Effect Of Oral Contraceptive Use Research Articles

(050) Vulvodynia: Risk Associated with Vulvar/Vaginal, Psychological and Physical Side Effects of Oral Contraceptive Use

Abstract Introduction Research has shown that hormonal contraceptive (HC) use is associated with risk for vulvar pain [1] and vulvodynia [2,3]. Although some literature has focused on combined hormonal contraceptives (CHCs), Bouchard et al [2] found that risk was higher for those using high progestin potency HCs. In addition to increased risk associated with HC use, research also suggests that characteristics of the menstrual cycle (eg., premenstrual symptoms) are associated with risk for vulvodynia [4]. Objective Test for associations between having a diagnosis of vulvodynia (including vestibulodynia) and experiencing vulvar/vaginal, psychological, and physical side effects from OC use. Test for differences in these associations across estroprogestinic OCs, progesterone only OCs, and OCs of an unknown composition (based on self-reports). Methods A sample of 2199 females participated in a larger study on genito-pelvic pain and sexuality and provided data on both HC use and genito-pelvic pain. Efforts were made to recruit a heterogenous sample, with an oversampling of females with genito-pelvic pain. The dependent variable was a dichotomous variable of whether they had ever received a diagnosis of vulvodynia or vestibulodynia. Predictor variables were: ever used each type of OC (analyses conducted separately for estroprogestinic, progesterone only, and unknown type); and experiencing the following side effects associated with each OC type: vulvar pain (dichotomous), vaginal dryness (dichotomous), decreased sexual desire (dichotomous), affective symptoms (sum of dichotomous responses to: anxiety, nervousness, depression, anger, mood swings) and physical symptoms (sum of dichotomous responses to: cramps, back and joint pain, bloating, cellulite, breast discomfort). Three nominal logistic regression analyses were conducted (one for each OC), and a final nominal logistic regression was conducted combining the relevant predictors for each OC into one analysis. Results Of the 2199 participants, n=673 had never used OCs, n=827 had used them in the past, and n=699 were currently using them. Regarding vulvar/vaginal pain, n=1083 had no vulvar or vaginal pain, n=341 had only vulvar pain, n=194 had only vaginal pain, and n=581 both vulvar and vaginal pain. Finally, regarding diagnoses, n=582 (26%) had a diagnosis of vulvodynia/vestibulodynia (all types combined). Results from the nominal logistic regressions are presented in Tables 1 and 2. Findings of central importance are: having ever used any of the three categories of OCs was associated with increased risk for a diagnosis; vulvar pain and vaginal dryness were the only side effects of OCs that demonstrated a consistent association with increased risk of having a diagnosis; side effects of estroprogestinic OCs were the most strongly associated with increased risk of having a diagnosis; and the effects observed in the first three models remained significant even when all were included in the same final analysis (with the exception of vulvar pain with progesterone only OC). Conclusions Use of both estroprogestinic and progesterone only OCs are associated with diagnosis of vulvodynia, but side effects of estroprogestinic OCs demonstrated the strongest association. Genital-specific side effects of OCs may represent indicators of a tissue-specific sensitivity to hormonal changes that are associated with risk for vulvodynia. Disclosure No.

Morphologic alterations of the fear circuitry: the role of sex hormones and oral contraceptives.

Endogenous sex hormones and oral contraceptives (OCs) have been shown to influence key regions implicated in fear processing. While OC use has been found to impact brain morphology, methodological challenges remain to be addressed, such as avoiding selection bias between OC users and non-users, as well as examining potential lasting effects of OC intake. We investigated the current and lasting effects of OC use, as well as the interplay between the current hormonal milieu and history of hormonal contraception use on structural correlates of the fear circuitry. We also examined the role of endogenous and exogenous sex hormones within this network. We recruited healthy adults aged 23-35 who identified as women currently using (n = 62) or having used (n = 37) solely combined OCs, women who never used any hormonal contraceptives (n = 40), or men (n = 41). Salivary endogenous sex hormones and current users' salivary ethinyl estradiol (EE) were assessed using liquid chromatography - tandem mass spectrometry. Using structural magnetic resonance imaging, we extracted surface-based gray matter volumes (GMVs) and cortical thickness (CT) for regions of interest of the fear circuitry. Exploratory whole-brain analyses were conducted with surface-based and voxel-based morphometry methods. Compared to men, all three groups of women exhibited a larger GMV of the dorsal anterior cingulate cortex, while only current users showed a thinner ventromedial prefrontal cortex. Irrespective of the menstrual cycle phase, never users exhibited a thicker right anterior insular cortex than past users. While associations with endogenous sex hormones remain unclear, we showed that EE dosage in current users had a greater influence on brain anatomy compared to salivary EE levels and progestin androgenicity, with lower doses being associated with smaller cortical GMVs. Our results highlight a sex difference for the dorsal anterior cingulate cortex GMV (a fear-promoting region), as well as a reduced CT of the ventromedial prefrontal cortex (a fear-inhibiting region) specific to current OC use. Precisely, this finding was driven by lower EE doses. These findings may represent structural vulnerabilities to anxiety and stress-related disorders. We showed little evidence of durable anatomical effects, suggesting that OC intake can (reversibly) affect fear-related brain morphology.

