Age At First Sexual Intercourse Research Articles

A comprehensive genome-wide cross-trait analysis of sexual factors and uterine leiomyoma.

Age at first sexual intercourse (AFS) and lifetime number of sexual partners (NSP) may influence the pathogenesis of uterine leiomyoma (UL) through their associations with hormonal concentrations and uterine infections. Leveraging summary statistics from large-scale genome-wide association studies conducted in European ancestry for each trait (NAFS = 214,547; NNSP = 370,711; NUL = 302,979), we observed a significant negative genomic correlation for UL with AFS (rg = -0.11, P = 7.83×10-4), but not with NSP (rg = 0.01, P = 0.62). Four specific genomic regions were identified as contributing significant local genetic correlations to AFS and UL, including one genomic region further identified for NSP and UL. Partitioning SNP-heritability with cell-type-specific annotations, a close clustering of UL with both AFS and NSP was identified in immune and blood-related components. Cross-trait meta-analysis revealed 15 loci shared between AFS/NSP and UL, including 7 novel SNPs. Univariable two-sample Mendelian randomization (MR) analysis suggested no evidence for a causal association between genetically predicted AFS/NSP and risk of UL, nor vice versa. Multivariable MR adjusting for age at menarche or/and age at natural menopause revealed a significant causal effect of genetically predicted higher AFS on a lower risk of UL. Such effect attenuated to null when age at first birth was further included. Utilizing participant-level data from the UK Biobank, one-sample MR based on genetic risk scores yielded consistent null findings among both pre-menopausal and post-menopausal females. From a genetic perspective, our study demonstrates an intrinsic link underlying sexual factors (AFS and NSP) and UL, highlighting shared biological mechanisms rather than direct causal effects. Future studies are needed to elucidate the specific mechanisms involved in the shared genetic influences and their potential impact on UL development.

Mendelian randomization analyses for the causal relationship between early age at first sexual intercourse, early age at first live birth, and postpartum depression in pregnant women.

There are insufficient epidemiological studies on the impact of age at first sexual intercourse (AFS) and age at first live birth (AFB) on postpartum depression (PPD) in pregnant women, and the conclusions of these studies are inconsistent. We performed a Mendelian randomization (MR) study to determine the causal relationship between AFS or AFB and the risk of PPD. The summary data were extracted from genome-wide association study (GWAS) summary datasets. We selected the instrumental variables according to the P value of exposure-related single nucleotide polymorphisms (P<5 ×10-9 for AFS and P<5 ×10-8 for AFB) and estimated the linkage disequilibrium using the clump parameter (10,000 kb, r2 < 0.001). Single nucleotide polymorphisms were considered instrumental variables that were significantly associated with exposure factors without linkage disequilibrium. The F-statistics of the instrumental variables should all be larger than 10.A random-effects model of IVW was constructed as the main method in our study. MR studies based on GWAS data revealed that both AFS (OR = 0.4, P <0.001) and AFB (OR = 0.38, P <0.001) were negatively correlated with the risk of PPD. Early AFS and early AFB should be studied as possible risk factors for PPD in the future. Public health departments should attach importance to sex education for young girls. The results of our TSMR should be verified by high-quality prospective epidemiological studies in the future.

Exploring the causal relationship between female reproductive traits and frailty: a two-sample mendelian randomization study.

