Oral contraceptive use by formulation and endometrial cancer risk among women born in 1947-1964: The Nurses' Health Study II, a prospective cohort study.
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SUBMITTER: Burchardt NA
PROVIDER: S-EPMC8416825 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Oral contraceptives (OCs) have been consistently associated with a reduced ovarian cancer risk; however, most previous studies included women in older birth cohorts using high-dose OC formulations. We assessed OC use, including type and dose, and ovarian cancer risk among women born between 1947 and 1964 using more recent formulations.We included 110,929 Nurses' Health Study II participants. Women reported duration of OC use and brands used from age 13 to baseline (1989) and every 2 years thereafter through 2009. We categorized brands by estrogen and progestin type, dose, and potency, and used Cox proportional hazards models, adjusted for age, calendar time, reproductive factors, and body mass index, to assess associations with ovarian cancer.Over 2,178,679 person-years of follow-up, we confirmed 281 cases. At baseline, 83% of participants reported ever using OCs. Compared to never use, we observed an increased risk of ovarian cancer with ?6 months of OC use (HR 1.82; 95% CI 1.13-2.93) but a non-significant 57% (95% CI 0.18-1.03) decreased risk with ?15 years of OC use. The increased risk among short-term users (?1 year) was restricted to OCs containing mestranol (HR 1.83; 95% CI 1.16-2.88) and first-generation progestin (HR 1.72; 95% CI 1.11-2.65).The associations between OCs and ovarian cancer observed for this younger birth cohort differ substantially from the results of previous cohort studies, possibly reflecting changes in OC formulations and use patterns over time, although these results could be due to chance. Additional studies should evaluate newer OC formulations and ovarian cancer risk.
| S-EPMC5441237 | biostudies-literature
Project description:ObjectiveTo determine whether use of oral contraceptives is associated with all cause and cause specific mortality.DesignProspective cohort study.SettingNurses' Health Study, data collected between 1976 and 2012.Population121,701 participants were prospectively followed for 36 years; lifetime oral contraceptive use was recorded biennially from 1976 to 1982.Main outcome measuresOverall and cause specific mortality, assessed throughout follow-up until 2012. Cox proportional hazards models were used to calculate the relative risks of all cause and cause specific mortality associated with use of oral contraceptives.ResultsIn our population of 121,577 women with information on oral contraceptive use, 63,626 were never users (52%) and 57,951 were ever users (48%). After 3.6 million person years, we recorded 31,286 deaths. No association was observed between ever use of oral contraceptives and all cause mortality. However, violent or accidental deaths were more common among ever users (hazard ratio 1.20, 95% confidence interval 1.04 to 1.37). Longer duration of use was more strongly associated with certain causes of death, including premature mortality due to breast cancer (test for trend P<0.0001) and decreased mortality rates of ovarian cancer (P=0.002). Longer time since last use was also associated with certain outcomes, including a positive association with violent or accidental deaths (P=0.005).ConclusionsAll cause mortality did not differ significantly between women who had ever used oral contraceptives and never users. Oral contraceptive use was associated with certain causes of death, including increased rates of violent or accidental death and deaths due to breast cancer, whereas deaths due to ovarian cancer were less common among women who used oral contraceptives. These results pertain to earlier oral contraceptive formulations with higher hormone doses rather than the now more commonly used third and fourth generation formulations with lower estrogen doses.
| S-EPMC4216099 | biostudies-literature
Project description:Women with Lynch syndrome have a 40% to 60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have shown that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown whether they are effective in women with Lynch syndrome. Asymptomatic women ages 25 to 50 with Lynch syndrome were randomized to receive the progestin compounds Depo-Provera (depo-MPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were conducted before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depo-MPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results show that women with Lynch syndrome do show an endometrial response to short-term exogenous progestins, suggesting that OCP and depo-MPA may be reasonable chemopreventive agents in this high-risk patient population.
