Oral Hormone Replacement Therapy Research Articles

P126 Use of oral contraceptives in females with rheumatoid arthritis is not associated with an increased risk of venous thromboembolism: United Kingdom-population based study

Abstract Background/Aims While the use of oral contraceptives in females with immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) is acknowledged as a risk factor for venous thromboembolism (VTE), the interaction between oral contraceptive use and RA is poorly understood. In a large population-based study, we aimed to estimate RA-attributable VTE risk in females using oestrogen contraceptives and/or on hormone replacement therapy (HRT). Methods Females registered with a general practice from January 1999 to December 2018 were identified from the Royal College of General Practitioners Research (RCGP) and Surveillance Centre (RSC) database. Female RA patients and VTE outcome (composite of pulmonary embolism and deep vein thrombosis) were determined using previously-validated algorithms. Female unaffected controls (UCs) were matched 4:1 with RA patients by current age (per year), calendar time, and years since practice registration using nearest neighbour matching, with replacement. Absolute VTE rates over 20 years were compared in RA patients versus matched UCs, overall and in two different subgroups defined by the use of oestrogen contraceptives or HRT. Relative VTE risk over the same period was estimated using Cox proportional hazards models adjusted for sociodemographic and clinical features and established VTE risk factors (BMI [body-mass index], smoking status, alcohol use, evidence of reduced mobility, thrombophilia, fracture of the lower limb and family history of VTE). Results A total of 82,082 female adults were included in this study, of whom 16,634 were RA patients and 65,448 were UCs. Average study follow-up was 8.3 years (standard deviation [SD]=6.2 years). Female RA patients (mean age 58.3, SD 16.5; mean BMI 27.0, SD 5.9) were similar to matched UCs in their clinical characteristics. Compared to UCs, females with RA were less likely to receive oral contraceptives (RA n = 545 [3.3%], UCs n = 2,542 [3.9], p < 0.001) but more likely to receive HRT (RA n = 752 [4.5%], UCs n = 2,460 [3.8], p < 0.001). Unadjusted VTE events rates were consistently higher in females with RA compared to UCs (430.2 per 100,000 person-years [py], 95% confidence interval [CI]: 396.1, 466.3; UC: 260.5 per 100,000 py, 95%CI: 247.1, 274.4) and in those receiving and not receiving oral contraceptives and HRT. Overall, relative risk of VTE was 52% higher in females with RA compared UCs (adjusted hazard ratio [aHR]= 1.52, 95%CI: 1.36, 1.71, p < 0.001). Compared to UCs, relative risk increases were not statistically significant for females with RA receiving oral contraceptives (aHR 1.43; 95%CI 0.60, 3.63, p = 0.46) and HRT (aHR 2.32; 95%CI 0.92, 5.85, p = 0.08). Conclusion UK data suggest that all women with RA are at a similarly increased risk of VTE irrespective of the use of oestrogen contraceptives or HRT, although larger studies are needed to confirm this finding. It is therefore advisable to conduct routine VTE risk factor assessments for all females with RA. Disclosure J. Galloway: Honoraria; JG has received honoraria from Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UC. V. Basey: Corporate appointments; Pfizer employee. A. Barkaway: Corporate appointments; Pfizer employee. S. de Lusignan: Grants/research support; SdeL has received funding through his universities from Eli Lilly, GSK, Astra Zeneca, MSD, Sanofi, Seqirus, Takeda and Moderna. Other; Director of the RCGP RSC. M.H. Buch: Consultancies; M.H.B. has provided expert advice and received/paid to employer consultant fees from AbbVie, Eli Lilly, EMD serono, Gilead, Pfizer and Sanofi. Grants/research support; .H.B. has received research grants paid to her employer from Gilead Ltd, Pfizer Ltd, Roche and UCB.

Hormones and thrombosis: the dark side of the moon.