Background: The impact of female reproductive factors, including age at menarche (AAM), age at first birth (AFB), age at first sexual intercourse (AFS), age at natural menopause (ANM), and pregnancy abortion (PA), on the risk of developing frailty remains uncertain. Our objective is to examine the potential causal relationship between female reproductive traits and frailty through the utilization of two-sample univariable Mendelian Randomization (UVMR) and multivariable Mendelian Randomization (MVMR) analyses. Methods: Leveraging large-scale Genome-Wide Association Study (GWAS) data from individuals of European ancestry, we performed two-sample UVMR and MVMR analyses to examine the causal relationship between female reproductive traits and frailty. The primary analysis employed inverse-variance-weighted (IVW) estimation, and sensitivity analyses were conducted to assess the robustness of the findings. Results: The UVMR analysis revealed a significant causal relationship between female reproductive traits (AFS, AFB, AAM) and frailty [IVW: OR = 0.74, 95%CI(0.70-0.79), p = 0.000; OR = 0.93, 95%CI(0.92-0.95), p = 0.000; OR = 0.96, 95%CI(0.95-0.98), p = 0.000]. However, there was no significant effect of ANM and PA on frailty (p > 0.05). The sensitivity analysis results were robust, supporting the findings. Furthermore, this association remained significant even after adjusting for body mass index (BMI) and educational attainment (EA) in the MVMR analysis [IVW: OR = 0.94, 95%Cl (0.91-0.97), p = 0.000; OR = 0.77, 95%Cl (0.70-0.86), p = 0.000; OR = 0.95, 95%Cl (0.94-0.97), p = 0.000]. BMI and EA serve as mediators in this process. Conclusion: Our research has established a significant causal relationship between female reproductive traits (AFS, AFB, AAM) and frailty, with BMI and EA acting as mediating factors in this process. However, further research is warranted to validate our findings and elucidate the underlying biological mechanisms.

The impact of obesity and sexual behavior on prostate cancer risk is mediated by testosterone levels: a mendelian randomization study and mediation analysis

BackgroundThe relationship between obesity, sexual behavior, and prostate cancer (PCa) has been widely debated, contributing to a lack of understanding of its potential mechanisms and hindering the development of effective prevention measures. PurposeThe aim of this study was to examine the causal effect of body mass index (BMI), age at first sexual intercourse (AFS), and bioavailable testosterone levels on PCa while also quantifying the potential roles of mediators. MethodWe conducted a Mendelian randomization (MR) study using summary statistics from genome-wide associations of BMI (152,893 European males), AFS (182,791 European males), bioavailable testosterone (184,205 European males), and PCa (79,148 cases, 61,106 controls, European ancestry). Inverse-variance weighted method, weighted median method, MR-Egger regression, Least Absolute Shrinkage and Selection Operator (LASSO), and outlier test were used for MR analyses. Reverse MR and mediation analysis were performed. Data analyses were conducted from December 2022 to July 2023. ResultsThe results showed that genetic liability to BMI was protective of PCa (OR, 0.82; 95% CI: 0.74-0.91; P = 3.29 × 10−4). Genetic liability to later AFS (OR, 1.28; 95% CI: 1.08-1.53; P = 5.64 × 10−3) and higher bioavailable testosterone levels (OR = 1.11, 95% CI: 1.01–1.24, P = 0.04) were associated with an increased risk of PCa. All of these potential causal effects could only be forwarded and were not affected by prostate specific antigen (PSA) screening. After controlling for bioavailable testosterone levels, the causal impact of BMI and AFS on PCa was no longer significant. The mediation analysis suggested that the causal influence of AFS/BMI on PCa relied on bioavailable testosterone levels. ConclusionIn conclusion, the difference between the univariable and multivariable MR results suggested that the causal influence of BMI and AFS on PCa relied on bioavailable testosterone levels. Further work is needed to identify other risk factors and to elucidate the specific mechanisms that underlie this causal pathway.

Identifying causal associations between women’s reproductive traits and risk of schizophrenia: a multivariate validated two-sample Mendelian randomization analysis

BackgroundA significant association between women’s reproductive traits and the risk of schizophrenia (SCZ) has been discovered, but the causalities remain unclear. We designed a two-sample univariate Mendelian randomization (MR) study using female-specific SNPs collected from a large-scale genome-wide association study as a genetic tool to explore the causal effect of female reproductive traits on the risk of SCZ, and conducted a multivariate MR study to re-validate the above findings.MethodsFrom extensive genome-wide association studies (GWAS) of people with European ancestry (n = 176,881 to 418,758 individuals), summary-level data on five female reproductive variables were extracted. Summary-level information on SCZ was taken from a GWAS meta-analysis involving 320,404 people with European ancestry. The inverse variance weighting estimations for both univariable MR (UVMR) and multivariable MR (MVMR) were presented as the primary results. MR-Egger, weighted median, simple mode, and weighted mode regression methods for UVMR, and MVMR-Egger, MVMR-Lasso, and MVMR-median methods for MVMR were used for sensitivity analyses.ResultsThe UVMR produced compelling proof for a connection between genetically predicted later age at first sexual intercourse (AFS) (OR, 0.632; 95% CI, 0.512–0.777; P < 0.01) and decreased SCZ risk. Pleiotropy analysis of the AFS-SCZ association confirmed the robustness of the MR results (P > 0.05). Consistent, substantial causal effects of AFS (OR, 0.592; 95%CI, 0.407–0.862; P < 0.01) on the risk of SCZ were demonstrated after adjusting for body mass index, years of schooling, and smoking initiation using MVMR.ConclusionsOur findings provide convincing evidence that early AFS is a risk factor for SCZ. SCZ risk may be decreased by raising awareness of reproductive healthcare for women.

