Search Results (35)

The heart rate variability (HRV), influenced by female sex hormone fluctuations, is an indicator of athletes’ adaptation. This case study explores HRV responses over 18 months across a natural menstrual cycle (MC) and during oral contraceptive (OC) use in two Olympic female swimmers. HRV measurements—including mean heart rate (HR); root mean square of successive differences (RMSSD); and frequency-domain indices—were collected at rest in supine (SU) and standing (ST) positions across two competitive seasons. Nocturnal HR and RMSSD were assessed using the Ōura^® ring. MC and OC phases were identified through specific tracking, and training load was controlled. In both athletes, resting HR was lower during bleeding phases, increasing from menstruation to the luteal phase (MC) and from withdrawal to active pill phases (OC). In the ST position, RMSSD was higher but decreased throughout the phases. Nocturnal measurements confirmed these trends. Overall, findings suggest a phase-related parasympathetic overactivity shift. This study provides novel insights into HRV responses across hormonal cycles in elite female athletes, which present unique characteristics. Such monitoring tools may support a data-informed approach to guide and periodize training more effectively. Full article

Background: The relationship between oral contraceptive (OC) use and pancreatic cancer (PC) risk remains controversial, with inconsistent findings reported in observational studies. To clarify this relationship and better identify potential risk factors for PC prevention, more unbiased and robust approaches are needed. Methods: We investigated the potential causal relationship between OC use and PC risk using a two-sample Mendelian randomization (MR) analysis, with blood protein quantitative trait loci (pQTLs) as instrumental variables. To ensure the robustness of our findings, we performed a series of sensitivity analyses, colocalization analyses, and reverse MR. The causal effects of protein-coding genes on PC risk, as well as their expression patterns across different single-cell types, were subsequently investigated. To elucidate the potential pathogenic pathways, we conducted pathway enrichment analysis, protein–protein interaction (PPI) network analysis, and causal inference. Results: Our MR analysis identified five drug-targeted proteins significantly associated with PC risk. Higher levels of COMT, AGT, FN1, and UGT1A1, as well as lower levels of SERPINC1, were associated with an increased risk of PC. Among these, AGT, FN1, and COMT demonstrated consistent associations across sensitivity analyses and downstream analyses, providing robust evidence supporting their involvement in PC risk. Conclusions: This study provides genetic evidence suggesting, in European groups, a potential causal link between OC use and increased PC risk, possibly mediated through drug-targeted proteins such as AGT and FN1. These results highlight the importance for further research to elucidate the underlying mechanisms and assess the implications of OC use on PC risk. Full article

Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that significantly impacts quality of life, particularly among women. Previous studies have suggested that oral contraceptive (OC) use may influence RA risk, but conflicting findings from earlier meta-analyses necessitate an updated analysis incorporating more recent data. Methods: We conducted a systematic review and meta-analysis of observational studies on OC use and RA risk by searching MedLine (via PubMed), Scopus, and Cochrane Databases up to September 2024. Results: Our analysis demonstrated that current or prior use of OCs is associated with a statistically significant reduction in RA risk (OR 0.80, 95% CI 0.70–0.91). In contrast, the associations for current use (OR 0.59, 95% CI 0.34–1.02) and past use (OR 0.83, 95% CI 0.69–1.01) were less definitive, likely due to substantial heterogeneity among studies. Cumulative meta-analysis revealed a modest temporal trend toward a protective effect of OC use. Conclusions: This meta-analysis supports a protective association between current or prior OC use and the development of RA, highlighting the potential role of hormonal factors in RA pathogenesis. Full article

Background: Incidence of breast cancer (BrCa) may be correlated with country development, with a rise in cases anticipated in regions of the world that are currently undergoing an economic transformation. Herein, differences with regard to the occurrence of breast cancer between individual countries may depend on the distribution of risk factors, the level of early detection, also ethnicity and race, as well as clinical characteristics. The aim of our study was to identify and then investigate observational studies in which the risk of breast cancer was associated with the use of oral hormonal contraceptives (OCs), with particular emphasis on geographic region, and to conduct a systematic review and meta-analysis of the obtained data. Methods: RR (relative risk) was calculated and displayed in forest plots for visual interpretation. Accordingly, 74 studies involving a total of 198,579 women were eligible for inclusion in the meta-analysis. This is the first meta-analysis to comprehensively summarize the evidence between OC use and BrCa risk in connection with geographical region. Results: The cumulative results of the meta-analysis for specific parts of the world are: Africa (RR = 1.16, p = 0.216) and the Americas (RR = 1.03, p = 0.597); Asia (RR = 1.29, p = 0.014); European countries (RR = 1.01, p = 0.904); and Middle East countries (RR = 1.29, p = 0.043). Subgroup analyses showed an increased risk of BrCa for the analyzed variables that depended upon the geographical region. Conclusions: Our meta-analysis suggests that OC use may be associated with a higher BrCa risk, although a statistically significant association was not found for all geographical regions of the world. Full article