The main drawback of oral contraceptives (OC) and hormone replacement therapy (HRT) is an increased risk of venous and, to a lesser extent, arterial thrombosis. This narrative, case-based review describes the effect of available estrogens and progestogens on the hemostatic system and their potential impact on the risk of thrombosis. Clinical cases are used to illustrate different options for prescribing OC and HRT in the real-word. The aim is to offer discussion topics that could be helpful to guide the choice of different hormonal treatments over a woman's lifetime and in the presence of risk factors. We describe physio-pathological changes occurring during the administration of hormonal therapies. Furthermore, we analyze the risk of venous and arterial thrombosis associated with different products, routes of administration and additional risk factors. New hormonal preparations, such as estradiol combined with dienogest, as well as non-oral hormonal therapies, are suggested to decrease thrombotic risk significantly. The availability of many products and different routes of administration allow most women to safely use contraception, as well as HRT. We encourage careful counselling instead of inflexible or fearful behavior, as expanding options and choices will allow women to make the best decisions for their health.

Abstract B125: Reproductive factors and thyroid cancer risk: The multiethnic cohort study

Abstract Background : Thyroid cancer is the most common endocrine cancer worldwide, with the incidence in women being three times that of men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and hormone replacement therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods : A prospective cohort study of women of diverse racial and ethnic groups in the Multiethnic Cohort Study (n=118,344) was used. Included were 373 papillary thyroid cancer cases, linked to SEER cancer incidence and statewide death certificate files in Hawaii and California. Exposures investigated include age at menarche, parity, menopausal status and type, birth control use, and outcomes of first pregnancy. Cox proportional hazards models of papillary thyroid cancer were used to obtain relative risk (RR) and 95% confidence intervals (CI) to examine the associations with reproductive/hormonal factors. Results : We observed a statistically significant increased risk of papillary thyroid cancer for hysterectomy, oophorectomy, surgical menopause, and not having a child by age 20. The adjusted estimates for oophorectomy RR 1.66 (95% CI: 1.31, 2.11) and hysterectomy RR 1.82 (95% CI: 1.42, 2.34). Menopause due to surgery was associated with a 55% increase in risk (RR 1.55, 95% CI: 1.22, 1.97) and nulliparity vs ≤ 20 years of age at first livebirth was related to a 51% increased risk (adjusted RR 1.51, 95% CI: 1.07, 2.15). Adjustment factors included age and race/ethnicity and menopausal status, menopausal type, and oral contraception where appropriate. Former use of estrogen menopausal hormone therapy was associated with a 35% increased risk (adjusted RR: 1.35, 95% CI: 1.02, 1.79). No significant heterogeneity was seen in these associations by race/ethnicity (p het >0.48). Conclusion : The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in our multiethnic population. Our analysis finds having a hysterectomy or oophorectomy and the use of MHT are associated with an increased risk of papillary thyroid cancer, and having a child at a younger age is associated with a reduction in thyroid cancer risk. Citation Format: Janine V. Abe, Song-Yi Park, Christopher A. Haiman, Loïc Le Marchand, Brenda Y. Hernandez, Lynne R. Wilkens. Reproductive factors and thyroid cancer risk: The multiethnic cohort study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B125.

Exogenous hormone therapy and non-melanoma skin cancer (keratinocyte carcinoma) risk in women: a systematic review and meta-analysis

Previous studies reported inconsistent results regarding the association between keratinocyte carcinoma (KC) and exogenous hormone therapy. This study aimed to investigate the association between the use of exogenous sex hormones and the risk of KC among women. The databases of PubMed, Ovid Medline, Cochrane, and Web of Science were searched until May 2023. A total of 5293 patients with KC and 106,424 controls were included for analysis. The meta-analysis indicated that oral contraceptives (OC) and hormonal replacement therapy (HRT) use were associated with an increased risk of squamous cell carcinoma (SCC) (OR/RR = 1.25, 95% CI 1.10 to 1.43, I2 = 41.6%, p = 0.080). Subgroup analysis showed that OC use increased the risk of SCC (OR/RR = 1.37, 95% CI 1.15 to 1.63), whereas no significant association was shown between HRT use and risk of SCC (OR/RR = 1.13, 95% CI 0.93 to 1.37). Additionally, OC and HRT use were linked to an increased risk of basal cell carcinoma (BCC) (OR/RR = 1.16, 95% CI 1.09 to 1.25, I2 = 30.1%, p = 0.188). Further subgroup analysis suggested both OC and HRT use were associated with an increased risk of BCC (OC: OR/RR = 1.13, 95% CI 1.01 to 1.25; HRT: OR/RR = 1.19, 95% CI 1.09 to 1.30). In conclusion, our findings support the hypothesis that the risk of KC among women may be affected by the use of exogenous hormones.