Assessing the association between age at first sexual intercourse and migraine: a Mendelian randomization study.

As indicated by observational and genetic variation studies, age at first sexual intercourse (AFS) may be associated with migraine attack, but there is a lack of evidence from real-world studies due to ethical concerns. Therefore, we conducted a Mendelian randomization study to determine the causal relationship between AFS and migraine. We extracted instrumental variables from summary data of a genome-wide association study (GWAS) on AFS and migraine and then conducted two-sample Mendelian randomization analyses. GWAS data for AFS and migraine were obtained from 397,338 unrelated individuals (214,547 females and 182,791 males) and 306,314 individuals (18,477 patients and 287,837 control individuals), respectively. There was a causal relationship between AFS and risk for migraine (odds ratio (OR) = 0.73, 95% confidence interval (CI) [0.61 to 0.86]), both for migraine with aura (MWA; OR = 0.72, 95% CI [0.58 to 0.89]) and migraine without aura (MOA; OR = 0.66, 95% CI [0.51 to 0.86]). Stratified analyses provided suggestive evidence of the causal relationship between delayed AFS and a decreased risk of migraine for both males (OR = 0.71, 95% CI [0.59 to 0.84]) and females (OR = 0.73, 95% CI [0.61 to 0.89]). Reverse Mendelian randomization did not reveal any effect of migraine on AFS (p > 0.05). No pleiotropy was detected. A delayed AFS is a protective factor against migraine (for both MWA and MOA) in both males and females. This causal relationship indicates the presence of extracranial regulatory pathways of migraine.

The causal effect of reproductive factors on pelvic floor dysfunction: a Mendelian randomization study

BackgroundPelvic floor dysfunction (PFD) is an extremely widespread urogynecologic disorder, the prevalence of which increases with aging. PFD has severely affected women’s quality of life and has been called a social cancer. While previous studies have identified risk factors such as vaginal delivery and obesity for PFD, other reproductive factors, including age at menarche (AAMA), have been largely overlooked. Therefore, we used a Mendelian randomization (MR) study for the first time to investigate the potential causal relationship between reproductive factors and PFD.MethodsWe obtained summary statistics from genome-wide association studies (GWAS) for female genital prolapse (FGP), stress urinary incontinence (SUI), and five reproductive factors. Two-sample Mendelian randomization analysis (TSMR) was performed to explore the causal associations between these factors. The causal effects of reproductive factors on FGP and SUI were primarily estimated using the standard inverse variance weighting (IVW) method, with additional complementary and sensitivity analyses conducted using multiple approaches. A multivariate Mendelian randomization (MVMR) study was also conducted to adjust for pleiotropic effects and possible sources of selection bias and to identify independent exposure factors.ResultsOur findings revealed that advanced age at first sexual intercourse (AFS) and age at first birth (AFB) exhibited negative causal effects on both FGP and SUI. AAMA showed negative causal effects solely on FGP, while age at last live birth (ALB) and age at menopause (AAMO) did not demonstrate any causal effect on either FGP or SUI. And the MVMR results showed that AFB and AFS had independent negative causal effects on FGP and SUI, respectively.ConclusionsThis study, for the first time, investigates the causal relationship between reproductive factors and PFD. The results suggested a causal relationship between some reproductive factors, such as AFB and AFS, and PFD, but there were significant differences between FGPand SUI. Therefore, future studies should explore the underlying mechanisms and develop preventive measures for reproductive factors to reduce the disease burden of PFD.

Association of age at first sexual intercourse and lifetime number of sexual partners with cardiovascular diseases: a bi-directional Mendelian randomization study.

