Depo medroxyprogesterone acetate (DMPA) and combined oral contraceptives and cervical carcinoma in-situ in women aged 50 years and under

Most low-resource settings depend on hormonal contraceptives for their family planning programmes and cervical cancer occurs in higher frequency in these populations. To determine whether hormonal contraception use increases cervical carcinoma in-situ (CIS) risk, a case-control study was conducted in the Kingston and St Andrew Corporate area of Jamaica, using 119 cases from the Jamaica Tumour Registry and 304 population controls matched on year of Papanicolaou (Pap) smear and clinic where Pap smear was obtained. While CIS cases were more likely to have 'ever used' combined oral contraceptives (COC) (OR = 1.4, 95 CI: 0.8, 2.5), depo-medroxyprogesterone acetate (DMPA) use was similar. Compared to women who never used hormonal contraceptives, the risk of CIS was elevated in: women who had used COCs five years or more (OR = 2.1, 95 CI: 1.0, 4.6), women who first used COC for less than 10 years prior to the interview (OR = 1.8, 95 CI: 0.9, 3.7) and women who were 18 to 24 years old when they first used COCs (OR = 1.8, 95 CI: 0.9, 3.4). Similarly, compared to women who never used DMPA, the risk of CIS was elevated in: women using DMPA five years or more (OR = 1.9, 95 CI: 0.7, 4.8), women reporting use within a year prior to interview (OR = 2.8, 95 CI: 0.7, 10.7) and women who initiated use of DMPA when they were 20 and 24 years old (OR = 1.4, 95 CI: 0.7, 3.1). These results suggest that if hormonal contraceptive use confers any risk of CIS, it is confined to long-term users. Increased risk in some groups, however, warrant further study

Depo medroxyprogesterone acetate (DMPA) and combined oral contraceptives and cervical carcinoma in-situ in women aged 50 years and under.

Most low-resource settings depend on hormonal contraceptives for their family planning programmes and cervical cancer occurs in higher frequency in these populations. To determine whether hormonal contraception use increases cervical carcinoma in-situ (CIS) risk, a case-control study was conducted in the Kingston and St Andrew Corporate area of Jamaica, using 119 cases from the Jamaica Tumour Registry and 304 population controls matched on year of Papanicolaou (Pap) smear and clinic where Pap smear was obtained. While CIS cases were more likely to have 'ever used' combined oral contraceptives (COC) (OR = 1.4, 95% CI: 0.8, 2.5), depo-medroxyprogesterone acetate (DMPA) use was similar. Compared to women who never used hormonal contraceptives, the risk of CIS was elevated in: women who had used COCs five years or more (OR = 2.1, 95% CI: 1.0, 4.6), women who first used COC for less than 10 years prior to the interview (OR = 1.8, 95% CI: 0.9, 3.7) and women who were 18 to 24 years old when they first used COCs (OR = 1.8, 95% CI: 0.9, 3.4). Similarly, compared to women who never used DMPA, the risk of CIS was elevated in: women using DMPA five years or more (OR = 1.9, 95% CI: 0.7, 4.8), women reporting use within a year prior to interview (OR = 2.8, 95% CI: 0.7, 10.7) and women who initiated use of DMPA when they were 20 and 24 years old (OR = 1.4, 95% CI: 0.7, 3.1). These results suggest that if hormonal contraceptive use confers any risk of CIS, it is confined to long-term users. Increased risk in some groups, however, warrant further study.

Safety and effectiveness of vasectomy.

OBJECTIVE: To recommend further research on vasectomy based on a systematic review of the effectiveness and safety of vasectomy. DESIGN: A systematic MEDLINE review of the literature on the safety and effectiveness of vasectomy between 1964 and 1998. MAIN OUTCOME MEASURE(S): Early failure rates are <1%; however, effectiveness and complications vary with experience of surgeons and surgical technique. Early complications, including hematoma, infection, sperm granulomas, epididymitis-orchitis, and congestive epididymitis, occur in 1%-6% of men undergoing vasectomy. Incidence of epididymal pain is poorly documented. Animal and human data indicate that vasectomy does not increase atherosclerosis and that increases in circulating immune complexes after vasectomy are transient in men with vasectomies. The weight of the evidence regarding prostate and testicular cancer suggests that men with vasectomy are not at increased risk of these cancers. CONCLUSION(S): Publications to date continue to support the conclusion that vasectomy is a highly effective form of contraception. Future studies should include evaluations of the long-term effectiveness of vasectomy, evaluating criteria for postvasectomy discontinuation of alternative contraception for use in settings where semen analysis is not practical, and characterizing complications including chronic epididymal pain syndrome.