Association between female-specific reproductive factors and leukocyte telomere length.

What are the associations between female-specific reproductive factors and leukocyte telomere length (LTL)? Early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of oral contraceptives (OCs) and hormone replacement therapy (HRT) were associated with shorter LTL. Reproductive factors have been associated with age-related diseases, but their associations with cellular aging, as indicated by LTL, are unclear. This population-based study included 224 965 women aged 40-69 years from the UK Biobank between 2006 and 2010. Women aged 40-69 were included. Female-specific reproductive factors, including age at menarche, age at natural menopause, reproductive lifespan, number of live births, age at first live birth, history of stillbirth, history of miscarriage, and use of OCs and HRT were self-reported. LTL was measured using a validated polymerase chain reaction method. Multiple linear regression and restricted cubic spline models were applied to explore the association between each reproductive factor and LTL. After adjustment for potential confounders, early menarche (<12 years; percent change, per unit change in LTL Z score: -1.29%, 95% CI: -2.32%, -0.26%), early menopause (<45 years; percent change: -7.18%, 95% CI: -8.87%, -5.45%), short reproductive lifespan (<30 years; percent change: -6.10%, 95% CI: -8.14%, -4.01%), multiparity (percent change: -3.38%, 95% CI: -4.38%, -2.37%), early age at first live birth (<20 years; percent change: -4.46%, 95% CI: -6.00%, -2.90%), and use of OCs (percent change: -1.10%, 95% CI: -2.18%, -0.02%) and HRT (percent change: -3.72%, 95% CI: -4.63%, -2.80%) were all significantly associated with shorter LTL. However, no significant association was found for history of miscarriage and stillbirth. We observed nonlinear relationships of age at menarche, age at natural menopause, reproductive lifespan, and age at first live birth with LTL (Pnonlinear < 0.05). Considering that the participants were predominantly of European ethnicity, the findings may not be generalizable to women of other ethnic backgrounds. Our findings suggest that early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of OCs and HRT were associated with shorter LTL, which has been linked to various chronic diseases. The accelerated shortening of telomeres may potentially contribute to the development of chronic diseases related to reproductive factors. This study was funded by the National Natural Science Foundation of China (82003479, 82073660), Hubei Provincial Natural Science Foundation of China (2023AFB663), and the China Postdoctoral Science Foundation (2019M662646, 2020T130220). The authors have no competing interests to disclose. N/A.

Simultaneous voltammetric determination of female hormones using different carbonaceous electrodes in a non-aqueous environment

An undemanding electroanalytical method for the simultaneous determination of estrogens, namely 17β-estradiol (E2) or synthetic 17α-ethinylestradiol (EE2), with dienogest (DGN) has been developed for the analysis of oral contraceptives and hormone replacement therapy products. This approach is based on their anodic oxidation at carbonaceous electrode materials in pure acetonitrile using square-wave voltammetry. The electrochemical behaviour of these hormones at a glassy carbon electrode (GCE) in a nonaqueous environment was investigated using cyclic voltammetry to verify their reaction mechanisms. As part of the optimisation, commercially available GCE and boron-doped diamond electrodes were found to provide similar analytical performance, characterized by a wide linear range (>100 μmolL−1) with limits of quantification approximately 1.6 μmolL−1 for each hormone. A satisfactory precision (relative standard deviation < 4%) has been achieved for a mixture of 10 μmolL−1 E2 and DGN. Finally, the developed electroanalytical method was applied to the determination of female hormones present in pharmaceutical preparations and the results acquired were comparable to those obtained by a reference method employing reversed-phase high-performance liquid chromatography coupled to a diode array detector, which confirmed the practical use of this method in routine pharmaceutical analysis.

Recommendations for risk minimization when using Janus kinase inhibitors for the treatment of chronic inflammatory skin diseases.

