Oral contraceptives causing adverse effects in therapeutic use

In view of continuous clinical reports of liver damage following oral contraceptive use, morphologic changes of the liver following the administration of a combined type of oral contraceptive (Norinyle) were studied in guinea pigs by light and electron microscopic examinations. Two interesting changes, one in Kupffer cells and another in the hepatocytes were observed. The Kupffer cells were hyperplastic and enlarged due to the phagocytosis of a large amount of fibrin which were apparently formed intravascularly and were being cleared by Kupffer cells. It is thought that enlarged Kupffer cells and excessive fibrin formation beyond the clearing capacity of Kupffer cells may lead to blockage of sinusoids resulting in a Budd-Chiari like syndrome. The nucleus of the hepatocytes showed mild enlargement and a clear nucleolar segregation which is regarded as one of the ultrastructural evidences of chemical carcinogenesis. Therefore, it is speculated that this change may be related to tumorigenesis in the liver following oral contraceptive administration. Other changes consisted of ischemic necrosis and fatty changes in occasional animals, alteration of mitochondrial configuration and hyperplasia of smooth endoplasmic reticulum in hepatocytes.
Animal ; Blood Coagulation/drug effects ; Contraceptives, Oral/adverse effects* ; Contraceptives, Oral, Combined/adverse effects* ; Guinea Pigs ; Liver/drug effects ; Liver/pathology* ; Liver/ultrastructure ; Mestranol/adverse effects* ; Norethindrone/adverse effects*

OBJECTIVETo evaluate the associations of oral contraceptives (OC) exposure, angiotensinogen (AGT) gene polymorphism and joint effects on the risk of stroke in Chinese women.

METHODSOn the basis of a prospective female cohort of contraceptive use, the first-ever-developed (FED) stroke cases, as well as, two sets of age-(± 3 years) and region-matched controls (including neighborhoods and hospitalized patients) were recruited. Between 1 July 2000 and 30 June 2009, a total of 453 FED stroke cases and 919 controls were recruited. Genotyping for polymorphisms of AGT gene was detected by Taqman method.

RESULTS(1) The risk of stroke gradually increased with the cumulative time of OC use in women (P < 0.0001). Compared with the non-users, the risk of hemorrhagic stroke slightly increased among those with OC use (OR = 1.83, 95%CI: 1.25 - 2.66). (2) Women with AG/GG genotypes of A-6G locus or CA/AA genotypes of C11535A locus indicated that there was a slightly reduced risk of stroke (OR = 0.78, 95%CI: 0.61 - 0.99; OR = 0.73, 95%CI: 0.56 - 0.95). (3) Women with AA genotypes of A-20C locus and AG/GG genotypes of A-6G, when incorporated with CA/AA genotypes of C11535A locus with OC, it could increase the risk of hemorrhagic stroke (OR = 1.99, 95%CI: 1.34 - 2.97; OR = 1.84, 95%CI: 1.15 - 2.94; OR = 1.73, 95%CI: 1.06 - 2.85).

CONCLUSIONThe AGT gene polymorphisms showed that they did have an impact on the risk of stroke. And the joint effect between women using OC and AGT gene polymorphisms could slightly increase the risk of stroke.

Aged ; Angiotensinogen ; genetics ; Case-Control Studies ; Contraceptives, Oral ; adverse effects ; Female ; Genotype ; Humans ; Middle Aged ; Risk Factors ; Stroke ; etiology ; genetics

To explore breast cancer etiology, literature was searched using Medline. We explored the 1) plausibility of smoking in breast carcinogenesis; 2) physiological properties, susceptibility windows, and exposure timing of breast cells; 3) role of exogenous hormones in breast carcinogenesis; 4) biological mechanism of synergistic interactions between smoking and exogenous hormones in breast carcinogenesis; and 5) evidence from epidemiologic studies and the fitted secular trend between smoking rate, exogenous hormone use, and breast cancer incidence in past decades. We deduced that exogenous hormone use per se is not a significant cause and its association with breast cancer is distorted by chronic exposure to environmental carcinogens, especially smoking. We hypothesize that smoking is one of the causes of breast cancer and that this causality is strengthened by synergistic interaction between smoking and exogenous hormone use. Physicians should be cautious of prescribing exogenous hormones for those with chronic exposure to environmental carcinogens to prevent breast cancer.
Breast Neoplasms ; chemically induced ; epidemiology ; etiology ; China ; epidemiology ; Contraceptives, Oral, Hormonal ; adverse effects ; Estrogens ; adverse effects ; Female ; Hormone Replacement Therapy ; adverse effects ; Humans ; Incidence ; MEDLINE ; Progestins ; adverse effects ; PubMed ; Smoking ; adverse effects ; United States ; epidemiology

OBJECTIVETo examine the significance of crossover analysis in gene-environmental interaction studies.

METHODSThrough elaboration of a case-control study on the increased risk of venous thrombosis in oral-conceptive users who were carriers of factor V Leiden mutation, core information from 2 x 4 crossover table were analyzed and compared with stratified analysis and 'case only' study.

RESULTSDifferent models (additive or multiplicative) in analyzing gene-environmental interaction yielded different results. The result of interaction based on multiplicative model was 1.35 (P > 0.05), compatible with that of stratified analysis and case only study. Calculated by crossover analysis based on additive model, synergy index S(S), attributable proportion of interaction (AP) and relative excess risk of interaction (RERI) appeared to be 3.90, 72.24%, 25.08 (P > 0.05) respectively.