Exploring the interactive effects of oral contraceptive use and dietary fat intake on blood pressure, cardiovascular reactivity, and glucose tolerance in normotensive women.

Objective: To understand how dietary fat consumption and the use of oral contraceptives interact to affect blood pressure, cardiovascular reactivity, and glucose tolerance in normotensive women. Study Design: Cross-section study. Setting: Hayatabad Medical Complex, Peshawar. Period: December 2022 to April 2023. Material & Methods: A total of 120 normotensive women aged between 18 and 35 years were recruited from local healthcare centers, clinics, and educational institutions. Demographic characteristics, oral contraceptive use, and dietary fat intake were assessed through self-reporting and validated food frequency questionnaires. Resting blood pressure measurements, cardiovascular reactivity during standardized stressors, and glucose tolerance through oral glucose tolerance tests were recorded. Results: The study found no significant associations between oral contraceptive use and blood pressure, cardiovascular reactivity, or glucose tolerance. Similarly, dietary fat intake did not significantly influence these health parameters. Conclusion: The results emphasize the importance of personalized healthcare recommendations for women using oral contraceptives, considering individual variations and other lifestyle factors. Further research with larger, longitudinal studies is warranted to elucidate the potential long-term effects of these interactions and promote cardiovascular health for women worldwide.

The risk of venous thromboembolism in oral contraceptive users: the role of genetic factors—a prospective cohort study of 240,000 women in the UK Biobank

More than 150 million women worldwide use oral contraceptives. Women with inherited thrombophilia and carriers of certain thrombophilia gene variants, such as factor V Leiden and the prothrombin, are at an increased risk for venous thromboembolism, especially when combined with oral contraceptive use. Venous thromboembolism is a complex disorder involving many genetic risk factors, and recently, polygenic risk scores have been proposed to capture a significant proportion of the genetic risk of venous thromboembolism. The aim of this study was to estimate the risk for developing venous thromboembolism when initiating oral contraceptive use (first 2 years) and during continued use among women with a high genetic liability. We used a prospective study design in which 244,420 participants from the UK Biobank were followed from birth. The effect of oral contraceptive use during the first 2 years and in the remaining years of oral contraceptive use on the risk of developing venous thromboembolism was estimated using a Cox regression with a time-dependent exposure variable. Women were stratified according to their polygenic risk scores and whether they were carriers of factor V Leiden and/or prothrombin variants. When genetic risk was not considered, an increased risk for venous thromboembolism was observed during the first 2 years of oral contraceptive use (hazard ratio, 3.09; 95% confidence interval, 3.00-3.20) but not during continued use (hazard ratio, 0.92; 95% confidence interval, 0.80-1.05). However, when genetic risk was considered, women in the highest polygenic risk score category had a more pronounced risk of developing a venous thromboembolism during the first 2 years of oral contraceptive use (hazard ratio, 6.35; 95% confidence interval, 4.98-8.09), and a high risk was also observed among factor V Leiden (hazard ratio, 5.73; 95% confidence interval, 5.31-6.17) and prothrombin variant carriers (hazard ratio, 5.23; 95% confidence interval, 4.67 - 5.87). A high polygenic risk score in combination with being a factor V Leiden and prothrombin variant carrier conferred the highest risk for developing a venous thromboembolism during the first 2 years of oral contraceptive use (hazard ratio, 14.8; 95% confidence interval, 9.28-23.6). Women with a high genetic liability also had an increased risk during continued use but it was less pronounced, and the highest risk was conferred to carriers of both factor V Leiden and the prothrombin variant (hazard ratio, 4.93; 95% confidence interval, 3.16-7.7). Evaluating polygenic risk can identify additional venous thromboembolism risk that is not captured in the commonly investigated genes for inherited thrombophilia. Our results indicate that oral contraceptive use is associated with an increased risk for developing a venous thromboembolism, particularly among women with a high genetic predisposition, and that oral contraceptive use dramatically increases the risk thereof short after initiation of use, which decreases with continued use. This suggests that the polygenic risk score could be used to identify women who are at high risk for developing a venous thromboembolism and advise them on alternative methods of contraception.