PIP: Vasectomy has been recognized as a simple and highly effective contraceptive method. In order to recommend further research on vasectomy, researchers conducted a systematic review of the literature on the safety and effectiveness of vasectomy between 1964 and 1998. Early failure rates are 1%; however, effectiveness and complications vary with experience of surgeons and surgical technique. Early complications, which include hematoma, infection, sperm granulomas, epididymitis-orchitis, and congestive epididymitis, occur in 1-6% of men undergoing vasectomy. Incidence of epididymal pain is poorly documented. Animal and human data suggest that vasectomy does not increase atherosclerosis and that increases in circulating immune complexes following vasectomy are transient. The weight of the evidence regarding prostate and testicular cancer suggests that men with vasectomy are not at increased risk of these diseases. The findings indicate that publications to date continue to support the conclusion that vasectomy is a highly effective form of contraception. Future research should include evaluations of the long-term effectiveness of this method, evaluating criteria for post-vasectomy discontinuation of alternative contraception for use in settings where semen analysis is not practical, and characterizing complications including chronic epididymal pain.

Estimates of the risk of cardiovascular death attributable to low-dose oral contraceptives in the United States.

OBJECTIVE: Our purpose was to estimate the annual risk of death in the United States from cardiovascular disease attributable to low-dose combination oral contraceptives. STUDY DESIGN: Estimates of the risk of death from cardiovascular disease attributable to low-dose oral contraceptives were modeled on data from studies published through 1997 and from age-specific mortality rates in the United States for 1993 and 1994. RESULTS: Attributable risk of death from cardiovascular disease resulting from oral contraceptive use is 0.06 and 3.0 per 100,000 nonsmokers 15 to 34 years of age and 35 to 44 years of age, respectively. In smokers this risk increases, respectively, to 1.73 and 19.4 per 100,000 users in these 2 age groups; however, 97% and 85% of this risk is due to the combined effects of smoking and using oral contraceptives. The attributable risk of death from cardiovascular disease in nonsmoking oral contraceptive users is lower than the risk of death from pregnancy in nonusers of oral contraceptives at all ages; however, among smoking oral contraceptive users more than 35 years of age, the excess risk of death from oral contraceptives is higher than the risk of death from pregnancy. CONCLUSION: There is virtually no excess attributable risk of death from cardiovascular disease related to oral contraceptive use in young women. However, smokers more than 35 years of age should use a nonestrogen contraceptive.

PIP: The annual risk of death in the US from cardiovascular disease attributable to low-dose combination oral contraceptives (OCs) was estimated through use of data from studies published in 1980-1997 and from age-specific mortality rates for 1993 and 1994. Four cardiovascular disease categories were included: myocardial infarction, venous thromboembolism and pulmonary embolism, ischemic stroke, and hemorrhagic stroke. The overall risk of death from cardiovascular disease among nonsmoking users of low-dose OCs is 0.06/100,000 women in the 15-34 year age group and 3.03/100,000 women in the 35-44 year age group. For young nonsmokers, the excess mortality risk associated with OC use is smaller than the risk of death from pregnancy, whether terminated by abortion or carried to term. Among OC users who smoke, the risk of cardiovascular mortality is 1.73/100,000 in 15-34 year olds and 19.4/100,000 in women 35-44 years old; however, 97% and 85% of this risk, respectively, is composed of the combined OC-smoking risk. Among smoking OC users over 35 years of age, the excess risk of death from OCs exceeds the risk of death from pregnancy. Young nonsmokers raise their risk of death from cardiovascular disease by less than 10% (0.60-0.65/100,000) by using OCs, while young women who do not use OCs increase their risk of death by 260% (0.60-1.57/100,000) by smoking cigarettes. For older women, the corresponding increases are 95% among nonsmoking OC users and 315% among smoking nonusers. These estimates indicate that women over 35 years of age who smoke should not be permitted to use either low- or high-dose OCs because of the excess attributable risk of death from cardiovascular disease.