Limited studies have explored the association between sexual factors [age at first sexual intercourse (AFS) and lifetime number of sexual partners (LNSP)] and cardiovascular diseases (CVDs), leaving the causality inconclusive. We performed a bi-directional Mendelian randomization (MR) study to investigate the causality between sexual factors and CVDs, including coronary artery disease, myocardial infarction, atrial fibrillation (AF), heart failure (HF), and ischemic stroke (IS). Single-nucleotide polymorphisms (SNPs) for sexual factors were extracted from the UK Biobank. Statistics for each CVD were derived from two different databases. MR estimates were calculated per outcome database and were combined through meta-analysis. Several complementary sensitivity analyses were also performed. The primary analysis suggested that AFS was causally associated with the risk of CVDs; the odds ratios (ORs) ranged from 0.686 [95% confidence interval (CI), 0.611-0.770] for HF to 0.798 (95% CI, 0.719-0.886) for AF. However, the association between AFS and IS (OR, 0.844; 95% CI, 0.632-1.126) was not consistent in the meta-analysis after excluding SNPs related to confounders. Moreover, non-significant associations were found between LNSP and CVDs. Reverse direction MR analysis showed that CVDs were not associated with sexual factors. Genetic evidence suggested that AFS was causally associated with the risk of CVDs except for IS, whereas non-significant association of LNSP with CVDs was detected. Further investigation into AFS could be warranted in preventing the progression of CVDs.

Effect of women’s fertility and sexual development on epigenetic clock: Mendelian randomization study

Background and objectivesIn observational studies, women’s fertility and sexual development traits may have implications for DNA methylation patterns, and pregnancy-related risk factors can also affect maternal DNA methylation patterns. The aim of our study is to disentangle any potential causal associations between women’s fertility and sexual development traits and epigenetic clocks, as well as to search for probable mediators by using the Mendelian randomization (MR) method.MethodsInstrumental variables for exposures, mediators, and outcomes were adopted from genome-wide association studies data of European ancestry individuals. The potential causal relationship between women’s fertility and sexual development traits and four epigenetic clocks were evaluated by inverse variance weighted method and verified by other two methods. Furthermore, we employed multivariable MR (MVMR) adjusting for hypertension, hyperglycemia, BMI changes, and insomnia. Then, combining the MVMR results and previous research, we performed two-step MR to explore the mediating effects of BMI, AFS, and AFB. Multiple sensitivity analyses were further performed to verify the robustness of our findings.ResultsLeveraging two-sample MR analysis, we observed statistically significant associations between earlier age at first birth (AFB) with a higher HannumAge, PhenoAge and GrimAge acceleration(β = − 0.429, 95% CI [− 0.781 to − 0.077], p = 0.017 for HannumAge; β = − 0.571, 95% CI [− 1.006 to − 0.136], p = 0.010 for PhenoAge, and β = − 1.136, 95% CI [− 1.508 to − 0.765], p = 2.03E−09 for GrimAge respectively) and age at first sexual intercourse (AFS) with a higher HannumAge and GrimAge acceleration(β = − 0.175, 95% CI [− 0.336 to − 0.014], p = 0.033 for HannumAge; β = − 0.210, 95% CI [− 0.350 to − 0.070], p = 0.003 for GrimAge, respectively). Further analyses indicated that BMI, AFB and AFS played mediator roles in the path from women’s fertility and sexual development traits to epigenetic aging.ConclusionsOur study suggested that AFS and AFB are associated with epigenetic aging. These findings may prove valuable in informing the development of prevention strategies and interventions targeted towards women’s fertility and sexual development experiences and their relationship with epigenetic aging-related diseases.

Women's reproductive traits and cerebral small-vessel disease: A two-sample Mendelian randomization study.

