The independent associations of parity, age at first full term pregnancy, and duration of breastfeeding with the risk of breast cancer. Cancer and Steroid Hormone Study Group.

Although the important influence of a woman's reproductive history on her risk of breast cancer is widely recognized, it is not clear whether this is wholly accounted for by the age at her first full-term pregnancy, or whether there are additional, independent influences of breastfeeding or number of children. To examine the respective contributions to the risk of breast cancer of these reproductive factors, we used logistic regression methods to analyze data from a multicenter case-control study, the Cancer and Steroid Hormone Study. Included in the analysis were 4599 women, 20-55 years of age, identified as having an initial diagnosis of breast cancer by one of eight collaborating population-based cancer registries. The 4536 controls were women of similar ages selected by random dialing of households with telephones in the same eight areas. As expected, age at first full-term pregnancy exerted a strong influence on the risk of breast cancer. However, after it and other potentially confounding factors had been controlled for, parity and duration of breastfeeding also had a strong influence on the risk of breast cancer. Compared with women of parity one, women of parity seven or greater had an adjusted relative risk of breast cancer of 0.59 (95% CL, 0.44-0.79). Compared with parous women who never breastfed, women who had breastfed for 25 months or more had an adjusted relative risk of 0.67 (0.52-0.85). These results do not support the supposed preeminent importance of age at first full-term pregnancy among the reproductive determinants of breast carcinogenesis. Resolution of this issue may have important implications for elucidating hormonal influences on breast cancer and for projecting future trends in the disease.

Agreement between women's histories of oral contraceptive use and physician records.

The histories of oral contraceptive (OC) use provided by women participating in a study of hepatocellular adenoma (HCA) were compared with records obtained from their physicians. In the HCA study two memory aids were used to assist women in their recall: a calendar of significant events during a woman's lifetime to which she might relate her use of OCs and a book of colour photographs of the 90 OC preparations available up to the time of the study. Using the number of months of a woman's history which could be checked against physician records (mean for all women of 33 months) as the denominator, the highest proportion of concordance was for month-specific duration of OC use (90%) with lower agreement for duration and brand (62%) and duration, brand, and dose (54%). Agreement was better for cases than for controls.

PIP: The adequacy of women's verbal accounts in determining oral contraceptive (OC) exposure was assessed by comparing the respondents' histories with prescribers' records. The study participants were selected from 299 women who had participated in a case-control study of hepatocellular adenoma. 2 memory aids were utilized during the interview: a calendar of significant life events to which a woman might relate her OC use and a color photograph book of 90 OC preparations available up to the time of the study. 61 cases and 69 controls were actually included in the study. Agreement for month-specific duration was 90%; for duration and brand, 62%; and for duration, brand and dose, 54%. Each of these categories was significantly different from the others and agreement was significantly higher for cases than for controls. The results compare favorably to 2 other studies, even with the increased complexity of this study, i.e., longer interval between OC use and interviews and a much greater number of brands and doses to choose from. The memory aids proved useful in recall performance.

Ectopic pregnancy and intrauterine contraceptive devices: new perspectives. The Women's Health Study.

In the period 1965 through 1977 the number of ectopic pregnancies in the United States tripled. A collaborative multicenter case-control study was set up to examine ectopic pregnancy as well as several other suspected complications related to use of an intrauterine contraceptive device (IUD). To determine to what extent IUD use might be related to this increase, the authors analyzed 615 women who had had an ectopic pregnancy and 3453 controls. Most important, women who had never used an IUD were equally likely to have an ectopic pregnancy as women who had used an IUD. Looking at the comparative risks for current contraceptive users, all current users, including IUD users, were less likely to have had an ectopic pregnancy than women not currently using contraceptives. Likelihood of ectopic pregnancy was the same regardless of whether a copper-containing or an inert plastic IUD was used. Among current IUD users, those who had used an IUD for a long time (25 months or more) were 2.6 times as likely to have had an ectopic pregnancy as short-term (less than 25 months) users. This difference between long- and short-term IUD users persisted for some time (not longer than 1 year) after removal of the IUD. Use of the IUD probably did not play a role in the recent tripling of ectopic pregnancies in the United States.

Risk of wound and pelvic infection after laparoscopic tubal sterilization: instrument disinfection versus sterilization.

