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Background: Tamoxifen has been successfully administered as adjunctive therapy for breast cancer. However, the effect of tamoxifen as an estrogen agonist and antagonist can cause pathological changes in the uterus. The agonist effect may stimulate endometrial proliferation leading to endometrial polyps, hyperplasia, and, rarely, endometrial cancer. Objective: We present the case of tamoxifen-treated breast cancer case to better understand one of the most serious consequences, endometrial cancer. Case presentation: A 37-year-old woman came to our centre with complaints of abnormal vaginal bleeding. She has diagnosed with grade I infiltrative ductal carcinoma in 2018, with primary complaints of right breast mass and axillary lymphadenopathy. During this period, adjuvant chemotherapy was given tamoxifen 20 mg once daily. There were no complaints or relapses at a six-month follow-up over three years. In the fourth year, the patient complained of vaginal bleeding. A vaginal biopsy was performed, and the results showed low-grade endometrioid-type endometrial carcinoma. Total hysterectomy and bilateral salpingo-oophorectomy were performed with the resultant mass of up to half of the myometrial lining with metastatic negative parallax lymph nodes. Conclusion: Following tamoxifen therapy, endometrial cancer is more likely to occur in patients. Patients who experience irregular vaginal hemorrhage should have hysteroscopy or uterine ultrasound performed, and if the cause is unknown, a biopsy should be performed.

Research should equitably reflect responses in men and women. Including women in research, however, necessitates an understanding of the ovarian hormones and menstrual phase variations in both cellular and systems physiology. This review outlines recent advances in the multiplicity of ovarian hormone molecular signaling that elucidates the mechanisms for menstrual phase variability in exercise metabolism. The prominent endogenous estrogen, 17-β-estradiol (E2), molecular structure is bioactive in stabilizing plasma membranes and quenching free radicals and both E2 and progesterone (P4) promote the expression of antioxidant enzymes attenuating exercise-induced muscle damage in the late follicular (LF) and mid-luteal (ML) phases. E2 and P4 bind nuclear hormone receptors and membrane-bound receptors to regulate gene expression directly or indirectly, which importantly includes cross-regulated expression of their own receptors. Activation of membrane-bound receptors also regulates kinases causing rapid cellular responses. Careful analysis of these signaling pathways explains menstrual phase-specific differences. Namely, E2-promoted plasma glucose uptake during exercise, via GLUT4 expression and kinases, is nullified by E2-dominant suppression of gluconeogenic gene expression in LF and ML phases, ameliorated by carbohydrate ingestion. E2 signaling maximizes fat oxidation capacity in LF and ML phases, pending low-moderate exercise intensities, restricted nutrient availability, and high E2:P4 ratios. P4 increases protein catabolism during the luteal phase by indeterminate mechanisms. Satellite cell function supported by E2-targeted gene expression is countered by P4, explaining greater muscle strengthening from follicular phase-based training. In totality, this integrative review provides causative effects, supported by meta-analyses for quantitative actuality, highlighting research opportunities and evidence-based relevance for female athletes.

There are significant differences between men and women in the efficacy and tolerability of antipsychotic drugs. Here, we provide a comprehensive overview of what is currently known about the pharmacokinetics and pharmacodynamics of antipsychotics in women with schizophrenia spectrum disorders (SSDs) and translate these insights into considerations for clinical practice. Slower drug absorption, metabolism and excretion in women all lead to higher plasma levels, which increase the risk for side-effects. Moreover, women reach higher dopamine receptor occupancy compared to men at similar serum levels, since oestrogens increase dopamine sensitivity. As current treatment guidelines are based on studies predominantly conducted in men, women are likely to be overmedicated by default. The risk of overmedicating generally increases when sex hormone levels are high (e.g. during ovulation and gestation), whereas higher doses may be required during low-hormonal phases (e.g. during menstruation and menopause). For premenopausal women, with the exceptions of quetiapine and lurasidone, doses of antipsychotics should be lower with largest adjustments required for olanzapine. Clinicians should be wary of side-effects that are particularly harmful in women, such as hyperprolactinaemia which can cause oestrogen deficiency and metabolic symptoms that may cause cardiovascular diseases. Given the protective effects of oestrogens on the course of SSD, oestrogen replacement therapy should be considered for postmenopausal patients, who are more vulnerable to side-effects and yet require higher dosages of most antipsychotics to reach similar efficacy. In conclusion, there is a need for tailored, female-specific prescription guidelines, which take into account adjustments required across different phases of life.

