Meta-Analyses of the Relation between Silicone Breast Implants and the Risk of Connective-Tissue Diseases

BACKGROUND: The postulated relation between silicone breast implants and the risk of connective-tissue and autoimmune diseases has generated intense medical and legal interest during the past decade. The salience of the issue persists, despite the fact that a great deal of research has been conducted on this subject. To provide a stronger quantitative basis for addressing the postulated relation, we applied several techniques of meta-analysis that combine, compare, and summarize the results of existing relevant studies. METHODS: We searched data bases and reviewed citations in relevant articles to identify studies that met prestated inclusion criteria. Nine cohort studies, nine case-control studies, and two cross-sectional studies were included in our meta-analyses. We conducted meta-analyses of the results of these studies, both with and without adjustment for confounding factors, and a separate analysis restricted to studies of silicone-gel-filled breast implants. Finally, we estimated the annual number of new cases of connective-tissue disease that could be attributed to breast implants. RESULTS: There was no evidence that breast implants were associated with a significant increase in the summary adjusted relative risk of individual connective-tissue diseases (rheumatoid arthritis, 1.04 [95 percent confidence interval, 0.72 to 1.51]; systemic lupus erythematosus, 0.65 [95 percent confidence interval, 0.35 to 1.23]; scleroderma or systemic sclerosis, 1.01 [95 percent confidence interval, 0.59 to 1.73]; and Sjögren's syndrome, 1.42 [95 percent confidence interval, 0.65 to 3.11]); all definite connective-tissue diseases combined (0.80; 95 percent confidence interval, 0.62 to 1.04); or other autoimmune or rheumatic conditions (0.96; 95 percent confidence interval, 0.74 to 1.25). Nor was there evidence of significantly increased risk in the unadjusted analyses or in the analysis restricted to silicone-gel-filled implants. CONCLUSIONS: On the basis of our meta-analyses, there was no evidence of an association between breast implants in general, or silicone-gel-filled breast implants specifically, and any of the individual connective-tissue diseases, all definite connective-tissue diseases combined, or other autoimmune or rheumatic conditions. From a public health perspective, breast implants appear to have a minimal effect on the number of women in whom connective-tissue diseases develop, and the elimination of implants would not be likely to reduce the incidence of connective-tissue diseases

Benefits and risks of menopausal estrogen and/or progestin hormone use,

Current evidence is reviewed here on risks and benefits of estrogen and progestin use by peri- and postmenopausal women in relation to the following conditions: endometrial cancer, breast cancer, osteoporosis, and coronary artery disease (CAD). On balance, estrogen therapy appears to be beneficial for menopausal women, as it probably reduces the risks of CAD and osteoporosis, two of the major causes of mortality and morbidity. Although unopposed estrogen therapy increases the risk of endometrial cancer, that cancer is relatively rare and is not fatal in the vast majority of cases associated with estrogen use. Definitive conclusions about the relation of menopausal estrogens to breast cancer cannot be drawn due to inconsistent evidence to date. Although evidence from randomized controlled trials is lacking, biochemical and clinical evidence suggest that progestin supplementation is associated with a reduction in endometrial cancer risk in women taking menopausal estrogens. Progestin supplementation also may augment the beneficial effects of estrogens in providing protection against osteoporosis, although this effect is not yet well established. There is little direct evidence bearing on the relation of menopausal progestins to breast cancer. Although studies of CAD per se are lacking at present, progestins probably unfavorably alter lipoprotein profiles, thereby increasing a user's risk of CAD. Given the relatively high incidence and mortality of CAD in postmenopausal women, any negative effects on CAD risk could potentially counterbalance beneficial effects on other causes. We conclude that estrogen replacement therapy is of potential benefit to postmenopausal women, but that the question of progestin supplementation requires further study, particularly for CAD risk.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27382/1/0000412.pd

Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk

OBJECTIVE: To determine if blood levels of 25-hydroxyvitamin D (25-D) or its active metabolite, 1,25-dihydroxyvitamin D (1,25-D), are lower in women at the time of first diagnosis of breast cancer than in comparable women without breast cancer. DESIGN: This was a clinic-based case-control study with controls frequency-matched to cases on race, age, clinic and month of blood drawing. SETTING: University-based breast referral clinics. SUBJECTS: One hundred and fifty-six women with histologically documented adenocarcinoma of the breast and 184 breast clinic controls. RESULTS: There were significant mean differences in 1,25-D levels (pmol ml(-1)) between breast cancer cases and controls; white cases had lower 1,25-D levels than white controls (mean difference +/-SE: -11.08+/-0.76), and black cases had higher 1.25-D levels than black controls (mean difference +/-SE: 4.54+/-2.14), although the number of black women in the study was small. After adjustment for age, assay batch, month of blood draw, clinic and sample storage time, the odds ratio (95% confidence interval, CI) for lowest relative to highest quartile was 5.2 (95% CI 2.1, 12.8) for white cases and controls. The association in white women was stronger in women above the median age of 54 than in younger women, 4.7 (95% CI 2.1, 10.2) vs. 1.5 (95% CI 0.7, 3.0). There were no case-control differences in 25-D levels in either group. CONCLUSIONS: These data are consistent with a protective effect of 1,25-D for breast cancer in white women

Oral Contraceptive Use and Cervical Intraepithelial Neoplasia

To explore the somewhat controversial relationship between oral contraceptives and and-invasive cervical cancer, 103 cases of biopsy-confirmed cervical intraepithelial neoplasia (CIN) II or CIN III were compared with 258 controls who had normal cervical cytology. Cases were slightly less likely than controls to have ever used oral contraceptives; the odds ratio, controlling for age, socioeconomic status, barrier method use, smoking history, age at first sexual intercourse, number of sex partners, current marital status, and number of Pap smears, was 0.7 (95% CI 0.3–1.6). Recency, latency, duration, and age at first oral contraceptive use were evaluted and in no instance was oral contraceptive use positively associated with CIN. This study adds to the body of knowledge that oral contraceptives are not associated with pre-invasive cervical cancer. Further, if oral contraceptive users continue to be regularly screened, their risk of developing the more invasive lesions should be very low

Active and Passive Cigarette Smoke Exposure and Cervical Intraepithelial Neoplasia

This case-control analysis presents odds ratios for active and passive cigarette smoke exposure and cervical intraepithelial neoplasia of levels II and III (CIN II and CIN III) while controlling for confounders. From 1987 to 1988, 103 biopsy-conformed incident cases of CIN II or III and 268 controls with normal cervical cytology were enrolled. Seventy % of cases were cigarette smokers, while only 30% of controls had ever smoked. The adjusted odds ratio for current cigarette smoking was 3.4 (95% confidence interval, 1.7-7.0). The following confounders were included in logistic regression models: age, race, education, number of sex partners, contraceptive use, sexually transmitted disease history, and Pap smear history. The risk of CIN II/III increased with increasing years of cigarette smoking and with increasing pack-years of exposure. Smoking was associated more strongly with CIN III than CIN II. The effect of passive cigarette smoke exposure was explored separately for smokers and nonsmokers and was found not to be consistently associated with CIN II/III when controlling for confounders

Barrier Methods of Contraception and Cervical Intraepithelial Neoplasia

This North Carolina-based case-control study examined risk factors for cervical intraepithelial neoplasia (CIN). Cases were 103 women with biopsy-confirmed CIN II or III who were recruited from a referral dysplasia clinic. Controls were 258 family practice patients with normal cervical cytology. All subjects were interviewed regarding their sexual and reproductive history, Pap smear screening, active and passive cigarette exposures, and contraceptive use patterns. When compared with controls, cases were half as likely to have ever used barrier methods of contraception; the adjusted odds ratio was 0.5 (95% CI 0.2–0.9). The risk of CIN II/III decreased further with increasing years of barrier method use. Recency, latency, and age at first barrier method use were all associated with a reduced risk of CIN. Men and women should carefully consider the range of benefits of barrier method use as a means to reduce their risk of unwanted pregnancies, sexually transmitted diseases, and cervical neoplasia