Oral Contraceptive Users Research Articles

Epidemiology of vulvar neoplasia in the NIH-AARP Study

ObjectiveTo clarify risk factors for rare vulvar neoplasms. MethodsWithin the NIH-AARP Study, among 201,469 women interviewed in 1995–1996 and followed for a mean of 13.8years, there were 370 diagnoses of incident vulvar neoplasms, including 170 invasive and 198 vulvar intraepithelial neoplasms grade 3 (VIN3). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated via multivariate logistic regression for various demographic, reproductive and lifestyle factors, with separate consideration of relations according to invasiveness, histology and age at diagnosis. ResultsConsistent with descriptive data, we found non-white women at lower risks of vulvar neoplasia than white women (HR=0.59, 95% CI 0.36–0.95). Significant risk factors for VIN3 included being divorced/separated (HR vs. currently married=1.77, 95% CI 1.24–2.51), a current cigarette smoker (3.88, 95% CI 2.64–5.72), a user of oral contraceptives (1.46, 95% CI 1.06–2.01), or a current user of menopausal hormones (1.73, 95% CI 1.24–2.41). Significant risk factors for invasive cancers were being obese (HR for BMI ≥30 vs. <25=1.62, 95% CI 1.10–2.40) or a current smoker (1.86, 95% CI 1.21–2.87). Cigarette smoking was a risk factor mainly for neoplasms shown in other investigations to be HPV-related, namely VIN3 and invasive squamous cell cancers (SCCs) occurring in the younger stratum of cases. In contrast, obesity was primarily associated with the development of invasive SCCs. ConclusionsOur results support that vulvar neoplasia is a heterogeneous disease. VIN3 demonstrated risk factors consistent with an HPV-related etiology, while invasive cancers were additionally affected by obesity, suggesting that further attention should focus on the role of chronic inflammatory conditions.

Mood disturbances during combined oral contraceptive use and the effect of androgen supplementation. Results of a double-blind, placebo-controlled, single-case alternation design pilot study

Objectives: To evaluate the effect of androgen supplementation in healthy combined oral contraceptive (COC) users who experience mood disturbances during COC-use only. Methods: Six women with mood disturbances during COC-use only, received COC with co-treatment of 50 mg dehydroepiandrosterone (DHEA) during three cycles and placebo during another three cycles in an individualized random order. Daily mood rating was measured by a single item: ‘In what kind of mood have you been in the past 24 h?’ The results were analysed using a randomisation test for single-case experimental designs. Results: The p values for the alternation design randomisation tests on the raw data of the six healthy individuals varied between 0.21 and 1, indicating that the average daily mood ratings of the active treatment DHEA are not statistically significantly larger than the average daily mood ratings of placebo. The combined p value of the subjects using a DRSP-containing pill was 0.97, and of the subjects using an LNG-containing pill was 0.65, indicating no statistically significant treatment effect for any of the pill types. Conclusions: In this single-case alternation design study, concomitant treatment with DHEA for intermittent periods of 4 weeks did not result in improvement of mood disturbances related to COC-use, but had also no side-effects.

Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners’ Oral Contraception Study

