Sex-specific differences in risk factors, comorbidities, diagnostic challenges, optimal management, and prognostic outcomes of heart failure with preserved ejection fraction: A comprehensive literature review.

Due to hormonal variations, heart failure with preserved ejection fraction (HFpEF) remains prevalent in women and affects almost half of the heart failure (HF) patients. Given the yearly death rate of 10-30% and the unavailability of medications targeting HFpEF, the need arises for a better understanding of the fundamental mechanisms of this syndrome. This comprehensive review explores sex-specific differences in traditional risk factors; female-specific factors that may impact HFpEF development and response to therapy, including variations in hormone levels that may occur pre- and post-menopausal or during pregnancy; and disparities in comorbidities, clinical presentation, and diagnostic challenges. Lastly, the review addresses prognostic outcomes, noting that women with HFpEF have a poor quality of life but a higher survival rate. It also discusses novel biomarkers and precision medicine, emphasizing their potential to improve early detection and personalized treatment.

Cardiovascular risk assessment in women: which women are suited for menopausal hormone therapy?

Individual risk assessment for atherosclerotic cardiovascular disease is important for safe menopausal hormone prescription. Besides the traditional risk factors, female-specific risk variables related to pregnancy and gynecologic conditions importantly contribute to a more tailored risk assessment in women at middle age. Of these, prior pre-eclampsia/HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome and early spontaneous menopause (<40 years) seem to be the strongest adverse risk variables. Concomitant inflammatory disorders should also be taken into account. Adding a coronary artery calcium score with a computed tomography scan to risk assessment has a high predictive value for future cardiovascular events. This should be considered to discriminate between low-risk and high-risk women when uncertainty exists. In women at intermediate risk, menopausal hormone therapy can be easily combined with preventive medication if cardiovascular risk factors are present. In women at higher risk who have severe disabling vasomotor symptoms, a lower dosage of hormone therapy can be considered in good collaboration between the gynecologist and the cardiologist/vascular specialist.

Identifying the genes involved in the egg-carrying ovigerous hair development of the female blue crab Callinectes sapidus: transcriptomic and genomic expression analyses.

BACKGROUND: Crustacean female sex hormone (CFSH) controls gradually developing adult female-specific morphological features essential for mating and brood care. Specifically, ovigerous hairs are developed during the prepuberty molt cycle of the blue crab Callinectes sapidus that are essential for carrying the eggs until they finish development. Reduced CFSH transcripts by CFSH-dsRNA injections result in fewer and shorter ovigerous hairs than the control. This study aimed to identify the specific genes responsible for ovigerous hair formation using transcriptomic, genomic and expression analyses of the ovigerous setae at three stages: prepuberty at early (OE) and late premolt (OL), and adult (AO) stages. RESULTS: The de novo Trinity assembly on filtered sequence reads produced 96,684 Trinity genes and 124,128 transcripts with an N50 of 1,615 bp. About 27.3% of the assembled Trinity genes are annotated to the public protein sequence databases (i.e., NR, Swiss-Prot, COG, KEGG, and GO databases). The OE vs. OL, OL vs. AO, and OE vs. AO comparisons resulted in 6,547, 7,793, and 7,481 differentially expressed genes, respectively, at a log2-fold difference. Specifically, the genes involved in the Wnt signaling and cell cycle pathways are positively associated with ovigerous hair development. Moreover, the transcripts of ten cuticle protein genes containing chitin-binding domains are most significantly changed by transcriptomic analysis and RT-qPCR assays, which shows a molt-stage specific, down-up-down mode across the OE-OL-AO stages. Furthermore, the expression of the cuticle genes with the chitin-binding domain, Rebers and Riddiford domain (RR)-1 appears at early premolt, followed by RR-2 at late premolt stage. Mapping these 10 cuticle protein sequences to the C. sapidus genome reveals that two scaffolds with a 549.5Kb region and 35 with a 1.19 Mb region harbor 21 RR1 and 20 RR2 cuticle protein genes, respectively. With these findings, a putative mode of CFSH action in decapod crustaceans is proposed. CONCLUSIONS: The present study describes a first step in understanding the mechanism underlying ovigerous hair formation in C. sapidus at the molecular level. Overall, demonstrating the first transcriptome analysis of crustacean ovigerous setae, our results may facilitate future studies into the decapod female reproduction belonging to the suborder Pleocyemata.

The effect of the menstrual cycle on the circulating microRNA pool in human plasma: a pilot study.

