Attributable Causes of Breast Cancer and Ovarian Cancer in China:Reproductive Factors,Oral Contraceptives and Hormone Replacement Therapy

Objective： To provide an evidence-based, consistent assessment of the burden of breast cancer attributable to reproductive factors （RFs, including nulliparity, mean number of children, age at first birth and breastfeeding）, use of oral contraceptives （OCs, restricted to the age group of 15-49 years）, and hormone replacement therapy （HRT）, as well as of the burden of ovarian cancer attributable to the mean number of children in China in 2005. Methods： We derived the prevalence of these risk factors and the relative risk of breast and ovarian cancer from national surveys or large-scale studies conducted in China. In the case of RFs, we compared the exposure distributions in 2001 and counterfactual exposure. Results： Exposure of RFs in 2002 was found to account for 6.74% of breast cancer, corresponding to 9,617 cases and 2,769 deaths, and for 2.78% of ovarian cancer （712 cases, 294 deaths）. The decrease in mean number of children alone was responsible for 1.47% of breast cancer and 2.78% of ovarian cancer. The prevalence of OC use was 1.74% and the population attributable fraction （PAF） of breast cancer was 0.71%, corresponding to 310 cases and 90 deaths. The PAF of breast cancer due to HRT was 0.31%, resulting in 297 cases and 85 deaths. Conclusion： RFs changes in China contributed to a sizable fraction of breast and ovarian cancer incidence and mortality, whereas HRT and OCs accounted for relatively low incidence of breast cancer in China.

The impact of combined oral contraceptives on ocular tissues:a review of ocular effects

The aim of this manuscript is to review the action and adverse effects of combined oral contraceptives（COCs）on ocular tissues.The percentage of unwanted pregnancies and the subsequent abortions make contraception crucial worldwide.Over 100 million women around the world use common contraceptive methods,including intrauterine devices,combined estrogen and progestin oral contraceptives,as well as progestin only preparations（oral contraceptives,implants or injections）.COCs are widely used for contraception,but they are also indicated in menorrhagia,endometriosis,acne and hirsutism,fibroid uterus and premenstrual syndrome.However,they have been associated with high rates of cardiovascular events,venous thromboembolic disease,ischemic strokes and breast cancer.The incidence of COCs-related ocular complications is estimated to be 1 in 230 000,including dry eye symptoms,corneal edema,lens opacities and retinal neuro-ophthalmologic or vascular complications.We may infer that the serious ocular complications of COCs can be prevented by eliminating the estrogen dosage and choosing third-generation progestins.In any case,doctors should take into consideration the systemic and ocular history of the patients before selecting any method of contraception.

Use of oral contraceptives and risk of pancreatic cancer in women:A recalculated meta-analysis of prospective cohort studies

In a recent systematic review and meta-analysis of observational studies,the author found potential errors in the selection and extraction processes.The recalculated summary relative risks and the results of a dose-response metaanalysis showed that oral contraceptive use may not be associated with the risk of pancreatic cancer in women.

Electrical Activities and Pressure Pain Threshold in Oral Contraceptives Users and Nonusers

The aim is to evaluate the influence of oral contraceptive intake and menstrual cycle on the electrical activity and pressure pain threshold from anterior temporal and masseter muscles. Twenty-eight women on reproductive age were selected, 13 OC users and 15 nonusers. They were weekly submitted to electromyography and algometry of the anterior temporal and masseter muscles during three consecutive menstrual cycles. Electrical activities at rest position and PPTs of temporal and masseter muscles were not affected by menstrual cycle or by OCs uses. Comparison between groups demonstrated that working side electrical activity was increased in OC users in both muscles, except during lutheal phase for the anterior temporal. However, comparison within weeks did not demonstrate statistical difference. It was suggested that, in healthy women, oral contraceptive use may influence electrical activity, but different phases of the cycle may not.