Background: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine syndromes affecting women at reproductive age. With increasing knowledge of the role of the microbiota in the pathogenesis of PCOS, new management strategies began to emerge. However, data on the impact of established treatment regimens, such as metformin and oral contraceptive agents, on the gut microbiota composition are scarce. This study aimed to evaluate the specificity of the gut microbiota in women with PCOS before and after treatment with oral contraceptives. Methods: We have systematically searched the following databases: PubMed/MEDLINE, Scopus, Web of Science and Google Scholar. The last search was performed on 13 May 2024. We included only full-text original research articles written in English. The risk of bias was assessed using a modified version of the Newcastle–Ottawa Scale. Results: The above described search strategy retrieved 46 articles. Additionally, 136 articles were identified and screened through Google Scholar. After removing duplicates, we screened the titles and abstracts, resulting in three eligible articles constituting the final pool. They were published between 2020 and 2022 and are based on three ethnically distinct study populations: Turkish, Spanish and American. The studies included a total of 37 women diagnosed with PCOS and using OCs. Conclusions: OC treatment does not seem to affect the gut microbiota in a significant way in patients with PCOS in short observation. Well-designed randomized controlled studies with adequate, unified sample size are lacking. Full article

Background and Objectives: Oral contraceptives (OCs) are usually used to treat endometriosis; however, the evidence is inconsistent about whether OC use in the past, when given to asymptomatic women, is protective against the development of future disease. We aimed to assess the relationship between the use of OCs and the likelihood of discovering endometriosis, considering the length of time under OCs during their fertile age. Materials and Methods: This was a monocentric retrospective cohort study in a tertiary-care University Hospital (Department of Human Reproduction, Division of Gynaecology and Obstetrics, University Medical Centre Ljubljana, Slovenia) carried out from January 2012 to December 2022. Reproductive-aged women scheduled for laparoscopic surgery for primary infertility and subsequent histopathological diagnosis of endometriosis were compared to women without an endometriosis diagnosis. They were classified based on the ratio of years of OC use to fertile years in four subgroups: never, <25%, between 25 and 50%, and >50. Results: In total, 1923 women (390 with and 1533 without endometriosis) were included. Previous OC use was higher in those with endometriosis than controls (72.31% vs. 58.64%; p = 0.001). Overall, previous OC usage was not related to histopathological diagnosis of endometriosis (aOR 1.06 [95% CI 0.87–1.29]). Women who used OCs for less than 25% of their fertile age had reduced risk of rASRM stage III endometriosis (aOR 0.50 [95% CI 0.26–0.95]; p = 0.036) or superficial implants (aOR 0.88 [95% CI 0.58–0.95]; p = 0.040). No significant results were retrieved for other rASRM stages. Using OCs for <25%, between 25 and 50%, or >50% of fertile age did not increase the risk of developing superficial endometriosis, endometriomas, or DIE. Conclusions: When OCs are used at least once, histological diagnoses of endometriosis are not increased. A protective effect of OCs when used for less than 25% of fertile age on superficial implants may be present. Prospective research is needed to corroborate the findings due to constraints related to the study’s limitations. Full article

In this narrative review, we attempt to provide an overview of the evidence regarding the role of estrogen (receptors) in cutaneous melanoma (CM). We reviewed 68 studies and 4 systematic reviews and meta-analyses published from 2002 up to and including 2022. The prevailing presence of estrogen receptor β (ERβ) instead of estrogen receptor α (ERα) in CM is notable, with ERβ potentially playing a protective role and being less frequently detected in progressive cases. While men with CM generally experience a less favorable prognosis, this distinction may become negligible with advancing age. The role of oral contraceptives (OC) and hormone replacement therapy (HRT) in CM remains controversial. However, recent studies tend to associate the use of these exogenous hormones with a heightened risk of CM, mostly only when using estrogen therapy and not in combination with progesterone. On the contrary, the majority of studies find no substantial influence of in vitro fertilization (IVF) treatment on CM risk. Reproductive factors, including younger age at first childbirth, higher parity, and shorter reproductive life, show conflicting evidence, with some studies suggesting a lower CM risk. We suggest an important role for estrogens in CM. More research is needed, but the integration of estrogens and targeting the estrogen receptors in melanoma therapy holds promise for future developments in the field. Full article