STUDY QUESTION: Do ovarian hormone changes influence the levels of cell-free or circulating microRNA (cf-miRNA) across the menstrual cycle? SUMMARY ANSWER: This exploratory study suggests that fluctuations in hormonal levels throughout the menstrual cycle may alter cf-miRNAs levels. WHAT IS KNOWN ALREADY: cf-miRNA levels vary with numerous pathological and physiological conditions in both males and females and are regulated by exogenous and endogenous factors, including hormones. STUDY DESIGN, SIZE, DURATION: A prospective, monocentric study was conducted between March and November 2021. Since this was a pilot study, the sample size was based on feasibility as well as previous similar human studies conducted in different tissues. A total of 20 participants were recruited for the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: We conducted an exploratory study where blood samples were collected from 16 eumenorrheic females in the early follicular phase, the ovulation phase and the mid-luteal phase of the menstrual cycle. The levels of oestrogen, progesterone, LH and FSH were measured in serum by electrochemiluminescence. The levels of 174 plasma-enriched miRNAs were profiled using a PCR-based panel, including stringent internal and external controls to account for the potential differences in RNA extraction and reverse-transcription stemming from low-RNA input samples. MAIN RESULTS AND THE ROLE OF CHANCE: This exploratory study suggests that cf-miRNAs may play an active role in the regulation of the female cycle by mediating the expression of genes during fluctuating hormonal changes. Linear mixed-models, adjusted for the relevant variables, showed associations between phases of the menstrual cycle, ovarian hormones and plasma cf-miRNA levels. Validated gene targets of the cf-miRNAs varying with the menstrual cycle were enriched within female reproductive tissues and are primarily involved in cell proliferation and apoptosis. LARGE SCALE DATA: All relevant data are available from the Mendeley database: LEGER, Bertrand (2022), 'MiRNA and menstrual cycle', Mendeley Data, V1, doi: 10.17632/2br3zp79m3.1. LIMITATIONS, REASONS FOR CAUTION: Our study was conducted on a small participant cohort. However, it was tightly controlled for endogenous and exogenous confounders, which is critical to ensure robust and reproducible cf-miRNA research. Both adjusted and non-adjusted P-values are presented throughout the article. WIDER IMPLICATIONS OF THE FINDINGS: Measures of ovarian hormones should be rigorously included in future studies assessing cf-miRNA levels in females and used as time-varying confounders. Our results reinforce the importance of accounting for female-specific biological processes in physiology research by implementing practical or statistical mitigation strategies during data collection and analysis. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Clinique romande de réadaptation, Sion, Switzerland. S.L. was supported by an Australian Research Council (ARC) Future Fellowship (FT10100278). D.H. was supported by an Executive Dean's Postdoctoral Research Fellowship from Deakin University. The authors declare no competing interests.

Horizons of nanotechnology applications in female specific cancers.

Female-specific cancers are the most common cancers in women worldwide. Early detection methods remain unavailable for most of these cancers, signifying that most of them are diagnosed at later stages. Furthermore, current treatment options for most female-specific cancers are surgery, radiation and chemotherapy. Although important milestones in molecularly targeted approaches have been achieved lately, current therapeutic strategies for female-specific cancers remain limited, ineffective and plagued by the emergence of chemoresistance, which aggravates prognosis. Recently, the application of nanotechnology to the medical field has allowed the development of novel nano-based approaches for the management and treatment of cancers, including female-specific cancers. These approaches promise to improve patient survival rates by reducing side effects, enabling selective delivery of drugs to tumor tissues and enhancing the uptake of therapeutic compounds, thus increasing anti-tumor activity. In this review, we focus on the application of nano-based technologies to the design of novel and innovative diagnostic and therapeutic strategies in the context of female-specific cancers, highlighting their potential uses and limitations.

Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists.

Women undergo important changes in sex hormones throughout their lifetime that can impact cardiovascular disease risk. Whereas the traditional cardiovascular risk factors dominate in older age, there are several female-specific risk factors and inflammatory risk variables that influence a woman's risk at younger and middle age. Hypertensive pregnancy disorders and gestational diabetes are associated with a higher risk in younger women. Menopause transition has an additional adverse effect to ageing that may demand specific attention to ensure optimal cardiovascular risk profile and quality of life. In this position paper, we provide an update of gynaecological and obstetric conditions that interact with cardiovascular risk in women. Practice points for clinical use are given according to the latest standards from various related disciplines (Figure 1).

Female-specific genomic regions and molecular sex identification of the clearhead icefish (Protosalanx hyalocranius).