Modeled estimates of myocardial infarction and venous thromboembolic disease in users of second and third generation oral contraceptives.

Consistent reports from several recent studies suggest that users of third generation oral contraceptives (OCs) containing gestodene and desogestrel may be at increased risk of venous thromboembolic disease (VTE). Paradoxically, other reports indicate that these users may be at decreased risk of acute myocardial infarction (MI) compared with users of second generation OCs. To determine whether the potentially increased risk of VTE would outweigh the potentially reduced risk of MI in users of third generation OCs, we conducted an analysis to quantify the trade-offs providers and users may be faced to make between these formulations. The baseline rates of VTE and MI among non-users were calculated using US data on incidence and mortality of these conditions and estimates of the proportion of women exposed to these formulations in the US. These were multiplied by relative risks published in recent studies on third generation progestins to produce age- and formulation-specific risks. Results indicate that there would be small differences in disease burden between users of second and third generation OCs under the model assumptions at younger ages. However, among women 35-44 years of age, modeling results indicate that the potentially decreased incidence of MI among users of third generation OCs more than offsets the potentially increased risk of VTE at this age.

Epithelial ovarian cancer risk among women with polycystic ovary syndrome.

OBJECTIVE: To investigate the relationship between polycystic ovary syndrome (PCOS) and ovarian cancer, and to present three hypotheses regarding hormonal factors and the risk of ovarian cancer in women. METHODS: Data were analyzed from a population-based, case-control study, the Cancer and Steroid Hormone Study, to test the hypotheses. Four hundred seventy-six subjects with histologically confirmed epithelial ovarian cancer were identified from eight tumor registries of the Surveillance Epidemiology and End Results program. The study included 4081 controls ascertained via random-digit telephone dialing. All subjects and controls were aged 20-54 years. RESULTS: Seven subjects with ovarian cancer and 24 controls reported that they had been diagnosed with PCOS before the study period. Ovarian cancer risk was found to increase 2.5-fold (95% confidence interval [CI] 1.1-5.9) among women with PCOS. This association is found to be stronger among women who never used oral contraceptives (odds ratio [OR] 10.5, 95% CI 2.5-44.2) and women who were in the first quartile of body mass index (13.3-18.5 kg/m2) at age 18 (OR 15.6, 95% CI 3.4-71.0). CONCLUSION: The data suggest that the hormonal status of women with PCOS featuring abnormal patterns of gonadotropic secretion (enhanced levels of LH) in lean women may be a mitigating factor for the observed association between PCOS and ovarian cancer. We hope that our preliminary data stimulate further investigation of the testable hypotheses.

A medical record linkage analysis of abortion underreporting.

Inaccuracy in women's reports of their abortion histories affects many areas of interest to reproductive health professionals and researchers. The identification of characteristics that affect the accuracy of reporting is essential for the improvement of data collection methods. A comparison of the medical records of 104 American women aged 27-30 in 1990-1991 with their self-reported abortion histories revealed that 19% of these women failed to report one or more abortions. Results of logistic regression analysis indicate that nonwhite women were 3.3 times as likely as whites to underreport. With each additional year that had elapsed since the first recorded abortion, women became somewhat more likely to underreport (odds ratio of 1.3), while each additional year of a woman's education slightly decreased the likelihood of underreporting (odds ratio of 0.7).