| S-EPMC3737517 | biostudies-literature
Project description:Background Epidemiological evidence that glioma has a slight male predominance implies that factors associated with sex hormones may play a role in the development of glioma. The association between oral contraceptive (OC) use and glioma risk remains controversial. Method In the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial of 70,516 women in the USA, Cox proportional hazards regression analyses were adopted to calculate the crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Additionally, a meta-analysis combining the PLCO findings with those of other prospective cohorts was performed. Results During a mean follow-up of ~11.7 years, 110 of 70,516 women aged 50–78 years at baseline were diagnosed with glioma in PLCO studies. Compared with never users, an inverse association of borderline significance was found for OC users (HR 0.67, 95% CI 0.44–1.04, P = 0.074). Analyses assessing glioma risk according to the duration of OC use yielded no significant association. When PLCO was combined with four other prospective studies, there was an inverse association between OC use and glioma risk (HR 0.85, 95% CI 0.75–0.97, I2 = 0.0%). Further dose-response analysis showed a nonlinear, inverse relationship between OC use and glioma risk (P < 0.001). Conclusions This study provided some evidence of a nonlinear, inverse association between OC use and glioma risk. Future larger studies are warranted to validate this finding.
| S-EPMC9330220 | biostudies-literature
Project description:Few studies have evaluated the association between pregravid oral contraceptive (OC) use and birth weight, and findings have been conflicting. We conducted a prospective cohort study of 5921 pregnancy planners in Denmark to evaluate recency, duration, and type of OC used before conception in relation to infant birth weight. Participants completed online questionnaires and reported detailed information on contraceptive history and covariates at baseline. Participants completed bimonthly follow-up questionnaires to update their pregnancy status for up to 12 months or until conception occurred. Birth weight data were ascertained from the Danish Medical Birth Registry for 4046 live births delivered by study participants between 2008 and 2010. We used multivariable linear and log-binomial regression analyses to control for confounding. Mean birth weight was higher among women who had used OCs within 0-1 months (mean difference = 97 g, CI 26, 168) or 2-6 months (mean difference = 40 g, CI -5, 85) before conception, compared with more than 12 months before conception. Mean birth weight was lower among women who had used OCs for long durations (mean difference comparing ?12 with <4 years of OC use = -85 g, CI -158, -11). Our findings indicate that pregravid OC use within 6 months of conception may be associated with a small increase in birth weight, but that long duration of use may have the opposite effect. Results were stronger among male infants, among 2nd and 4th generation OC users, and among users of OCs with a higher estrogen dose.
| S-EPMC4681689 | biostudies-literature
Project description:BackgroundBecause of the widespread use of oral contraceptives (OCs) and the devastating effects of depression both on an individual and a societal level, it is crucial to understand the nature of the previously reported relationship between OC use and depression risk. Insight into the impact of analytical choices on the association is important when interpreting available evidence. Hence, we examined the association between adolescent OC use and subsequent depression risk in early adulthood analyzing all theoretically justifiable models.MethodsData from the prospective cohort study TRacking Adolescents' Individual Lives Survey, among women aged 13-25 years were used. Adolescent OC use (ages 16-19 years) was used as a predictor and major depressive disorder (MDD) in early adulthood (ages 20-25 years), as assessed by the Diagnostic and Statistical Manual of Mental Disorders-IV oriented Lifetime Depression Assessment Self-Report and the Composite International Diagnostic Interview, was used as an outcome. A total of 818 analytical models were analyzed using Specification Curve Analysis in 534 adolescent OC users and 191 nonusers.ResultsOverall, there was an association of adolescent OC use and an episode of MDD in early adulthood [median odds ratio (OR)median = 1.41; ORmin = 1.08; ORmax = 2.18, p < .001], which was driven by the group of young women with no history of MDD (ORmedian = 1.72; ORmin = 1.21; ORmax = 2.18, p < .001).ConclusionsIn summary, adolescent OC use was associated with a small but robust increased risk for experiencing an episode of MDD, especially among women with no history of MDD in adolescence. Understanding the potential side effects of OCs will help women and their doctors to make informed choices when deciding among possible methods of birth control.