BACKGROUND: The clearhead icefish, Protosalanx hyalocranius, is an economically important fishery species in China. Since 1980s, P. hyalocranius was widely introduced into lakes and reservoirs of northern China for aquaculture. However, the lack of a rapid and cost-effective sex identification method based on sex specific genetic markers has hindered study on sex determination mechanisms and breeding applications. RESULTS: Female-specific genomic regions were discovered by comparing whole genome re-sequencing data of both males and females. Two female-specific genomic regions larger than 50 bp were identified, and one (598 bp) contained a putative FOXI gene, which was paralogous to another FOXI gene with sex-associated SNPs. The two FOXI sequences displayed significant length difference with nine deletions of total length of 230 bp. This deletion-type structural variation could be easily and efficiently detected by traditional PCR and agarose gel electrophoresis with one 569 bp band for males and two bands (569 and 339 bp) for females, which were validated in 50 females and 40 males with known phenotypic sexes. CONCLUSIONS: The results provided structural genomic evidence for the ZZ/ZW sex determination system in P. hyalocranius discovered in our previous study with association analysis of SNPs. Moreover, the female-specific markers and rapid and cost-effective PCR-based genetic sex identification method should have applications in further studies of sex determination mechanism for this species.

Functional characterization of the cis-regulatory region for the vitellogenin gene in Plutella xylostella.

The vitellogenin gene promoter (VgP) is an essential cis-regulatory element that plays a significant role in transcription of the vitellogenin (Vg) gene, leading to the production of yolk protein in insects, including lepidopterans. However, the function of VgP is still not clear in Plutella xylostella. Here, we cloned a 5.1 kb DNA fragment of the cis-regulatory region adjacent to the 5' end of the Vg gene of P. xylostella (PxVg). We identified two promoter sites in that 5' upstream sequence of PxVg and performed in vitro analysis of two promoter sequences (PxVgP1, 4.9 kb, and PxVgP2, 2.9 kb) in the embryonic cell line of P. xylostella. PxVgP2 exhibited higher enhanced green fluorescent protein (EGFP) expression, so PxVgP2 was used for in vivo analysis. Strong EGFP fluorescence was observed in adult females and the fat body of females, with low expression in embryos. Our results suggest that PxVgP is an important stage-, tissue- and sex-specific endogenous cis-regulatory element in P. xylostella.

Genome-wide RAD sequencing to identify a sex-specific marker in Chinese giant salamander Andrias davidianus.

BACKGROUND: Chinese giant salamander Andrias davidianus is an endangered species. The success of artificial breeding provides a useful way to protect this species. However, the method to identify the sex and mechanism of sex determination were unclear which hinder the improvement of the artificial breeding. Detection of a sex specific marker provides an effective approach to identify genetic sex and investigate the sex determination mechanism. RESULTS: We used restriction-site-associated DNA (RAD) sequencing to isolate a sex-specific genetic marker in A. davidianus to expand knowledge of the sex determination mechanism. Four male and four female specimens were subjected to RAD sequencing, which generated 934,072,989 reads containing approximately 134.4 Gb of sequences. The first round of comparison of the assembled sequence against the opposite sex raw reads revealed 19,097 female and 17,994 male unmatched sequences. Subsequently, 19,097 female sequences were subjected to a BLAST search against male genomic data, which revealed 308 sequences unmapped to the male genome. One hundred of these were randomly selected and validated by PCR in five male and five female specimens, and four putative sex-specific sequences were produced. Further validation was performed by PCR in another 24 females and 24 males, and all female individuals exhibited the expected specific bands, while the males did not. To apply the sex-specific marker, three specimens reversed from genetic female to physiological male were found in a group exposed to elevated temperature, and 13 individuals reversed from genetic male to physiological female were obtained in a 17ß-estradiol exposed group. CONCLUSION: This is the first report of a sex-specific marker in A. davidianus and may have potential for elucidation of its sex determination mechanism and, hence, its conservation.

Identification of critical sex-biased genes in Andrias davidianus by de novo transcriptome.