Introduction: An increased incidence of endometrial cancer has been noted, especially in premenopausal women in countries with rapid socioeconomic transition. In one of the largest patient cohorts of women ≤50 years, with manually validated register data, we aim to examine the pattern of disease of endometrial cancer and to evaluate the prognosis according to tumor and patient characteristics, focusing on body mass index. Material and Methods: This is a nationwide population-based study on women ≤50 years with endometrial cancer, 2010–2021, using data from Swedish registries complemented by the reviewing of medical records. Overall survival and disease-free survival were calculated by the Kaplan–Meier method and the log-rank test. Multivariable regression analyses were performed. Results: Of the total endometrial cancer cohort, 797 (5%) patients were ≤50 years of age (the PremEnCa cohort) with 0.9% under 40 years of age. Women ≤50 years of age had a higher prevalence of stage IA and endometrioid histology than older women. Among women ≤50 years of age, 46% met the criteria for obesity. No associations between socioeconomic factors and stage at diagnosis were found. Notably, women with lower Body Mass Index <20, had a higher proportion of non-endometrioid histology and higher stage of disease at the time of diagnosis. Median follow-up time was 4.2 (IOR 1.9–5.4) years. The recurrence rate was 6.1% in the PremEnCa cohort during the follow-up period, and the 5-year overall survival was 94.6% (95% CI: 92.6–96.0) for endometrioid and 68.5% (95% CI: 51.1–80.8) for non-endometrioid endometrial cancer. Only 36 of the 74 deaths were caused by endometrial cancer. In adjusted analyses for disease-free survival, non-endometrioid histology and International Federation of Gynecology and Obstetrics (FIGO) stage were associated with worse prognosis. Conclusions: Endometrial cancer in premenopausal women is very rare and is associated with an excellent prognosis. Histology and FIGO stage were the strongest prognostic factors. Half of the deaths were due to other causes, which emphasizes the importance of focusing on general health aspects in this young endometrial cancer population.

Summary Pregnancy and lactation associated osteoporosis is a rare and often severe osteoporosis presentation. Little information is available about etiology, clinical characteristics, risk factors and predictors of severity. Using an anonymized questionnaire, we defined clinical characteristics and potential risk factors for disease severity in PLO including primiparity, heparin exposure and celiac disease. Purpose Pregnancy and lactation associated osteoporosis (PLO) is a rare form of early-onset osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. Little information is available about etiology, clinical characteristics, risk factors and predictors of disease severity. Methods PLO patients were recruited to complete an anonymized online questionnaire. Disease severity was defined as total number of fractures during or after the first pregnancy associated with a fracture(s). Analyses related disease severity to potential predictors including diseases/conditions or medication exposures. Results 177 completed surveys were received between 5/29/2018 and 1/12/2022. Average age at initial PLO fracture event was 32 ± 5 years. The majority were primiparous with singleton pregnancy and 79% fractured during lactation. Subjects reported 4.7 ± 2.7 total PLO fractures, with 48% reporting ≥ 5 fractures. Vertebral fractures, reported by 164/177 responders (93%), were the most common fracture type. Conditions and medications most commonly reported included vitamin D deficiency, amenorrhea unrelated to pregnancy, nephrolithiasis, celiac disease (CD), oral steroid use, heparin products during pregnancy and progestin only contraceptive after pregnancy. CD and heparins exposure during pregnancy were significantly related to disease severity. Conclusion This is the largest study characterizing clinical features of PLO to date. The large number of participants and broad range of clinical and fracture characteristics queried has yielded novel information on the characteristics of PLO and potential risk factors for its severity, including primiparity, exposure to heparin and CD. These findings provide important preliminary data that can help target future mechanistic investigations.