Oral contraceptives have been used by hundreds of millions of women around the world. Important questions remain regarding the very long-term cancer risks that are associated with oral contraception. Despite previous research, important questions remain about the safety of these contraceptives: (1) How long do endometrial, ovarian, and colorectal cancer benefits persist? (2) Does combined oral contraceptive use during the reproductive years produce new cancer risks later in life? (3) What is the overall balance of cancer among past users as they enter the later stages of their lives? The purpose of this study was to examine the very long-term cancer risks or benefits associated with the use of combined oral contraceptives, including the estimated overall life-time balance. The 46,022 women who were recruited to the UK Royal College of General Practitioners' Oral Contraception Study in 1968 and 1969 were observed for up to 44 years. Directly standardized rates of specific and any cancer were calculated for "ever" and "never" users of combined oral contraceptives; data were standardized for age, parity, social class, and smoking. Attributable risk and preventive fraction percentages were calculated. Poisson regression that adjusted for the same variables was used to estimate incidence rate ratios between ever and never users and to examine effects by time since last oral contraceptive use. There were 4661 ever users with at least 1 cancer during 884,895 woman-years of observation and 2341 never users with at least 1 cancer during 388,505 woman-years of observation. Ever use of oral contraceptives was associated with reduced colorectal (incidence rate ratio, 0.81; 99% confidence interval, 0.66-0.99), endometrial (incidence rate ratio, 0.66; 99% confidence interval, 0.48-0.89), ovarian (incidence rate ratio, 0.67; 99% confidence interval, 0.50-0.89), and lymphatic and hematopoietic cancer (incidence rate ratio, 0.74; 99% confidence interval, 0.58-0.94). An increased risk of lung cancer was seen only among ever users who smoked at recruitment. An increased risk of breast and cervical cancer that was seen in current and recent users appeared to be lost within approximately 5 years of stopping oral contraception, with no evidence of either cancer recurring at increased risk in ever users with time. There was no evidence of new cancer risks appearing later in life among women who had used oral contraceptives. Thus, the overall balance of cancer risk among past users of oral contraceptives was neutral with the increased risks counterbalanced by the endometrial, ovarian, and colorectal cancer benefits that persist at least 30 years. Most women who choose to use oral contraceptives do not expose themselves to long-term cancer harms; instead, with some cancers, many women benefit from important reductions of risk that persist for many years after stopping.

Recurrence risk of venous thromboembolism and hormone use in women from England: a cohort study using clinical practice research datalink.

It is vital to identify people with low recurrence risk of venous thromboembolism (VTE) so as to protect them from dangers of prolonged anticoagulation therapy. Among women who develop VTE following hormone use, the evidence as to whether their risk of recurrence is low if they cease this therapy is conflicting. We investigated whether women whose initial VTE event was hormone-related have a lower risk of VTE recurrence than women whose initial event had no obvious cause (unprovoked). A cohort study utilising the Clinical Practice Research Datalink linked to Hospital Episode Statistics data from England was conducted. We selected 4170 women aged between 15 and 64years who were diagnosed with a first VTE event between 1997 and 2011. Cox regression models were used to obtain hazard ratios (HR). Hormone users had 29% lower recurrence risk than non-users (adjusted HR=0·71; 95% confidence interval 0·58-0·88), a relationship which existed both in women aged 15-44years (predominantly oral contraceptive users) and those aged 45-64years (predominantly hormone replacement therapy users). In conclusion, having a hormone-associated VTE is associated with a lower recurrence risk than one that is unprovoked after discontinuation of the hormone-containing preparation. Prolonged anticoagulation may therefore be unjustified in such women.

High-risk sexual behaviors while on depot medroxyprogesterone acetate as compared to oral contraception

BackgroundDepot medroxyprogesterone acetate (DMPA) contraceptive use is associated with an increased risk for Chlamydia infection. However, prior studies inadequately account for potential differences in sexual behavior between users of DMPA and users of other contraceptive methods. In this study we compare sexual risk-taking behavior in women using DMPA to women using oral contraceptive pills (OCP) to assess risk of Chlamydia trachomatis infection.MethodsIn this cross-sectional study of 630 reproductive-aged women seeking routine gynecologic care (449 OCP and 181 DMPA users) sexual risk-taking was evaluated by use of the Safe Sex Behavior Questionnaire, a validated measure of sexual behaviors and attitudes. All women were screened for Chlamydia. Logistic regression estimated the association of contraceptive choice, sexual behaviors, and Chlamydia infection.ResultsOral contraceptive pill users differed from DMPA users in age, race, marital status, education level, and pregnancy history (p-values all <0.05). Oral contraceptive pill users had used their method of contraception for longer average duration (p < 0.01) and reported greater frequency of condom use (p < 0.01). Eleven (2.5%) OCP and 2 (1.1%) DMPA users had Chlamydia (p = NS).ConclusionsOral contraceptive pill and DMPA users differed with respect to both demographic factors and frequency of condom use. Odds of current Chlamydia infection did not differ between OCP and DMPA users when controlling for sexual risk-taking or demographic factors, though due to low Chlamydia rates in our population, this study was underpowered to detect this difference.