Background: Injuries of the patellar tendon commonly occur as a result of mechanical loading of the tendon during physical activity. Shear wave elastography (SWE) is an established technique for assessing tendon stiffness, and has good interindividual reliability. The aim of this study was to investigate the impacts of physical parameters and different sports on patellar tendon stiffness in professional athletes using SWE. Methods: Standardized patellar tendon SWE was performed in a relaxed supine position with a small roll under the knee (20° flexion) in 60 healthy professional athletes (30 female, 30 male). Multiple linear regression was performed for patellar tendon stiffness including gender, age, body mass index (BMI), and type of sport. Results: Patellar tendon stiffness showed no significant difference between female (3.320 m/s) and male (3.416 m/s) professional athletes. Mean age (female: 20.53 years; male: 19.80 years) and BMI (female: 23.24 kg/m²; male: 23.52 kg/m²) were comparable. Female professional athletes with oral contraceptive (OC) intake showed higher patellar tendon stiffness than athletes without OC intake (3.723 versus 3.017; p = 0.053), but not significantly. Conclusion: In professional athletes, there are no significant differences in patellar tendon stiffness according to gender, age, BMI and type of sport (handball, volleyball, soccer, sprint, hammer throw). Oral contraceptives may not have an impact on patellar tendon stiffness in female athletes. Further studies are necessary. Full article

To assess the use of oral contraceptives (OC) in adolescents, using data from a longitudinal, population-based pediatric cohort study (LIFE Child). We also investigated associations between OC use and socioeconomic status (SES), and associations between OC use and potential adverse drug reactions such as effects on blood pressure. We included 609 female participants of the LIFE Child cohort, aged ≥13 to <21 years, who visited the study center between 2012 and 2019. Data collection compromised drug use in the past 14 days, SES, and anthropometric data such as blood pressure. An analysis of covariance was used to detect potential associations between participants’ blood pressure and OC. Multivariate binary logistic regression was used to obtain odds ratios (aOR) adjusted for age and 95% confidence intervals (95% CI). The prevalence of OC use was 25.8%. OC intake was less common in participants with a high SES (aOR 0.30, 95% CI 0.15, 0.62). The mean age at OC initiation did not change between 2012 and 2019. We observed an increased use of second-generation OC (2013: 17.9%, 2019: 48.5%; p = 0.013) and a decreased use of fourth-generation OC (2013: 71.8%, 2019: 45.5%; p = 0.027). We found a higher systolic (mean: 111.74 mmHg, p < 0.001) and diastolic (69.15 mmHg, p = 0.004) blood pressure in OC users compared to non-users (systolic: 108.60 mmHg; diastolic: 67.24 mmHg). Every fourth adolescent took an OC. The share of second-generation OC increased during the study period. OC intake was associated with low SES. OC users had a slightly higher blood pressure than non-users. Full article

Smoking-derived nicotine (N) and oral contraceptive (OC) synergistically exacerbate ischemic brain damage in females, and the underlying mechanisms remain elusive. In a previous study, we showed that N + OC exposure altered brain glucose metabolism in females. Since lipid metabolism complements glycolysis, the current study aims to examine the metabolic fingerprint of fatty acids in the brain of female rats exposed to N+/−OC. Adolescent and adult Sprague–Dawley female rats were randomly (n = 8 per group) exposed to either saline or N (4.5 mg/kg) +/−OC (combined OC or placebo delivered via oral gavage) for 16–21 days. Following exposure, brain tissue was harvested for unbiased metabolomic analysis (performed by Metabolon Inc., Morrisville, NC, USA) and the metabolomic profile changes were complemented with Western blot analysis of key enzymes in the lipid pathway. Metabolomic data showed significant accumulation of fatty acids and phosphatidylcholine (PC) metabolites in the brain. Adolescent, more so than adult females, exposed to N + OC showed significant increases in carnitine-conjugated fatty acid metabolites compared to saline control animals. These changes in fatty acyl carnitines were accompanied by an increase in a subset of free fatty acids, suggesting elevated fatty acid β-oxidation in the mitochondria to meet energy demand. In support, β-hydroxybutyrate was significantly lower in N + OC exposure groups in adolescent animals, implying a complete shunting of acetyl CoA for energy production via the TCA cycle. The reported changes in fatty acids and PC metabolism due to N + OC could inhibit post-translational palmitoylation of membrane proteins and synaptic vesicle formation, respectively, thus exacerbating ischemic brain damage in female rats. Full article