PIP: Underreporting of abortion, prevalent both between and within populations, threatens to undermine the validity of research in this area. Estimates of abortion, contraceptive failure, miscarriage, and other reproductive history events that rely on self-reports are vulnerable to bias. This study sought to identify the characteristics associated with the likelihood of underreporting an abortion history. 651 respondents from the Child Health and Development Studies who were 27-30 years old in 1990-91 filled out self-administered reproductive health questionnaires; these results were then compared to the women's 1980-92 medical records. The final sample consisted of 104 women with a medical record of a total of 170 abortions. 90% of women who had at least one abortion in their medical record reported at least one abortion; only 56% reported all of their abortions within 1 year of the medical record date, however. Overall, 19% underreported their abortion history. Of these, half reported no abortions and half reported fewer abortions than were in the medical record. Another 46% reported the exact number of abortions, and 35% reported more abortions than were in the record. Non-White women were 3.3 times more likely than Whites to underreport abortion. For each year that elapsed since the procedure, the odds of underreporting increased by 26%. Finally, every additional year of schooling decreased the likelihood of underreporting abortion by 30%.

Risk factors for menopausal hot flashes.

OBJECTIVE: To find predictors of hot flashes at natural menopause. METHODS: A cross-sectional sample of 334 black and white, naturally menopausal women was selected from a control group in a population-based study of reproductive cancers in central North Carolina. Women reported whether they had experienced hot flashes at the time of menopause. Life-style factors and reproductive histories of those with and without hot flashes were compared. RESULTS: Compared to women who were older at menopause, those reporting natural menopause before age 52 years had a significantly increased probability of having hot flashes (prevalence ratio 1.5, P = .04). Less than a high school education was significantly related to an increased probability of hot flashes (prevalence ratio 1.4, P = .20). There was significant interaction between cigarette smoking and body mass index (BMI), so that thin women who smoked in the premenopausal period were most likely to experience hot flashes (prevalence ratio 1.9, P = .03). Among non-smokers, BMI appeared to have no effect on the probability of hot flashes. Alcohol use, although not statistically significant, suggested a positive relation with hot flashes over and above that incurred from smoking. In addition, menarche before the age of 12 (prevalence ratio 0.6, P = .08) and a history of irregular menstrual cycles (prevalence ratio 0.6, P = .08) were marginally related to a decreased prevalence of hot flashes. Race, parity, and age at first and last pregnancy had no relation to hot flashes. CONCLUSION: Socioeconomic factors and those related to the decline of estrogen production are related to the occurrence of hot flashes at the time of menopause.

Breech presentation and fetal growth retardation.

Although it has been consistently demonstrated that breech presentation is associated with fetal growth retardation, this relationship has not been clarified. This study intends to elucidate this association by use of live births recorded in North Carolina in 1988 and 1989. A remarkable difference in birth weight between breech and vertex infants existed only in the preterm births. Although the breech infants had a higher proportion of small for gestational age than the vertex infants, the difference in the proportions decreased with advancing gestational age. Our analysis indicated that breech presentation is unlikely to be a cause of fetal growth retardation. Results of the study also implied that the significant association between breech presentation and increased perinatal mortality may be due in part to the common correlation with premature delivery and fetal growth retardation.

A case-control study of paternal smoking and birth defects.

Although the influence of paternal smoking on birth defects is of great public interest, epidemiological evidence concerning this potential relationship is extremely limited. A stratified random sample of 29 hospitals in the Shanghai Municipality, China, was used to select 1012 birth defects cases and controls. Mothers of the cases and controls were interviewed in the hospitals from October 1986 to September 1987. A modest relationship between paternal smoking and overall birth defects in offspring was identified [odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.01-1.45]. More markedly elevated risks were identified for anencephalus (OR = 2.1), spina bifida (OR = 1.9), pigmentary anomalies of the skin (OR = 3.3) and varus/valgus deformities of the feet (OR = 1.8). Our analysis also shows that paternal smoking is more likely to be associated with multiple rather than isolated malformations. A paternally-mediated effect of smoking on birth defects is suggested and further studies are encouraged.