In accordance with article 20 of Regulation (EC) No 726/2004, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has re-evaluated the safety of Janus kinase inhibitors for the treatment of inflammatory diseases and formulated safety information deviating from the previous indications in the respective summary of product characteristics of the products concerned. These refer to the consideration of a possibly increased risk of venous thromboembolic or severe cardiovascular events, an increased infection rate and an increase in the prevalence of skin cancer across drugs and indications. Therefore, in patients with independent risk factors (age 65 years and older, smokers or former smokers, patients with oral contraception or hormone replacement therapy and other risk factors), it is recommended to use Janus kinase inhibitors therapeutically only if there are no suitable treatment alternatives. To facilitate a pragmatic and thorough detection of high-risk patients in everyday clinical practice, an interdisciplinary checklist was developed that is suitable as a working tool from the perspective of the dermatologist.

Risk Factors for Voice Disorders among Fado Singers: A Cross-Sectional Study

Fado is an urban Portuguese musical style rooted in popular culture. Previously found data suggests that Fado singers may have an increased risk of developing voice disorders. (1) Aim: To determine the risk factors for the development of voice disorders among Fado singers. (2) Methods: A cross-sectional study was conducted through the administration of a questionnaire containing questions related to voice disorders in singers. The relationship between personal and social data, musical background, performance demands and habits, vocal health and wellbeing, and strategies to overcome voice problems are reported. Beyond a comprehensive characterization, odds ratios (ORs) and their 95% confidence intervals (CIs) for the association with voice disorders were calculated through univariate and multivariate logistic regression analyses. (3) Results: The significant risk factors for voice disorders were as follows in decreasing order: nose-related disorders; decongestants or antihistamines; oral contraceptives or hormone replacement therapy; previous smoking habits; and vocal fatigue after performances. (4) Conclusion: These activities significantly increased the risk of developing voice disorders. The evidence from this study and the relative low prevalence of self-reported voice disorders suggest that these singers may develop a kind of protective combination of factors beyond the scope of this research.

Pharmacological interventions and hormonal therapies for depressive symptoms in peri- and post-menopausal women: a network meta-analysis of randomized controlled trials

Although significant portion of women experience depressive symptoms during or after menopausal transition, there has been considerable controversy over the benefits of hormone replacement therapy (HRT) and antidepressants due to insufficient evidence supporting the superiority of either treatment. This frequentist model based network meta-analysis (NMA) included randomized controlled trials (RCTs) of menopausal depression symptoms management in menopausal women. Seventy RCTs involving a total of 18,530 women (mean age 62.5) were analyzed. The results demonstrated that fluoxetine plus oral HRT [standardized mean difference (SMD)=-1.59, 95% confidence interval (95%CIs)=-2.69 to -0.50] were associated with the largest improvement in depressive symptoms than placebos in overall menopausal women. Similar findings were also noted in the subgroup of participants with a definite diagnosis of depression, while no pharmacological or hormone replacement therapy was better than placebo in the subgroup of post-menopausal women (amenorrhea > 1 year) or in patients without diagnosis of depression. This NMA presented evidence that fluoxetine plus HRT may be beneficial to menopausal women with a definite diagnosis of depression but not to those without depression or post-menopausal women.Trial registration: PROSPERO (CRD42020167459).

Association between hormone replacement therapy and sex hormones in postmenopausal women: a systematic review and meta-analysis.

The aim of the study was to systematically review and meta-analyze the available data on changes in the hormonal profile of postmenopausal women treated with hormone replacement therapy (HRT). Full-text articles published up to April 30, 2021, were searched through PUBMED, EMBASE, the Cochrane library and Web of Science (WOS) databases and were screened strictly according to inclusion criteria. Randomized clinical trials and case control studies were enrolled. Studies not reporting steroid serum levels or not providing a control group were excluded from the analysis. Studies enrolling women with genetic defects or severe chronic systemic diseases were excluded. Data are expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Random effect models were used for the meta-analysis. HRT administration increases estradiol (E2) and reduces follicle stimulating hormone (FSH) serum levels compared with pre-treatment. Their changes are evident when oral and transdermal HRT are administered, while vaginal HRT not. No significant effect on E2 and FSH was found between 6 and 12 months, as well as between 12 and 24 months. No significant effect on E2 and FSH was shown between different regimes. No difference was observed between different HRT regarding their effect on lipid profiles, breast pain and vaginal bleeding, but oral estrogen combined synthetic progestin caused a reduction in sex hormone-binding globulin (SHGB). The review suggested oral and transdermal HRT could lead to a rise in E2 serum levels and a decrease in FSH. The types and doses of HRT did not seem to modify the E2 and FSH level. Also, oral estrogen combined synthetic progestin could cause a reduction in SHGB. This might be crucial when choosing the best possible treatment for each patient individually taking into consideration if potential benefits outweigh the risks.