Women are two to four times more prone to anterior cruciate ligament (ACL) injuries than men. This raises questions about the role of the hormonal cycle in knee laxity, which may lead to increased tibial displacement and thus ACL tears. The objective was to update scientific knowledge on the influence of the menstrual cycle on knee laxity and the risk of ACL injury, with a focus on anterior tibial displacement, and on hormonal levels influenced or not by oral contraceptive use. Observational studies obtained from Pubmed, Web of Sciences and Scopus and published between 2015 and 2022 were included in this review. Studies were required to include data on menstrual cycle with/without oral contraceptives (OC) and knee laxity and/or ACL injury. A total of ten studies were selected for this systematic review. Three studies about hormone concentration and knee laxity showed an increase in estradiol during the ovulatory phase compared to the follicular phase. Of the five studies on OC, four showed a decrease in ACL laxity. Finally, four studies assessed ACL injury. The menstrual cycle appears to influence knee laxity in women. An increase in certain hormone levels was observed in the ovulatory and luteal phases when the anterior tibial translation was greater in the knee. However, based on the literature, we cannot conclude that there is a correlation between the menstrual cycle and the risk of ACL injury. Full article

Breast cancer is divided into four molecular subtypes. Each one has distinct clinical features. The aim of this study was to assess individual breast cancer subtype risk in premenopausal women taking oral contraceptives (OCs). Databases (MEDLINE; PubMed, EMBASE, and the Cochrane Library) were searched to January 2022 to identify case-control studies meeting the inclusion criteria. The influence of OCs intake on the risk of ER-positive breast cancer (ER+BC) was revealed to be non-significant with regard to reduction: OR = 0.9134, 95% CI: 0.8128 to 1.0265, p = 0.128. Assessment of ER-negative subtype breast cancer (ER−BC) risk indicated that OCs use significantly increased the risk: OR = 1.3079, 95% CI: 1.0003 to 1.7100, p = 0.050. Analysis for HER2-positive breast cancer (HER2+BC) risk showed that OCs use statistically non-significantly lowered the risk: OR = 0.8810, 95% CI: 0.5977 to 1.2984, p = 0.522. Meta-analysis with regard to Triplet-negative breast cancer (TNBC) risk showed non-statistically significant increased risk: OR = 1.553, 95% CI: 0.99 to 2.43, p = 0.055. The findings of the meta-analysis suggest that breast cancer risk in premenopausal women may vary with respect to molecular subtypes. Extensive scientific work is still necessary in order to understand the impact of OCs use on breast cancer risk in young women. Full article

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. Full article

High body mass index (BMI) may influence muscle strength, muscle thickness (Mtk), and fiber composition. We evaluated these parameters in 31 and 27 women grouped in non-oral contraceptive (non-OC) groups and OC groups, respectively, and further divided them into groups based on BMI: BMI_low, BMI_norm, and BMI_high. Maximum isometric force (F_max), Mtk, and the relative percentage of muscle fiber composition (%) were examined in both groups. F_max and Mtk values were significantly greater in the BMI_high than the BMI_low within the OC group. However, there was no significant difference in the non-OC group. BMI_low and BMI_norm groups showed a difference in the distribution of muscle fiber types 1 and 2 with almost the same proportions in both non-OC and OC groups. However, the BMI_high group showed a difference in the distribution of muscle fiber types 1 and 2, with type 1 about 18.76% higher in the non-OC group. Contrastively, type 2 was about 34.35% higher in the OC group. In this study, we found that there was a significant difference in F_max and Mtk according to the BMI level in the OC group, but no significant difference was found in the non-OC group. Moreover, the distribution of type 2 muscle fibers tended to be higher in the OC group of BMI_high, although the sample size was small. Therefore, although no significant difference of F_max and Mtk was found according to BMI level in the non-OC group in this study, the increase in BMI level appeared to be more associative of muscle strength in the OC group. Based on the present results, future studies are needed that consider the BMI level as well as the presence or absence of OC in future research about women’s muscle strength. Full article

Bleeding irregularities are one of the major reasons for discontinuation of oral contraceptives (OCs), and therefore clinicians need to set expectations during consultations. In this review we provide an overview of bleeding data of recently marketed cyclic combined OCs (COCs) and one progestin-only pill (POP). We evaluated data from phase 3 trials (≥12 months) used to gain regulatory approval. Overall, each type of OC has its own specific bleeding pattern. These patterns however were assessed by using different bleeding definitions, which hampers comparisons between products. In COCs, the estrogen balances the effects of the progestin on the endometrium, resulting in a regular bleeding pattern. However, this balance seems lost if a too low dose of ethinylestradiol (EE) (e.g., 10 µg in EE/norethindrone acetate 1 mg) is used in an attempt to lower the risk of venous thromboembolism. Replacement of EE by 17β-estradiol (E2) or E2 valerate could lead to suboptimal bleeding profile due to destabilization of the endometrium. Replacement of EE with estetrol (E4) 15 mg in the combination with drospirenone (DRSP) 3 mg is associated with a predictable and regular scheduled bleeding profile, while the POP containing DRSP 4 mg in a 24/4 regimen is associated with a higher rate of unscheduled and absence of scheduled bleeding than combined products. Full article