Effectiveness of visual inspection with acetic acid as a test for cervical cancer screening

Objective: To assess the effectiveness of visual inspection of cervix with acetic acid (VIA test) as an accepted method for screening of cervical Cancer. Materials and Methods: Two hundred women attending the Cervical and Breast Cancer Screening Program and outpatient department (OPD) of Department of Obstetrics and Gynecology at our center were examined by both Pap smear and VIA tests. Results: Patients were aged between 21 and 70 years (mean 35.8 years). Nearly 45% got married between 16 and 20 years and 44% before 15 years of age. Oral contraceptives users were 23%. Nearly 14% of the women tested positive by VIA. Pap smear showed atypical squamous cells of undetermined significance in 9.5%, low-grade lesion in 6%, and high-grade lesions in 1.5%. Colposcopy showed cervical intraepithelial neoplasia (CIN-I) in 9%, 2% had CIN-II/III, invasive cancer in 1%, and 7% had unsatisfactory colposcopy findings. Thirty-six women required biopsy for histopathological confirmation. Among them, 7.5% had chronic cervicitis/koilocytic changes, 4.5% had CIN-I, 2% had CIN-II, 1.5% had CIN-III, 0.5% had invasive cancer, and 2% had normal result. Sensitivity of VIA was 76.5% and specificity was 91.8%. Sensitivity of Pap smear was 64.7% and specificity was 87.4%. Conclusion: Sensitivity and specificity of VIA was higher than that of Pap smear test. VIA can be used as an effective screening test to detect the precancerous and cancerous lesions of the cervix in Bangladesh.

Oral Contraceptive Use May Modulate Global Genomic DNA Methylation and Promoter Methylation of APC1 and ESR1

Background:There are challenging reports in the public health sphere regarding associations between oral contraceptive (OC) use and cancer risk.Methods:To evaluate possible effects of OCs on cancer susceptibility, we quantified of global 5-methyl cytosine (5-mC) levels and assessed methylation patterns of CpG islands of two key tumor suppressor genes, APC1 and ESR1, in serum of users by enzyme-linked immunosorbent assay and methylation specific PCR methods, respectively.Results:Our results indicated that OCs significantly decrease the level of global DNA methylation in users relative to control non-users. However, our data revealed no significant differences between CpG island methylation patterns for ESR1 and APC1 in healthy control and OC-treated women. However, we did find a trend for hypermethylation of both tumor suppressor genes in OC users.Conclusion:Our data suggest that the level of 5-mC but not individual CpG island patterns is significantly influenced by OCs in our cross-section of adult users.

Experience of taking Oral Contraceptives in Adult Women.

The purpose of this study was to explore essences and meanings of using oral contraceptives among adult women. The interview was conducted with 20 adult women who lived in Seoul, Gyeongi Province, Jeolla Province, Chungcheong Province, and Gangwon Province. Participants with the experience of using oral contraceptives for contraception were selected by convenience sampling. Semi-structured interviews were conducted for data collection. The data were analyzed using Colaizzi's method. Five themes revealed: 'Lack of information and knowledge regarding oral contraceptives', 'Inconvenient and difficult purchase process of oral contraceptives', 'Pressure and fear regarding other people's reaction', 'Self-centered thinking toward the use of oral contraceptives', 'A need for a change in public awareness and policy'. A change in society's perception about oral contraceptives is required for safe contraceptives use. Therefore, it is necessary to educate the correct usage of oral contraceptives, and to develop a program for changing the paradigm of sex education.