A case-control study of 10,757 individuals to assess potentially modifiable risk factors, including stress, for breast cancer among Chinese patients in Hong Kong.

e22522 Background: Breast cancer is the most common cancer in women worldwide. Both intrinsic and environmental factors contribute to the disparities in breast cancer incidence across different regions. In Hong Kong, the incidence has been increasing in the past decades. With over 4700 women diagnosed in 2019, breast cancer is responsible for 27% of all female cancers in Hong Kong. Apart from intrinsic non-modifiable risk factors, some risk factors are modifiable and may reduce cancer risk. Methods: We conducted a case-control study that involved breast cancer patients from the Hong Kong Breast Cancer Registry with matched healthy controls from the community between 2014 and 2017. A standardized written questionnaire was used through face-to-face interviews of all study participants. The questionnaire collected information on participants’ demographics, general health, smoking history and other lifestyle factors including physical activity, self-assessed dietary habits (balanced, vegetarian, meat and dairy-rich diets), self-perceived stress levels (measured with a 4-point Likert scale, and high stress level was defined as having over 50% of the participant’s time with stress being scored 3 or above out of a Likert scale of 4), body mass index, family history, menstrual and reproductive history, and history on the use of oral contraceptives and hormone replacement therapy. Multiple logistic regression was fitted to compare all risk factors. Results: A total of 5,186 breast cancer patients and 5,571 controls were recruited. Modifiable risk factors that were shown to be associated with an increased risk of breast cancer included self-perceived high stress level (adjusted odd ratios [aOR] = 3.44; 95% CI = 3.13-3.78), meat-rich diet (aOR = 1.77; 95% CI = 1.54-2.04), dairy-rich diet (aOR = 3.33; 95% CI = 2.01-5.52), overweight/obese status (aOR = 1.21; 95% CI = 1.10-1.32), delayed child-bearing (aOR = 2.23; 95% CI = 1.79-2.79), nulliparity (aOR = 1.21; 95% CI = 1.08-1.35) and ever use of oral contraceptives (aOR = 1.34; 95% CI = 1.22-1.47), while exercise (OR = 0.62; 95% CI = 0.56-0.68) and breast-feeding (aOR = 0.76; 95% CI = 0.69-0.83) were associated with reduced risk. Conclusions: In Hong Kong, high stress level, meat- and dairy- rich diet, overweight/obese, reproductive history and use of oral contraceptives were identified to be modifiable risk factors for breast cancer. Adjusting these factors through lifestyle modification may curb the increasing trend of breast cancer incidences in the coming decades.

Perioperative Management of Estrogen Therapy As It Relates to Venous Thromboembolism in Aesthetic Surgery Patients

Abstract Goals/Purpose Perioperative management of estradiol therapy varies considerably among plastic surgeons performing aesthetic surgeries. This study aimed to review available literature regarding perioperative management of estradiol therapy in aesthetic surgery patients, and the risk it poses for developing VTE in the perioperative period. Methods/Technique A literature search was performed using online databases to identify studies evaluating VTE in aesthetic surgery patients taking oral contraceptives (OCPs) or hormone replacement therapy (HRT), and transgender patients on feminizing hormone therapy undergoing non-flap feminization surgery (facial feminization and breast augmentation procedures). Reported outcomes were extracted from these studies and summarized. Results/Complications A systematic review of the literature yielded 225 studies. Five of these studies met inclusion criteria. One study that was excluded, referenced an article that met inclusion criteria, which was ultimately included in our review for a total of six studies, representing 3,635 patients. Conclusion Data regarding perioperative management of estrogen therapy is limited in the literature, and standardized guidelines for aesthetic surgery patients have not been elucidated. This has led to inconsistencies in how estrogen is managed for elective, cosmetic procedures. Further research is needed to determine standardized practice guidelines. In the meantime, case-by-case evaluation of surgical appropriateness should continue. Surgeons should also consider risk-mitigating strategies, such as a focus on patient education, more intentional patient questioning regarding estrogen-containing product use, a preoperative coagulability workup for patients with a personal or family history indicative of possible coagulopathy, and specialty-wide efforts to create an aesthetics database and evidence-based guidelines.

