy C. Lee, Herbert B. Peterson, and Susan Y. Chu INTRODUCTION Until the 1960s rhythm and barrier contraceptives were the only methods of birth control widely available to couples desiring to plan the number and spacing of their children. In the 1 960s oral contraceptives (OCs) were introduced and new efficacious intrauterine devices (IUDs) became widely available, so that the choice of effective methods of contraception increased substantially. Later, in the 1970s, female and male sterilization techniques became much more widely ac- cepted and used. Couples were then able to choose from several different temporary and permanent methods of contraception and to switch from one to another. Worldwide, family planning programs expanded, and the prevalence of contraceptive use increased. As these methods of contraception became more widely used, anecdotal re- ports of adverse health effects associated with their use began to appear. Since the late 1960s and early l970s, epidemiologic studies have more rigorously evaluated the health effects associated with the use of different contraceptive methods. Most of these studies have been conducted in the United States and Europe. In the process researchers have recognized that different contraceptive methods have Nancy C. Lee and Herbert B. Peterson are deputy chief and chief, respectively, of the Epidemiologic Studies Branch, Division of Reproductive Health, Center for Chronic Disease Prevention and Health Promotion of the Centers for Disease Control. Susan Y. Chu is epidemiologist in the Special Projects Section, Surveillance Branch, AIDS Program, Center for Infectious Diseases, of the Centers for Disease Control. 48

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IlEALTH EFFECTS OF CO=RACE"ION 49 important beneficial health effects, in addition to the desired effect of preventing pregnancy. Although much research is still needed, especially targeted to the developing world, a large body of information is now available to assess the health effects of the venous contraceptive methods. The various contraceptive methods have health risks, but pregnancy itself has attendant risks of morbidity and mortality. In 1983, Ory et al. attempted to quantify the mortality risks associated with using the various methods of contra- ception. Those risks were compared with the risks associated with using no method of contraception, which are actually the mortality risk associated with pregnancy. These estimates are presented in Table 1. Using no method of contraception cames a higher cumulative risk of death than using any contracep- tive method except that of OCs by older women who smoke. The mortality risks associated with using no contraception and with using OCs are higher in older women than in younger women. For all other contraceptive methods, the mortal- ity risk does not appear to vary by age. Although the estimates are not presented in Table 1, vasectomy involves no mortality risk for women and virtually none for the male partner (Ory et al., 1983~. Below we will present in detail the health effects of the venous widely available methods of contraception, limiting our discussion to those methods that are considered moderately to highly effective. Most epidemiologic and clinical studies of the health effects of contraceptives have been earned out in developed counties. We recognize the difficulty in generalizing these results to the special health and cultural situations in the less developed countnes. Furthermore, the TABLE 1 Estimated Cumulative Number of Deaths per 100,000 Nonsterile Women Aged 17-44, Aunbutablc to Contraceptive Method, by Age Group Age Group Method 17-34 35-44 Total (17-44) No method 179 270 449 PilVnonsmoker 20 230 250 PilUsmoker 127 845 972 IUD 22 20 42 Condom 17 4 21 Diaphragm/spennicide 24 25 49 Rhythm 31 32 63 Tubal sterilizations - 4 Not available by age group. Source: Modified from Ory et al., 1983, p. 36, Figure 16.

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50 ~E, PETERSON, AND CHU effects of the venous contraceptive methods on the risk of diseases generally limited to less developed countries have had very little characterization. Because of the expanding role of family planning programs and contraceptive use in these countries, studies to evaluate the health effects of contraceptives in various regions and cultures are needed. Modern contraceptive methods vary substantially in how effectively they prevent pregnancies. Because pregnancy itself has attendant health risks and benefits, the rates of accidental pregnancy associated with the various methods of contraception are one important aspect to consider when measuring the health effects of these methods. In 198? Trussell and Kost published their comprehen- sive review assessing failure rates for each method of contraception. After reviewing all available studies, they estimated the rate of failure (i.e., accidental pregnancy) in the first year of use associated with "perfect)' use of each con~ace~ five. They called this estimate the "lowest expected" failure rate; this rate should reflect the frequency of failures caused by the contraceptive itself. They also reported for each method a "typical" failure rate, defined as the rate of accidental pregnancy in the first year of use among typical couples who use that method. The typical failure rate is determined both by failures as a result of imperfect use of a contraceptive and by failures directly related to the method itself. Most of the typical failure rates were derived from national surveys of U.S. women. The authors summarized these rates, by contraceptive method, in a single table (Trussell and Kost, 1987, p. 271~. We present a modified version of that table here Cable 2~. In our table and throughout the text we have substituted the term method failure rate for lowest expectedfailure rate and userfailure rate for typicalfailure rate to follow more closely the terminology used in much of the existing litera- ture. Note that the method failure rates are consistently low for most modern contraceptives. However, user failure rates vary widely, a function of the degree of acceptability and compliance required for successful use of each method. ORAL CONTRACEPTIVES OCs, a highly effective method of birth control, are available in two types. Combination OCs, the most widely used, consist of both an estrogen and a progestin component. Most combination OCs contain a fixed daily dose of an estrogen and progestin and are talcen for 21 of 28 days of each menstrual cycle (Hatcher et al., 1988~. Recently introduced, phasic combination OCs contain varying doses of the estrogen and progestin components throughout the menstrual cycle. The second type of OC is the progestin-only pill (often called the minipill), which contains only a progestin. Combination OCs with fixed doses of estrogen and progestin have been used much more frequently than phasic or progestin-only pills; hence, most epidemiologic studies on the health effects of OCs are essen- tially studies of the effects of this type of OC.

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HE'UTH EFFECTS OF CONTRA CEPrION 5 ~ TABLE 2 Method Failure and User Failure Rata During the First Year of Use of a Contraceptive Method, United States Contraceplivc Method Percentagc of Women E'cpenencing an Accidental Pregnancy in the First Year of Use Method Failures User Failurc. Pin Combination 0.1 Progestin~y 0.5 IUD 6 Medicated 1 Non m cd ic at ed 2 Injectable progesiin DMPA 0.3 0.3 NET 0.4 0.4 Implants ~ORP~9 0.2 0.2 Diaphragm with spcnnicidc 3 18 Condom 2 12 SpcmucidesC 3 21 Sponge (Todays) Nulliparous 5 18 Parous >8 >28 Gp/spemucide 5 18 Periodic abstinence 20 Ovulation method 8 Symp~ermal 6 Calendar 10 Posto~rulation 2 Withdrawal 4 18 Female sterilization 0.2 0.4 Male sterilization 0.1 0.15 Among couples who use a method perfectly (both consistently and correctly), an estimate of the percentage expected to c~cperience an accidents] pregnancy during the first year if they do not stop use for any reason. Among typical couples who use a method, the percentage who c~penence an accidental pregnancy during Tic first year if they do not stop use for any reason. Idcludes failures due to the method itself as well as failures due to imperfect use of the method. Roams, creams, jellies, and vaginal suppositones. Source: Modified from Tmsscll and Kost, 1987, p. 271.