The Chinese giant salamander Andrias davidianus is a protected amphibian with high nutritional and economic value. Understanding its sex determination mechanism is important for improving culture techniques and sex control in breeding. However, little information on the characterization of critical genes involved in sex is available. Herein, sequencing of ovary and test produced 40,783,222 and 46,128,902 raw reads, respectively, which were jointly assembled into 80,497 unigenes. Of these, 36,609 unigenes were annotated, of which 8907 were female-biased and 10,385 were male-biased. Several sex-related pathways were observed, including the Wnt signaling pathway. After elevated temperature and estrogen exposure, neomale and neofemale specimens were identified by a female-specific marker for the first time. RT-qPCR analysis showed the expression profile of ten selected sex-biased genes to be exhibited consistently in male and neomale and in female and neofemale, with the exception of the Amh and TfIIIa genes. Results suggested that these genes may play important roles in A. davidianus sex determination and gonad development. This provides a basis for further investigation of the molecular mechanisms of sex determination in amphibians.

Female-specific SNP markers provide insights into a WZ/ZZ sex determination system for mud crabs Scylla paramamosain, S. tranquebarica and S. serrata with a rapid method for genetic sex identification.

BACKGROUND: Mud crabs, Scylla spp., are commercially important large-size marine crustaceans in the Indo-West Pacific region. As females have the higher growth rate and economic value, the production of all female stocks is extremely essential in aquaculture. However, the sex determination mechanism is still unclear. Development of sex-specific genetic markers based on next-generation sequencing proved to be an effective tool for discovering sex determination system in various animals. RESULTS: Restriction-site associated DNA sequencing (RAD-seq) was employed to isolate sex-specific SNP markers for S. paramamosain. A total of 335.6 million raw reads were obtained from 20 individuals, of which 204.7 million were from 10 females and 130.9 million from 10 males. After sequence assembly and female-male comparison, 20 SNP markers were identified to be sex-specific. Furthermore, ten SNPs in a short sequence (285 bp) were confirmed heterozygous in females and homozygous in males in a large population by PCR amplification and sequencing. Subsequently, a female-specific primer was successfully designed according to the female-specific nucleotide which could amplify an expected band from females but not from males. Thus, a rapid and effective method for molecular sexing in S. paramamosain was developed, meanwhile, this method could successfully identify the sex of S. tranquebarica and S. serrata. Finally, nine and four female-specific SNP markers were detected in S. tranquebarica and S. serrata, respectively. CONCLUSIONS: Sex-specific SNP markers were firstly identified in crab species and showed female heterogamety and male homogamety, which provided strong genetic evidence for a WZ/ZZ sex determination system in mud crabs S. paramamosain, S. tranquebarica and S. serrata. These findings will lay a solid foundation for the study of sex determination mechanism, sex chromosome evolution, and the development of mono-sex population in crustaceans.

Long-term incidence of female-specific cancer after bariatric surgery or usual care in the Swedish Obese Subjects Study.

OBJECTIVE: To examine the long-term effects of bariatric surgery on female-specific cancer in women with obesity. METHODS: The prospective, matched Swedish Obese Subjects (SOS) study was designed to examine outcomes after bariatric surgery. This study includes 1420 women from the SOS cohort that underwent bariatric surgery and 1447 contemporaneously matched controls who received conventional obesity treatment. Age was 37-60years and BMI was ≥38kg/m2. Information on cancer events was obtained from the Swedish National Cancer Registry. Median follow-up time was 18.1years (interquartile range 14.8-20.9years, maximum 26years). This study is registered with ClinicalTrials.gov, NCT01479452. RESULTS: Bariatric surgery was associated with reduced risk of overall cancer (hazard ratio=0.71; 95% CI 0.59-0.85; p<0.001). About half of the observed cancers were female-specific, and the incidence of these were lower in the surgery group compared with the control group (hazard ratio=0.68; 95% CI 0.52-0·88; p=0.004). The surgical treatment benefit with respect to female-specific cancer was significantly associated with baseline serum insulin (interaction p value=0.022), with greater relative treatment benefit in patients with medium or high insulin levels. Separate analyses of different types of female-specific cancers showed that bariatric surgery was associated with reduced risk of endometrial cancer (hazard ratio=0.56: 95% CI 0.35-0.89; p=0.014). CONCLUSIONS: In this long-term study, bariatric surgery was associated with reduced risk of female-specific cancer, especially in women with hyperinsulinemia at baseline. FUNDING: This project was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R01DK105948 (the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health), the Swedish Research Council K2013-99X-22279-01, K2013-54X-11285-19, Sahlgrenska University Hospital ALF research grant and Swedish Diabetes Foundation.

Tetracycline-suppressible female lethality and sterility in the Mexican fruit fly, Anastrepha ludens.