CONCLUSIONCrossover analysis should further be applied in gene-environmental interaction studies.

Case-Control Studies ; Contraceptives, Oral ; adverse effects ; Cross-Over Studies ; Environment ; Factor V ; genetics ; Female ; Genetic Markers ; Genotype ; Humans ; Mutation ; Risk Factors ; Venous Thrombosis ; chemically induced ; genetics

Anticoagulants ; therapeutic use ; Contraceptives, Oral ; adverse effects ; Female ; Humans ; Middle Aged ; Pulmonary Embolism ; drug therapy ; etiology ; Venous Thrombosis ; drug therapy ; etiology

OBJECTIVE: To investigate the role of previous gynecologic surgery, hormone use, and use of non-steroidal anti-inflammatory drugs on the risk of type 1 and type 2 ovarian cancer. METHODS: We utilized data collected for the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. All diagnosed ovarian cancers were divided into three groups: type 1, endometrioid, clear cell, mucinous, low grade serous, and low grade adenocarcinoma/not otherwise specified (NOS); type 2, high grade serous, undifferentiated, carcinosarcoma, and high grade adenocarcinoma/NOS; and other: adenocarcinoma with grade or histology not specified, borderline tumors, granulosa cell tumors. The odds ratios for type 1, type 2, and other ovarian cancers were assessed with regard to historical information for specific risk factors. RESULTS: Ibuprofen use was associated with a decrease in risk for type 1 ovarian cancer. Tubal ligation and oral contraceptive use were associated with a decrease in risk for type 2 ovarian cancer. A history of ectopic pregnancy was associated with a decreased risk for all ovarian cancers by almost 70%. CONCLUSION: These findings support the hypothesis that carcinogenic pathways for type 1 and type 2 ovarian cancer are different and distinct. The marked reduction in all ovarian cancer risk noted with a history of ectopic pregnancy and salpingectomy implies that the fallopian tube plays a key role in carcinogenesis for both type 1 and type 2 ovarian cancer.
Aged ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Contraceptives, Oral, Hormonal/adverse effects ; *Early Detection of Cancer ; Female ; Gynecologic Surgical Procedures/adverse effects ; Humans ; Ibuprofen/adverse effects ; Middle Aged ; Ovarian Neoplasms/chemically induced/diagnosis/*etiology/pathology ; Pregnancy ; Pregnancy, Ectopic/epidemiology ; Risk Factors ; Surveys and Questionnaires

ABO blood type has been associated with risk of several malignancies. However, results are not consistent. In this population-based case-control study including 1204 incident endometrial cancer cases and 1212 population controls, we examined the association of self-reported serologic blood type with endometrial cancer risk using a logistic regression model. Women with endometrial cancer were more likely to have blood type A. Compared to women with blood type O, the adjusted odds ratios for endometrial cancer were 1.00 [95% confidence interval (CI), 0.79-1.28] for type B, 1.24 (95% CI, 0.90-1.69) for type AB, and 1.50 (95% CI, 1.19-1.90) for type A. A significant dose-response relationship was observed for cancer risk and level of antigen A (P for trend = 0.0003). The positive association of blood type A with cancer risk was observed regardless of menopausal status, body mass index, oral contraceptive use, or family cancer history. Our results suggest that ABO blood type may be involved in the development of endometrial cancer.
ABO Blood-Group System ; Adult ; Aged ; Body Mass Index ; Case-Control Studies ; China ; epidemiology ; Confidence Intervals ; Contraceptives, Oral ; adverse effects ; Endometrial Neoplasms ; blood ; chemically induced ; etiology ; Female ; Humans ; Logistic Models ; Middle Aged ; Odds Ratio ; Risk Factors

OBJECTIVETo set a quantitative criteria for determining the risks on cerebral vascular disease (CVD) so to identify that potential risk of an individual dying from CVD and to predict the individual risk of CVD.

METHODSData on case-control and cohort studies published during 1978 to 2003 was collected through retrieval of literatures, and data on surveillance of behavior exposure was provided by Chengdu Municipal Center for Disease Control and Prevention. Pooled odds ratio (OR) and relative risk (RR) of all risk factors for CVD were estimated using software for meta-analysis to enable the varied levels of risk factors be converted into risk fractions by statistical models.

RESULTSA risk score conversion table (quantitative criteria for assessment) of main risk factors for CVD was developed for men and women aged 35 - 69 at an interval of five years, including smoking, passive smoking, hypertension, high blood cholesterol levels, body mass index, lack of physical activity, alcohol drinking, dietary fat consumption, milk intake, oral contraceptive use, past history of diabetes and CVD, family history of CVD etc. Individuals with all these risk factors had a risk score beyond 1.00, but was equal to or below 1.00 when without. The risk score would increase along with the rise of one's risk level.

CONCLUSIONEstimation of risk of dying from CVD was based on risk score conversion table of risk factors for CVD, which could be used to predict individual potential risk of dying from CVD in the following 10 years. Our data provides evidence that education to be strengthened to persuade people to change their unhealthy lifestyles and behaviors.

Alcoholism ; complications ; Body Constitution ; Case-Control Studies ; Cerebrovascular Disorders ; epidemiology ; etiology ; China ; epidemiology ; Cohort Studies ; Contraceptives, Oral, Hormonal ; adverse effects ; Diabetes Complications ; Exercise ; Feeding Behavior ; Female ; Humans ; Hypertension ; complications ; Male ; Odds Ratio ; Risk Assessment ; Risk Factors ; Smoking ; adverse effects ; Urban Population ; statistics & numerical data