Observational studies have suggested that women's reproductive factors (age at menarche (AAM), age at first birth (AFB), age at first sexual intercourse (AFS), age at natural menopause (ANM), and pregnancy loss) may influence the risk of cerebral small-vessel disease (CSVD) although the causality remains unclear. We conducted two-sample univariable Mendelian randomization (UVMR) and multivariable MR (MVMR) to simultaneously investigate the causal relationships between five women's reproductive traits and CSVD clinical [intracerebral hemorrhage (ICH) by location or small-vessel ischemic stroke (SVS)] and subclinical measures [white matter hyperintensities (WMH), fractional anisotropy (FA), and mean diffusivity (MD)], utilizing data from large-scale genome-wide association studies of European ancestry. For both UVMR and MVMR, the inverse-variance-weighted (IVW) estimates were reported as the main results. The MR-Egger, weighted median, generalized summary-data-based MR (GSMR), and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods for UVMR and MVMR-Egger, and the MVMR-robust methods for MVMR were used as sensitivity analyses. Sex-combined instruments for AFS and AFB were used to assess the impact of sex instrumental heterogeneity. Positive control analysis was implemented to measure the efficacy of selected genetic instruments. We found no evidence to support causal associations between genetic liability for women's reproductive factors and the risk of CSVD in UVMR (all P-values > 0.05). Using MVMR, the results were consistent with the findings of UVMR after accounting for body mass index and educational attainment (all P-values > 0.05). Sensitivity analyses also provided consistent results. The putative positive causality was observed between AAM, ANM, and ovarian cancer, ensuring the efficacy of selected genetic instruments. Our findings do not convincingly support a causal effect of women's reproductive factors on CSVD. Future studies are warranted to investigate specific estrogen-related physiological changes in women, which may inform current researchers on the causal mechanisms involved in cerebral small-vessel disease progression.

Women's reproductive traits and major depressive disorder: A two-sample Mendelian randomization study

BackgroundEvidence suggested strong associations between women's reproductive factors and major depressive disorder (MDD), but their causalities are unclear. MethodsUsing female-specific SNPs as genetic instruments obtained from large-scale genome-wide association studies for women's reproductive traits, we designed two-sample univariable and multivariable Mendelian randomization (MR) analysis to evaluate the causal effects of women's reproductive traits on MDD. For both univariable MR (UVMR) and multivariable MR (MVMR), the inverse variance weighting estimates were reported as main results. MR-Egger, weighted median, and generalized summary-data-based MR (GSMR) methods for UVMR, and MVMR-Egger and MVMR-robust methods for MVMR were used as sensitivity analyses. Negative control analyses, MVMR of age at first birth (AFB) and age at first sexual intercourse (AFS) on MDD, and sex-combined genetic variants for AFB and AFS were performed to enhance the robustness of our study. ResultsThere was substantial evidence for associations of genetically predicted later age at menarche (AAM) (odds ratio (OR) = 0.97, 95 % confidence interval (CI) = 0.94–0.99, P = 0.007), AFB (OR = 0.91, 95 % CI = 0.86–0.97, P = 0.002) and AFS (OR = 0.70, 95 % CI = 0.60–0.80, P < 0.001) with lower MDD risk in UVMR. After adjustment of BMI and educational attainment using MVMR, we found consistently significant causal effects of AAM (OR = 0.95, 95 % CI = 0.92–0.99, P = 0.006), AFB (OR = 0.88, 95 % CI = 0.84–0.91, P < 0.001) and AFS (OR = 0.71, 95 % CI = 0.64–0.79, P < 0.001) on MDD. ConclusionsOur results provide compelling evidence that early AAM, AFB, and AFS are risk factors for MDD. Promoting the cognition of reproductive health care for women may reduce the risk of MDD.

Women's reproductive traits and ischemic stroke: a two-sample Mendelian randomization study.

We conducted a Mendelian randomization (MR) study to disentangle causal associations between women's reproductive behaviors and ischemic stroke (IS) and investigate the roles of two modifiable risk factors (body mass index (BMI) and educational attainment (EA)) in these associations. Using summary-level data from large-scale genome-wide association studies, we performed univariable MR to examine whether there is genetic evidence that women's reproductive traits are causally associated with IS and its subtypes. Multivariable MR and MR mediation analysis were used to investigate whether BMI and EA are common mechanisms or mediators for these associations. A set of sensitivity analyses were conducted to test valid MR assumptions. We observed consistent and statistically significant associations across female and sex-combined analyses for earlier age at first birth (AFB) and age at first sexual intercourse (AFS) with a higher risk of IS and large-artery atherosclerotic stroke (LAS) risk in the primary analysis. The odds ratios of IS per 1 SD increase in genetically predicted early AFB and AFS were 0.93 (95% CI, 0.86-0.99; p=0.046) and 0.83 (95% CI, 0.70-0.97, p=0.020), respectively. Further analyses indicated that BMI played a shared role in AFS and IS/LAS while EA played a shared role in AFS/AFB and IS/LAS as well as a mediator in the path from AFS to IS/LAS. These findings may inform prevention strategies and interventions directed toward relative women's reproductive behaviors and IS. Future studies are warranted to explore other factors related to EA which are responsible for these causalities.