Relieving the Impacts of Oral Contraceptives on Lipids Profile by Taking Pills in a Novel Scheme

Objective To explore whether the changes on lipids profile induced by oral contraceptives could be reduced through alternatively administering two oral contraceptives of different formulations (either predominant in progestogen or estrogen) Materials &. Methods A total of 59 women aged 25- 45 were divided into two treatment groups.The subjects in Group A received oral contraceptive A (Oc A: NET 0. 600 mg + EE 0. 035 mg) and B (OcB: LNG 0. 15mg + EEO. 03 mg) alternatively during 12 treatment cycles. Each contraceptive was administrated for three cycles consecutively with starting from OcA. The subjects in the B group received OcB only during 12 treatment cycles. Fasting blood were drawn before treatment, at the end of each trimester treatment and at the end of one cycle after stopping treatment respectively. The concentrations of lipids and apolipoproteins were measured.Results OcA increased the levels of triglyceride(TG) , total cholesterol (TC), high density lipoprotein-cholesterol(HDL-c) , and apolipoprotein AI (apo AI) with statistical significance, whereas OcB significantly decreased all parameters above. As compared with the control group, the overall mean of variation in the study group was much less than that of the control group.Conclusion It indicates that the impacts of oral contraceptives on lipids profile could be moderated by means of alternatively administering Ocs of two different formulations , with estrogen-dominant or progestogen-dominant.

Comparison of Drospirenone-with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders： A Prospective Randomized Control Trial

Background：While combined oral contraceptives （COCs） are commonly used to treat polycystic ovary syndrome （PCOS）,comparative data regarding metabolic effects of different progestogens on this patient population are missing.This study aimed to compare the different effects of drospirenone （DRP）-containing COCs with cyproterone acetate （CPA）-containing COCs,combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders.Methods：Ninety-nine women with PCOS and a metabolic disorder between January 2011 and January 2013 were enrolled into this prospective randomized clinical trial.Participants were randomized into two groups such as DRP-containing COCs,and CPA-containing COCs.Participants took COCs cyclically for 6 months,combined with metformin administration （1.5 g/d） and lifestyle modifications （diet and exercise）.Clinical measures and biochemical and hormone profiles were compared.Comparisons for continuous variables were evaluated with paired and unpaired Student＆#39;s t-tests.The Wilcoxon signed rank test was used when the data were not normally distributed.Analysis of covariance was used to control for age,body mass index （BMI）,and baseline data of each analyzed parameter when compared between the two groups.Results：A total of 68 patients have completed the study.The combination regimen of COCs,metformin,and lifestyle modifications in these patients resulted in a significant decrease in BMI,acne,and hirsutism scores when compared to baseline levels in both groups （P 〈 0.05）.Blood pressure （BP） was significantly different in the CPA group when compared to baseline （75.14 ± 6.77 mmHg vs.80.70 ± 5.60 mmHg,P 〈 0.01）,and after 6 months of treatment,only the change in systolic BP was significantly different between the two groups （4.00 [-6.00,13.00] mmHg vs.-3.50 [-13.00,9.00] mmHg,P =0.009）.Fasting glucose,fasting insulin,and homeostasis model assessment-insulin resistance decreased significantly in the DRP group （5.40 ± 0.41 mmol/L vs.5.21 ± 0.32 mmol/L,P =0.041;13.90 [10.50,18.40] μU/ml vs.10.75 [8.60,13.50] μU/ml,P =0.020;3.74 [2.85,4.23] vs.2.55 [1.92,3.40],P =0.008） but did not differ between the two groups.While individual lipid profiles increased in both groups,no statistically significant difference was observed.Conclusions：DRP-containing COCs combined with metformin and lifestyle modifications could better control BP and correct carbohydrate metabolism in women with PCOS and metabolic disorders compared with CPA-containing COCs.