| S-EPMC9291927 | biostudies-literature
Project description:OBJECTIVE:To determine if a combined oral contraceptive (COC) initiated shortly after ulipristal acetate (UPA) administration interferes with its mechanism of action. STUDY DESIGN:Healthy, reproductive-age women of normal BMI with proven ovulation (serum progesterone >3 ng/ml) were enrolled for three cycles (Cycle 1, UPA only; Cycle 2 washout; Cycle 3 UPA plus COC). During Cycles 1 and 3, subjects were monitored with transvaginal ultrasound and blood sampling for progesterone and LH every other day until a dominant follicle measuring >15 mm was visualized. In both treatment cycles, subjects received UPA (30mg) and were followed daily with similar monitoring for up to 7 days. In Cycle 3 only, subjects initiated a daily COC (0.15 mg levonorgestrel/30 ?g ethinyl estradiol) 2 days after UPA. The study had 80% power to detect a 15% difference in the proportion of cycles with at least a 5-day delay in follicle rupture. We assessed follicle rupture as >50% decrease in mean size and adjudicated unclear outcomes with serum hormones. RESULTS:A total of 36 women enrolled and 33 completed all study procedures [age 28.4 years (SD 3.9); BMI 23.4 (SD 2.4)]. Compared to Cycle 1, more subjects demonstrated evidence of follicle rupture in <5 days in Cycle 3 [1/33 (3%) vs. 9/33 (27%), p = .008]. We also included data from 2 subjects who experienced rupture prior to COC dosing in the analysis. CONCLUSION:UPA's effectiveness is significantly reduced by administering COCs 2 days later. IMPLICATIONS:This study demonstrates that UPA's efficacy as an emergency contraceptive is reduced with early exposure to COCs.
| S-EPMC6204102 | biostudies-literature
Project description:ImportanceA secular trend for earlier menarcheal age has been established in girls but there are few studies of pubertal timing for boys.ObjectiveTo determine if there is a secular trend for earlier pubertal timing among boys.Design, setting, and participantsFor this population-based retrospective cohort study conducted in Gothenburg, Sweden, we collected heights and weights from school health records for boys born consecutively from January 1 and onwards in 1947 and every 5 years from 1951 to 1996 (n = 375 for each birth cohort from 1947-1991, n = 340 for the birth cohort in 1996, and n = 4090 for the total cohort). We estimated age at the peak height velocity (PHV), the maximum growth velocity during puberty, and childhood body mass index (BMI) at age 8 years for all study participants. The data were analyzed during 2018 and 2019. Boys were eligible if they had a complete personal identity number and data to calculate their age at PHV and childhood BMI. Approximately 2.4% of the original study population was excluded because they lacked a personal identity number, and in the remaining study population, 4090 (69%) had sufficient data to calculate childhood BMI and age at PHV.ExposuresThe exposure was birth year and a potential confounding factor was childhood BMI.Main outcomes and measuresThe outcome was age at PHV.ResultsOf the 4090 participants, most were white and the mean (SD) age at PHV was 13.9 (1.1) years. A linear regression model revealed a significant association between year of birth and age at PHV. Age at PHV was 1.5 months earlier for every decade increase in birth year (95% CI, -1.72 to -1.19; P < .001). After adjusting for childhood BMI, age at PHV was 1.2 months earlier per decade increase in birth year (95% CI, -1.41 to -0.89). All analyses were repeated in the subgroup of boys born in Sweden and with parents born in Sweden with similar results, indicating that the secular trend was not explained by demographic changes in the population between 1947 and 1996.Conclusions and relevanceWe provide evidence of a secular trend for earlier pubertal timing in boys that is partially explained by an increased childhood BMI, but other factors that are unknown contribute.