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52 ~E, PETERSON, AND CHU OCs prevent pregnancy chiefly by~inhibiting ovulation in almost all menstrual cycles, although OC-related changes in the cervical mucus and endometrium may also have contraceptive effects. Failure rates associated with OC use are low. The method failure rate for combination OCs is 0.1 percent per year and for progestin-only OCs is 0.5 percent per year (Table 2~. The user failure rate cannot be readily determined for the two types of OCs separately, but it is about 3 percent per year for any type of OC. Because this user failure rate was derived from data where the vast majority of women used combination OCs, the figure probably is closest to the user failure rate for combination OCs. Most experts believe that the progestin-only pill has a higher user failure rate. The health risks and benefits of OC use have been extensively studied and documented (Ory, 1982; Ory et al., 1983; Stadel, 1986; Prentice and Thomas, 1987~. For a recent extensive review and list of references, see Stadel (1986) or Prentice and Thomas (1987~. Because OCs are highly effective at preventing any pregnancy, they appear to decrease greatly the risk of ectopic pregnancy. Results from a large case-control study of ectopic pregnancies conducted in the United States showed that current OC users had a relative riisk of ectopic pregnancy of 0.1 (95 percent confidence interval, 0.1~.2) compared with women who were using no contraceptive method (Ory, 1981~. Noncontraceptive Benefits An important benefit from OC use is a reduction in risk of two serious reproductive system cancers, endometrial and ovarian cancers. This reduction has been documented in at least 9 and 11 epidemiologic studies, respectively C1he Cancer and Steroid Hormone Study [CASH], 1987a, 1987b). Although the theoretical mechanisms that may explain these protective effects are quite differ- ent for the two types of cancer, the magnitude and characteristics of the protective effects are similar. The most detailed characterization of these protective effects comes from the CASH Study, a large case-control study conducted in the United States by the Centers for Disease Control, with support from the National Institute of Child Health and Human Development (CASH, 1987a, 1987b). OC use was associated with a 40 percent reduction in the risk of endometrial cancer as well as a 40 percent reduction in the risk of ovarian cancer, regardless of the specific formulation of combination OC used. The effect appeared to persist long after OC use had been discontinued; furthermore, protection increased with increasing cumulative duration of OC use. The protective effect of OCs on endometrial cancer is most likely related to direct effects on the endometrium. Among current OC users the carcinogenic effect of unopposed estrogen on the endometrium is probably reduced because combination OCs contain both estrogen and progestin. The continued protection

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HEALTH EFFECTS OF CO=RACE~ION 53 seen among past OC users is less well understood. Perhaps the combination of estrogen and progestin irreversibly changes endometrial cells so that they are not susceptible to carcinogens or to malignant transformation (CASH, 1987a). Suppression of ovulation and suppression of pituitary secretion of gonadotropins have both been postulated as mechanisms by which OCs protect against ovarian cancer (Weiss, 1982~. Two other factors that provide protection from ovarian cancer, increasing parity and breastfeeding (Gwinn et al., submitted), may also derive their protective effects from one of these two proposed mechanisms. Available epidemiologic studies do not provide sufficient information to choose one of these postulated mechanisms over the other. Fourteen epidemiologic studies have found a decreased risk of benign breast disease (RED) associated with OC use, including both case-control and cohort studies (Stadel, 1986~. Evidence suggests that OCs decrease the risk of f~brocys- tic disease and fibroadenoma diagnosed by biopsy as well as the risk of breast lumps observed clinically but not biopsied. Results from a large cohort study conducted in the United Kingdom by the Oxford Family Planning Association have provided especially useful information about the relationship between OC use and BBD (Brinton et al., 1981~. The decreased risk of BBD seen among women who use OCs occurs primarily among current or recent users who have used them for 2 years or longer. The relative risk among women who have used OCs for more than 2 years compared with nonusers is about 0.6 for fibrocystic disease and about 0.5 for unbiopsied breast lumps. The relative risk of fibroade- noma among women who have used OCs for less than 2 years is about 0.4, which is essentially the same as the relative risk of 0.3 among women who have used OCs for 2 or more years. The decreased risk of BBD does not persist among past OC users who have not used OCs for more than 1 year. Many epidemiologic studies have found that a history of BBD increases a woman's risk of breast cancer. Even though OCs decrease the risk of BBD, epidemiologic studies have not found that OCs decrease the risk of breast cancer, as might be suggested by the OCs-BBD relationship. The most likely explana- tion for this paradox is that OCs probably decrease the risk of the large proportion of BBD that is not closely linked to breast cancer risk but do not decrease the risk of the types of BBD that increase a woman's risk of breast cancer (Stadel, 1986~. Clearly, more information about the interrelationship between OC use, histologic types of BBD, and breast cancer is needed. Seven epidemiologic studies have found that current or recent OC use reduces the risk of pelvic inflammatory disease (PID) (Stadel, 1986~. On average, these studies have found that the risk of PID among OC users is about 40 percent lower than the risk among women using no contraceptive method. The most detailed analysis of this issue comes from the U.S.-based Women's Health Study, a large hospital-based case-control study conducted from 1976 to 1978 (Rubin et al., 1982~. This study found that the overall relative risk of PID

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54 r FE, PETERSON, AND CIlU among current OC users was about 0.5 compared with women using no contra- ception. However, this protective effect was limited to women who had been using OCs for at least 1 year. Furthermore, women not currently using OCs but who had used them in the past were no longer protected. Two mechanisms have been proposed to explain how OCs protect against the development of PID. First, OCs may change cervical mucus so that it prevents pathogenic organisms from ascending into the upper genital tract. Second, because OCs reduce menstrual blood flow, a decreased amount of medium may be available for bacterial growth (Rubin et al., 1982~. Most of the studies of the relationship between OCs and PID have been hospital-based studies, so that case groups in these studies consisted of women hospitalized for PID. Because many women diagnosed with acute PID are not hospitalized, findings about women who are may not be generally extended to women who develop asymptomatic PID or symptomatic PID that does not require hospitalization (Washington et al., 1985~. Specifically, gonorrhea may be an important cause of PID that requires hospitalization, whereas other bacterial etiologies such as chlamydia may cause much of the PID among women who do not require hospitalization. If OCs only protect against the bacterial etiologies of PID that are likely to require hospitalization, using OCs may not protect against some important causes of PID. Little epidemiologic evidence exists to clarify this question. Results from a large cohort study in the United Kingdom have provided clear evidence that OC use decreases the risk of iron-deficiency anemia, in both current and past OC users (Royal College of General Practitioners, [RCGPl, 1970~. The protective effect provided by current OC use is probably due to the decrease in menstrual blood flow routinely seen among OC users. An increase in iron reserves probably accounts for the persistence of the decreased risk in past users. In countries where the prevalence of iron-deficiency anemia is high, this benefit to OC users may be especially important (Stadel, 1986~. Three epidemiologic studies have found that OC use decreases the risk of functional ovarian cysts, including follicular, granulosa lutein, and theca lutein cysts (Stadel, 1986~. Decrease in risk appears to be confined to current OC users and is probably related to the suppression of ovulation that occurs during OC use. Evidence from a case-control study that used data collected from the Oxford Family Planning Association cohort study suggests that OC use protects a woman from developing uterine fibroids (Ross et al., 1986~. The risk of fibroids de- creased with increasing duration of OC use: each 5 years of OC use contributed another 17 percent reduction in fibroid risk. The mechanism of the protective effect is still speculative. The authors proposed that circulating estrogens, either exogenous or endogenous, may promote the formation of fibroids and that the decreased risk associated with OC use may be explained by the modifying effect of the progestins in OCs.