Mental rotation, episodic memory, and executive control: Possible effects of biological sex and oral contraceptive use

Oral contraceptives (OCs) are one of the most common forms of hormonal birth control. A small literature suggests that OC use may affect visuospatial ability, episodic memory, and executive control. However, previous studies have been criticized for small sample sizes and the use of different, single cognitive tests. We investigated the degree to which biological sex and OC use might affect individual mental rotation, episodic memory, and executive control in a large sample of healthy, young adults (N = 155, including 52 OC users, 53 naturally cycling females, and 50 males) tested individually over videoconference. To measure cognition, we used a set of neuropsychological tasks inspired by Glisky and colleagues’ two-factor episodic memory and executive control battery, from which two composite scores (based on principal component analysis) were derived for each participant. Our pre-registered analysis revealed a clear female advantage in episodic memory, independent of OC use. In an exploratory analysis, gist memory was elevated in OC users. Interestingly, we found no significant sex-related differences nor effects of OC use on mental rotation or executive control. Duration of OC use was also not related to any of our cognitive measures. These results suggest that the use of combined, monophasic OCs does not lead to many significant changes in cognition in young adults, although young females overall may have better episodic memory than young males. Additional studies, including longitudinal designs and looking in more detail at the menstrual cycle and OC use history, will further clarify the effects of different types of OCs and their duration of use on different aspects of cognition.

Population-based cohort study of oral contraceptive use and risk of depression.

Research on the effect of oral contraceptive (OC) use on the risk of depression shows inconsistent findings, especially in adult OC users. One possible reason for this inconsistency is the omission of women who discontinue OCs due to adverse mood effects, leading to healthy user bias. To address this issue, we aim to estimate the risk of depression that is associated with the initiation of OCs as well as the effect of OC use on lifetime risk of depression. This is a population-based cohort study based on data from 264,557 women from the UK Biobank. Incidence of depression was addressed via interviews, inpatient hospital or primary care data. The hazard ratio (HR) between OC use and incident depression was estimated by multivariable Cox regression with OC use as a time-varying exposure. To validate causality, we examined familial confounding in 7,354 sibling pairs. We observed that the first 2 years of OC use were associated with a higher rate of depression compared to never users (HR=1.71, 95% confidence interval [CI]: 1.55-1.88). Although the risk was not as pronounced beyond the first 2 years, ever OC use was still associated with an increased lifetime risk of depression (HR=1.05, 95% CI: 1.01-1.09). Previous OC use were associated with a higher rate of depression compared to never users, with adolescent OC users driving the increased hazard (HR=1.18, 95% CI: 1.12-1.25). No significant association were observed among adult OC users who had previously used OCs (HR=1.00, 95% CI: 0.95-1.04). Notably, the sibling analysis provided further evidence for a causal effect of OC use on the risk of depression. Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life. Our results are consistent with a causal relationship between OC use and depression, as supported by the sibling analysis. This study highlights the importance of considering the healthy user bias as well as family-level confounding in studies of OC use and mental health outcomes. Physicians and patients should be aware of this potential risk when considering OCs, and individualized risk-benefit assessments should be conducted.

