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.

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.

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.

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.

Two cases of venous sinus thrombosis in women taking the oral contraceptive pill, Yaz (dropirenone/ ethinyl estradiol), and review of the literature

Cerebral venous sinus thrombosis (CVT) is a rare cause of stroke and the clinical presentation is variable, thus mimicking other neurologic pathologies. One of the more common acquired risk factors of venous sinus thrombosis is oral contraceptive medications such as Yaz. While the prognosis for CVT is favorable, it is important to identify and treat early to prevent neurologic deficits. We report two cases of young female patients who presented with sinus thrombosis and review the current literature on this topic. CVT accounts for 0.5% of strokes and most commonly presents with headaches and in many cases focal neurologic deficits. Diagnosis is confirmed with neuroimaging including CT angiography or MR angiography. Treatment consists of anticoagulation and in some cases, thrombolytic therapy is beneficial. The overall prognosis of CVT is favorable but, further research is needed to outline optimal treatment options including the duration of anticoagulation therapy and the role of thrombolytic therapy to prevent serious neurologic deficits.

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.

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.

Combined Oral Contraceptive Use at the University of Port Harcourt Teaching Hospital, Port Harcourt, Southern Nigeria: A-20 Year Review

Background: While the combined oral contraceptive pill (COCP) is one of the most commonly used methods of birth control especially in the developed countries, robust and current information on the pill use in developing countries including Nigeria is at best lacking. Objectives: The study was conducted to determine the prevalence rate, efficacy and side effects of COCP at the University of Port Harcourt Teaching Hospital (UPTH), Port Harcourt, Southern Nigeria. Methods: It was a retrospective analysis of all clients who used the COCP between 1st January 1997 and 31st December, 2016, at the family planning clinic of UPTH Port Harcourt. Data on sociodemographic profile, side effects and source of information were extracted from the clients’ case notes coded and fed into Excel spread sheet and analysed. Results: Of the 8310 new acceptors of modern contraceptive methods in UPTH, 399 clients used the COCP, giving a prevalence rate of 4.8%. The mean age of the acceptors was 26.42 ± 4.27 years while the mean parity was 1.90 ± 0.36. Menstrual disruption was the most common complications with 78 episodes constituting 47.0% of all the complications. One unintended pregnancy occurred during the period of observation, giving a Pearl index of 0.01. Conclusion: The study showed that although COCP is very effective, readily available, safe and reliable method of fertility control, the acceptance rate is very low and the patronage rapidly declining and may therefore go into extinction as a family planning method in Port Harcourt, Southern, Nigeria.

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.

A multivariate analysis of the factors that influence the modification of sexual desire in oral hormonal contraceptive (OC) users

Objective. This work studied the influencing factors of age, level of education, family planning awareness, relationship with partner, the age at which sexual relationships were initiated, parity, the method of contraceptive previously used, the type of contraceptive pill used and the duration of oral hormonal contraception (OC) use in relation to the modification of sexual desire in OC users. Materials and Methods. Prospective study of 760 OC users at the Family Planning Center “Marina Alta” in Alicante (Spain). A logistical regression analysis was carried out to study the relative risk of reduction in libido, taking other risk factors into account. Results. In the simple analysis, women who initiated sexual relationships between 18 and 25 years of age had a lower sexual desire in comparison with women who were sexually active before the age of 18 (OR = 2.11;CI: 1.15 - 3.91). Nulliparous women had a reduced sexual desire compared with those women that had given birth (OR = 2.32;CI: 1.41 - 3.82). An OC use of between 6 months and 1 year reduced sexual desire in comparison with a use of less than 6 months (OR = 0.24;CI: 0.09 - 0.64). In the multivariate analysis, age (OR = 1.12;CI: 1.01 - 1.21) and the use of OC within an initial 6 month to a year period (OR = 0.24;CI: 0.09 - 0.64) presented a statistically significant relationship with the modification of sexual desire. The level of education, family planning awareness, relationship with partner, the method of contraception previously used and the type of contraceptive pill prescribed showed no statistical significance with the modification of sexual desire in OC users. Conclusions. Sexual desire in OC users decreases as a woman’s age increases and in an early stage of use in the first six months after beginning OC treatment.

Effective Treatment of Vulvar-Vaginal Complaints in Women Taking Combined Oral Contraceptive with a New Medical Device in Gel: A Pilot Study

Objective: To assess efficacy and tolerability of a new medical device in gel based on the synergic combination of NioskinTM Red Clover Extract noisome (NRC) and SylTechTM system (SB), a complex of silicium microcrystals covalently bound with silver ions associated with hyaluronic acid to the treatment of vulvo-vaginal dryness and dyspareunia in women taking combined oral contraceptive (COC). Methods: Forty eight women were treated for 12 weeks with NRC + SB vaginal gel (0.75 g/day) for 3 weeks. After therapy, symptoms (dyspareunia and dryness) were evaluated through a 10-cm VAS. Visual examination of the vagina and vulvar vestibule was also conducted, which included observations for petechiae, pallor, friability, dryness, and redness in the mucosa. Ratings were based on a 4-point scale (0, none;1, mild;2, moderate;3, severe). Results: NRC + SB vaginal gel appears to be effective for relief vulvo-vagianl dryness and dyspareunia and an improvement of vaginal and vestibular trophism was noted. Conclusion: NRC + SB vaginal gel proved good treatment options for relief of vulvovaginal symptoms in women who take COC.

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.

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.

Meta-analysis of the risk factors of breast cancer concerning reproductive factors and oral contraceptive use

The authors performed a meta-analysis of case-control studies that addressed whether reproductive factors and oral contraceptive use were associated with breast cancer by searching the MEDLINE,PubMed,Proquest,Embase,ScienceDirect,African Healthline,BMJ Health Intelligence and Chinese Periodical net databases for all English-language and Chinese-language papers published from January 1,1997 to December 31,2007.A total of 15 studies calculating pool ORs indicated that menopausal age>50 yr[odds ratio(OR),1.39;95%confidence interval(CI),1.22–1.57]and oral contraceptive use(OR,2.12*,“*”:summary OR was adjusted;95%CI,1.24–3.62)were correlated with the increase in breast cancer risk while the summary OR based on number of full-term pregnancies≥1(OR,0.63*;95%CI,0.60–0.68)and breast-feeding(OR,0.76;95%CI,0.64–0.90)indicated no association with breast cancer risk.The correlation was statistically significant.Menopausal age>50 yr and oral contraceptive use are positively correlated with an increase in breast cancer risk while breast-feeding and number of full-term pregnancies≥1 are protective factors.

25岁以下未育女性人工流产后即时落实宫内节育器和短效口服避孕药的临床对照观察

目的:观察25岁以下未育女性人工流产后即时放置宫内节育器(IUD)和使用短效复方口服避孕药(COC)的可行性和使用情况。方法:将≤25岁未育早孕自愿要求人工流产的女性作为观察对象,根据其意愿术后放置IUD或使用COC避孕。IUD组148例,COC组204例,随访6个月观察两组的避孕情况。结果:两组均无妊娠发生。IUD组1例因完全脱落而终止使用,终止率为0.7%。COC组术后3月的累积停用率69.1%,6月达92.1%,停用的主要原因是嫌麻烦/不能坚持服药,占31.4%。术后1,3个月的不适主诉率IUD组高于COC组(P<0.010,P<0.001)。结论:≤25岁未育女性人工流产后即时放置IUD或使用COC避孕均可行高效。IUD组6个月续用率高;COC副作用轻,但需加强咨询,提高续用率。