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I!EALTH EFFECTS OF CO=RACE~ION 55 Adverse Health Effects Cardiovascular Effects Most epidemiologic evidence suggests that OC use increases the risk of cardio- vascular disease, in particular the risk of venous thromboembolism, myocardial infarction (MI), and stroke (Stadel, 1986~. However, the risk of serious illness or death from cardiovascular disease that can be attributed to OC use is apparently concentrated among certain groups of women, primarily older women and women who smoke cigarettes. At least 11 case-control and 4 cohort studies have found that OC use increases the risk of venous thromboembolism (Vessey, 1980~. Results from those studies have shown that current OC use increases the risk of venous thromboembolism, although the increased risk does not appear to persist among past users. Further- more, the risk among current users remains constant with increasing duration of OC use. The risk of both superficial and deep vein thrombosis among current OC users is directly related to the estrogen content of OCs: the higher the estrogen content of the OC, the greater the risk of venous thromboembolism (Stadel, 1986~. The pathogenesis of venous thromboembolism among OC users probably involves an increase in the size of intravascular clots formed in response to thrombotic stimuli, most likely a result of estrogen-induced decreases in an- tithrombin III and plasminogen activators. Unlike the associations between OC use and MI and stroke, available studies have not found any interrelationship between OCs, venous thromboembolism, and cigarette smoking. The increased risk of venous thromboembolism is an important source of illness attributable to OC use but is a very infrequent cause of mortality (Stadel, 1986~. In contrast to the low attributable risk of death from venous thromboembolism associated with OC use, the increased risk of MI and stroke observed in women currently using OCs has been demonstrated to be an important source of the mortality risk attributable to OCs (Stadel, 1986~. Current OC use increases the risk of MI, thrombotic stroke, and hemorrhagic stroke. The risk of MI and stroke associated with current OC use is strongly influenced by age and by the presence of other cardiovascular risk factors, such as cigarette smoking, hypertension, and diabetes. For example, the risk of MI that is attributable to OCs among nonsmok- ing women 30 to 39 years of age is about 4 cases per 100,000 current users per year, but it increases to about 185 cases per 100,000 current users per year among women aged 40 to 44 years who smoke heavily (Table 3~. The risk attributable to past OC use appears also to be concentrated among older women and older women who smoke heavily. The risk of adverse cardiovascular events among current OC users appears to be directly related to the estrogen content of the OCs; although less conclusive, risk may also be related to progestin content. The pathogenesis of MI and stroke among current OC users may be related both to the

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56 [ARE, PETERSON, AND CHU TABLE 3 Current Use of Oral Contraceptives (OCs), Cigarette Smoking, and Risk of Myocardial farcuon (MI) MIs per 100,000 Current OC Users MIs per 100,000 per Year Cigarettes Women per Year Relative Attributable Age per say OC Users Nonusers Riska Risk 30-39 yr All women 11 4 3 7 0-14 6 2 3 4 >15 30 1 1 3 19 40-44 yr All women 89 22 4 67 0-14 47 12 4 35 >15 246 61 4 185 aRelauve risk of ~ for OC users compared with nonusers. Source: Modified from Stadel, 1986, p. 17. intravascular coagulation system and to the effects of increased blood pressure and metabolic changes. Current OC use has been found to elevate blood pressure slightly in most women about 1 to 2 mm Hg diastolic and 5 mm Hg systolic (Stadel, 1986~. OC use leads to approximately a threefold to sixfold increased risk of overt hyperten- sion. This risk has been observed to increase with increasing age and with increasing duration of OC use. Whether other risk factors for hypertension may be related to the increased risk attributable to OC use has not be established. Metabolic Effects The progestin component of OCs has been found to decrease the concentration of high-density lipoprotein-cholesterol (HDL-C), whereas the estrogen compo- nent has been found to increase HDL-C concentration (Stadel, 1986~. lIence, the effects of different OC formulations on HDL-C concentration apparently depend on the specific estrogen-progestin content. A U.S. study provided information about 10 combination OCs: 3 lowered HDL-C concentrations, 2 had no effect, and 5 increased HDL-C levels (Bradley et al., 1978~. If the progestin component has a strong anti-estrogen effect, the tendency of the estrogen component to increase HDL-C concentration may be overpowered (Stadel, 1986~. Current OC use has been found to decrease glucose tolerance among most women, although this decrease appears to be small, unrelated to duration of use,

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HEALTH EFFECTS OF CONTRACTION 57 and only additive to the effects of other risk factors for impaired glucose tolerance (Stadel, 1986~. This decrease in glucose tolerance is directly related to the estrogen content of the OCs, although there may be a relationship to the progestin content also. More important, OCs containing relatively small amounts of estro- gen-~ 50 micrograms of ethinyl estradiol-do not appear to decrease glucose tolerance to any appreciable extent. Neoplastic Diseases Epidemiologic studies clearly indicate that OC use increases the risk of hepato- cellular adenoma (HCA), a rare, benign neoplasm of the liver. Although benign, HCA can cause serious abdominal hemorrhage and death, with a death-to-case ratio of approximately ~ percent (Rooks et al., 1979~. Among women of repro- ductive age who have never used OCs or who used them for a short time, HCA develops at an annual rate of about 1.0 to 1.3 per million women 16 to 44 years of age. However, OC use is a strong risk factor for HCA, with a relative risk greater than 100 among women who have used OCs for 3 or more years compared with women who have used OCs for 1 year or less. The increased risk appears to be directly related to the duration of use, the age of the user, and the estrogen content of the OC. However, the absolute risk of HCA associated with OC use is small because of the rarity of the tumor. Among women who have used OCs for 5 years or longer, the attributable risk is estimated to be about 2 cases of HCA per 100,000 users per year (Stadel, 1986~. Epidemiologic studies have well demonstrated that OC use protects women from developing endometrial and ovarian cancers. However, the effect OCs may have on the risk for developing certain other malignancies remains unclear. Hepatocellular carcinoma and malignant melanoma have both been associated with OC use, although the strength of the associations has not been great. For this reason as well as the fact that those tumors are quite rare, the public health impact of a true positive association would not be great for either type of malignancy. Conversely, the debate about whether OC use increases the risk of cervical and breast cancers remains heated; some studies have found no effect on cancer risk, while others have found disturbing increases in risk. Because breast and cervical cancers are two of the most common cancers affecting women, contraceptive providers and epidemiologists feel an urgent need to resolve these discrepant results. However, as will be discussed subsequently, the possibility of a quick resolution to the controversies is unlikely. Both case-control and cohort studies have assessed the relationship between OC use and malignant melanoma. Generally, they have not found substantial increases in the risk of melanoma associated with OC use (Stadel, 1986~. Certain studies do suggest that O{ s may increase the risk among certain subgroups of women, especially those who have used OCs for a long time (Ramcharan et al., 1981; Bain et al., 1982; Holly et al., 1983; Beral et al., 1984~. Few studies have