Haemorheological changes associated with the menstrual cycle and oral contraceptive therapy

In this study of 3 normal females and 30 receiving oral contraceptives (OCs) no association was established between plasma viscosity whole blood viscosity (WBV) corrected for a 45% packed cell volume red cell filterability and levels of plasma estrogen and progesterone. In OC users there was a transient rise in both plasma and WBV recorded after 1 month with reversal by 3 months and stabilization thereafter. (authors)

Factors associated with the contraindicated use of oral contraceptives in Brazil.

ABSTRACTOBJECTIVE To estimate the prevalence of the contraindicated use of oral contraceptives and the associated factors in Brazilian women.METHODS 20,454 women who answered the VIGITEL survey in 2008 also participated in this study, of which 3,985 reported using oral contraceptives. We defined the following conditions for the contraindicated use of contraceptives: hypertension; cardiovascular diseases such as heart attack, stroke/cerebrovascular accident; diabetes mellitus; being smoker and 35 years old or older. We estimated the prevalence and 95% confidence intervals of contraindicated use in users of oral contraceptives and the factors associated with contraindication by prevalence ratio and 95% confidence intervals.RESULTS In the total population, 21% (95%CI 19.7–21.9) of women showed some contraindication to the use of oral contraceptives, of which 11.7% (95%CI 10.6–13.7) belonged to the group of users of oral contraceptives. The most frequent contraindication in users of oral contraceptives was hypertension (9.1%). The largest proportion of women with at least one contraindication was aged between 45 and 49 years (45.8%) and with education level between zero and eight years (23.8%). The prevalence of contraindication to oral contraceptives was higher in women less educated (zero to eight years of study) (PR = 2.46; 95%CI 1.57–3.86; p < 0.05) and with age between 35-44 years (PR = 4.00; 95%CI 2.34–6.83) and 45-49 years (PR = 5.59; 95%CI 2.90–10.75).CONCLUSIONS Age greater than or equal to 35 and low education level were demographic and iniquity factors, respectively, in the contraindicated use of oral contraceptives.

Assessment of knowledge, awareness and preventive measures of cervical cancer among female medical students

Objectives: The main objective of the study to evaluate the knowledge about cervical cancer causes, vaccination and treatment among female medical students.Materials and Methods: It was a cross sectional study conducted in Melaka Manipal Medical College (Manipal campus), Manipal during October 2012 to April 2013. This study included 194 female medical students from MBBS and BDS undergraduate courses. Data were collected by using validated questionnaire. Data were analysed by SPSS 16 Software.Results The present results shows that the female students demonstrated good knowledge about cervical cancer, pap smear test, prevention and treatment. Among the respondents 97% had heard about cervical cancer, only 3% of female students had the family history of cervical cancer. However many students are did not know that smoking (34%), many child birth (40%) and usage of oral contraceptives (38%) are the risk factors for the cervical cancer.Conclusion: The present study shows adequate levels of knowledge and awareness about pap smear test, prevention and treatment of cervical cancer. Many of the students they did not have the adequate knowledge about risk factors of cervical cancer. This study indicates that further educational programs, especially about risk factors, needed in female medical students.Bangladesh Journal of Medical Science Vol.15(4) 2016 p.583-587

Cardiometabolic and Hemostatic Profiles of Women Carriers of Hemoglobin Variants Using Combined Oral Contraceptives