Shared genetic basis between reproductive behaviors and anxiety-related disorders.

Reproductive behaviors are associated with risks for psychiatric disorders. Reproductive phenotypes are moderately heritable and have genetic overlaps with risks for psychiatric disorders. However, the genetic and causal relationships between anxiety-related disorders or specific anxiety disorders and reproductive phenotypes remain unknown. We utilized large-scale genome-wide association study (GWAS) results (n = 9537-542,901) for five reproductive phenotypes [age at menarche, age at first sexual intercourse (AFS), age at first birth (AFB), number of children ever born (NEB), and age at menopause] and five anxiety-related disorders [panic disorder, anxiety disorders from the ANGST and the UK biobank (UKBB), posttraumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD)]. To assess genetic correlations and causal associations, linkage disequilibrium score regression and Mendelian randomization analyses, respectively, were performed. We found that AFS and AFB were negatively correlated with anxiety disorders ANGST (AFS: rg ± SE = -0.28 ± 0.08, p = 6.00 × 10-4; AFB: -0.45 ± 0.11, p = 3.26 × 10-5), anxiety disorders UKBB (AFS: -0.18 ± 0.03, p = 9.64 × 10-9; AFB; -0.25 ± 0.03, p = 2.90 × 10-13) and PTSD (AFS: -0.42 ± 0.12, p = 4.00 × 10-4; AFB: -0.44 ± 0.12, p = 2.00 × 10-4) and positively correlated with OCD (AFS: 0.25 ± 0.05, p = 2.46 × 10-6; AFB: 0.25 ± 0.05, p = 3.92 × 10-7). Conversely, NEB was negatively correlated with OCD (-0.28 ± 0.08, p = 6.00 × 10-4). We revealed bidirectional effects between earlier AFS and AFB and anxiety disorders (odds ratios: ORearlier AFS→Anxiety = 1.64, p = 2.27 × 10-8; ORearlier AFB→Anxiety = 1.15, p = 2.28 × 10-3; ORAnxiety→earlier AFS = 1.02, p = 6.62 × 10-8; ORAnxiety→earlier AFB = 1.08, p = 1.60 × 10-4). In contrast, we observed unidirectional effects of later AFS and AFB on OCD (ORlater AFS→OCD = 2.18, p = 2.16 × 10-6; ORlater AFB→OCD = 1.22, p = 0.016). We suggest that those who have earlier sexual debut and childbirth are prone to risk for anxiety disorders and vice versa, while those who have later sexual debut and childbirth are genetically prone to risk for OCD. Our findings further support revising the diagnostic criteria (DSM-5) such that OCD is independent from anxiety disorders.

How Can Unintended Pregnancies Be Prevented among Adolescents Who Engaged in Sexual Intercourse at Earlier Ages? The Role of Female Education and Partner Age Difference.

Several studies have identified explicative factors for adolescents’ sexual risk behaviors and related outcomes such as unintended pregnancy; however, less is known about the mechanisms through which such factors act. Our study explored the role of female education and partner age difference as explicative mechanisms of the association between age at first sexual intercourse (AFSI) and unintended pregnancy while controlling for the role of other contextual factors (i.e., socioeconomic status, ethnicity, religious beliefs, and place of residence) and sexual-related mechanisms (i.e., number of sexual partners) that are known to be associated with adolescent pregnancy. The sample consisted of 613 sexually experienced female adolescents who did not intend to become pregnant: 349 were pregnant for the first time, and 264 had never been pregnant. Mediation and moderation analyses were performed. An earlier AFSI was associated with unintended pregnancy 1–6 years after first sexual intercourse by increasing the adolescents’ likelihood of having less education and being involved with partners older than themselves. There was no significant direct effect of AFSI on pregnancy occurrence after controlling for the mediators. Our findings bring to light nonsexual mechanisms that must be considered in public health interventions aimed at preventing unintended pregnancies among adolescents who engaged in sexual intercourse at early ages. Specific implications are discussed.