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58 l:FE, PETERSON, AND CIlU adequately addressed the risk by histologic type of melanoma. Future studies of this association will have 'several issues to consider, including the rarity of the tumor among women, the different histologic subtypes of melanoma, and the potentially confounding effects of exposure to sunlight. The association between OC use and benign liver tumors, as well as a number of case reports of liver cancer among OC users, have led to theoretical concerns that OC use might increase the risk of malignant liver tumors. Three case-control studies published since 1983 have found increased risks of hepatocellular carci- noma among OC users (Henderson et al., 1983; Forman et al., 1986; Neuberger et al., 1986~. Generally, the increased risk has been confined to women with a history of long-term OC use. However, each of the studies had few women in the case group ~30) and had methodological problems that may have biased the results. In developed countries hepatocellular carcinoma is extremely rare among reproductive-aged women. In the United States in 1982 only 59 women died from liver cancer among approximately 52 million women aged 15 to 44 years (Na- hona1 Center for Health Statistics, 1982~. Hence, even if OC use substantially increases the relative risk of liver cancer, the attributable risk would still be very low. In many developing countries -liver cancer is a much more common problem, primarily because of the relationship between hepatocellular carcinoma and chronic hepatitis B virus infection, which has a high prevalence in some regions. In those areas the possible interrelationships between OC use, hepatitis B infection, and liver cancer are more troublesome. Currently, the World Health Organization (WHO) is conducting a multicenter case-control study to address the relationship between OC use and liver cancer. Data are being collected from three developing countries with high rates of hepatitis B infection and liver cancer. It is hoped that results from this study will shed light on the relationship between OC use and this ~ . serious malignancy. The potentially positive association between OC use and cervical cancer has added importance when considered in the setting of less developed countries. Surveillance information from developing countries, although sometimes frag- mentary and incomplete, suggests that cancer of the cervix is the most frequent malignancy among women in those countries (Lunt, 1984~. Unfortunately, screen- ing efforts in those countries usually reach very limited segments of the female population. Unlike the situation in developed countries where provision of contraceptive services is usually accompanied by routine Papanicolaou (Pap) screening for cervical cancer, family planning programs in developing countries often do not have the resources to provide Pap screening for their clients. To date, no definite causal relationship has been established between OC use and cervical cancer. Of 15 major epidemiologic studies, ~ have found no in- creased risk of cervical neoplasia and 7 have found significantly increased risks overall or increases among certain subgroups of users (Piper, 1985; Brinton et al.,

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HEALTH EFFECTS OF CONTRACEPTION 535 REFERENCES Affandi, B., S. S. I. Santoso, Djajadilaga, et al. 1987 Pregnancy after removal of Norplant~implants contraceptive. Contraception 36:203-209. Alexander, N. J., and D. J. Anderson 1979 Vasectomy: consequences of autoimmunity to sperm antigens. Fertility & Sterility 32:253-260. Alexander, N. J., B. J. Wilson, and B. D. Patterson 1974 Vasectomy: immunological effects on rhesus monkeys and men. Fertility & Sterility 25:149-156. Anonymous 1986 Oral contraceptives and breast cancer. Uncut 2:665 666. Ansbacher, R. 1971 Sperm-agglutinating and sperm-immobilizing antibodies In vasectorruzed men. Fer- tility & Sterility 22:629-632. Association for Voluntary Sterilization 1983 Minutes prepared for a Vasectomy Senunar. Science Committee, New York, June 6. Austin, H., W. C. Louv, and W. J. Alexander 1984 A case-control study of spermicides and gonorrhea. Journal of the American Medical Association 251:2822-2824. BaeHer, E. A., W. P. Dillon, T. J. Cumbo, et al. 1982 Prolonged use of a diaphragm and toxic shock syndrome. Fertility & Sterility 38:248-250. Bain, C., C. H. Hennekens, F. E. Speizer, et al. 1982 Oral contraceptive use and malignant melanoma. Journal of the National Cancer Institute 68:537-539. Barlow, D. 1977 The comedown and gcnonhea. L~ncet 2:811-813. Beral, V., S. Evans, H. Shaw, et al. 1984 Oral contraceptive use and malignant melanoma in Australia. British Journal of Cancer 50:681~85. Bhiw&ndiwala, P. P., S. D. Mumford, and P. J. Feldblum 1982 A comparison of different laparoscopic sterilization occlusion techniques In 24,439 procedures. American Journal of Obstetrics and Gynecology 144:319-331. Menstrual pattern changes following laparoscopic sterilization with different occlu sion techniques: a review of 10,004 cases. American Journal of Obstetrics and Gynecology 145:684-694. Bhiwandiwala, P. P., S. D. Mumford, and K. I. Kennedy 1985 Canparison of the safety of open and conventional laparoscopic sterilization. Obstet- rics and Gynecology 66:391-394. Bradley, D. D., J. Wingerd, D. B. Petitti, et al. 1978 Serum high density lipoprotein cholesterol in women using oral contraceptives, estro- gens, and progestins. New England Journal of Medicine 299:17-20. Bnnton, L. A., M. P. Vessey, R. Flavel, et al. 1981 Risk factors for benign breast disease. American Journal of Epidemiology 113:203-214. Bnnton, L. A., G. R. Huggins, H. F. I=ham, et al. 1986 I=ng-term use of oral contraceptives and risk of invasive cervical cancer. Interna- tional Journal of Cancer 38:330344. 1983

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86 LEE, PETERSON, AND CHU The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development 1986 Oral-contraceptive use and the risk of breast cancer. New England Journal of Medicine 315:405-411. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development 1987a Combination oral contraceptive use and the risk of endometnal cancer. Journal of the American Medical Association 257:796-800. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development 1987b The reduction in risk of ovarian cancer associated with oral-contracep~ve use. New England Journal of Medicine 316:65~655 Celentano, D. D., A. C. Klassen, C. S. Weissman, et al. 1987 The role of contraceptive use in cervical cancer: the Maryland cervical cancer case- control study. American Journal of Epidemiology 126:592 604. Centers for Disease Control 1987 Antibody to human irnmunodeficiency virus in female prostitutes. Morbidity and Mortality Weekly Report 36:157-161. 1988 Condoms for prevention of sexually transmitted diseases. Morbidity and Mortality Weekly Report 37:133-137. Chamberlain, G., and J. C. Brown, eds. 1978 Gynaecological Laparoscopy: The Report of the Working Party of the Confulential Inquiry info Gynaecological Laparoscopy. London: The Royal College of Obstetri- cians and Gynaecologists. Chi, I.-C., and P. J. Feldblum 1981 Luteal phase pregnancies in female sterilization patients. Contraception 23:10. Oaricson, T. B., N. J. Alexander, and T. M. Morgan 1988 Atherosclerosis of cynomolgus monkeys hyper- and hyporesponsive to dietary cho- lesterol: lack of an effect of vasectomy. Arteriosclerosis 8:488-498. Cohen, M. M. 1987 Long-term risk of hysterectomy after tubal sterilization. American Journal of Epi demiology 125:410-419. Conant, M. A., D. W. Spicer, and C. D. Smith 1984 Herpes simplex virus transmission: condom studies. Sexually Transmitted Diseases 11 :94-95. Conant, M., D. Hardy, J. Sematinger, et al. 1986 Condoms prevent transmission of AlDS-associated retrovirus. Journal of the Ameri- can Medical Association 255:1706. Cordero, J. F., and P. M. Layde 1983 Vaginal spermicides, chromosomal abnormalities and limb reduction defects. Family Planning Perspective 15:16. Cowan, M. E., and G. E. Cree 1973 A note on the susceptibility of N. gonorrhocae to contraceptive agent Nonyl-P. British Journal of Venereal Diseases 49:65-66. Cramer, D. W., I. Schiff, S. C. Schoenbaum, et al. 1985 Tubal infertility and the intrauterine device. New England Journal of Medicine 312:941-947. Cramer, D. W., M. B. Goldman, I. Schiff, et al. 1987 The relationship of tubal infertility to barrier method and oral contraceptive use. Journal of the American Medical Association 257:244~2450.