Introduction: Several studies reported combined contraceptives influence in hemostatic and lipid profile besides the concern about the thromboembolism and cardiovascular risks due to the steroids hormones use. As women with hemoglobin (Hb) variants have a pre-existing inflammatory condition and considering the high frequency of hemoglobin variant worldwide, this study aims to evaluate the association of hematological, lipid, glicemic, inflammatory and hemostatic profiles in women using combined oral contraceptives and carriers of hemoglobin variants.Methods: We performed a cross-sectional study including 591 women in reproductive-age. We investigated their hemoglobin profile and COCs use. Of them, we included 60 women with HbAA, 21 with HbAC, 25 with HbAS and 7 with HbSC profiles, all of them combined oral contraceptives users. Among those combined oral contraceptives nonusers, 9 were HbAC and 19 HbSC. We evaluated fasting serum glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), C-reactive protein (CRP), fibrinogen, D-dimer and hematological profile among the studied groups. This study was conducted in accordance and approved by the Research Ethics Committee of the Fundação Oswaldo Cruz - FIOCRUZ, Brazil; and also with the Helsinki Declaration of 1975, and its revisions. Mann-Whitney U tests were used to compare two groups of values within the same variable.Results: We observed significant differences in some hematological and cardiometabolic parameters in women carriers of different Hb variants and using COCs. We found relevant increases in CRP levels in HbSC and HbAC women that seem to be associated with different types of progestins present in combined oral contraceptives formulations. Also, combined oral contraceptives use seems to be associated with decreased HDL-c levels in HbAC women. Otherwise, D-dimer levels were increased in all women with Hb variants, independently of the contraceptive use.Conclusions: Although combined oral contraceptive remains an important method to prevent unintended pregnancy, our data suggest that contraception in women carriers of Hb variants, including those in heterozygosis, should be carefully evaluated, especially, considering the pre-existent inflammatory and pro-thrombotic conditions that together with combined oral contraceptive use may result in additional health problems, such as cardiovascular and thromboembolic diseases. DisclosuresNo relevant conflicts of interest to declare.

Cortisol reactivity and emotional memory after psychosocial stress in oral contraceptive users.

Oral contraceptive (OC) users typically show a blunted or no cortisol response to psychosocial stress. Although most OC regimens include both an inactive (dummy) and active pill phase, studies have not systematically investigated cortisol responses during these pill phases. Further, high levels of cortisol following a stressor diminish retrieval of emotional material, but the effects of stress on memory among OC users are poorly understood. We examined the effects of a psychosocial stressor, the Trier Social Stress Test, vs. a control condition on cortisol responsivity and emotional memory retrieval in women tested either during their active (n = 18) or inactive pill phase (n = 21). In secondary analyses, we quantitatively compared OC users with normally cycling women and showed a significant lack of cortisol response during both active and inactive pill phase. Emotional recall did not differ between active and inactive pill phases. Stress differentially diminished recall of negative words compared with positive or neutral words, but cortisol levels were unrelated to memory performance. These findings indicate that OC users have distinct cortisol and memory responses to stress that are similar between the active and inactive pill phases. © 2016 Wiley Periodicals, Inc.

Sex, age, and sex hormones affect recall of words in a directed forgetting paradigm.

During the course of serious discussion, an unexpected interruption may induce forgetting of the original topic of a conversation. Sex, age, and sex hormone levels may affect frequency and extension of forgetting. In a list-method directed forgetting paradigm, subjects have to learn two word lists. After learning list 1, subjects receive either a forget or a remember list 1 cue. When the participants had learned list 2 and completed a distraction task, they were asked to write down as many recalled items as possible, starting either with list 1 or list 2 items. In the present study, 96 naturally cycling women, 60 oral contraceptive users, 56 postmenopausal women, and 41 young men were assigned to one of these different experimental conditions. Forget-cued young subjects recall fewer list 1 items (list 1 forgetting) but more list 2 items (list 2 enhancement) compared with remember-cued subjects. However, forget-cued postmenopausal women showed reduced list 1 forgetting but enhanced list 2 retention. Remember-cued naturally cycling women recalled more list 1 items than oral contraceptive users, young men, and postmenopausal women. In forget-cued follicular women, salivary progesterone correlated positively with recalled list 2 items. Salivary 17β-estradiol did not correlate with recalled list 1 or list 2 items in either remember- or forget-cued young women. However, salivary 17β-estradiol correlated with item recall in remember-cued postmenopausal women. Our findings suggest that sex hormones do not globally modulate verbal memory or forgetting, but selectively affect cue-specific processing. © 2016 Wiley Periodicals, Inc.