The genetic relationship between female reproductive traits and six psychiatric disorders

Female reproductive behaviours have important implications for evolutionary fitness and health of offspring. Here we used the second release of UK Biobank data (N = 220,685) to evaluate the association between five female reproductive traits and polygenic risk scores (PRS) projected from genome-wide association study summary statistics of six psychiatric disorders (N = 429,178). We found that the PRS of attention-deficit/hyperactivity disorder (ADHD) were strongly associated with age at first birth (AFB) (genetic correlation of −0.68 ± 0.03), age at first sexual intercourse (AFS) (−0.56 ± 0.03), number of live births (NLB) (0.36 ± 0.04) and age at menopause (−0.27 ± 0.04). There were also robustly significant associations between the PRS of eating disorder (ED) and AFB (0.35 ± 0.06), ED and AFS (0.19 ± 0.06), major depressive disorder (MDD) and AFB (−0.27 ± 0.07), MDD and AFS (−0.27 ± 0.03) and schizophrenia and AFS (−0.10 ± 0.03). These associations were mostly explained by pleiotropic effects and there was little evidence of causal relationships. Our findings can potentially help improve reproductive health in women, hence better child outcomes. Our findings also lend partial support to the evolutionary hypothesis that causal mutations underlying psychiatric disorders have positive effects on reproductive success.

Predictive factors for persistent and recurrent cervical dysplasia after loop electrosurgical excision procedure in postmenopausal women

The aim of this study was to prospectively evaluate the outcomes of conservative treatment for pathological proven CIN2/3 (cervical intraepithelial neoplasia) in postmenopausal women and the risk factors potentially involved in the persistence/recurrence of cervical dysplasia. A prospective cohort study was performed over an 18-months period on 132 post-climax women with CIN2/3 treated by loop electrosurgical excision procedure (LEEP) attending follow-up visits. We assessed the relationship between age, parity, AFSI (age at first sexual intercourse), smoking status, use of oral contraceptives, high-risk human papillomavirus (HR-HPV) status, surgical margins, glandular involvement and risk of persistent/recurrent disease. Unadjusted and adjusted analyses were performed. Residual/recurrent disease was proved by colposcopically guided biopsy in 25 patients (18.9%). On a multivariate logistic regression analysis, age>50 years (OR 4.85 95%CI 1.09-21.53, p<0.0001), positive surgical margins (OR 4.26, 95% CI 1.64-11.04, p<0.001) and HR - HPV persistence (OR 5.73, 95% CI 1.93-16.97, p<0.001) were statistically predictive for persistent/recurrent lesions. The most important predictive factors for persistent/recurrent disease in postmenopause women treated conservatively for CIN2/3 are advanced age, positive surgical margins and HR-HPV post treatment persistence; the combined evaluation of these three factors allows placing patients with LEEP into different categories at risk, thus requiring special attention with a rigorous follow -up protocol and preventing a primarily radical therapeutic approach in this particular age - group.

‚See and treat’ strategy for HSIL: correlation between colposcopy and histopathology

We sought to determine the correlation between the colposcopic impression (by means of RCI- Reid Colposcopic Index) and histopathology in patients who have undergone LEEP (‚see and treat’ strategy) for cytological high-grade dysplasia. This was a prospective study carried out in ”Prof. Dr. Panait Sârbu” Hospital in Bucharest over a 10-month period. A total of 112 women diagnosed with HSIL on PAP exam underwent LEEP without prior colposcopically directed biopsy. We assessed the relationship between the histologic diagnosis and the colposcopic aspect (RCI), age, parity, AFSI (age at first sexual intercourse) and AFP (age at first pregnancy) AFSI latency. Among 112 women treated, 102 (91.07%) had histologically proven high-grade dysplasia (≥CIN2) and 2 (1.78%) of them had microinvasive squamous cell carcinoma. 80 patients (78.43%) of the 102 had high-grade colposcopic impression; of the 30 patients with normal/ low-grade colposcopy, 22 (73.3%) had high-grade lesions on final histologic exam. The correlation between RCI and histology was fair (κ=0,205; 95% CI, 0.08-0.32, p=0.001). There was no statistically significant connection between age, AFSI, parity, AFP-AFSI latency and RCI and histologic result. The correlation between RCI and histologic findings is fair , especially for CIN3 lesions; the high percentage (91.07%) of histologically proven high-grade dysplasia on LEEP specimens make ‚see and treat’ strategy an attractive option in the management of HSIL results on PAP smears.