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IlEALTH EFFECTS OF CONTRA CAPTION 557 Dating, J. R., N. S. Weiss, B. J. Metch, et al. 1985 Primary tubal infertility in relation to the use of an intraulennc device. New England Journal of Medicine 312:937-941. DeStefano, F., H. B. Peterson, P. M. Layde, et al. 1982 Risk of ectopic pregnancy following tubal sterilization. Obstetrics and Gynecology 60:32~330. DeStefano, F., J. R. Greenspan, R. C. Dicker, et al. 1983a Complications of interval laparoscopic tubal sterilization. Obstetrics and Gynecology 61:153-158. DeStefano, F., C. M. Huezo, H. B. Peterson, et al. 1983b Menstrual changes after tubal sterilization. Obstetrics and Gynecology 62:673-681. DeStefano, F., J. A. Perlman, H. B. Peterson, et al. 1985 Long-term risk of menstrual disturbances after tubal sterilization. American Journal of Obstetrics and Gynecology 152:835-841. Diaz, S., M. Pavez, P. Miranda, et al. 1987 Long-term follow-up of women treated with Norplant,M implants. Contraception 35:551-567. District Court of Appeals of Florida 1964 Dunn v. Campbell, Flonda, 166 SO. 2d217. July 1, Second Distnct. Ebeling, K., P. Nischan, and C. Schindler 1987 Use of oral contraceptives and risk of invasive cervical cancer in previously screened women. International Journal of Cancer 39:427~30. Faich, G., K. Pearson, D. Fleming, et al. 1986 Toxic shock syndrome and the vaginal contraceptive sponge. Journal of the American Medical Association 255:21~218. Feldblum, P. J., and J. A. Fortney 1988 Condoms, speTmicides, and the transmission of human immunodeficiency virus: a review of the literature. American Journal of Public Health 78:52-54. Finn, S. D., R. H. Latham, P. Roberts, et al. 1985 Association between diaphragm use and urinary tract infection. Journal of the American Medical Association 254:24~245. Fischl, M. A., G. M. Dickinson, G. B. Scott, et al. 1987 Evaluation of heterosexual partners, children, and household contacts of adults with AIDS. Journal of the Americar: Medical Association 257:64~44. Forman, D., T. J. Vincent, and R. Doll 1986 Cancer of the liver and the use of oral contraceptives. British Medical Journal 292:1357-1361. Fortney, J. A., L. P. Cole, and K. I. Kennedy 1983 A new approach to measuring menstrual pattern change after sterilization. American Journal of Obstetrics and Gynecology l4/:83~836. Fothe~by, K., I. Trayner, I. Howard, et al. 1982 Effect of injectable norethisterone oenanthate ~origest) on blood lipid levels. Contra- ception 2S:435~46. Foulkes, J., and G. Chamberlain 1985 Effects of sterilization on menstruation. Southern Medical Journal 78:544. Foxman, B., and R. R. Frerichs 1985 Epidemiology of urinary tract infections. I: Diaphragm use and sexual intercourse. American Journal of Public Health 75:1308-1313. Francis, D. P., and J. Chin 1987 1be prevention of acquired immunodeficiency syndrome in the United States. Jour- nal of the American Medical Association 257:1357-1366.

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8~3 ~E, PETERSON, AND CHU Gallen, M. E., L Liskin, and N. Kak 1986 Men-new focus for family planning programs. Population Reports Series J. No. 33. Goldacre, M. J., J. A. Clarke, M. A. Heasman, et al. 1978 Follownp of vasectomy using medical record linkage. American Journal of Epidemi- ology 108: 176-180. Goldacre, M., M. Vessey, J. Clarke, et al. 1979 Record linkage study of morbidity following vasectomy. Pp. 567-579 in I. H. Lepow and R. Crazier, eds. Vasectomy: Immunologic and Pathophysiologic Effects in Anunals and Man. New York: Academic Press. Gray, R. H. 1985 Reduced risk of pelvic inflammatory disease with injectable contraceptives. Lancet 1:1046. Grimes, D. A. 1987 Intrauterine devices and pelvic inflammatory disease: recent developments. Contra- ception 36:97-109. Grimes, D. A., H. B. Peterson, M. J. Rosenberg, et al. 1982a Sterilization-aunbutable deaths in Bangladesh. International Journal of Gynaecology and Obstetrics 20:149-154. Grimes D. A., A. P. Sattenhwaite, R. W. Rochat, et al. 1982b Deaths fran contraceptive sterilization in Bangladesh: rates, causes, and prevention. Obstetrics and Gynecology 60:635~40. Grubb, G. S., and H. B. Peterson 1985 Luteal phase pregnancy and tubal stenlization. Obstetrics and Gynecology 66:784-788. Grubb, G. S., H. B. Peterson, P. M. Layde, et al. 1985 Regret after decision to have a tubal sterilization. Fertility & Sterility 44:248-253. Gwinn, M. L., N. C. Lee, P. H. Rhodes, et al. n.d. Pregnancy, breast feeding, and oral contraceptives and the risk of epithelial ovarian cancer. Journal of Clinical Epidemiology. (Submitted for publication) Hams, R. W. C., L. A. Brinton, R. H. Cowdell, et al. 1980 Characteristics of women with dysplasia or carcinoma in situ of the cervix uteri. British Journal of Cancer 42:35~369. Hatcher, R. A., F. Guest, F. Stewart, et al. 1988 Contraceptive technology: 1988-1989. New York: Printed Matter, Inc./Irvington Publisher, Inc. Heartwell, S. F., and S. Schlesselman 1983 Risk of uterine perforation among users of intrauterine devices. Obstetrics and Gynecology 61:31-36. Henderson, B. E., S. Preston-Martin, H. A. Edmondson, et al. 1983 Hepatocellular carcinoma and oral contraceptives. 48:437 410. Henshaw, S. K., and S. Singh British Journal of Cancer 1986 Sterilization regret among U.S. couples. Family Planning Perspectives 18:23~240. Hicks, D. R., L. S. Martin, J. P. Getchell, et al. 1985 Inactivation of HTLV-m/LAV-infected cultures of normal human lymphocytes by nonoxynol-9 in vitro. Lancet 1422-1423. Holly, E. A., N. S. Weiss, and J. M. Liff 1983 Cutaneous melanoma in relation to exogenous hormones and reproductive factors. Journal of the National Cancer Institute 70:827-831. Hopper, R. R., G. H. Reynolds, O. G. Jones, et al. 1978 Cohort study of venereal disease. I. The risk of gonorrhea transmission from infected women to men. American Journal of Epidemiology 108:13~144.