Vocal Range in the Speech of Users of Low-Dose Oral Contraceptives

The study aimed to investigate the vocal range of oral contraceptive (OC) users aged between 20 and 30 years. This is a cross-sectional study. Forty-eight women aged 20-30 years who used low-dose OCs and 24 age-matched women who did not use oral monophasic contraceptives (w/oOC) were enrolled. Acoustic analysis was performed using the Motor Speech Profile program, Model 4341 (Kay Elemetrics Corp). Data were analyzed using generalized estimating equation. In the w/oOC group, the highest vocal tones in the sentence uttered using exclamatory intonation were similar in the follicular phases of two cycles (F1: 289 ± 46 Hz; F2: 284 ± 61 Hz). In the luteal phase of the first cycle, the vocal tones were lower, whereas in the second cycle they were higher than the tones in both follicular phases (L1: 274 ± 42 Hz; L2: 291 ± 62 Hz) (P = 0.056). In the highest vocal tones of the same sentence uttered using exclamatory intonation, the OC group showed lower tones (284 ± 53 Hz) than the w/oOC group (298 ± 44 Hz) (P = 0.048). In the lowest vocal tones of utterances of joy, the OC group showed higher values (180 ± 39 Hz) than the w/oOC group (169 ± 44 Hz) (P = 0.024). The close proximity of the highest to the lowest values of utterances of joy in the OC group (321 ± 59 Hz and 180 ± 39 Hz), when related to the w/oOC group (338 ± 65 Hz and 169 ± 44 Hz), suggests a reduced vocal modulation. The present findings demonstrate that the use of low-dose OCs influences the vocal range of women during menacme.

Contraception during perimenopause: oral contraception versus LARC

Introduction: Perimenopause marks the transition from normal ovulation to anovulation and ultimately to permanent loss of ovarian function. Although the absolute risk of pregnancy is lower, unintended pregnancy occurs. Therefore all perimenopausal women should receive counselling on contraception. A variety of contraceptive options may be offered to perimenopausal women, including oral contraception (OC) and long-acting reversible contraception (LARC), such as intrauterine devices and subcutaneous implants. Until the age of 50, no contraceptive method is specifically considered unsuitable due to age alone. Objective: To describe and compare the most used contraceptive methods in Portuguese perimenopausal women. Study design: Comparative study between OC and LARC in Portuguese women aged between 40 and 49 years. We used the data from a cross-sectional study, with a representative subset of the female Portuguese population aged between 15 and 49, carried out by applying an anonymous survey between December 2014 and March 2015. Data were analyzed using STATA version 13.1. Results: A total of 1244 women aged between 40 and 49 years responded to the survey. 84.1% (n = 1045) of these women were using contraception. OC was the contraceptive option in 50.6% (n = 529) and LARC in 30.6% (n = 320) (26.3% intrauterine devices and 4.3% subcutaneous implants). 91.8% (n = 1140) of these women were sexually active [99.7% in OC group vs. 98.9% in LARC group (p > 0.05)] and 92.8% (n = 1154) were not nulliparous [95.5% in OC group vs. 98.1% in LARC group (p = 0.04)]. Only 23.0% (n = 286) had an high education level [21.4% in OC group vs. 25,0% in LARC group (p > 0.05)] and 5% (n = 62) had access to information on sexuality and/or sexual education [4.0% in OC group vs. 5.0% in LARC group (p > 0.05)]. Nevertheless, 74.8% (n = 931) had regular reproductive health care appointments [81.9% in OC group vs. 76.9% in LARC group (p > 0.05)]. In OC users, 8.9% (n = 47) admitted omission of at least one pill every cycle and 51.6% (n = 273) admitted that, in case of omission, they did not have any preventive action in order to avoid pregnancy; although 76.8% (n = 406) were aware of emergency contraception, only 6.7% (n = 27) of them had used it. An inferior age [aOR = 0.77 (0.73–0.81)], a not high education level [aOR = 0.59 (0.43–0.82)], regular reproductive health care appointments [aOR = 1.50 (1.08–2.09)] and an inferior parity [aOR = 0.71 (0.60–0.85)] were associated with the option for OC. Contrariwise a superior age [aOR 1.22 (1.16–1.28)] and parity [aOR = 2.87 (1.17–7.04)] were associated with the option for LARC. Conclusions: Despite the wide range of contraceptive options, OC remain the most frequent contraceptive option in Portuguese perimenopausal women. An inferior age, a lower education level, regular reproductive health care appointments and an inferior parity were associated with the option for OC. Contrariwise a superior age and parity were associated with the option for LARC.