Oral Contraceptive Use and Breast Cancer Risk According to Molecular Subtypes Status: A Meta-Analysis

Abstract Background Breast cancer is a heterogeneous disease with distinct molecular signatures of disease etiology, evidenced by the joint expression of molecular tumor markers. Differential effects of oral contraceptive use on breast cancer risk by molecular subtypes have been reported. This is the first meta-analysis to investigate associations between oral contraceptive use and subsequent breast cancer risk stratified by combined estrogen receptor (ER) and progesterone receptor (PR) status alongside the Luminal A and B subtypes, which additionally consider the human epidermal growth factor receptor 2 (HER2) status. Methods A systematic review and meta-analysis of case-control and cohort studies was conducted in PubMed and Web of Science. The odds ratios (ORs) were summarized using a random-effects model. Results Eleven studies met the inclusion criteria for qualitative and quantitative analysis. Random effects meta-analyses revealed significant risk increasing effects for ever-users of oral contraception on ER-PR- breast cancer compared to never-users (OR = 1.30, 95% CI; 1.07 to 1.56, p < 0.01). Ever-use of oral contraception was not associated with breast cancer risk when stratified by the ER+PR+ breast cancer subtype (OR = 1.00, 95% CI; 0.86 to 1.16, p = 0.99). Data on Luminal A and B subtypes was limited and not suggestive for associations with breast cancer risk in ever-users of OCs compared to never-users. Furthermore, a significant increased risk of ER-PR- breast cancer was observed for OC use duration of > 4 years compared to never-users (OR = 1.74, 95% CI: 1.15 to 2.63, p < 0.01). Conclusions The current state of the evidence suggests that OC use longer than 4 years is associated with an increased breast cancer risk, pertaining to the estrogen and progesterone double negative breast cancer subtype. Large-scale prospective observational studies including more comprehensive molecular signature of breast cancer aetiology, including HER2 status, are needed. Key messages • The use of oral contraception was associated with estrogen and progesterone receptor double negative breast cancer, but not hormone receptive positive cancer. • This is the first meta-analysis to investigate oral contraceptive use and associations with breast cancer risk by combined estrogen and progesterone receptor status.

Oral contraceptives in the central nervous system: Basic pharmacology, methodological considerations, and current state of the field

Millions of women around the world use combined oral contraceptives (OCs), yet surprisingly little is known about their central nervous system (CNS) effects. This article provides a short overview of the basic pharmacology of OCs, emphasizing features that may be relevant to understanding their effects in the CNS. Historical and recent findings from studies of cognitive function, mood, and negative affect (depressive changes under OC use) are then reviewed. We also present data from an archival dataset from our own laboratory in which we explore dysphoric changes in women using four generations of contraceptive progestins. Current data in the field are consistent with a modest effect of OC use on CNS variables, but conclusions based on current findings must be made very cautiously because of multiple methodological issues in many published studies to date, and inconsistencies in the findings. Directions for future research over the next 10 years are suggested. (150 words)

Oral Contraceptive Use and Breast Cancer Risk for BRCA1 and BRCA2 Mutation Carriers: Systematic Review and Meta-Analysis of Case-Control Studies.

Simple SummaryThe aim of the present work was to systematically review and meta-analysis the available evidence regarding the effects of oral contraceptives using on breast cancer risk in BRCA germline mutations. The included studies were published between 2002 and 2021. Data were pooled from nine case–control studies, comprising a total of 33,162 woman. The association between oral contraceptive use and risk of breast cancer may differ in breast cancer defined by BRCA mutation status. This meta-analysis showed a diverse effect of oral contraceptive use against breast cancer in BRCA carrier mutations. However, futher case control studies are necessary to examine breast cancer risk.Oral contraceptive use is one of the major modifiable risk factors for breast cancer. To investigate the effect of oral contraceptive taking on breast cancer risk by BRCA 1 and BRCA 2 mutation status, we conducted a systematic review and meta-analysis of case-controlled studies. Therefore, English language articles were retrieved by searching MEDLINE (PubMed), EMBASE and the Cochrane Library up to August 2021. Data were pooled from none case–control studies, comprising a total of 33,162 subjects, including 23,453 who had never used oral contraceptives. Overall meta-analysis indicated a statistically insignificant risk reduction: OR = 0.86, 95% CI: 0.70 to 1.06, p = 0.1594. However, increased breast cancer risk was associated with age at first use of OCs ≥20 years: OR = 1.21, 95% CI:1.07 to 1.36, p = 0.002. Multivariable meta-regression with covariates of age of first OC use (β = 0.21, 95% CI: −0.25 to 0.67, p = 0.3767), duration of OC use (β = −0.08, 95% CI; −0.51 to 0.34, p = 0.7093), and time since last OC use (β = 0.32, 95% CI: −0.22 to 0.85, p = 0.2461) did not have a significant effect on the breast cancer risk. This meta-analysis suggests a diverse effect of oral contraceptive use against breast cancer in BRCA carrier mutation. The association between OC use and breast and ovarian cancers needs more investigation.