Abstract Hyperandrogenism in women, such as polycystic ovary syndrome, ovarian hyperthecosis, congenital adrenal hyperplasia, and androgen-secreting tumors, are all associated with increased prevalence of cardiovascular risk factors that include type 2 diabetes, hypertension, dyslipidemia, and metabolic syndrome. However, it is not clear whether this also implies enhanced risk of cardiovascular disease and mortality. Furthermore, the involvement of obesity and menopausal status for cardiometabolic risk in these women has not been elucidated. Based on the most recent systematic reviews and meta-analyses, this review summarizes the latest scientific evidence. To conclude, hyperandrogenism in premenopausal women is associated with enhanced prevalence of cardiovascular risk factors, as well as increased risk of cardiovascular disease and mortality, independently of body mass index. In contrast, elevated cardiovascular risk factors and increased risk of myocardial infarction and stroke in hyperandrogenic postmenopausal women are dependent on obesity. Furthermore, the overall risk of cardiovascular disease and coronary artery disease in hyperandrogenic postmenopausal women is similar to controls. The reason for a reduced cardiometabolic risk after menopause in hyperandrogenic women compared to nonhyperandrogenic women is not clear. It can be speculated that the difference in endocrine balance and metabolic status between women with and without hyperandrogenism might decrease after menopause because hyperandrogenism usually improves with age, whereas menopausal transition itself is associated with androgen dominance and abdominal obesity. Although we have gained increased knowledge about cardiometabolic risks in women with hyperandrogenism, it must be acknowledged that the quality of data is overall low. More research is needed, especially longer and larger follow-up studies in women with hyperandrogenism of different etiologies and phenotypes.

Background Saudi women are at risk of vitamin D deficiency because they are fully covered by traditional clothing and because of their indoor lifestyle. The latest national study reported that vitamin D deficiency (serum 25(OH)D < 50 nmol/L) affects 72% of young Saudi women. Because little information is available regarding knowledge on vitamin D, attitudes toward sun exposure, and the vitamin D status of premenopausal women in Jeddah, more research is necessary in order to develop effective intervention programs. The purpose of this study is to explore how the relationship between knowledge of vitamin D and attitudes about sun exposure affect the serum 25(OH)D levels in premenopausal Saudi women. Methods This cross-sectional study included 257 women aged 20–50 years attending the primary care clinic in Jeddah, Saudi Arabia. Participants completed questionnaires about socio-demographics, dietary vitamin D intake, attitudes toward sun exposure, and were tested on their knowledge of vitamin D. Serum 25(OH)D was evaluated using chemiluminescent microparticle immunoassay. Results Although 99% of participants had heard of vitamin D and 91% knew that sunlight exposure is a primary source of vitamin D, they also expressed the feeling of having insufficient knowledge regarding vitamin D sources. Furthermore, the majority of participants had negative attitudes toward sun exposure. High fish consumption was associated with a higher level of knowledge regarding vitamin D. The binary logistic regression indicated that low levels of knowledge about vitamin D were associated with low education levels (odds ratio = 0.397, 95% CI = [0.206, 0.765], p  = 0.019) and with being married (odds ratio = 0.522, 95% CI = [0.281, 0.971], p  = 0.04). In addition, spending time outside in the sun was significantly associated with increased serum 25(OH)D levels ( p  = 0.006), and the wearing of colored abaya was significantly associated with increased serum 25(OH)D levels ( p  = 0.008). Conclusion Suboptimal vitamin D status and insufficient knowledge of vitamin D intake sources are common in premenopausal women in Jeddah. Based on this data, health professionals could provide medical intervention to the most vulnerable female patients, as well as offer clear guidelines and information to the general public.