Endocrine-disrupting substances: I. Relative risks of PFAS in drinking water.

Concentrations of per and polyfluorinated alkyl substances (PFAS) in drinking water are significantly lower than in vivo levels of the native target hormone. These concentrations are orders of magnitude lower than the hormone in question, particularly when corrected for transactivation. A pregnant woman can excrete about 7,000 μg/day of total estrogens. A low-dose oral contraceptive pill contains 20 μg estradiol. Soy-based baby formula contains phytoestrogens equivalent to a low-dose oral contraceptive pill. A woman on a low-dose oral hormone replacement therapy consumes about 0.5-2 mg/day of one or more estrogens. The levels of endocrine-disrupting substances (EDSs) exposure by oral, respiratory, or dermal routes have the potential to make removing PFAS from drinking water due to its estrogenic activity divert valuable resources. These levels become even less of a threat when their estrogenic potencies are compared with those of the target hormones present as contaminants in water and even more so when compared with levels commonly present in human tissues. The fact that PFAS constitute a tiny fraction compared to exposure to phytoestrogens makes the effort even more insignificant. If PFAS are to be removed from drinking water, it is not due to their estrogenic activity.

Abstract ED2-3: Hormonal exposure and risk in BRCA1/2 carriers

Abstract Women who inherit a pathogenic variant (mutation hereafter) in the BRCA1 or BRCA2 geneface extremely high lifetime risks of developing breast and ovarian (or fallopian tube) cancer. More than two decades since the discovery of these genes, and primary prevention with bilateral mastectomy and salpingo-oophorectomy remain the most effective options to manage cancer risk in this population. Understanding the impact of exogenous hormone use is important for both the clinical management of high-risk women and for furthering our knowledge of the pathogenesis of BRCA-associated disease. In this session, I will review the current epidemiologic data surrounding the role of exogenous (anti)hormone use on BRCA-cancer risk. Specifically, I will discuss the role of tamoxifen in preventing BRCA-associated breast cancer and I will describe whether use of oral contraceptives or hormone replacement therapy (HRT) increase the risk of breast cancer. Where possible, I will present data by gene mutation. Potential associations with the risk of ovarian cancer will also be referred to, given that managing BRCA-cancer risks is a balancing act. Finally, I will review how the epidemiologic information has contributed to the discovery of novel targets for the non-surgical prevention of BRCA1-associated breast cancer and gaps in the literature to be addressed in future research. Citation Format: Joanne Kotsopoulos. Hormonal exposure and risk in BRCA1/2 carriers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED2-3.

Stratifying the risk of ovarian cancer incidence by histologic subtypes in the Korean Epithelial Ovarian Cancer Study (Ko-EVE).

This study aimed to verify the association between ovarian cancer (OC) and reproductive- and lifestyle-related risk factors stratified by the subtype of OC. In this matched case-control study derived from the Korean epithelial ovarian cancer study (Ko-EVE), we calculated the risk of OC subtypes using odds ratios (ORs) and 95% confidence intervals (95% CIs) in a logistic regression model. As a result of matching, 531 cases and 2,124 controls were selected. Smoking had positive association with high-grade serous (HGS) OC (OR=2.69, 95% CI=1.15-6.30), whereas alcohol consumption had positive association with mucinous type (MUC) (OR=3.63, 95% CI=1.39-9.49). Obesity (≥30 kg/m2 ) was associated with clear cell type (CLC) (OR=4.57, 95% CI=1.06-19.77). Spontaneous abortion was negatively associated with CLC (OR=0.34, 95% CI=0.13-0.90), in contrast to HGS (OR=1.43, 95% CI=0.96-2.15). Tubal ligation, hysterectomy, and oophorectomy were associated with decreased risk of HGS (OR=0.14, 95% CI=0.05-0.39; OR=0.23, 95% CI=0.07-0.73; OR=0.28, 95% CI=0.08-0.97, respectively). Early menarche was strongly associated with increased risk of CLC, but not MUC (OR=6.11, 95% CI=1.53-24.42; OR=3.23, 95% CI=0.98-10.86). Further, childbirth (≥2 times) was negatively associated with endometrioid type OC and CLC (OR=0.11, 95% CI=0.04-0.35; OR=0.12, 95% CI=0.02-0.37, respectively). Oral contraceptives and hormone replacement therapy were negatively associated with OC (OR=0.61, 95% CI=0.40-0.93; OR=0.51, 95% CI=0.32-0.80, respectively), and similar negative associations were also observed in HGS (OR=0.69; OR=0.60, respectively). Associations between family history of breast cancer and OC, regular exercise (≥5/week), and artificial abortion and OC were similar across all subtypes (OR=3.92; OR=0.41; OR=0.72, respectively). A heterogeneous association between some risk factors and the incidence of each subtype of epithelial OC was observed, suggesting that the carcinogenic mechanisms of each subtype may be partly different.