Duration of oral contraceptive use relates to cognitive performance and brain activation in current and past users.

Previous studies indicate effects of oral contraceptive (OC) use on spatial and verbal cognition. However, a better understanding of the OC effects is still needed, including the differential effects of androgenic or anti-androgenic OC use and whether the possible impact persists beyond the OC use. We aim to investigate the associations of OC use duration with spatial and verbal cognition, differentiating between androgenic and anti-androgenic OC. Using functional magnetic resonance imaging (MRI), we scanned a group of 94 past and current OC-users in a single session. We grouped current OC users (N=53) and past OC users with a natural cycle (N=41) into androgenic and anti-androgenic user. Effects of OC use duration were observed for current use and after discontinuation. Duration of OC use was reflected only in verbal fluency performance but not navigation: The longer the current OC use, the less words were produced in the verbal fluency task. During navigation, deactivation in the caudate and postcentral gyrus was duration-dependent in current androgenic OC users. Only during the verbal fluency task, duration of previous OC use affects several brain parameters, including activation of the left putamen and connectivity between right-hemispheric language areas (i.e., right inferior frontal gyrus and right angular gyrus). The results regarding performance and brain activation point towards stronger organizational effects of OCs on verbal rather than spatial processing. Irrespective of the task, a duration-dependent connectivity between the hippocampus and various occipital areas was observed. This could suggest a shift in strategy or processing style with long-term contraceptive use during navigation/verbal fluency. The current findings suggest a key role of the progestogenic component of OCs in both tasks. The influence of OC use on verbal fluency remains even after discontinuation which further points out the importance of future studies on OC effects and their reversibility.

Effects of oral contraceptives on spatial cognition depend on pharmacological properties and phase of the contraceptive cycle.

The central nervous system effects of oral contraceptives (OCs) are not well-documented. In a set of 3 studies, we investigated a specific cognitive function, mental rotation, in healthy women currently using OCs for contraceptive purposes (n = 201) and in medication-free controls not using OCs (n = 44). Mental rotation was measured using a well-standardized and extensively validated psychometric test, the Vandenberg Mental Rotations Test (MRT). In an initial study (Study 1), current OC users (n = 63) were tested during the active or inactive phases of the contraceptive cycle in a parallel-groups design. Studies 2 and 3 were based on an archival dataset (n = 201 current OC users) that consisted of data on the MRT collected in real-time over a 30-year period and compiled for purposes of the present work. The OCs were combined formulations containing ethinyl estradiol (10-35 ug/day) plus a synthetic progestin. All 4 families of synthetic progestins historically used in OCs were represented in the dataset. Cognitive performance was evaluated during either active OC use (‘active phase’) or during the washout week of the contraceptive cycle (‘inactive phase’) when OC steroids are not used. The results showed a significant phase-of-cycle (POC) effect. Accuracy on the MRT was mildly diminished during the active phase of OC use, while scores on verbal fluency and speeded motor tasks were modestly improved. The POC effect was most evident in women using OCs that contained first- or second-generation progestins (the estrane family of progestins or OCs containing levonorgestrel), but not in women using OCs containing recently developed progestins and lower doses of ethinyl estradiol. Using independently established ratings of the estrogenic, androgenic, and progestogenic intensities of the different OC formulations, each brand of OC was classified according to its distinct endocrine profile. Multiple regression revealed that the effects of OC use on the MRT could be predicted based on the estrogenic strength of the contraceptives used. Estrogenic potency, not androgenic or anti-androgenic effects of the OC pill, may underlie the effects of OC usage on spatial cognition.