PIP: The effect of paternal smoking on birth defects was examined using data from the Shanghai Birth Defects Monitoring Program in Shanghai Municipality from October 1986 to September 1987. A stratified random sample of 29 hospitals was selected. A total of 75,756 births with weights of 1000 gm or over were recorded. The final sample included 1012 cases and 1012 controls without adjustment for confounding factors. Maternal exposure to radiation, chemicals, and pesticides during pregnancy and the smoking and alcohol consumption habit of the husband were recorded. The relative risk (RR) of birth defects associated with paternal smoking was 1.2. Paternal smoking was associated with a 2.1- fold increase of anencephalus; infants whose fathers smoked were 3.3 times as likely to have had pigmentary anomalies of the skin, and 2.3 times as likely to have a diaphragmatic hernia. The odds ratio (OR) of spina bifida was 1.9 and varus or valgus deformities of feet had an OR of 1.8. The OR of these anomalies was also over 1.5: eye anomalies, microtia or absence of ear, nasal bone absence, cleft palate without cleft lip, brachydactylia or adactylia, undescended testicle, and polycystic kidney. The possible dose-response relationship between paternal smoking and birth defects was assessed in 3 groups: 1-9, 10- 19, and 20 or more cigarettes per day. Similar increased RRs across smoking levels were found for anencephalus, cleft palate, and pigmentary anomalies of the skin. Increasing risk among the heavier smokers was apparent for spina bifida, nasal bone absence, varus or valgus deformities of the feet, and diaphragmatic hernia. Paternal smoking was slightly more related to multiple defects than to single defects. This suggests a modest link between paternal smoking and total birth defects and a stronger effect of paternal smoking and anencephalus and spina bifida risk, consistent with a previous study.

Influence of paternal age, smoking, and alcohol consumption on congenital anomalies.

The potential effects of paternal exposures on fetal development are of great public and scientific concern, yet few epidemiologic studies have examined this association. Single live births from 1959 to 1966 among 14,685 Kaiser Foundation Health Plan members who participated in the Child Health and Development Studies were analyzed to assess the impact of paternal age, cigarette smoking, and alcohol consumption on the occurrence of birth defects in the offspring. Prevalence odds ratios for anomalies identified by age 5 were analyzed, contrasting exposed to unexposed fathers with adjustment for maternal age, race, education, smoking, and alcohol use. Advanced paternal age was associated with increased risk of preauricular cyst, nasal aplasia, cleft palate, hydrocephalus, pulmonic stenosis, urethral stenosis, and hemangioma. Father's cigarette smoking was more common among children with cleft lip +/- cleft palate, hydrocephalus, ventricular septal defect, and urethral stenosis. Alcohol use by the father was most positively related to the offspring's risk of ventricular septal defect. For both smoking and alcohol use, inverse associations were more common than positive associations. These data generally do not indicate strong or widespread associations between paternal attributes and birth defects. However, because of this study's imprecision, limited ability to isolate defects most likely to be of paternal origin, and the identification of several suggestive associations with age and smoking, further study of this issue would be of value.

Prevalence of markers for hepatitis B and hepatitis D in a municipal house of correction.

Following an outbreak of hepatitis B (HBV) in a municipal house of correction, HBV markers were detected in 173/406 (43 percent) inmates and 10/129 (8 percent) staff. Of the 173 HBV-infected inmates, 14 (8 percent) had hepatitis D (HDV) markers compared to 0/10 staff members. Intravenous drugs use (IVDU) was most strongly associated with HBV marker presence. Increasing duration of imprisonment, history of hepatitis B and especially IVDU were associated with the prevalence of HDV markers.

The risk of myocardial infarction 10 or more years after vasectomy in men under 55 years of age.

To evaluate whether vasectomy is associated with a subsequent increase in the incidence of myocardial infarction 10 or more years after surgery and whether an effect is more pronounced in those already predisposed to a myocardial infarction, a hospital-based case-control study was carried out in men aged less than 55 years. The men were interviewed during 1980-1983 in 78 hospitals in Massachusetts, Rhode Island, Connecticut, and New York. Among 2,238 men with first episodes of myocardial infarction, 332 (15%) had undergone vasectomy, compared with 572 (16%) of 3,361 controls. Vasectomy greater than or equal to 10 years earlier was reported by 150 cases and 180 controls, to yield a multivariate relative risk estimate of 1.0 after allowance for potential confounding factors (95% confidence interval (Cl) = 0.8-1.3); for vasectomy greater than or equal to 15 years before, based on 34 cases and 33 controls, the estimate was 1.1 (95% Cl = 0.7-2.0). In men predisposed to myocardial infarction because of more advanced age, cigarette smoking, elevated cholesterol level, hypertension, angina pectoris, or other risk factors, vasectomy did not appear to increase the risk further, even after intervals of greater than or equal to 10 years. The results provide evidence against an increased risk of myocardial infarction greater than or equal to 10 years after vasectomy overall and in those known to be predisposed because of other risk factors.