To determine if disinfection, rather than sterilization, of laparoscopic equipment leads to an increase in the risk of postlaparoscopy infection, the authors analyzed data from a multicenter prospective study conducted by the Centers for Disease Control on the safety of sterilizing operations. From September 1978 through July 1981, 3903 women underwent laparoscopic tubal sterilization procedures in which the equipment was sterilized with ethylene oxide (58%) or disinfected with glutaraldehyde (42%). The overall risk of wound infection in each group was 1.5 per 100 women. The relative risk of wound infection for disinfection versus sterilization of the equipment was 0.5 when adjusted for differences in the two groups. The corresponding relative risk of pelvic infection was 1.2. These results suggest that laparoscopy equipment disinfected with glutaraldehyde is not associated with an increased risk of wound or pelvic infection compared with equipment sterilized with ethylene oxide.

Death following puncture of the aorta during laparoscopic sterilization.

Lacerations of major vessels have been associated with use of the Veress needle and sharp trocar for laparoscopy. A death caused by puncture of the aorta during insertion of a Veress needle is reported. Deaths from major vessel laceration can be prevented by using proper technique for inserting the needle and trocar or choosing alternative methods of sterilization that do not require these instruments. Should major vessel laceration occur, prompt recognition and treatment may prevent death.

Intrauterine device termination rates and the menstrual cycle day of insertion.

World-wide clinicians apparently prefer to insert the intrauterine device (IUD) during the bleeding phase of the menstrual cycle. To examine the benefits and risks of inserting IUDs at various times during the menstrual cycle, data on over 9000 women having copper T-200 IUD insertions were analyzed. During the first 2 months after IUD insertion: 1) rates of IUD expulsion are lower the later in the menstrual cycle ;he IUD is inserted; 2) rates of IUD removal for pain and bleeding and rates of accidental pregnancy, are higher the later in the menstrual cycle IUD is inserted, particularly after day 17. The present analysis suggests that the above are probably causal associations. It is estimated that 1000 insertions before day 11 will result in 9 more terminations of IUD use for expulsion, pain and bleeding, and accidental pregnancy than if the insertions are done after day 11. Furthermore, the copper T-200 IUD can be inserted with relative safety on the day it is requested if the woman's history indicates that she is unlikely to be pregnant. There is no justification for a blanket policy of inserting IUDs only during the menses.

World Health Organization studies of prostaglandins versus saline as abortifacients. A reappraisal.

The World Health Organization (WHO) Task Force on the Use of Prostaglandins for the Regulation of Fertility has sponsored a series of randomized clinical trials and case-series investigations to assess the effectiveness and safety of prostaglandins as abortifacients. Our reanalysis of the WHO studies found the prostaglandins to be faster and more hazardour than hypertonic saline as intraamniotic abortifacients. Moreover, studies by the Center for Disease Control imply that dilatation and evacuation (D&E) may be more effective, safe, convenient, and inexpensive than prostaglandins for abortions after 12 weeks' gestation, especially in the 13- to 16-week interval. For gestations of greater than or equal to 17 weeks, the occurrence of live births in prostaglandin-induced abortions has produced serious legal and ethical problems in the United States. Until the effectiveness and safety of other prostaglandins regimen approach that of D&E, we feel that D&E should be the index of comparison against which newer methods of inducing abortion are tested.

PIP: Reanalysis of WHO studies on the use-effectiveness and safety of prostaglandins as abortifacients found prostaglandins to be faster and more hazardous than hypertonic saline as intraamniotic abortifacients. New problems reported with prostaglandins include specific cardiac events associated with their use, including 1 case of serious cardiac arrhythmia and 2 confirmed deaths from sudden cardiac arrest; also, 2 cases of myocardial infarction have been associated with use of prostaglandin suppositories. Another problem with use of prostaglandin instillation is that it does not cause fetal death in utero, leading to ethical and legal problems resulting from a higher occurrence of live births with prostaglandins than with other abortifacient agents. Center for Disease Control studies imply that dilatation and curettage (D and C) is more effective, safe, convenient, and inexpensive than prostaglandins for abortions after 12 weeks of gestation. This is particularly true for 13-16 week gestations. For gestations 17 weeks, the live birth question becomes particularly relevant. It is concluded that until the effectiveness and safety of other prostaglandin regimens approach that of D and C, D and C should be the index of comparison against which newer methods of inducing abortion are tested.

Age-specific differences in the relationship between oral contraceptive use and breast cancer.