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HEALTH EFFECTS OF CONTRACEPTION 539 Horsburgh, C. R., J. M. Douglas, and F. M. LaForce 1987 Preventive strategies in sexually transmitted diseases for the primary care physician. Journal of the American Medical Association 258:815-821. Huggins, G., M. Vessey, R. Flavd, et al. 1982 Vaginal spennicides and outcome of pregnancy: findings in a large cohort study. Contraception 25:219. Hulks, J. F., H. B. Peterson, M. Surrey, ct al. 1987 American Association of Gynecologic Laparoscopists' 1985 membership surrey. Journal of Reproductive Medicine 32:732-73S. Hymowitz, E. E. 1981 Toxic shock syndrome and the diaphragm. New England Journal of Medicine 305:834. Indian Council of Medical Research 1982 Collaborative Study on Scquelae of Tubal Sterilization. Monograph. New Delhi. Twin, K. L., L. Rosero-Bixby, M. W. Oberlc, ct al. 1988 Oral contraceptives and cervical cancer risk in Costa Rica: Detection bias or causal association? Journal of He American Medical Association 259:59 64. Tick, H., A. M. Walker, K. J. Rothman, et al. 1981 Vaginal spennicides and congenital disorders. Journal of the American Medical Association 245:1329-1332. Tick, H., M. T. Hannan. A. Sterzachis, et al. 1982 Vaginal spermicides and gonorrhea. Journal of the American Medical Association 248:1619-1621. Judson, F. N., J. M. Enret, G. M. Bodin, et al. in In vitro evaluations of condoms with and without nonoxynol-9 as physical and chemical barriers against Chlamydia trachomatis, herpes simplex virus type 2, and human ~mmunodeficiency Virus. Set lly Transmitted Diseases (Suppl.) Katmelson, S., W. L. Drew, and ~ Mintz 1984 Efficacy of the condom as a barrier to the transmission of cytomegalo virus. Journal of Infectious Diseases 150:155-1S7. Kelaghan, J., G. ~ Rubin, H. W. Ory, et al. 1982 gamer-method contraceptives and pelvic inflammatory disease. Journal of the Ameri- can Medical Association 248:180187. Kenduck, J. S., E. P. Rhodenhiser, G. L. Rubin, et al. 1985 Charactenstics of vasectomy performed in selected outpatient facilities in the United States, 1980. Journal of Reproductive Medicine 30:93~938. Kendnclc, J. S., B. Gonzales, D. H. Huber, ct al. 1987 Complications of vasectomy in the United States. Journal of Family Practice 25:245-248. Krorunal, R. A., J. N. Krieger, J. W. Kennedy, et al. 1988 Vasectomy and urolithiasis. Lancet 1:22-23. Layde, P. M., M. P. Vessey, and D. Yeates 1982 Risk factors for gallbladder disease: a cohort study of young women attending family planning clinics. Journal a] Epidemiology and Corrvrumity Health 36:27~278. Ike, N. C., L. Rosero Bixby, M. W. Oberle, et al. 1987 A case control study of breast cancer and hormonal contraception in Costa Rica. Journal of the National Canecr Institute 79:1247-1254. Lee, N. C., G. L. Rubin, and R. Borucki 1988 The intrauterine device and pelvic inflammatory disease revisited: new results from the Women's Health Study. Obstetrics and Gynecology 72:1~. Lewis, E. L., C. K. Brazil, and J. W. Overstrcet 1984 Human sperm function in the ejaculate following vasectomy. Fertility & Sterility 42:895-898. press

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90 ~ FE, PETERSON, AND CH[J Liang, A. P., A. G. Levenson, P. M. Layde, et al. 1983 Risk of breast, uterine Corpus, and ovarian cancer in women receiving medro~cypro- gesterone injections. Journal of the American Medical Association 249:2909-2912. Liskin, L., and G. Fox 1982 IUDS: an appropriate contraceptive for many women. Population Reports Series B. No. 4. Liskin, L., and W. F. Quillin 1982 Long-acung progestins: promise and prospects. Population Reports Series K, No. 2. Liskin, L., J. M. Pile, and W. F. Quillin 1983 Vasectomy-safe and simple. Population Reports Series D, No. 4. Liskin, L., W. Rinehart, R. Blackburn, et al. 1985 Minilaparotomy and laparoscopy: safe, effective and widely used. Population Re- ports Series C, No. 9. Liskin, L., R. Blackbum, and R. Ghani 1987 Honnmal contraception: new long-acting methods. Population Reports Series K, No. 3. Lunt, R. 1984 Worldwide early detection of cervical cancer. Obstetrics and Gvn~oloa~v f~1~7nP~711 Mann, J., T. C. Quinn, and P. Plot 1987 Condom use and HIV infection among prostitutes-Zaire (Issuer). New England Journal of Medicate 316:345. Massey, F. J., G. S. Bemstein, W. M. O'Fallon, et al. 1984 Vasectomy and health: results from a large cohort study. Journal of the American Medical Association 252:1023-1029. McPherson, K., and J. O. Dnfe 1986 The pill and breast cancer: Why the unce~nty? British Medical Journal 293:709-710. McPherson, K., A. Neil, M. P. Vessey, et al. 1983 Oral contraceptives and breast cancer. Lancet 2:1414-1415. McPherson, K., P. A. Coope, and M. P. Vessey 1986 Early oral contraceptive use and breast cancer: theoretical effects of latency. Journal of Epidemiology and Community [lealth 40:289-294. Meirik, O., E. Lund, H.-O. Adami, et al. 1986 Oral contraceptive use and breast cancer in young women. Locket 2:650 654. Mills, J. L., E. E. Harley, G. F. Reed, et al. 1982 Are spermicides teratogenic? Journal of the American Medical Association 248:2148. Mintz, M. 1977 _,, - vies, v - ., it, A. Risk and prophylaxis in laparoscopy: a survey of 100,000 cases. Journal of Renro- ductive Medicine 18:269-272. Mumford, S. D., P. P. Bhiwandiwala, and I.-C. Chi 1980 Laparoscopic and minilaparotomy female sterilization compared in 15,167 cases. Lancet 2:10~1070. National Center for Health Statistics 1982 Vital Statistics of the United States. Vol. 2. Mortality Part A. Hyattsville, Md.: National Center for Health Statistics. Neuberger, J., D. Forman, R. Doll, et al. 1986 Oral contraceptives and hepatocellular carcinoma. British Medical Journal 292:1355-1357. Oberle, M. W., L. Rosero-Bixby, K. L Irwin, et al. 1988 Cervical cancer risk and use of depot-medroxyprogesterone acetate in Costa Rica. International Journal of Epidemiology 17:718-723. Ory, H. W. 1981 The Women's Health Study. Ectopic pregnancy and intrauterine contraceptive de vices: new perspectives. Obstetrics and Gynecology 57:137-144. , . . .