Effect of Two Kinds of Different Combined Oral Contraceptives Used on Bone Mineral Density in Women of Reproductive Age

Objective To compare bone mineral density （BMD） among users of ethinylestradiol/ desogestrel, ethinylestradiol/cyproterone acetate and nonhormonal control subjects. Methods The study included 154 women aged 25-40 years. Forty-six women were using ethinylestradiol/desogestrel （group A） and 55 women using ethinylestradiol/cyproterone acetate （group B）for 24 months and 53 women using nonhormonal contraception as control subjects （group C）. BMD of the lumbar spine and femoral neck were obtained using dual energy X-ray absorptiometry, comparing mean BMD changes in combined oral contraceptives （COCs） users with nonusers. Results For 24 months of treatment, lumbar spine and femoral neck BMD values in women who used ethinylestradiol/desogestrel and ethinylestradiol/cyproterone acetate were not significantly different compared with the baseline and the values of subjects in nonuser （P〉0.05）. Conclusion There was no statistical difference in BMD between the users of ethinylestradiol/desogestrel or ethinylestradiol/cyproterone acetate and nonusers.

Hepatic Adenoma Secondary to Long-Term Oral Contraception Use in a Young Female

Hepatic adenomas are a rare byproduct of oral contraceptive pill (OCP) use. Laboratory workup is often inconclusive. Diagnosis can be made via MRI;however, select cases may require further testing such as fine needle aspiration or core needle biopsy. We report a case of a 36-year-old female who was referred to gastroenterology for further evaluation of several liver lesions found incidentally on imaging. Due to risk factors, such as age, long-term oral contraceptive use and obesity, adenoma was high on the differential. Although infrequent, this case emphasizes the importance of a detailed history, including medication review, and physical examination.

Association between oral contraceptive use and pancreatic cancer risk:A systematic review and meta-analysis

BACKGROUND Studies on the association of oral contraceptive(OC)use and pancreatic cancer showed inconsistent findings.AIM To evaluate the relationship between OC use and pancreatic cancer risk.METHODS A literature search for observational studies(case-control and cohort studies)was conducted up to December 2020.A meta-analysis was performed by calculating pooled relative risks(RRs)and 95%confidence intervals(CIs).Heterogeneity was assessed using Cochran’s chi-square test and I2 statistic.Subgroup analyses were performed by study design,source of controls in case-control studies,number of cases of pancreatic cancers,study quality according to Newcastle-Ottawa Scale score,geographical region and menopausal status.All analyses were performed using Review Manager 5.3(RevMan 5.3).RESULTS A total of 21 studies(10 case-control studies and 11 cohort studies)were finally included in the present meta-analysis,comprising 7700 cases of pancreatic cancer in total.A significant association was observed between the ever use of OC and pancreatic cancer risk in the overall analysis(RR=0.85;95%CI=0.73-0.98;P=0.03).Duration of OC use(<1 year,<5 years,5-10 years,>10 years)was not significantly associated with the risk of pancreatic cancer.Subgroup analyses revealed a statistically significant subgroup difference for the geographic region in which the study was conducted(Europe vs Americas vs Asia;P=0.07).Subgroup analyses showed a statistically significant decrease in pancreatic cancer risk and OC use in high-quality studies,studies conducted in Europe,and in postmenopausal women.CONCLUSION Despite the suggested protective effects of OC use in this meta-analysis,further epidemiological studies are warranted to fully elucidate the association between the use of OC and pancreatic cancer risk.

A drospirenone-containing oral contraceptive improved bleeding pattern and personal satisfaction in 914 women from Jordan, Lebanon and Syria