Nearly all studies have suggested that the use of oral contraceptives (OC) is not associated with the aggregate risk of breast cancer diagnosed in women aged 20-54. Because of age-specific differences in the breast cancer-parity relationship and because of age-specific differences in other breast cancer risk factors, the Centers for Disease Control reexamined data from the Cancer and Steroid Hormone Study to assess whether OC use has different effects on the risk of breast cancer at different ages of diagnosis. This was a population-based case-control study conducted in eight geographic areas in the United States during 1980-1982. In these data, the relationship between the risk of breast cancer and OC use appeared to vary by age at diagnosis. Among women aged 20-34 years at diagnosis or interview, those who had ever used OC had a slightly increased risk of breast cancer (odds ratio 1.4, 95% confidence interval 1.0-2.1) when compared with women of the same ages who had never used OC. Among these women, there were no trends of increasing or decreasing risk with any measure of OC use. Among women aged 35-44 years, there was no association between OC use and breast cancer. Among women aged 45-54 years, those who used OC had a slightly decreased risk of breast cancer (odds ratio 0.9, 95% confidence interval 0.8-1.0). Among these women, the risk estimates decreased significantly with increasing time since first and last use. Although the slightly increased risk estimates for the youngest women are compatible with findings by other investigators, the decreased risk estimates for the oldest women have not been described in as many studies. Available data provide no reasons for changes in prescribing practices or in the use of OC as related to breast cancer risk.

Type of intrauterine device and the risk of pelvic inflammatory disease.

To study the association of pelvic inflammatory disease and various types of intrauterine devices (IUDs), data from the Women's Health Study were analyzed. The analysis included data from interviews of 622 women hospitalized with an initial episode of pelvic inflammatory disease and 2369 hospitalized control subjects reporting no history of pelvic inflammatory disease. Compared to the risk in women using no contraception, the relative risk of pelvic inflammatory disease in women currently using the Dalkon Shield was 8.3 (95% confidence limits 4.7 to 14.5). This represented a fivefold increase in risk compared to women currently using other types of IUDs. In this study, only 10% of women wearing an IUD were using the Dalkon Shield, yet they accounted for almost 20% of the excess risk of pelvic inflammatory disease occurring among all the IUD users. Most of the increased risk of pelvic inflammatory disease for women currently using other IUDs (excluding the Dalkon Shield) occurred in the first four months after insertion. These associations were not explained by differences between cases and controls in demographic variables, level of sexual activity, or medical history. The authors recommend that women still using a Dalkon Shield have it removed.

Risk factors for complications of interval tubal sterilization by laparotomy.

The complication rate among 282 women undergoing interval tubal sterilization by laparotomy was studied as part of the prospective multicenter Collaborative Review of Sterilization. Using a standard definition of major complications, the overall complication rate was 5.7 per 100 procedures. Women experiencing complications had a significantly lengthened postoperative recovery period before the resumption of normal activities. Important risk factors for complications included diabetes, cigarette smoking, previous abdominal or pelvic surgery, and a history of pelvic inflammatory disease. Women with an initial abdominal incision of 7 cm or longer had three times the complication rate of women with shorter incisions. These results provide objective evidence that, for tubal sterilizations, minilaparotomy (laparotomy with a small abdominal incision) is associated with lower morbidity than is conventional laparotomy.

Menstrual changes after tubal sterilization.

The authors used data from a multicenter prospective study of female sterilization surgery to study changes in menstrual function following tubal sterilization. Duration of menstrual bleeding, menstrual cycle length, cycle regularity, amount of menstrual bleeding, menstrual pain, and intermenstrual bleeding were examined. The authors followed 2456 women for two years after tubal sterilization surgery. Each woman served as her own control; her menstrual function at the two-year follow-up interview was compared with her menstrual function at the preoperative interview. Except for menstrual pain among women who underwent unipolar electrocoagulation procedures, there was no increase in the prevalence of adverse menstrual function after tubal sterilization. For all menstrual variables, 50% or more of women with adverse function preoperatively had an improvement by two years after tubal sterilization.

Cardiovascular safety of oral contraceptives. What has changed in the last decade?

PIP: As a result of careful patient selection, the cardiovascular safety of oral contraceptives (OCs) has improved dramatically in the past decade. The incidence of stroke and myocardial infarction is exceedingly low among women who use OCs containing 35 mcg or less of ethinyl estradiol, and formulations containing under 50 mcg of estrogen account for almost all current use in the US. This article reviews the epidemiologic data on use of OCs of varying steroid dosages on the risks of myocardial infarction, hemorrhagic and ischemic stroke, and venous thromboembolism. Although four studies published since 1995 have suggested that OCs containing desogestrel or gestodene increase the risk of venous thromboembolism above that associated with levonorgestrel, these findings are likely due to prescribing bias and differences in the duration of use. The greatest risk of an arterial cardiovascular event comes from smoking while taking OCs.^ieng

The association of depo-medroxyprogesterone acetate and breast cancer.