Stroke in Women and Unique Risk Factors.

There has been a plethora of studies focused on female-specific risk factors and sex differences in stroke published in the past year. This article summarizes several of those novel studies which provide new knowledge about the field of stroke in women. The Nurses' Health Study II provides new data on the association between laparoscopically proven endometriosis and future stroke, accounting for the mediation effects of hysterectomy and oophorectomy. In a cohort of women from China, the relationship between hysterectomy, oophorectomy, and stroke is further clarified, accounting for the age at which the procedure is performed. The UK Biobank study provides new information on the relationship between oral contraceptive and hormone replacement therapy and stroke, with analytical techniques that focus on the timing of events related to duration of exposure. Finally, 2 new meta-analyses address the question of whether sex differences exist in the presentation of stroke symptoms.

The Endocrine Approach of Melanoma: The Puzzle of Estrogen Receptors Expression

"Melanoma outcome seems different between females and males, with a potential protective role of estrogen (E) through estrogen receptors (ER) expression into the tumor. In the study of ERs, both alfa (ERα) and beta (ERβ) is a well-known endocrine elements in non-melanoma tumors, like mammary and endometrial cancer. Immunohistochemistry (IHC) assessment of melanoma concerning ERs represents a path to explore the tumor profile to provide useful information concerning the prognostic and potential adjuvant treatment. Currently, this is not a routine practice, nor a mandatory step for deciding the medical therapy. Typically, IHCs are based on usual kits for mammary tumors regarding ERs configuration. Prior/concomitant use of oral contraceptives and hormonal replacement therapy is not correlated with a better prognostic in melanoma; neither have they represented a contraindication for survivors of melanoma; a subset of tumors might present a higher ER expression which is potentially targeted by the hormone-based treatment as SERMs (Selective Estrogen Receptors Modulator), for instance, tamoxifen. Experimental studies on melanoma cell lines confirmed the anti-tumor activity of ERβ which might function as a prognostic marker. G-protein-coupled estrogen receptors in melanocytes and keratinocytes might be involved, too. Additional crosstalk of TGF-β (Transforming Growth Factor β), respective IGF1 (Insulin-like Growth Factor), and ERα expression are involved in tumorigenic pathways. Recent preclinical studies showed the potential benefits of diarylpropionitrile, a selective agonist of ERβ; pyrazole derivates 21-23 can block ERs. Murine melanoma models showed the interference of anti-estrogenic medication (like molecule fulvestrant) to enhance immune checkpoint blockade, a modern approach to solid cancers. The proliferation of melanoma might be partially explained by ERs; whether this is generally applicable or there is a subgroup of tumors particularly related to E status is still debatable. The subject of E status in melanoma is far from clear at this point and further studies are necessary concerning this particular issue to implement it as a practical approach in the daily management of a disease that still has a very severe prognostic nowadays "

Does the use of oral contraceptives or hormone replacement therapy offer protection against the formation or rupture of intracranial aneurysms in women?: a systematic review and meta-analysis.