Aim: We assessed bleeding pattern, tolerance and patient satisfaction of an oral contraceptive containing 3 mg drospirenone and 30 mcg ethinyl estradiol (DRSP/EE) under real-life conditions. Study Design: We performed a multicenter, prospective, 6-cycle, observational study in Canada, Europe and the Middle East. Detailed analyses of the three Middle East countries, Jordan, Lebanon andSyriawere presented here. The efficacy variables included an assessment of bleeding patterns, premenstrual symptoms of water retention and patient satisfaction, as determined by a visual analogue scale. Results: A total of 914 women were enrolled. The percentage of women with intermenstrual bleeding decreased from 37.4%, 48.7% and 32.2% at baseline to 9.7%, 6.1% and 10.9% at the end of cycle6 inJordan, Lebanon and Syria, respectively (creased sharply in all three countries (p Amenorrhea decreased significantly in Lebanon and Syria (p < 0.005). In addition, signs of water retention like abdominal bloating, breast tenderness and swelling of extremities decreased significantly over the course of 6 treatment cycles (p < 0.001). Patient satisfaction increased for all investigated items. Upon completion of the study, 82.7% of women answered “Yes” to continue treatment with this oral contraceptive. Conclusion: The oral contraceptive containing 3 mg drospirenone and 30 mcg ethinyl estradiol has beneficial effects on bleeding pattern, symptoms of water retention and patient satisfaction.

Acute mesenteric ischemia secondary to oral contraceptive-induced portomesenteric and splenic vein thrombosis:A case report

BACKGROUND Mesenteric ischemia represents an uncommon complication of splanchnic vein thrombosis,and it is less infrequently seen in young women using oral contraceptives.Diagnosis is often delayed in the emergency room;thus,surgical intervention may be inevitable and the absence of thrombus regression or collateral circulation may lead to further postoperative ischemia and a fatal outcome.CASE SUMMARY We report a 28-year-old female patient on oral contraceptives who presented with acute abdominal pain.Her physical examination findings were not consistent with her symptoms of severe pain and abdominal distention.These findings and her abnormal blood tests raised suspicion of acute mesenteric ischemia(AMI)induced by splanchnic vein thrombosis.Contrast-enhanced abdominal computed tomography revealed ischemia of the small intestine with portomesenteric and splenic vein thrombosis(PMSVT).We treated the case promptly by anticoagulation after diagnosis.We then performed delayed segmental bowel resection after thrombus regression and established collateral circulation guided by collaboration with a multidisciplinary team.The patient had an uneventful postoperative course and was discharged 14 d after surgery and took rivaroxaban orally for 6 mo.In subsequent follow-up to date,the patient has not complained of any other discomfort.CONCLUSION AMI induced by PMSVT should be considered in young women who are taking oral contraceptives and have acute abdominal pain.Prompt anticoagulation followed by surgery is an effective treatment strategy.

Complete spontaneous regression of giant focal nodular hyperplasia of the liver: Magnetic resonance imaging evaluation with hepatobiliary contrast media

Focal nodular hyperplasia(FNH) of the liver is a benign lesion occurring in 0.6%-3% of the general population that probably reflects a local hyperplastic response of hepatocytes to a vascular abnormality. Most lesions are diagnosed incidentally and the natural history of the disease remains largely unknown. It has been shown that most FNH remain stable, or even regress, over a long follow-up period. We present a patient with FNH of the liver who was followed up for 7 years. A 26-yearold woman with a 5-year history of oral contraceptive use was referred to our hospital in February 2005 for further examination of a liver tumour. The diagnosis of FNH was made using magnetic resonance(MR) imaging with hepatospecific contrast media; this technique allows a correct diagnosis, in particular distinguishing FNH from hepatic adenoma, avoiding an invasive procedure such as the lesion biopsy. After 7-year from the diagnosis, we observed the complete spontaneous regression of the lesion by enhanced MR scanning. In this patient, discontinuation of oral contraceptive use and two childbirths may have influenced the natural history of FNH. To our knowledge, in the English literature there is no report illustrating a complete regression of giant FNH but only studies of decreasing in size. The present case suggests that a young patient with giant FNH should be managed conservatively rather than by resection, because FNH has the potential for spontaneous regression.