Stroke in young adults, stroke types and risk factors: a case control study

BackgroundStroke is the second leading cause of death above the age of 60 years, and the fifth leading cause in people aged 15 to 59 years old as reported by the World Health Organization global burden of diseases. Stroke in the young is particularly tragic because of the potential to create long-term disability, burden on the victims, their families, and the community at large. Despite this, there is limited data on stroke in young adults, and its risk factors in Uganda. Therefore, we determined the frequency and risk factors for stroke among young adults at Mulago hospital.MethodsA case control study was conducted among patients presenting consecutively to the general medical wards with stroke during the study period September 2015 to March 2016. A brain Computerized Tomography scan was performed to confirm stroke and classify the stroke subtype. Controls were patients that presented to the surgical outpatient clinic with minor surgical conditions, matched for age and sex. Social demographic, clinical and laboratory characteristics were assessed for both cases and controls. Descriptive statistics including frequencies, percentages, means, and standard deviation were used to describe the social demographics of case and controls as well as the stroke types for cases. To determine risk factors for stroke, a conditional logistic regression, which accounts for matching (e.g., age and sex), was applied. Odds ratio (with 95% confidence interval) was used as a measure for associations.ResultsAmong 51 patients with stroke, 39(76.5%) had ischemic stroke and 12(23.5%) had hemorrhagic stroke. The mean age was 36.8 years (SD 7.4) for stroke patients (cases) and 36.8 years (SD 6.9) for controls. Female patients predominated in both groups 56.9% in cases and 52.9% in controls. Risk factors noted were HIV infection, OR 3.57 (95% CI 1.16–10.96), elevated waist to hip ratio, OR 11.59(95% CI 1.98–68.24) and sickle cell disease, OR 4.68 (95% CI 1.11–19.70). This study found a protective effect of oral contraceptive use for stroke OR 0.27 95% CI 0.08–0.87. There was no association between stroke and hypertension, diabetes, and hyperlipidemia.ConclusionAmong young adults with stroke, ischemic stroke predominated over hemorrhagic stroke. Risk factors for stroke were HIV infection, elevated waist to hip ratio and sickle cell disease.

The effect of oral contraceptive use on sympatic nerve activity in patients with polycystic ovary syndrome

Objective High sympathetic nerve activity, is thought to be a cardiovascular risk factor, has been shown to correlate with circulating high testosterone levels. However its role on the pathophysiology of the polycystic ovarian syndrome has not been clearly established. The aim of our study is to compare the sympathetic nerve activity between polycystic ovarian syndrome and control group and to determine whether the use of oral contraceptives for contraception has any effect on this activity. Materials and methods Our study has designed as a prospective, case–control study including patients diagnosed with polycystic ovarian syndrome. Antropometric measurements were calculated, hormone levels were measured and sympathetic skin response and heart rate variability measurements were performed in the laboratory to assess sympathetic activity before starting oral contraceptive pill therapy and at the end of 1 month follow up. Results In the baseline condition LH/FSH ratio, LH, DHEAS, and total testosterone levels were significantly higher in women with PCOS. After 1 month of treatment, reductions in Ferriman–Gallwey score, ovarian volumes, number of follicles, LH/FSH ratio, LH, and androgen hormone levels were statistically significant. The mean values of sympathetic skin response amplitude and R–R analysis-Valsalva test were higher in PCOS group as compared to the control group. However, these differences were not statistically significant. Similarly, no statistically significant difference in SSR latency and R–R analysis-standup test were demonstrated between PCOS and control groups. Conclusion In conclusion, our study supports the increased sympatovagal activity in patients with polycystic ovarian syndrome.

Stable Anxiety and Depression Trajectories in Late Adolescence for Oral Contraceptive Users.

BackgroundThe use of oral contraceptives (OCs) has been associated with increased incidences of anxiety and depression, for which adolescents seem to be particularly vulnerable. Rather than looking at singular outcomes, we examined whether OC use is associated with depressive and anxiety symptom trajectories from early adolescence into early adulthood.Materials and MethodsData from 178 girls were drawn from the Research on Adolescent Development and Relationships (RADAR-Y) younger cohort study. We used assessments on 9 waves from age 13 until 24. Developmental trajectories of ratings on the Reynolds Adolescent Depression Scale (RADS-2) and the Screen for Child Anxiety Related Emotional Disorders (SCARED) were compared between never and ever users of OCs.ResultsNever users showed increases in depressive and anxiety symptoms in late adolescence, whereas OC users showed a stable level of symptoms throughout adolescence. This effect remained after adjusting for baseline differences between groups in romantic relationships, sexual debut, educational level, smoking, drinking, and drug use. Age of OC use onset did not significantly predict symptom development.ConclusionsOC use in adolescence was related to an altered developmental trajectory of internalizing symptoms, in which OC users did not show an increase in depressive and anxiety symptoms in late adolescence, whereas never users did. The question remains whether this altered symptom trajectory can be considered a protective effect of OC use on psychopathology. Additional research is needed to improve our understanding of the long-term consequences of OC use on mental health.