| S-EPMC6647355 | biostudies-literature
Project description:ObjectiveTo evaluate the association between pregravid use of a variety of contraceptive methods and subsequent fecundability.DesignProspective cohort study.SettingDenmark and North America, 2007-19.Participants17 954 women who had tried to conceive for up to six menstrual cycles at study entry. At baseline, participants reported their contraceptive histories, and personal, medical, and lifestyle characteristics.Main outcome measuresPregnancy, determined by bimonthly follow-up questionnaires for up to 12 months.ResultsApproximately 38% (n=6735) of participants had recently used oral contraceptives, 13% (n=2398) had used long acting reversible contraceptive methods, and 31% (n=5497) had used barrier methods. Women who had recently stopped using oral contraceptives, the contraceptive ring, and some long acting reversible contraceptive methods experienced short term delays in return of fertility compared with users of barrier methods. Use of injectable contraceptives was associated with decreased fecundability compared with use of barrier methods (fecundability ratio 0.65; 95% confidence interval 0.47 to 0.89). Users of injectable contraceptives had the longest delay in return of normal fertility (five to eight menstrual cycles), followed by users of patch contraceptives (four cycles), users of oral and ring contraceptives (three cycles), and users of hormonal and copper intrauterine devices and implant contraceptives (two cycles). Lifetime length of use of hormonal contraceptive methods was not associated with fecundability.ConclusionsUse of some hormonal contraceptive methods was associated with delays in return of fertility, with injectable contraceptives showing the longest delay. The findings indicated little or no lasting effect of long term use of these methods on fecundability.
| S-EPMC7656314 | biostudies-literature
Project description:ImportanceAlthough oral contraceptive (OC) use is common, the influence of OC use on carcinogenesis is not fully understood. A recent Agency for Healthcare Research and Quality report identified a need to understand the consistency of OC use and cancer associations across subpopulations, including smokers and obese women.ObjectiveTo determine whether associations between duration of OC use and risk of specific cancers were modified by lifestyle characteristics.Design, setting, and participantsThe prospective NIH-AARP Diet and Health Study (enrolled 1995-1996, followed until 2011), with population-based recruitment of AARP members in 6 states and 2 metropolitan areas. All analyses included at least 100 000 women who reported OC use at enrollment. We identified 1241 ovarian, 2337 endometrial, 11 114 breast, and 3507 colorectal cancer cases during follow-up. Data analysis was performed between September 2016 and April 2017.ExposuresDuration of OC use (never or <1 year [reference], 1-4, 5-9, or ≥10 years).Main outcomes and measuresDevelopment of ovarian, endometrial, breast, and colorectal cancers. We examined effect modification by modifiable lifestyle characteristics: cigarette smoking, alcohol consumption, body mass index (BMI), and physical activity. We used Cox models adjusted for age, race, age at menarche, and the modifiers of interest.ResultsThe analytic population was aged 50 to 71 years (median, 62 years) at enrollment and largely white (91%) and postmenopausal (96%). For ovarian cancer, OC use-associated risk reductions strengthened with duration of use (long-term OC use [≥10 years] HR, 0.60; 95% CI, 0.47-0.76; P < .001 for trend) and were similar across modifiable lifestyle factors. Risk reductions for endometrial cancer strengthened with duration of use (long-term OC use HR, 0.66; 95% CI, 0.56-0.78; P < .001 for trend); the most pronounced reductions were among long-term OC users who were smokers (HR, 0.47; 95% CI, 0.25-0.88), had obese BMIs (0.36; 95% CI, 0.25-0.52), and who exercised rarely (HR, 0.40; 95% CI, 0.29-0.56). Associations between OC use and breast and colorectal cancers were predominantly null.Conclusions and relevanceLong-term OC use is consistently associated with reduced ovarian cancer risk across lifestyle factors. We observed the greatest risk reductions for endometrial cancer among women at risk for chronic diseases (ie, smokers, obese BMI). Oral contraceptive use may be beneficial for chemoprevention for a range of women with differing baseline cancer risks.
| S-EPMC5885214 | biostudies-literature