ABCB4 mutations underlie hormonal cholestasis but not pediatric idiopathic gallstones

AIM:To investigate the contribution of ABCB4 mutations to pediatric idiopathic gallstone disease and the potential of hormonal contraceptives to prompt clinical manifestations of multidrug resistance protein 3 deficiency.METHODS:Mutational analysis of ABCB4,screening for copy number variations by multiplex ligation-dependent probe amplification,genotyping for low expression allele c.1331T>C of ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with cholesterol gallstones in adults was performed in 35 pediatric subjects with idiopathic gallstones who fulfilled the clinical criteria for low phospholipid-associated cholelithiasis syndrome(LPAC,OMIM#600803)and in 5young females with suspected LPAC and their families(5 probands,15 additional family members).The probands came to medical attention for contraceptiveassociated intrahepatic cholestasis.RESULTS:A possibly pathogenic variant of ABCB4was found only in one of the 35 pediatric subjects with idiopathic cholesterol gallstones whereas 15 members of the studied 5 LPAC kindreds were confirmed and another one was highly suspected to carry predictably pathogenic mutations in ABCB4.Among these 16,however,none developed gallstones in childhood.In 5index patients,all young females carrying at least one pathogenic mutation in one allele of ABCB4,manifestation of LPAC as intrahepatic cholestasis with elevated serum activity of gamma-glutamyltransferase was induced by hormonal contraceptives.Variants ABCB11c.1331T>C and ABCG8 c.55G>C were not significantly overrepresented in the 35 examined patients with suspect LPAC.CONCLUSION:Clinical criteria for LPAC syndrome caused by mutations in ABCB4 cannot be applied topediatric patients with idiopathic gallstones.Sexual immaturity even prevents manifestation of LPAC.

Obesity is associated with colitis in women but not necessarily causal relationship

The relationship between obesity and female risk of microscopic colitis remains to be discussed.

Non-viral causes of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the most common primary liver malignancy and represents an international public health concern as one of the most deadly cancers worldwide.The main etiology of HCC is chronic infection with hepatitis B and hepatitis C viruses.However,there are other important factors that contribute to the international burden of HCC.Among these are obesity,diabetes,non-alcoholic steatohepatitis and dietary exposures.Emerging evidence suggests that the etiology of many cases of HCC is in fact multifactorial,encompassing infectious etiologies,comorbid conditions and environmental exposures.Clarification of relevant non-viral causes of HCC will aid in preventative efforts to curb the rising incidence of this disease.

Liver cell adenoma with malignant transformation:A case report

A 57-year-old woman was referred to our hospital because of a liver mass detected by computed tomography.She had taken oral contraceptives for only one month at the age of thirty.Physical examination revealed no abnormalities,and laboratory data,including hepatic function tests,were within the normal range,with the exception of elevated levels of those serum proteins induced by the absence of vitamin K or by raised levels of the antagonist (PIVKA)-Ⅱ (3 502 AU/ml). Abdominal ultrasonography revealed a hyperechoic mass measuring 10×10 cm in the left posterior segment of the liver.Because hepatocellular carcinoma could not be completely excluded,this mass was resected.The tumor consisted of sheets of uniform cells with clear cytoplasm, perinuclear eosinophilic granules and round nuclei.These histological findings were consistent with liver cell adenoma. Background hepatic tissue appeared normal.After resection of the tumor,serum PIVKA-Ⅱ fell to within the normal range. An area of hepatocellular carcinoma (HCC) with a mid- trabecular pattern was immunohistochemically found,which was positive for PIVKA-Ⅱ.Sinusoidal endothelial cells were CD34-positive,containing scattered PIVKA-Ⅱ positive cells. This tumor was therefore finally diagnosed as liver cell adenoma with focal malignant transformation to HCC.