Effects of oral contraceptive use on muscle strength, muscle thickness, and fiber size and composition in young women undergoing 12 weeks of strength training: a cohort study

BackgroundIt is suspected that hormonal fluctuations during menstruation may cause different responses to strength training in women who use oral contraceptives (OC) versus those who do not. However, previous studies that investigated the existence of such differences produced conflicting results. In this study, we hypothesized that OC use has no effect on muscle strength and hypertrophy among women undergoing strength training. Thus, we compared the differences in muscle strength and thickness among women who used OCs and those who did not.MethodsWe investigated the influence of OC use on muscle strength (Fmax), muscle thickness (Mtk), type 1-to-type 2 muscle fiber (NO) ratio, muscle fiber thickness (MFT), and nuclear-to-fiber (N/F) ratio. Seventy-four healthy young women (including 34 who used OCs and 40 who did not) underwent 12 weeks of submaximal strength training, after which Fmax was evaluated using a leg-press machine with a combined force and load cell, while Mtk was measured using real-time ultrasonography. Moreover, the NO ratio, MFT, and N/F ratio were evaluated using muscle needle biopsies.ResultsParticipants in the non-OC and OC groups experienced increases in Fmax (+ 23.30 ± 10.82 kg and + 28.02 ± 11.50 kg respectively, p = 0.073), Mtk (+ 0.48 ± 0.47 cm2 and + 0.50 ± 0.44 cm2 respectively, p = 0.888), Fmax/Mtk (+ 2.78 ± 1.93 kg/cm2 and + 3.32 ± 2.37 kg/cm2 respectively, p = 0.285), NO ratio (type 2 fibers: + 1.86 ± 6.49% and − 4.17 ± 9.48% respectively, p = 0.169), MFT (type 2 fibers: + 7.15 ± 7.50 µm and + 4.07 ± 9.30 µm respectively, p = 0.435), and N/F ratio (+ 0.61 ± 1.02 and + 0.15 ± 0.97 respectively, p = 0.866) after training. There were no significant differences between the non-OC and OC groups in any of these parameters (p > 0.05).ConclusionsThe effects of 12 weeks of strength training on Fmax, muscle thickness, muscle fiber size, and composition were similar in young women irrespective of their OC use.

Long term use of oral contraceptives comprising synthetic estrogens induces an excessive breast cancer risk in BRCA mutation carrier women: a meta-analysis

Background: The relationship between oral contraceptive (OC) use and breast cancer risk is highly debated. Recent publications support a slight increase in overall breast cancer risk among OC user women, in particular among the current users. Women with inherited BRCA1 (Breast cancer type 1) or BRCA2 (Breast cancer type 2) gene mutations are at increased risk of breast and ovarian cancers, which is often mistakenly attributed to their elevated endogenous estrogen levels. The aim of presented meta-analysis was to assess the effects of OC use on breast cancer risk in BRCA mutation carrier women with minimal bias. Methods: A systematic search strategy was used to identify relevant studies, Stata (version 15) was used for meta-analysis. Results: Individual datasets from 13 studies totaling 20,202 patients were analyzed. The combined results showed no significant increase in risk of breast cancer in BRCA mutation carriers who had ever used oral contraceptive (HR = 1.09, 95% CI: 0.71–1.69 among BRCA1 mutation carriers and HR = 1.19, 95% CI: 0.73–1.95 among BRCA2 mutation carriers, respectively). However, in correlation with long-term (>5 years) OC users, the breast cancer risk was significantly increased in both BRCA1 mutation carriers (HR = 1.39, 95% CI: 1.19–1.60) and BRCA1 mutation carriers (HR = 1.61, 95% CI: 1.25–1.96). Conclusion: The presented results indicate that in BRCA mutation carriers women who have defective liganded activation of estrogen receptors (ERs), the use of synthetic estrogens means an additive factor for ER deregulation further increasing the risk for breast cancer. Long term OC use in BRCA mutation carriers results in a significantly increased risk for breast cancer by exhausting the compensatory genome defending process.

Stress-Hormone Dynamics and Working Memory in Healthy Women Who Use Oral Contraceptives Versus Non-Users.

