Oral Hormone Replacement Therapy Research Articles

Cell representation in cytopathological examinations of the cervix

The objective of this study was to analyze the relationship between the representation of JEC/ZT in cervical cytopathological tests with the age and clinical variables of women. A retrospective study was carried out, with data collected from the Cancer Information System, referring to cytopathological tests collected in public health services. Most of the tests (60%) showed representation of JEC/ZT cells. It was observed that the younger the woman, the higher the proportion of tests with JEC/ZT cells, and as age advanced, the representation decreased. Most women using oral contraceptives or hormone replacement therapy, as well as most pregnant women, also had JEC/ZT cells in the test. All examinations with the result of squamous intraepithelial lesion or with atypical squamous cells, not excluding lesions of the present grade, showed JEC/ZT cells. The results found corroborate the importance of sample quality in the identification of precursor lesions of cervical cancer, and it is evident that more attention should be paid to collections carried out in older women in order to be successful in representing JEC/ZT.

O-083 Sexual function in women with Premature Ovarian Insufficiency (POI): systematic review and meta-analysis

Abstract Study question What is the impact of idiopathic premature ovarian insufficiency (POI) on sexual function in women? Summary answer Women with POI exhibit significant reduced sexual function and a higher risk of sexual dysfunction than healthy control women. What is known already POI is a life-changing diagnosis with profound physical and psychological consequences. The impact of POI on sexual complaints, seems multifaceted. Many women report vaginal dryness, dyspareunia (painful intercourse), and diminished libido, but also psychosexual function could be impaired, with potential effects on sexual identity, sexual function, and sexual relationships. Furthermore, the POI diagnosis can have a significant impact on a woman's self-esteem and body image, which could result in problems with sexual function. The ESHRE Guideline emphasizes the importance of providing psychological support and counseling to address the emotional and psychosexual impact of POI. Study design, size, duration This systematic review and meta-analysis is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The following online databases were systematically searched: EMBASE, Medline(Ovid), Web of Science, Coachrane, PsychInfo and Google Scholar up to January 2023. Participants/materials, setting, methods A total of ten studies were included in the systematic review and five studies involving 352 women with POI were included in the meta-analysis. Random effects models were used for analyses, with data reported as Hedges’ g and 95% confidence interval, and the risk of heterogeneity was evaluated. Main results and the role of chance Eight of the ten studies concluded that women with POI have a reduced sexual function. An overall medium Hedges’ g effect size of −0.72 was found (ranging between −0.20 to −1.29) in favor of control women, with moderate heterogeneity (I2 = 64%). When we stratified studies in which women were using hormone replacement therapy (HRT) we calculated an even higher Hedges’ g effect size of −0.82 (95% CI −1.18, −0.47). Pooled data from the different FSFI domains, revealed that women with POI scored significantly lower on all domains. Especially the domain ‘dyspareunia’ exhibited the greatest dissimilarity (Hedges g of −0.63, 95%CI −0.86, −0.39) in women with POI compared to control. Limitations, reasons for caution We have reported a moderate heterogeneity which may be caused by differences in age, duration of diagnosis, infertility status, and socioeconomic background in the various studies. Additionally, limitations such as selection bias, data duplication, and questionnaire variation were identified. Wider implications of the findings The results show that women with POI have reduced sexual function, and HRT use did not improve sexual function. This suggest that oral HRT is less effective for sexual dysfunction. There could be an important role for psychological factors in improving sexual well-being among women with POI. Trial registration number CRD42023437203 (PROSPERO)

A Narrative Review of the Role of Estrogen (Receptors) in Melanoma.

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

Oral Hormone Replacement Therapy and Uterine Volume in Korean Adolescents with Turner Syndrome: A Retrospective Case-Control Study

Study ObjectiveWe aimed to identify critical factors for uterine development by comparing uterine volume (UV) among patients with Turner syndrome (TS) who underwent pubertal induction (PI), patients with TS who had natural menarche (NM), and patients in a non-TS control group. MethodsThis retrospective case-control study included patients with TS who had undergone PI with oral estrogen in a PI group(n=31) and a NM group(n=7). The control group included patients without TS with spontaneous puberty who underwent pelvic ultrasound at 16 years of age. For TS patients, both the UV from the first ultrasound performed at age 16 or older (1st-UV) and the UV from the most recent final ultrasound (final-UV) were obtained. ResultsThe 1st-UV was larger for patients in the NM group than those in the PI group (p<0.001), but did not differ significantly between the NM and control groups (p=0.375). The final-UV of the PI group was larger than their 1st-UV (p<0.001), but still smaller than the NM group (p=0.021). HRT duration and 1st-UV of PI group were positively correlated (p=0.048). There were no variables that were significantly correlated with final-UV of PI group. ConclusionPatients with TS who experienced NM showed normal uterine development, but TS patients who underwent PI showed significantly smaller, undeveloped UV. While HRT duration and UV are positively correlated at the beginning of HRT, it is unclear what determines the final UV; however, late PI initiation and use of oral estrogen probably contributed to the lack of UV development.