The use of depo-medroxyprogesterone acetate (DMPA) as an injectable contraceptive for women has continued to be controversial for over 10 years. The U.S. Food and Drug Administration has not approved it for contraceptive use but the World Health Organization has. We undertook a case-control study to clarify the possible association of breast cancer and DMPA use. Subjects were selected from women enrolled in the Grady Memorial Hospital Family Planning Clinic in Atlanta, Georgia, from 1967 to 1979. The risk of breast cancer in DMPA users compared to nonusers is identical. The small number of women with breast cancer, the short average exposure to DMPA, and the lack of detail about the subjects themselves caused us to interpret our results cautiously. However, it seems reasonable to conclude that short-term use of DMPA among black women is not associated with any increased risk of breast cancer.

PIP: This case-control study attempted to determine the possible association of breast cancer and depo-medroxyprogesterone acetate (DMPA) injectable contraceptive use. Of 11,400 women who had received the drug, 30 had breast cancer. 29 of these 30 were black women. 70% of cases were aged 30 years or older. Controls were matched for age and parity. Of the women with breast cancer, 16.7% had been exposed to DMPA whereas only 17.9% of controls had been exposed. The risk of breast cancer in DMPA users compared to nonusers was exactly 1. Controlling for parity did not alter this. For all 5 exposed cases, DMPA exposure preceded the diagnosis of the disease by an average of 4 years. The mean number of injections for women with breast cancer and for controls was 2.8 and 3.3, respectively. Hence, though the number of cases was small and the average exposure was short, it is still concluded that short-term use of DMPA among black women is not associated with any increased risk of breast cancer.

Febrile spontaneous abortion and the IUD.

A case-control study was done to determine the risk and pathogenesis of febrile spontaneous abortion for intrauterine device (IUD) wearers compared to non-wearers. Four groups of women coming to a large city hospital between 1970 and 1975 were compared: 1) women presenting with febrile spontaneous abortion, 2) women presenting with afebrile spontaneous abortion, 3) women presenting with afebrile spontaneous abortion which subsequently became febrile, and 4) women delivering a live infant. Pregnant women with an IUD in situ had a 5-fold higher risk of both febrile and afebrile spontaneous abortion compared to pregnant women without an IUD in situ. Women who had a spontaneous abortion that shifted from afebrile to febrile were somewhat more likely to be IUD wearers than the other 2 spontaneous abortion groups. In our study population, the increased risk of febrile spontaneous abortion for IUD wearers appeared primarily due to the increased risk of the spontaneous abortion event itself, rather than a primary IUD-related infection causing febrile spontaneous abortion.

The safety and efficacy of tubal sterilization: an international overview.

This article presents a synthesis of some of the major published studies on the efficacy and safety of tubal sterilization. The conclusions of this overview are that tubal sterilization is a safe operation, long-term sequelae of tubal sterilization have not been well documented, and the risk of pregnancy following tubal sterilization is less than 1 in 100. Continued study is needed to determine how to make a safe and effective procedure even safer and more effective.

PIP: Over the past decade, tubal sterilization has emerged as one of the world's most frequently used methods of fertility control. It is estimated that up to 1980 over 60 million women had been surgically sterilized, making an understanding of the risks and benefits of tubal sterilization a matter of global concern. The current consensus, derived from international morbidity and mortality studies, is that tubal sterilization is a safe operation. Several large national studies, including ones conducted in the United Kingdom, have determined that major complication rates for tubal sterilization are low, on the order of 1-6/100 procedures. Several recent studies have demonstrated that death attributable to tubal sterilization is rare but does occur. 2 national studies of laparoscopic sterilization done in the United States and in Great Britain estimate case fatality rates for laparoscopic sterilization of 10 deaths and 2 deaths/100,000 procedures, respectively. Several studies have been conducted which address not only the risk of death but also the causes of death associated with tubal sterilization. In the United States, the Centers for Disease Control (CDC) has identified 27 deaths attributable to tubal sterilization that occurred since 1977. The single leading cause of these deaths was cardiorespiratory arrest during general anesthesia. The question whether tubal sterilization predisposes a woman to menstrual disturbances was raised as early as 1951. Since that time a variety of reports have suggested that observed differences in menstrual function after sterilization can be attributed to factors other than sterilization procedure, e.g., menstrual problems prior to sterilization; oral contraceptive use before sterilization; previous pelvic inflammatory disease; or age alone, the woman being older following sterilization than she was before sterilization. Intrauterine pregnancies and ectopic pregnancies are 2 concerns regarding the efficacy of tubal sterilization. Intrauterine pregnancies are unplanned and usually unwanted after sterilization. Although a substantial percentage of pregnancies after sterilization are ectopic gestations, there is no evidence that a woman's absolute risk of ectopic pregnancy is increased by having a sterilization performed.