Types of oral contraceptives and breast cancer survival among women enrolled in Medicaid: A competing-risk model

IntroductionOral contraceptive pills have been implicated in the pathophysiology of breast cancer. Although many studies have examined the relationship between combined oral contraceptives (COCs) and breast cancer, there is a paucity of literature that discusses progestin-only oral contraceptives (POCs) and breast cancer. The purpose of this investigation is to examine potential associations between different types of oral contraceptives and breast cancer mortality in the South Carolina Medicaid population among different racial/ethnic groups. MethodsSubjects included 4816 women diagnosed with breast cancer between 2000 and 2013. Kaplan-Meier curves were calculated to determine time-to-mortality rates among users of oral contraceptives. Competing-risks models and Cox multivariate survival models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer and other-cause mortality, as well as all-cause mortality. ResultsPOCs were associated with a significantly decreased risk of breast cancer mortality (HR: 0.07; 95% CI: 0.01, 0.52) and a non-significant increased risk of all-cause mortality (HR: 1.04; 95% CI: 0.52, 2.07). COCs increased the risk of breast cancer mortality (HR: 1.61; 95% CI: 1.14, 2.28) and all-cause mortality (HR: 1.83; 95% CI: 1.30, 2.57). ConclusionUse of POCs may be associated with a decreased risk of breast cancer mortality. Due to the small sample size of POC users in the current study, additional research is needed to confirm these findings.

Association of Hormonal Contraception With Depression

Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some women's mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed. To investigate whether the use of hormonal contraception is positively associated with subsequent use of antidepressants and a diagnosis of depression at a psychiatric hospital. This nationwide prospective cohort study combined data from the National Prescription Register and the Psychiatric Central Research Register in Denmark. All women and adolescents aged 15 to 34 years who were living in Denmark were followed up from January 1, 2000, to December 2013, if they had no prior depression diagnosis, redeemed prescription for antidepressants, other major psychiatric diagnosis, cancer, venous thrombosis, or infertility treatment. Data were collected from January 1, 1995, to December 31, 2013, and analyzed from January 1, 2015, through April 1, 2016. Use of different types of hormonal contraception. With time-varying covariates, adjusted incidence rate ratios (RRs) were calculated for first use of an antidepressant and first diagnosis of depression at a psychiatric hospital. A total of 1 061 997 women (mean [SD] age, 24.4 [0.001] years; mean [SD] follow-up, 6.4 [0.004] years) were included in the analysis. Compared with nonusers, users of combined oral contraceptives had an RR of first use of an antidepressant of 1.23 (95% CI, 1.22-1.25). Users of progestogen-only pills had an RR for first use of an antidepressant of 1.34 (95% CI, 1.27-1.40); users of a patch (norgestrolmin), 2.0 (95% CI, 1.76-2.18); users of a vaginal ring (etonogestrel), 1.6 (95% CI, 1.55-1.69); and users of a levonorgestrel intrauterine system, 1.4 (95% CI, 1.31-1.42). For depression diagnoses, similar or slightly lower estimates were found. The relative risks generally decreased with increasing age. Adolescents (age range, 15-19 years) using combined oral contraceptives had an RR of a first use of an antidepressant of 1.8 (95% CI, 1.75-1.84) and those using progestin-only pills, 2.2 (95% CI, 1.99-2.52). Six months after starting use of hormonal contraceptives, the RR of antidepressant use peaked at 1.4 (95% CI, 1.34-1.46). When the reference group was changed to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71). Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first diagnosis of depression, suggesting depression as a potential adverse effect of hormonal contraceptive use.