#357 Sex differences in the aldosterone-renin system must be taken into account during screening for primary aldosteronism

Abstract Background and Aims Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Patients with PA are at higher risk for cardiovascular and renal complications than those with essential hypertension. Screening for PA is rarely considered in the assessment of a hypertensive patient, in part because of difficulties in the diagnostic process. Nevertheless, identification of PA is crucial to guide patients towards optimal management, either by mineralocorticoid receptor blockade or by unilateral adrenalectomy, with the latter offering potential cure for patients with aldosterone-producing adenomas (APAs). Numerous studies show inadequate diagnostic accuracy of the aldosterone:renin ratio (ARR) for screening for PA, particularly in females, who have higher ARR variability and lower renin compared to males. Women have a higher risk of false-positive screening results leading to unnecessary confirmatory tests. Use of oral contraception (OC) or hormone replacement therapy (HRT) may also confound the ARR. The aim of this study was to develop improved screening tools for PA, including adjustments for sex-specific differences. Method PROSALDO is a multicenter prospective cohort study designed to test new diagnostic procedures for patients with suspected PA. Medication that interfere with the renin-angiotensin-aldosterone system are withdrawn before laboratory measurements. For screening, the routine ARR is calculated along with additional probability scores based on a peripheral venous steroid hormone profile (PVSP). The latter allows for identification of potentially false-negative ARR results. After a positive screening result of the ARR and/or a high probability score based on the PVSP, PA is confirmed or excluded with a saline infusion test (SIT). PA confirmation is followed by adrenal venous sampling (AVS) to identify patients with unilateral PA. We compared aldosterone, renin and ARR levels between females and males with and without PA. Renin- and sex dependent formulas for aldosterone screening cut-offs were derived from the study population. Logistic regression and the corresponding receiver operating characteristic (ROC) curves were used to determine and compare diagnostic accuracies. Results PA was confirmed in 159 (24.5%) of 649 (328 (50.5%) females and 321 (49.5%) males). Lateralization was shown in 58 out of 117 patients who underwent AVS. In hypertensive patients without PA, ARR was higher in females vs. males (26.4 vs. 11.7 pmol/mU, P &amp;lt; 0.0001), mainly due to a lower renin (9.2 vs. 16.2 mU/L, P &amp;lt; 0.0001). Furthermore, ARRs in patients with vs. without PA showed more overlap in females compared to males. Areas under ROC curves (AUROCs) for the ARR were 0.857 (CI 95%: 0.797-0.902) vs. 0.912 (CI 95%: 0.876-0.938) for females and males respectively. Using liquid chromatography mass spectrometry measurements (LC-MS/MS) of aldosterone, an ARR cut-off of 21.75 pmol/L yielded a sensitivity of 93% with only 45% specificity in females, while for males, a specificity of 66% was obtained for a sensitivity of 97.7%. This meant for females having a higher risk of false-positive screening results (OR 2.36 (CI 95%: 1.65-3.41)), even after excluding patients on OC or HRT (OR 2.17 (CI 95%: 1.5-3.17)). We derived a renin- and sex-dependent formula for the calculation of aldosterone cut-offs, which improved diagnostic accuracy for both males and females (ΔAUROC = 0.05 and 0.045, P &amp;lt; 0.0001 and 0.02 respectively): for a diagnostic sensitivity of 94-95%, specificity was improved to 61% in females and 82% in males. Conclusion Lower renin in females without PA leads to higher ARRs and thus a higher risk of false-positive screening results. Higher overlap of the ARR between females with and without PA compared to their male counterparts weakens utility of the ARR for discrimination of patients with and without PA. Sex- and renin-specific aldosterone cut-offs for screening for PA offer improved diagnostic accuracy. Diagnostic accuracy remains however superior in males, which highlights the need for further optimization of diagnostic procedures specifically in women.

Antidepressant use and ovarian cancer risk: Evidence from nationwide studies with >14,000 cases from Denmark and Sweden

ObjectiveGiven that the evidence regarding the link between antidepressant use and ovarian cancer risk is equivocal, we investigated this research question by conducting two nationwide nested case-control studies among the Danish and Swedish populations. MethodsAltogether, 14,121 women with epithelial ovarian cancer (30–84 years old) (Denmark: 8976 diagnosed 2000–2019, Sweden: 5145 diagnosed 2010–2018) were randomly age-matched with 564,840 female controls (359,040 from Denmark, and 205,800 from Sweden) using risk set sampling. We used conditional logistic regression to estimate odds ratios (OR) with 95 % confidence intervals (CI) and combined the estimates based on the fixed-effect assumption. We also investigated potential effect modification by well-established risk factors for ovarian cancer. ResultsAntidepressant use was associated with an overall reduced risk of ovarian cancer (OR = 0.92, 95%CI: 0.88–0.96), and that reduction was more pronounced in postmenopausal women and long-term users. The effect was most pronounced for serous ovarian tumors (OR = 0.90, 95%CI: 0.86–0.95) but was also observed in other subtypes, although not statistically significant. Among different types of antidepressants, selective serotonin reuptake inhibitors in general and citalopram in particular exhibited a noteworthy reduction in ovarian cancer risk (OR = 0.89, 95%CI: 0.82–0.96). Additionally, use of oral contraceptives and hormone replacement therapy individually modified the association between antidepressant use and ovarian cancer risk. ConclusionsUse of an antidepressant was associated with a slight, but statistically significant, decrease in ovarian cancer risk. Given the morbidity and mortality associated with ovarian cancer, and increasing use of antidepressants, these findings may be of significance to cancer prevention and should be studied in more detail mechanistically.

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 &amp;lt; 0.001) but more likely to receive HRT (RA n = 752 [4.5%], UCs n = 2,460 [3.8], p &amp;lt; 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 &amp;lt; 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 &amp;gt;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.