The aim of this study was to carry out a systematic review of the literature with meta-analysis to evaluate the effect of using oral contraceptive and hormone replacement therapy as a protective factor in the formation of intracranial aneurysms and subarachnoid hemorrhage. This is a systematic review of the literature with meta-analysis, using PubMed and Embase as databases and the PRISMA method. Case-control and cohort studies published until December 2022 were included in this review. Four studies were included in this review; three of which were eligible for meta-analysis. Regarding the use of oral contraceptive and the development of subarachnoid hemorrhage, there was a lower risk of aneurysm rupture with an odds ratio 0.65 (confidence interval 0.5-0.85). In the analysis of patients using hormone replacement therapy and developing subarachnoid hemorrhage, there was also a lower risk of aneurysm rupture with an OR 0.54 (CI 0.39-0.74). Only one article analyzed the formation of intracranial aneurysm and the use of hormone replacement therapy and oral contraceptive, and there was a protective effect with the use of these medications. oral contraceptive: OR 2.1 (CI 1.2-3.8) and hormone replacement therapy: OR 3.1 (CI 1.5-6.2). The use of hormone replacement therapy and oral contraceptive has a protective effect in intracranial aneurysm rupture and formation.

Sequestration of steroidal estrogen in aqueous samples using an adsorption mechanism: a systemic scientometric review.

Steroidal estrogens (SEs) remain one of the notable endocrine disrupting chemicals (EDCs) that pose a significant threat to the aquatic environment in this era owing to their interference with the normal metabolic functions of the human body systems. They are currently identified as emerging contaminants of water sources. The sources of SEs are either natural or synthetic active ingredients in oral contraceptive and hormonal replacement therapy drugs and enter the environment primarily from excretes in the form of active free conjugate radicals, resulting in numerous effects on organisms in aquatic habitats and humans. The removal of SEs from water sources is of great importance because of their potential adverse effects on aquatic ecosystems and human health. Adsorption techniques have gained considerable attention as effective methods for the removal of these contaminants. A systemic review and bibliometric analysis of the application of adsorption for sequestration were carried out. Metadata for publications on SE removal utilizing adsorbents were obtained from the Web of Science (WoS) from January 1, 1990, to November 5, 2022 (107 documents) and Scopus databases from January 1, 1949, to November 5, 2022 (77 documents). In total, 137 documents (134 research and 4 review articles) were used to systematically map bibliometric indicators, such as the number of articles, most prolific countries, most productive scholars, and most cited articles, confirming this to be a growing research area. The use of different adsorbents, include activated carbon graphene-based materials, single and multi-walled carbon nanotubes, biochar, zeolite, and nanocomposites. The adsorption mechanism and factors affecting the removal efficiency, such as pH, temperature, initial concentration, contact time and adsorbent properties, were investigated in this review. This review discusses the advantages and limitations of different adsorbents, including their adsorption capacities, regenerative potential, and cost-effectiveness. Recent advances and innovations in adsorption technology, such as functionalized materials and hybrid systems, have also been highlighted. Overall, the bibliographic analysis provides a comprehensive overview of the adsorption technique for the removal of SEs from other sources, serving as a valuable resource for researchers and policymakers involved in the development of efficient and sustainable strategies to mitigate the effects of these emerging contaminants.

Combined effect of physical exercise and hormone replacement therapy on cardiovascular and metabolic health in postmenopausal women: A systematic review and meta-analysis.

The cardioprotective effect of postmenopausal hormone replacement therapy (HRT) has been demonstrated in several studies. Similarly, physical exercise has yielded positive results. However, the effects of their combination remain inconclusive. This review describes the combined effects of physical exercise and hormone therapy on cardiovascular and metabolic health in postmenopausal women. We searched the Scopus, Web of Science, PubMed, and Embase databases and included randomized controlled trials published up to December 2021 on the combined effects of physical exercise and hormone therapy on cardiovascular and metabolic health in postmenopausal women. We identified 148 articles, of which only seven met the inclusion criteria (386 participants; 91 [23%] HRT + exercise; 104 [27%] HRT; 103 [27%] exercise; 88 [23%] placebo). The combined treatment further decreased systolic blood pressure (SBP) compared to the isolated effect of aerobic training (AT) (mean difference [MD]=-1.69; 95% confidence interval [CI]=-2.65 to -0.72, n=73). Nevertheless, it attenuated the decrease in diastolic blood pressure (DBP) (MD=0.78; 95%CI: 0.22-1.35, n=73), and the increase in peak oxygen consumption (VO2 peak) promoted by exercise (AT + HRT=2.8±1.4 vs AT + placebo=5.8±3.4, P=0.02). The combination of AT and oral HRT improved SBP. However, AT alone seemed to have a better effect on physical fitness and DBP in postmenopausal women.