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HEALTH EFFECTS OF CONTRACEPTION 91 1982 the noncontraceptive health benefits from oral contraceptive use. Family Planning Perspective 14:182-184. Only, H. W., J. D. Forrest, and R. Lincoln 1983 Making Choices: Evaluating the Health Risks and Benef Is of Birth Control Methods. New York: lye Alan Guttrnacher Institute. Pardthaisong, T., R. H. Gray, and E. B. McDaniel 1980 Return of fertility after discontinuation of depot-medroxyprogesterone acetate and intra-uterine devices in Northem Thailand. Lancet 1:509-512. Pasquale, S. A., V. Brandeis, R. I. Cruz, et al. 1987 NorplantTM contraceptive implants: rods versus capsules. Contraception 36:305-316. Paul, C., D. C. G. Skegg, G. F. S. Spears, et al. 1986 Oral contraceptives and breast cancer: a national study. British Journal of Medicine 293:723-726. Perrin, E. B., J. S. Woods, and N. Tsukasu, et al. 1984 Long-tenn effect of vasectomy on coronary heart disease. American Journal of Public Health 74:128-132. Peterson, H. B., H. W. Ory, J. R. Greenspan, et al. 1981a Deaths associated with laparoscopic sterilization by unipolar coagulating devices, 1978-1979. American Journal of Obstetrics and Gynecology 139:141. Peterson, H. B., D. A. Grimes, W. Cates, et al. 1981b Comparative risk of death from induced abortion at 12 weeks gestation performed with local vs. general anesthesia. American Journal of Obstetrics and Gynecology 141:763. Peterson, H. B., F. DeStefano, J. R. Greenspan, et al. 1982a Mortality risk associated with tubal sterilization in United States hospitals. American Journal of Obstetrics and Gynecology 143:125-129. Peterson, H. B., J. R. Greenspan, and H. W. Ory 1982b Death following puncture of the aorta during laparoscopic sterilization. Obstetrics and Gynecology 59:133. Peterson, H. B., F. DeStefano, G. L. Rubin, et al. 1983 Deaths attributable to tubal sterilization in the United States, 1977-1981. American Journal of Obstetrics and Gynecology 146: 131-136. Petitii, D. B., R. Klein, H. Kipp, et al. 1982 A survey of personal habits, symptoms of illness, and histories of disease in men with and without vasectomies. American Journal of Public Health 72:476-480. Petitti, D. B., R. Klein, H. Kipp, et al. 1983 Vasectomy and the incidence of hospitalized illness. Journal of Urology 129:76~762. Philp, T., J. Guillebaud, and B. Budd 1984 Late failure of vasectomy after 2 documented analyses showing azoosperrnic semen. British Medical Journal 289:77-79. Pike, M. C., B. E. Henderson, M. D. Krailo, et al. 1983 Breast cancer in young women and the use of oral contraceptives: possible modifying effects of formulation and age at use. Lancet 2:92~930. Piotrow, P. T., W. Rinehart, and J. C. Schmidt 1979 IUDs-update on safety, effectiveness, and research. Population Reports Series B. No. 3. Piper, I. N. 1985 Oral contraceptives and cervical cancer. Gynecologic Oncology 22:1-14. Prentice, R. L., and D. B. Thomas 1987 On the epidemiology of oral contraceptives and disease. Advances in Cancer Re- search 49:285~01.

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92 [FE, PETERSON, AND CHU Quinn, R. W., and K. R. O'Reilly 1985 Contraceptive practices of women attending the sexually transmitted diseases clinic in Nashville, Tennessee. Sexually Transmitted Diseases 12:99-102. Rameharan, S., F. A. Pellegrin, R. Ray, et al. 1981 We Walnut Creek contraceptive drug study. A prospective study of the side effects of oral eontraeeptives, Vol. m. Washington, D.C.: U.S. Government Printing Office. Reingold, A. ~ 1986 Toxic shock syndrome and the contraceptive sponge. Journal of the American Medical Association 255:242-243. Rietmeijer, C. A. M., J. W. Krebs, P. M. Feorino, et al. 1988 Condoms as physical and chemical barriers against human immunodefieieney virus. Journal of the American Medical Association 259:1851-1853. Rooks, J. B., H. W. Ory, K. G. Ishak, et al. 1979 Epidemiology of hepatoeellular adenoma: the role of oral contraceptive use. Journal of the American Medical Association 242:644 648. Rosenberg, L., P. J. Sehwingel, D. W. Kaufmann, et al. 1986 Ihe risk of myoeardial infarction 10 or more years after vasectomy in men under 55 years of age. American Journal of Epidemiology 123:1049-1056. Rosenberg, M. J., W. Rojanapithayakom, P. J. Feldblum, and J. E. Higgins 1987 Effect of the contraceptive sponge on ehlamydial infection, gonorrhea, and eandidiasis. Journal of the American Medical Association 257:2308-2312. Rosenfield, A., D. Maine, R. Roehat, et al. 1983 We Food and Drug Administration and medroxyprogesterone acetate. Journal of the American Medical Association 249:2922-2928. Ross, J. A., and D. H. Huber 1983 Acceptance and prevalence of vasectomy in developing countnes. Studies in Family Planning 14:67-72. Ross, J. A., S. Hong, and D. H. Huber 1985 Voluntary Sterilization: An International Fact Book New York: Association for Voluntary Sterilization. Ross, R. K., M. C. Pike, M. P. Vessey, et al. 1986 Risk factors for uterine fibroids: reduced risk associated with oral contraceptives. British Medical Journal 293:359-362. Royal College of General Practitioners 1970 Oral eontraeepiives and health. London: Pitman Medical. Royal College of General Practitioners Oral Contraception Study 1982 Oral eontraeepiives in gallbladder disease. Lancet 2:957-959. Rubin, G. L., H. W. Ory, and P. M. Layde 1988 1982 Oral contraceptives and pelvic inflammatory disease. American Journal of Obstetrics and Gynecology 144:630-635. Ryden, G., L. Fahraeus, L. Molin, et al. 1979 Do contraceptives influence the incidence of acute pelvic inflammatory disease in women with gonorrhea? Contraception 20:149-157. Salah, M., A. M. Ahmed, M. Abo-Eloyoun, et al. 1987 Five-year experience with NorplantlM implants in Assiut, Egypt. Contraception 35:543-550. Sehlesselman, J. J., B. V. Stadel, P. Mullay, et al. 1987 Consistency and plausibility in epidemiologic analyses: application to breast cancer in relation to use of oral contraceptives. Journal of Chronic Diseases 40:1033-1039. Breast cancer in relation to early use of oral contraceptives: no evidence of a latent effect. Journal of the American Medical Association 259:1828-1833.