The sterile insect technique (SIT) involves the mass release of sterile males to suppress insect pest populations. SIT has been improved for larval pests by the development of strains for female-specific tetracycline-suppressible (Tet-off) embryonic lethal systems for male-only populations. Here we describe the extension of this approach to the Mexican fruit fly, Anastrepha ludens, using a Tet-off driver construct with the Tet-transactivator (tTA) under embryo-specific Anastrepha suspensa serendipity α (As-sry-α) promoter regulation. In the absence of tetracycline, tTA acts upon a Tet-response element linked to the pro-apoptotic cell death gene lethal effector, head involuation defective (hid), from A. ludens (Alhid(Ala2) ) that contains a sex-specific intron splicing cassette, resulting in female-specific expression of the lethal effector. Parental adults double-homozygous for the driver/effector vectors were expected to yield male-only progeny when reared on Tet-free diet, but a complete lack of oviposited eggs resulted for each of the three strains tested. Ovary dissection revealed nonvitellogenic oocytes in all strains that was reversible by feeding females tetracycline for 5 days after eclosion, resulting in male-only adults in one strain. Presumably the sry-α promoter exhibits prezygotic maternal expression as well as zygotic embryonic expression in A. ludens, resulting in a Tet-off sterility effect in addition to female-specific lethality.

Cardiovascular risk assessment in women - an update.

Cardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women. Although it is a disease of aging, vascular disease initiates much earlier in life. Thus, there is a need to be aware of the potential to prevent the development of the disease from an early age and continue this surveillance throughout life. The menopausal period and early menopause present an ideal opportunity to assess cardiovascular risk and plan accordingly. Generally in this period, women will be seen by primary health-care professionals and non-cardiovascular specialists. This review addresses female-specific risk factors that may contribute to the potential development of cardiovascular disease. It is important for all health-care professionals dealing with women in midlife and beyond to be cognisant of these risk factors and to initiate female-specific preventative measures or to refer to a cardiovascular specialist.

Functional characterization of the vitellogenin promoter in the silkworm, Bombyx mori.

Genetic transformation and genome editing technologies have been successfully established in the lepidopteran insect model, the domesticated silkworm, Bombyx mori, providing great potential for functional genomics and practical applications. However, the current lack of cis-regulatory elements in B. mori gene manipulation research limits further exploitation in functional gene analysis. In the present study, we characterized a B. mori endogenous promoter, Bmvgp, which is a 798-bp DNA sequence adjacent to the 5'-end of the vitellogenin gene (Bmvg). PiggyBac-based transgenic analysis shows that Bmvgp precisely directs expression of a reporter gene, enhanced green fluorescent protein (EGFP), in a sex-, tissue- and stage-specific manner. In transgenic animals, EGFP expression can be detected in the female fat body from larval-pupal ecdysis to the following pupal and adult stage. Furthermore, in vitro and in vivo experiments revealed that EGFP expression can be activated by 20-hydroxyecdysone, which is consistent with endogenous Bmvg expression. These data indicate that Bmvgp is an effective endogenous cis-regulatory element in B. mori.

Breaking barriers: Exploring female-specific health challenges affecting performance in an elite multisport training environment.

OBJECTIVES: Female-specific issues, such as breast injuries, pelvic floor dysfunctions, saddle sores, and menstrual symptoms, can significantly impact female athletes. This study examined the prevalence, perceived impact on performance, and role of the support staff in addressing and managing these issues in elite athletes based at a multisport training centre. DESIGN: Anonymous online questionnaire. METHODS: A total of 180 female athletes from various sport disciplines at the Dutch Olympic Training Centre were invited to participate in the study. An anonymous, 39-item questionnaire was developed and hosted on Qualtrics collecting data on respondents' characteristics, breast injuries, pelvic floor dysfunctions, saddle sores, menstrual symptoms, contraceptive use, and communication about these issues. RESULTS: A total of 105 valid responses were analysed. The findings revealed that athletes regularly experience breast injuries (15.2 %), urinary incontinence (29.5 %), other pelvic floor problems (21.0 %), saddle sores (65.7 %), and menstrual cycle-related symptoms, with negative performance effects. Communication with support staff remained limited, with only 23.8 % of athletes discussing any of these issues, often due to concerns about understanding, shame, or a lack of opportunity for easy communication. CONCLUSIONS: The findings underscore the crucial role of creating a supportive environment, promoting early intervention, and utilising multisport centres to comprehensively address these concerns, emphasising the need for open communication, education, and support to enhance female athletes' performance and well-being.

A Female-Specific Treatment Group for ADHD-Description of the Programme and Qualitative Analysis of First Experiences.