Background Female sexual dysfunction affects 41% of reproductive-age women worldwide, making it a highly prevalent medical issue. Predictors of female sexual dysfunction are multifaceted and vary from country to country. A synthesis of potential risk factors and protective factors may aid healthcare practitioners in identifying populations at risk, in addition to revealing modifiable factors to prevent sexual dysfunction among reproductive-age women. Methods Observational studies which assessed the prevalence and predictors of female sexual dysfunction in reproductive-age women were systematically sought in relevant databases (2000–2014). Significant predictors were extracted from each included publication. A qualitative analysis of predictors was performed with a focus on types of sexual regimes and level of human development. Results One hundred thirty-five studies from 41 countries were included in the systematic review. The types of predictors varied according to the location of the study, the type of sexual regime and the level of gender inequality in that country/region. Consistently significant risk factors of female sexual dysfunction were: poor physical health, poor mental health, stress, abortion, genitourinary problems, female genital mutilation, relationship dissatisfaction, sexual abuse, and being religious. Consistently significant protective factors included: older age at marriage, exercising, daily affection, intimate communication, having a positive body image, and sex education. Some factors however had an unclear effect: age, education, employment, parity, being in a relationship, frequency of sexual intercourse, race, alcohol consumption, smoking and masturbation. Conclusions The sexual and reproductive lives of women are highly impacted by female sexual dysfunction, and a number of biological, psychological and social factors play a role in the prevalence of sexual dysfunction. Healthcare professionals who work with women should be aware of the many risk factors for reproductive-age women. Future prevention strategies should aim to address modifiable factors, e.g. physical activity and access to sex education; international efforts in empowering women should continue.

Breast cancer is one of the most common malignant tumors in women. More than half of breast cancer patients are not menopausal at the time of diagnosis. The occurrence and development of premenopausal breast cancer are affected by many factors. Intestinal flora, especially SCFA-producing bacteria, participates in the development of various tumors, and there is a lack of in-depth research in premenopausal breast cancer patients. We used 16S rRNA gene sequencing, targeted metabolomics, and cell culture methods to analyze the changes in the intestinal flora and metabolites of premenopausal breast cancer patients. In addition, we treated breast cancer cells with significantly altered propionate and butyrate in vitro to examine their effects on cell activity. This study followed STROBE guidelines. We found that compared with healthy premenopausal women, the composition and symbiosis of intestinal flora in patients with premenopausal breast cancer changed significantly. The abundance of short-chain fatty acid (SCFA)–producing bacteria was significantly reduced, and the key SCFA-producing enzymes were also significantly reduced. Pediococcus and Desulfovibrio could distinguish premenopausal breast cancer patients from normal premenopausal women. The related propionate and butyrate had a certain ability to inhibit breast cancer cell viability in vitro. As SCFA-producing bacteria, Pediococcus and Desulfovibrio showed potential reference value for the diagnosis of premenopausal breast cancer. The ability of propionate and butyrate to inhibit breast cancer cell lines in vitro suggests that the relevant SCFA receptor may be a new target for the treatment of premenopausal breast cancer.

While existing literature suggests an association between polycystic ovarian syndrome (PCOS) and endometrial cancer, the sparsity and inconsistency of current evidence indicates a lack of clarity regarding the exact strength of this association. It also remains uncertain whether the degree of risk of disease is affected by confounding factors, such as age and body mass index (BMI). The present meta-analysis is aimed to quantify the risk of endometrial cancer in female subjects with PCOS compared to those without PCOS. PubMed, MEDLINE, EMBASE, Scopus and Cochrane were searched from inception to October 31, 2022, to identify peer-reviewed case-control, cohort and cross-sectional studies that assessed the association between endometrial cancer and PCOS and contained original data. Two researchers independently extracted data and performed quality assessment using the Newcastle-Ottawa criteria. Pooled odds ratios (ORs) were calculated using the random-effect model and inverse variance. The degree of heterogeneity was assessed using I2 statistics. A total of 10 relevant studies were identified and included in the meta-analysis (comprising 12,248 female patients with PCOS and 54,120 controls). Females with PCOS had a significantly increased odds of developing endometrial cancer as compared to those without PCOS [OR, 4.07; 95% confidence interval (CI), 2.13-7.78; P<0.0001]. When postmenopausal subjects (age, >54 years) were excluded from the meta-analysis, the odds increased further (OR, 5.14; 95% CI, 3.22-8.21; P<0.00001). Patients with PCOS are up to 5 times more likely to develop endometrial cancer compared to those without PCOS. Larger, prospective studies that are well-controlled for confounding factors, such as BMI, are required.