The association between oral contraception and hepatocellular adenoma--a preliminary report.

Women with long-term use of oral contraception (OC) are at increased risk of developing a serious, though nonmalignant, liver tumor--hepatocellular ademona (HCA)--according to a case-control study conducted by the Center for Disease Control (CDC) in collaboration with the Armed Forces Institute of Pathology (AFIP). The tumor is sometimes fatal, deaths usually being due to sudden rupture and hemorrhage. This study suggests that, in addition to long-term OC use, a women's age and the hormonal potency of the OC she uses affect her changes of developing HCA. Women 27 years old and older who have used OC with high hormonal potency for 7 or more years are at the greatest risk.

A review of the association between intrauterine devices and acute pelvic inflammatory disease.

Six controlled epidemiologic studies of the association between intrauterine device (IUD) use and development of acute pelvic inflammatory disease (PID) are reviewed. The strength and weaknesses of each study are discussed as well as the consistencies of the results. All six studies point in the same direction: IUD use is associated with approximately a three-to fivefold increased risk of PID. The consistency of the association in six different studies, in three different countries and by five different investigators is strong evidence that the association is one of cause and effect. Evidence is presented for the biologic plausability of the association. There also is evidence that copper IUDs do not appear to offer any protection from gonococcal PID. Teenagers appear as likely as older women to be similarly affected by the use of IUDs. There is the intriguing but uncomfirmed suggestion that nulliparous IUD users are more likely to suffer from acute PID than are multiparous users. A public health measure that would control this effect of IUD use is to decrease the use of IUDs in populations at high risk of PID.

Deaths associated with laparoscopic sterilization in the United States, 1977-79.

In 1979, the Centers for Disease Control began epidemiologic surveillance of deaths associated with tubal sterilization as part of an effort to assess the mortality risks associated with different methods of fertility control. The surveillance system identified nine deaths following laparoscopic sterilization in the United States from 1977 through 1979. The causes of these deaths and how some of them might have been averted are discussed.

PIP: This report is concerned only with those deaths in the U.S. identified to date that were attributable to laparoscopic sterilization. In 1979 the Centers for Disease Control (CDC) asked state health departments and state maternal mortality review committees for assistance in identifying deaths attributable to tubal sterilization. A sterilization attributable death was considered to be a death resulting from complications of the operation itself, the chain of events that lead to death and were initiated by the operation, or aggravation of an unrelated condition by the physiologic or pharmacologic effects of the operation. 9 deaths attributable to laparoscopic sterilization that occurred after January 1, 1977 were identified. 5 of these deaths were reported to have been caused by cardiorespiratory arrests that occurred during the use of general anesthesia. 5 deaths were reviewed in detail. 1 patient died from an irreversible heart block that occurred intraoperatively. Of the other 4 deaths, 1 was related to the method of entry into the abdominal cavity; 3 were related to a single method of tubal occlusion. This series of 9 deaths represents an unknown fraction of the deaths that occurred following laparoscopic sterilization from 1977 through 1979. As many as 750,000 laparoscopic sterilizations were performed during that period. Thus far, the most frequently reported cause of death from laparoscopic sterilization was cardiorespiratory arrest occurring during general anesthesia.

Tubal sterilizations performed in freestanding, ambulatory-care surgical facilities in the United States in 1980.

In 1981 the American Association of Gynecologic Laparoscopists and the Division of Reproductive Health, Centers for Disease Control, jointly conducted a study of tubal sterilizations performed in 141 freestanding, ambulatory-care surgical facilities in 1980 in the United States. Information was collected through mailed questionnaires and telephone interviews. Of 330 potential responding facilities, 141 we identified as freestanding, ambulatory-care surgical facilities. About 16,500 tubal sterilizations were performed in these facilities in 1980. The mean number of tubal sterilizations per freestanding, ambulatory-care surgical facility was 212. Sixty-seven percent of tubal sterilizations were performed in the south and west. General anesthesia was the anesthetic method used in 97% of the procedures. Nearly 91% of tubal sterilizations were done via laparoscopy, with bipolar electrocoagulation the tubal-occlusion method used most frequently. After tubal sterilization the patients were observed for an average of 2.4 hours before discharge. The average cost of laparoscopic tubal sterilization was $801; for nonlaparoscopic tubal sterilization it was $850.