The prognostic impact of COX-2 expression in breast cancer depends on oral contraceptive history, preoperative NSAID use, and tumor size.

The association between tumor cyclooxygenase 2 (COX-2) expression and breast cancer prognosis has been inconsistent. The purpose of this study was to evaluate the prognostic significance of COX-2 tumor expression according to adjuvant treatment, and potential effect modifications of non-steroid anti-inflammatory drug (NSAID) use, and other tumor and lifestyle factors. A prospective cohort of 1,116 patients with primary breast cancer in Lund, Sweden, included 2002-2012 was followed until June 2014 (median 5 years). Tumor-specific COX-2 expression was evaluated on tissue microarrays using immunohistochemistry. Associations between COX-2 intensity (negative, weak-moderate, high) and patient and tumor characteristics as well as prognosis were analyzed. Tumor-specific COX-2 expression was available for 911 patients and was significantly associated with higher age at diagnosis and less aggressive tumor characteristics. Higher COX-2 expression was associated with lower risk for breast cancer events during the first five years of follow-up, adj HR 0.60 (95%CI: 0.37-0.97), per category. The association between COX-2 expression and prognosis was significantly modified by oral contraceptive (OC) use (Pinteraction = 0.048), preoperative NSAID use (Pinteraction = 0.009), and tumor size (Pinteraction = 0.039). COX-2 negativity was associated with increased risk for events during the first five years in ever OC users, adj HR 1.94 (1.01-3.72) and during the 11-year follow-up in preoperative NSAID users, adj HR 4.51 (1.18-11.44) as well as in patients with large tumors, adj HR 2.57 (1.28-5.15). In conclusion, this study, one of the largest evaluating COX-2 expression in breast cancer, indicates that the prognostic impact of COX-2 expression depends on host factors and tumor characteristics.

Oxidative Stress in Female Athletes Using Combined Oral Contraceptives.

BackgroundOxidative stress in female athletes is understudied. We investigated oxidative stress in sportswomen of different disciplines according to combined oral contraceptive (OC) use and lifestyle/alimentary habits.MethodsItalian sportswomen (n = 144; mean age 23.4 ± 4.2 years; body mass index 21.2 ± 2.2 kg m−2; sport activity 9.2 ± 4.1 h week−1) were analyzed; 48 % were volleyball players, 12.5 % soccer players, 10.4 % track-and-field sports, and followed by other disciplines’ athletes. Oxidative stress was evaluated by free oxygen radical test (FORT) assessing blood hydroperoxides and free oxygen radical defense (FORD) assay evaluating antioxidant capacity in OC users (n = 42) compared to non-OC users.ResultsElevated oxidative stress levels (≥310 FORT units) were found in 92.9 % of OC users and in 23.5 % of non-OC users (crude OR = 42, 95 % CI 12–149, p < 0.001; adjusted OR = 60, 95 % CI 11–322, p < 0.001). Continuous values of hydroperoxides were twofold higher in OC users versus non-OC users (median 484 versus 270 FORT units, p < 0.001) and were inversely related to FORD units in OC users (p = 0.01). Hydroperoxides were not associated with weekly hours of exercise. In OC users, lifestyle/alimentary habits were not correlated to hydroperoxides. In non-OC users only, hydroperoxide values were positively correlated with weight and BMI and inversely correlated with chocolate and fish consumption.ConclusionsThe markedly elevated oxidative stress we revealed in OC-user athletes could be detrimental to physical activity and elevate cardiovascular risk (as thromboembolism). Further research is needed to extend our results, to clarify the biochemical pathways leading to increased hydroperoxides (mainly lipid peroxides) and reduced antioxidant defense, and to elucidate the potential effects on athletic performance. OC use should be considered when developing gender-focused strategies against oxidative stress.