BackgroundWomen who use oral contraceptives (OCs) may have a higher risk of developing a depression, which is associated with both vulnerability to stress and cognitive dysfunction. OCs disrupt the hypothalamic-pituitary-gonadal (HPG) axis by suppressing endogenous sex steroid production including estradiol. The HPG axis and the hypothalamic-pituitary-adrenal (HPA) axis are known to interact, possibly through modulations driven by estradiol. OCs may affect HPA regulation capacity, i.e., disturb cortisol dynamics such as the cortisol awakening response (CAR), and influence cognition such as working memory (WM). We hypothesize that OC use is associated with blunted cortisol dynamics and impaired WM performance relative to non-users.MethodsData from 78 healthy women in the reproductive age were available from the CIMBI database. We evaluated if CAR and WM differed between OC users (n=25) and non-users (n=53) and if the level of estradiol modulated the OC use effect on CAR or WM in generalized least square models.ResultsWe found that OC users had a blunted CAR (p= 0.006) corresponding to a 61% reduction relative to non-users; however, no estradiol-BY-OC use interaction effect was observed on CAR. Also, OC users had higher cortisol levels at awakening compared to non-users (p = 0.03). We observed no effect of OC use or an estradiol-BY-OC use interaction effect on WM. Also, within the OC user group, neither CAR nor WM was associated with suppressed estradiol. CAR was not associated with WM.ConclusionHealthy women who use OCs have blunted cortisol dynamics relative to non-users. However, we could not detect OC use effects on working memory in our sample size. We speculate that disrupted cortisol dynamics may be important for the emergence of depressive symptoms in OC users.

Oral contraceptive use during relationship formation and current relationship satisfaction: Testing the congruency hypothesis in couples attending pregnancy and fertility clinics

According to the congruency hypothesis, relationship satisfaction is predicted by the congruency (or non-congruency) between current use of oral contraceptives (OC) and their use during relationship formation. This is based on findings that OC may alter women’s mate preferences, so that attraction to their partner may have changed in non-congruent women. Indeed, some studies find that women in a non-congruent state were less sexually satisfied with their partner, although they were more satisfied in non-sexual aspects of the relationship. However, some other studies have produced null results, calling the hypothesis into question. In this study, we tested the congruency hypothesis in two samples of pregnant women, and in two samples of couples attending a fertility clinic. In all four samples, couples completed questionnaires on relationship and sexual satisfaction and the women also reported their previous and current contraceptive use. In one sample of pregnant women, we found that women who used OC during relationship formation were more sexually satisfied with their partner compared to women who did not use OC at that time; this pattern has previously been interpreted as supporting the congruency hypothesis in view of certain similarities in hormonal profile between OC use and pregnancy. We did not find any significant effect of OC use during relationship formation on sexual and relationship satisfaction in the other sample of pregnant women, either sample attending the fertility clinic, or in the male partners of any of our samples. Our results thus provide mixed support for the congruency hypothesis. Finally, we discuss recommendations for future studies such as use of within-subject designs and more structured assessment of sexual satisfaction.

The Effects of Sex, Oral Contraception, and Menstrual Cycle Phase on Intraocular Pressure, Central Corneal Thickness, and Foveal Thickness: A Descriptive Analysis.

The primary goal of this study was to investigate the effects of sex, oral contraceptive (OC) use, and menstrual cycle phase on common ocular parameters assessed during ophthalmic evaluations, namely intraocular pressure (IOP), central corneal thickness (CCT), and foveal thickness (FT), in young healthy adults. We measured IOP, CCT, and FT in 60 participants (16 men, 16 contraceptive users, and 28 cycling women) over two sessions that characterized the menstrual cycle phase in women. For men in our study, two sessions were separated by two weeks. For women, the two sessions were scheduled during the follicular and luteal phases of the menstrual cycle. There was a trend towards higher IOP in men, and the difference was significant for white, non-Hispanic subjects and for white subjects considered separately. There was also a trend for thicker corneas in women, but men had significantly thicker foveae. CCT and FT were not different between men and OC-users, hinting at a moderating hormonal effect of oral contraceptive use. We found that IOP, CCT, and FT were equivalent between the follicular and luteal phases, which may be owing to the timing of our sessions. However, our findings strongly suggest that clinicians should consider contraceptive use during routine ophthalmic evaluations, as it could inform glaucomatous risk in women.

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

BACKGROUNDStudies on the association of oral contraceptive (OC) use and pancreatic cancer showed inconsistent findings. AIMTo evaluate the relationship between OC use and pancreatic cancer risk. METHODSA 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).RESULTSA 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. CONCLUSIONDespite 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.