Preventing Adolescent Pregnancy: Biological, Social, Cultural, and Political Influences on Age at First Sexual Intercourse

Age at first sexual intercourse (AFSI) is the initial factor related to adolescents' sexual life that may increase the risk of adolescent pregnancy. We explored the biological, social, cultural, and political predictors of AFSI addressing several gaps that prevent us from generalizing the results of past research to adolescent pregnancy prevention. We also explored the moderating effects of cultural variables on the links between social and political predictors and AFSI. Our sample consisted of 889 Portuguese female adolescents aged 12-19. Earlier age at menarche, non-intact family structure, maternal history of adolescent pregnancy, lower maternal emotional warmth, absence of religious involvement, and living in Portugal's mainland and in a legal context penalizing abortion predicted earlier AFSI. School attendance predicted earlier AFSI among adolescents of European ethnic origin; adolescents of non-European ethnic origin presented the opposite, but non-significant, pattern. These findings suggest that, in addition to isolated characteristics, factors from different ecological contexts should be considered when planning interventions designed to foster healthy and informed transitions to sexual initiation and prevent the related risks of unwanted outcomes. We discuss implications for future research and practice.

Developmental assets and age of first sexual intercourse among adolescent African American males in Mobile, Alabama

Background and Aims: Younger age at first sexual intercourse is associated with a variety of adverse health outcomes. We aimed to gain a clearer understanding of a wide range of individual, family and social factors that may influence sexual behavior of children and adolescents. Specifically, we examined the relationships of developmental assets with age of first sexual intercourse among a large sample (n = 1061) of adolescent African American males living in low-income neighborhoods in Mobile, Alabama. Methods: Using the Developmental Asset Model as a theoretical guide, we selected variables from adolescent survey data and conducted logistic regression analysis to determine predictors of early age of first sexual intercourse. Results: Nearly one half (49%) of the male survey participants reported that they first had sexual intercourse at the age of 12 or younger. The total number of assets was the strongest predictor of later age (13 years old or later) of first sexual intercourse (OR 1.49, 95% CI = 1.09, 2.04), followed by decision-making skills (OR 1.40, 95% CI = 1.04, 1.86), and positive view of the future (OR 1.36, 95% CI = 1.02, 1.74). Conclusion: There are several developmental assets related to the age of first sexual intercourse. This study found support for the Developmental Asset Model as a framework for promoting sexual and overall adolescent health. Recommendations for asset-building among this population are discussed.

Time since first sexual intercourse and the risk of cervical cancer

Young age at first sexual intercourse (AFI) is an important risk factor for cervical cancer, but no simple statistical model of its influence has been established. We investigated the relationship between risk of cervical carcinoma and time since first intercourse using data on monogamous women (5,074 cases and 16,137 controls) from the International Collaboration of Epidemiological Studies of Cervical Cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from pooled data on 20 studies using conditional logistic regression. The OR for invasive cervical carcinoma is approximately proportional to the square of time since first intercourse (exponent 1.95, 95% CI: 1.76-2.15) up to age 45. First cervical infection with human papillomavirus (HPV) often occurs soon after first sexual intercourse, so early AFI is a reasonable proxy for early age at first exposure to HPV. In addition, age-specific incidence rates of cervical cancer in unscreened populations remain fairly constant above age 45. Cervical cancer thus resembles other cancers caused by strong early-stage carcinogens, with incidence rates proportional to a power of time since first exposure and also resembles cancers of the breast and other hormone-dependent epithelia, where a similar flattening of age-specific incidence rates is seen at the time menopausal changes start. Taken together, these observations suggest that HPV vaccination may prevent the majority of cervical cancers by delaying HPV infection without necessarily providing lifetime protection against HPV.