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IlEALTW EFFECTS OF CONTRA CEPI ION 93 Schmidt, S. S. 1975 Complications of vas surgery. Pp. 78-88 in J. J. Sciarra, C. Markland, and J. J. Speidel, eds. Control of Male Fertility. Hagerstown, Md.: Harper & Row. Schmidt, S. S., and N. J. Free 1978 Cite bipolar needle for vasectomy. 1. E'cpenence with the first 1,000 cases. Fertility & Sterility 29:676~580. Schmidt, S. S., and R. R. Moms 1973 Spermatie granuloma: the complication of vasectomy. Fertility & Sterility 24:941-947. Schulman, S., E. Zappi, U. Ahmed, et al. 1972 Immunologic consequences of vasectomy. Contraception 5:269-278. Schwartz, B., S. Gaventa, C. V. Broome, et al. 1989 Nonmenstrual toxic shock syndrome associated with bamer contraceptives: report of a ease-control study. Review of Infectious Diseases 11 (Suppl. 1):S43-S49. Shain, R. N., W. B. Miller, and A. E. C. Holden 1986 Married wanen's dissatisfaction with tubal sterilization and vasectomy at first-year follow-up: effects of perceived spousal dominance. Fertility & Sterility 45:808-819. Shapiro, S., D. Stone, O. P. Heinonen, et al. 1982 Birth defects and vaginal spermieides. Journal of the American Medical Association 247:2381. Shems, J. D., S. H. Moore, and G. Fox 1984 New developments in vaginal contraception. Population Reports Series H. No. 7. Silber, S. J. 1978 Vasectomy and vaseetcxny reversal. Fertility & Sterility 29:125-140. Singh, B., J. C. Cutler, and A. M. Utidjian 1972 II. Effect in vitro of vaginal contraceptive and noncontracepiive preparation on Treponema pallidum and Neisseria gonorrhoeae. British Journal of Venereal Dis- eases 48:57~4. Singh, B., B. Postie, and J. C. Cutler 1976 Virucial effect of certain chemical contraceptives on type 2 herpes virus. American Journal of Obstetrics and Gynecology 126:422~25. sivin, I., and J. Stem 1979 Long acting, more effective Copper T IUD's: a summary of U.S. experience, 197~1975. Studies in Family Planning 10:263-281. Skegg, D. C. 1988 Potential for bias in ease-control studies of oral contraceptives and breast cancer. American Journal of Epidemiology 127:205-212. Smith,G.L.,andK.F.Smith 1986 Lack of HIV infection and condom use in licensed prostitutes (Lever). Lancet 2:1392. Spring, S. B., and J. Gruber 1985 Relationship of DNA viruses and cervical carcinoma. Journal of the National Cancer Institute 75:589-590. Stadel, B. 1986 Oral contraceptives and the occurrence of disease: clinical overview. Pp. 3~1 in A. T. Gregoire and R. G. Blye, eds. Coniraceptive Steroids~harmacology and Safety. New York: Plenum Press. Stadel, B. V., G. L. Rubin, L. A. Webster, et al. 1985 Oral contraceptives and breast cancer in young women. Lancet 2:97~973. Stone,K.M.,D. A.Grimes,and L.S.Magder 1986 Personal protection against sexually transmitted diseases. American Journal of Ob stetrics and Gynecology 155:18~188. Sun, M. 1984 Panel says Depo-Provera not proved safe. Science 226:95~951.

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94 ~E, PETERSON, AND ClIU Swan, S. H., and D. B. Petitti 1982 A rewew of problems of bias and confounding in epidemiologic studies of cervical neoplasia and oral contraceptives. American Journal of Epidemiology 115:1~18. Swenson, I., A. R. Khan, and F. A. Jahan 1980 A randomized, single blind comparative trial of norethindrone enanthate and depot- medroxyprogesterone acetate in Bangladesh. Contraception 2:207-215. Treirnan, K., and L. Iiskin 1988 IUDs a new look. Population Reports Series B. No. 5. Trussell, J., and K. Kost 1987 Contraceptive failure in the United States: a critical review of the literature. Studies in Family Planning 18:237-283. Vessey, M. P. 1980 Female hormones and vascular disease-an epidemiological overview. British Jour- nal of Family Planning 6:1-12. Vessey, M. P., N. H. Wnght, K. McPherson, et al. ~ 1978 Fertility after stopping different methods of contraception. British Medical Journal (6108) February:265-267. , D. Yeates, R. Flavel, et al. ~, . . ~.. . .. . . . . . . ^. .. . ~. Vessey, M. P., 1981 Pelvic inflammatory disease and the intrauterine device: findings in a large cohort study. British Medical Journal 282:855-857. Vessey, M., G. Huggins, M. Lawless, et al. 1983 Tubal stenlization: findings in a large prospective study. British Journal of Obstet- rics and Gynaecology 90:203-209. Vessey, M. P., M. A. Metcalfe, K. McPherson, et al. 1987 Urinary tract infection in relation to diaphragm use and obesity. International Journal of Epidemiology 16:441~44. Walker, A. M., H. Jick, J. R. Hunter, et al. 1981 Vasectomy and nonfatal myocardial infarction. Lancet 1:13-15. Washington, A. E., S. Gove, J. Schachter, et al. 1985 Oral contraceptives, chlamydia trachomatis infection, and pelvic inflammatory dis ease: a word of caution about protection. Journal of the American Medical Associa tion 253:224~2250. Weiss, N. S. 1982 Ovary. Pp. 871-880 in D. Schottenfeld and J. F. Fraumeni, Jr., eds. Cancer Epidemi ologyand Prevention. Philadelphia: W. B. Saunders. Westrom, L. 1987 Pelvic inflammatory disease. Bacteriology and sequelae. Contraception 36:111-128. World Federation of Health Agencies for the Advancement of Voluntary Surgical Contraception 1984 Safety of Voluntary Surgical Contraception. New York. World Health Organization Task Force on Long-Acting Systemic Agents for the Regulation of Fertility Multinational comparative clinical evaluation of two long-acting injectable contracep- tive steroids: norethisteronc oenanthate and medroxyprogesterone acetate. 2. Bleed- ing patterns and side effects. Contraception 17:395~06. World Health Organization Task Force on Female Sterilization 1982a ' ' ' - ~ World Health 1982b 1978 mmllaparotomy or laparoscopy tor sterll~zat~on: a multicenter, multinational random- ized study. American Journal of Obstetrics and Gynecology 143:645~52. Organization Task Force on Female Sterilization Randomized comparative study of culdoscopy and minilaparotomy for surgical contra- ception in women. Contraception 26:587-593.

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"~~ EFFECTS OF C ~93 Wodd Hat Org~i~d~ 198~ ~~ed~=eslemne (SPA) and Manor: memorandum _ s WHO mung. 8~ Iffy -~ IDA C~;~ ~:37~S2. Wodd Heat 0~1-on Task fog on ~ng~c~g Agent for Feat Region 198~ ~ sideman of Became de-~ed~x~mgesm~ne aceme, l5-g ~me- mo~, ~ undem~shed lacing then. B~ ~ -~6 O~- '^ ~87~94. Wow Heat OF Task ate ~ -At physic Acts for Feat Regular 1987 A ma ~= ~ ~m~mdve cb~c~ ~ ~ de~t-medmx~esm~ne ~ ~ an_ ~ ~- ~ lag ~ If: Hi. Bang prams. ~f~ 33:591~10. Wail, N. H., a. P. Valley, B. Kiowas, ~ a. 1978 Ne~ssia ad dysplasia of He cent umd ad coon: a Passive prove each of He ~aph~gm. Bri'bA WHIZ ~r 38:~3~9.