PIP: A hospital-based case-control study was conducted in men under age 55 to evaluate whether vasectomy is associated with a subsequent increase in the incidence of myocardial infarction 10 or more years after surgery and whether an effect is more pronounced in those already predisposed to a myocardial infarction. The men were interviewed during 1980-83 in 78 hospitals in Massachusetts, Rhode Island, Connecticut, and New York. A standard questionnaire was used to obtain information on history of vasectomy, personal characteristics, medical history, cigarette smoking, coffee and tea consumption, history of drug use, and other factors. In addition, the Framingham Type A Personality Scale questionnaire was administered, in which a higher score indicates a greater tendency to Type A behavior, and the men were asked about leisure time physical activities during the year before admission. After discharge, the diagnosis that led to admission was abstracted from the medical record. The participation rate was 87% among the potential cases and 93% among the potential controls. All cases were interviewed men 20-54 years of age admitted for a 1st episode of myocardial infarction, the diagnosis of which met WHO criteria. Men for whom it was judged that the myocardial infarction could have been caused by preexisting heart disease were excluded. There were 2238 cases: median age, 46 years; 97% white. All controls were interviewed men from the pool of potential controls who were 20-54 years old, had no history of myocardial infarction, and were admitted for diagnoses judged to be unrelated to vasectomy. There were 3361 controls: median age, 42 years; 96% white. Among the 2238 cases, 332 (15%) reported having had a vasectomy, compared with 572 (16%) of 3361 controls. Vasectomy more than 10 years previous was reported by 150 cases and 180 controls to yield a multivariate relative risk estimate of 1.0 after allowance for potential confounding factors; for vasectomy more than 15 years previous, based on 34 cases and 33 controls, the estimate was 1.1. In men predisposed to myocardial infarction because of more advanced age, cigarette smoking, elevated cholesterol level, hyperstension, angina pectoris, or other risk factors, vasectomy did not appear to increase the risk further, even after intervals of more than 10 years. The results offer evidence against an increased risk of myocardial infarction more than 10 years after vasectomy overall and in those known to be predisposed because of other risk factors.

Breast cancer and cigarette smoking.

It has been suggested that cigarette smoking may reduce the incidence of breast cancer, perhaps by as much as 20 per cent. To evaluate the relation between breast-cancer risk and smoking, we studied 2160 women with breast cancer and 717 controls who had been admitted to the hospital for cancer of the ovary, cancer of the colon or rectum, malignant melanoma, or lymphoreticular cancers. As compared with women who had never smoked, the estimated relative risk of breast cancer was 1.1 for current smokers of any amount (95 per cent confidence interval, 0.9 to 1.3), and 1.0 (0.8 to 1.3) for heavy smokers (15 or more cigarettes per day). Allowance for all identified potential confounding factors did not materially alter the results. There was no indication that age at commencement of smoking was related to the risk, nor was there evidence of an effect of smoking within the categories of age at first pregnancy or age at menopause. The data provide evidence against the hypothesis that smoking may reduce the incidence of breast cancer by 20 per cent.

Birth defects in relation to Bendectin use in pregnancy. II. Pyloric stenosis.

To test the hypothesis that the use of Bendectin in pregnancy increases the risk of pyloric stenosis, we determined rates of antenatal Bendectin exposure among 325 infants with pyloric stenosis and among two control groups comprising infants with other defects; one consisted of 3,153 infants with other conditions, and the other, a subset of that group, consisted of 724 infants with defects that may have had their origins at any time in pregnancy. Comparisons between the cases and the two control series yielded estimated relative risks of 0.9 (95% confidence interval, 0.6 to 1.2) and 1.0 (0.7 to 1.4), respectively. The findings from this large case-control study suggest that Bendectin does not increase the risk of pyloric stenosis.