Developing fertility control for rodents: a framework for researchers and practitioners

Fertility control is often heralded as a humane and effective technique for management of overabundant wildlife,including rodents.The intention is to reduce the use of lethal and inhumane methods,increase farm productivity and food security as well as reduce disease transmission,particularly of zoonoses.We developed a framework to guide researchers and stakeholders planning to assess the effectiveness of a potential contraceptive agent for a particular species.Our guidelines describe the overarching research questions which must be sequentially addressed to ensure adequate data are collected so that a contraceptive can be registered for use in broad-scale rodent management.The framework indicates that studies should be undertaken iteratively and,at times,in parallel,with initial research being conducted on(1)laboratory-based captive assessments of contraceptive effects in individuals;(2)simulation of contraceptive delivery using bait markers and/or surgical sterilization of different proportions of afield-based or enclosure population to determine how population dynamics are affected;(3)development of mathematical models which predict the outcomes of different fertility control scenarios;and(4)implementation of large-scale,replicated trials to validate contraceptive efficacy under various management-scalefield situations.In some circumstances,fertility control may be most effective when integrated with other methods(e.g.some culling).Assessment of non-target effects,direct and indirect,and the environmental fate of the contraceptive must also be determined.Developing fertility control for a species is a resource-intensive commitment but will likely be less costly than the ongoing environmental and economic impacts by rodents and rodenticides in many contexts.

Comparison of Risks of Thromboembolism of Drospirenone-Containing and Nondrospirenone -Containing Combined Oral Contraceptive Use: A Meta-Analysis

This study aimed to estimate the risk of venous thromboembolism(VTE),arterial thromboembolism(ATE),and other side effects following the use of drospirenone(DRSP)-containing combined oral contraceptives(COCs).When compared with non-DRSP-containing COCs,DRSP-containing COCs decreased the risk of VTE by 15%in the overall study population,although this was not statistically significant(adjusted hazard ratio/risk ratio[95%confidence interval]0.85[0.69,1.04]).DRSP-containing COCs also showed significant benefits in terms of ATE risk.The body mass index of the subjects significantly decreased by 0.64 kg/m^(2) after taking the DRSP-containing COCs for 6 months.We concluded that DRSP-containing COCs were safe for use and could be broadly recommended.

Effect of Combined Oral Contraceptive Use on Bone Mineral Density in Adolescent Females

Objective To compare adolescents＇ bone mineral density （BMD） between users of combined oral contraceptive （Marvelon, desogestrel/ethinylestradiol） and no.nhormonal control subjects. Methods The study included 127 women who aged between 16 and 18 years using Marvelon for 24 months and 115 women who aged between 16 and 18 years using nonhormonal contraception as control subjects. BMD of the lumbar spine and femoral neck were obtained using dual energy X-ray absorptiometry. Results After 24 months of Marvelon use, as compared with baseline, the mean BMD in lumbar spine and femoral neck were decreased by 0.30% and 0.61%, respectively. While in the nonusers group, the mean BMD were increased by 1.88% and 1.10%, respectively. Lumbar spine and femoral neck BMD in women who used Marvelon were not significantly different compared with the subjects who used nonhormonal contra- ception （P〉0. 05）. Conclusion Two years of Marvelon use had no significant effect on BMD, but it remains unknown whether longer than 2 years of use has a significant adverse effect on the attainment of peak bone mass.

Post-marketing Surveillance for Combined Oral Contraceptive Containing Desogestrel(Marvelon~) in Chinese Rural Areas

To assess the side effects and the continuation rate of combined oral contraceptive （COC） containing desogestrel （Marvelon） during 12 months. Methods This was a post-marketing surveillance study on Marvelon COC among 870 healthy rural women in 5 different counties of Jiangsu Province during 12 months. Results About 24.02% of the women who used Marvelon COC experienced side effects during 12 months. Gastrointestinal disorder, bleeding/spotting and chloasma were ranked the first three in the side effects. The rate of side effects of Marvelon COC users during the first 3 months in southern area of Jiangsu was significantly higher than that of users in northern area of Jiangsu. Most of the users did not experience obvious weight changes i.e., loss or increase in weight of more than 5 kg during 12 months. Blood pressure and biochemical indicators of almost 99% among users were within the normal range. The gross cumulative continuation rate for 12 months was 83.14%; the most common medical reason for discontinuation was gastrointestinal disorder. There was an increased risk of discontinuation use among women with lower educational level. Conclusion Marvelon COC brought fewer side effects and was well accepted when applied in Chinese rural women.