Background: The diagnostics and treatment of attention-deficit/hyperactivity disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period, and (peri)menopause are neglected, even though they impact ADHD symptoms and associated mood disorders. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. Methods: We describe the group programme and underlying rationale, offering a qualitative analysis of the participants' evaluation. Results: The seven bi-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47 years) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable, and the structure suited them well. Completing the premenstrual calendar augmented the awareness and recognition of individual cyclical symptoms. A lifespan approach increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care. Conclusions: Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

Women's health issues in solid organ transplantation: Breast and gynecologic cancers in the post-transplant population.

The success of solid organ transplant has steadily improved which has led to a unique set of post-transplant issues. The rates of de novo cancer in the solid organ transplant recipient population are higher than those in the general population. There is growing evidence that breast and gynecologic cancers may have a higher mortality rate in post-transplant patients. Cervical and vulvovaginal cancers specifically have a significantly higher mortality in this population. Despite this increased mortality risk, there is currently no consistent standard in screening and identifying these cancers in post-transplant patients. Breast, ovarian and endometrial cancers do not appear to have significantly increased incidence. However, the data on these cancers remains limited. Further studies are needed to determine if more aggressive screening strategies would be of benefit for these cancers. Here we review the cancer incidence, mortality risk and current screening methods associated with breast and gynecologic cancers in the post-solid organ transplant population.

The mortalities of female-specific cancers in China and other countries with distinct socioeconomic statuses: A longitudinal study.

INTRODUCTION: Female-specific cancers seriously affect physical and psychological health of women worldwide. OBJECTIVES: We aimed to elucidate trends in the age-standardized mortality rates (ASMRs) of breast cancer, cervical cancer, uterine cancer, and ovarian cancer in female populations with different socioeconomic statuses in China and in countries with different Human Development Index (HDI). METHODS: A longitudinal study was performed using the data of cancer death in China and other 39 countries. The mortality rates were standardized with the Segi's world population. Trends in the mortalities were exhibited by estimated annual percentage change (EAPC). Pearson correlation was used to assess the association between EAPC and HDI. RESULTS: In mainland China, female breast cancer, cervical cancer, uterine cancer, and ovarian cancer accounted for 6.60 %, 4.21 %, 2.50 %, and 2.02 % of cancer death (n = 1,314,040) in women with 1,220,251,032 person-years, respectively. The ASMRs of cervical cancer (EAPC = 3.87 %, P < 0.001) and ovarian cancer (EAPC = 1.81 %, P < 0.001) increased, that of female breast cancer unchanged, whereas that of uterine cancer was extremely higher and rapidly decreased (EAPC =  - 7.65 %, P < 0.001), during 2004-2019. The ASMRs of female breast and ovarian cancers were higher in urban and developed regions than in rural and undeveloped regions, in contrast to cervical and uterine cancers. The ASMRs of female breast and ovarian cancers were lower in China than in other countries, in contrast to uterine cancer. The ASMR of cervical cancer decreased, that of uterine cancer increased, in other countries during 2004-2017. EAPCs for the ASMRs of breast and ovarian cancers were inversely correlated to HDI. CONCLUSION: The ASMRs of cervical and ovarian cancers increased, in contrast to uterine cancer, in China during socioeconomic transition. Trends in the ASMRs of breast and ovarian cancers were inversely associated with HDI. These data help control female-specific cancers.

Assessment of Cardiovascular Risk in Women: Progress so Far and Progress to Come.

Cardiovascular disease is the leading cause of death in women worldwide. Nonetheless, there exist several uncertainties in the prediction, diagnosis, and treatment of cardiovascular disease in women. A cornerstone in the prediction of cardiovascular disease is the implementation of risk scores. A variety of pregnancy- and reproductive-factors have been associated with lower or higher risk of cardiovascular disease. Consequently, the question has been raised, whether these female-specific factors also provide added value to cardiovascular risk prediction. In this review, we provide an overview of the existing literature on sex differences in the association of established cardiovascular risk factors with cardiovascular disease and the relation between female-specific factors and cardiovascular risk. Furthermore, we systematically reviewed the literature for studies that assessed the added value of female-specific factors beyond already established cardiovascular risk factors. Adding female-specific factors to models containing established cardiovascular risk factors has led to little or no significant improvement in the prediction of cardiovascular events. However, analyses primarily relied on data from women aged ≥40 years. Future investigations are needed to quantify whether pregnancy-related factors improve cardiovascular risk prediction in young women in order to support adequate treatment of risk factors and enhance prevention of cardiovascular disease in women.