Estrogen Use Research Articles

O-083 Tumors of the central nervous system among women treated with fertility drugs: a population-based cohort study

Abstract Study question Is the use of fertility drugs among infertile women associated with tumors of the central nervous system (CNS)? Summary answer The use of most specific types of fertility drugs is not associated with an increased risk of CNS tumors overall. What is known already Few previous studies have investigated the association between fertility drugs and CNS tumors. Studies have reported inconsistent results regarding the risk of CNS tumors associated with assisted reproductive technologies such as in vitro fertilization (IVF). No studies have reported the risk associated with various specific fertility drugs. Study design, size, duration Retrospective population-based cohort study of all women included in the Danish Infertility Cohort. The study cohort consisted of 148 016 infertile women after exclusion of women who emigrated, died, were diagnosed with cancer before infertility diagnosis, and women for whom information on level of education was missing. The cohort was linked to various national health- and civil registers to study all 20- to 45-year old infertile women in Denmark during 1995-2017. Participants/materials, setting, methods The study cohort was linked to various national health and population registers to obtain information on fertility drugs (clomiphene citrate, gonadotropins, human chorionic gonadotropin, gonadotropin-releasing hormone receptor modulators and progesterone), CNS tumors, relevant covariates and vital and emigration status. Cox proportional hazard regression models were used to calculate hazard ratios and 95% confidence intervals for CNS tumors overall and for gliomas, meningiomas and diverse benign tumors of the brain and other parts of the CNS. Main results and the role of chance During a median 11.3 years of follow-up, 328 women were diagnosed with a CNS tumor. No marked associations were observed between use of most types of fertility drugs (clomiphene citrate, gonadotropins, gonadotropin releasing hormone receptor modulators and progesterone) and CNS tumors. However, ever use of human chorionic gonadotropin was associated with an increased rate of gliomas (HR 2.13 95% CI 0.90-5.01) but a decreased rate of meningiomas (HR 0.49 95% CI 0.28-0.87). No clear associations with CNS tumors were observed according to time since first use or cumulative dose for any specific fertility drugs. Additional studies with longer follow-up are necessary to support these findings. Limitations, reasons for caution The median age at end of follow-up (43.5 years) was lower than the median age for CNS tumors diagnosis (60 years). Information on estrogen use, treatment regimens and number of cycles is only partly available in the registers and these were not included in this study. Wider implications of the findings This study presents reassuring results regarding the risk of tumors of the CNS among women treated with fertility drugs. Our study is only generalizable to premenopausal women, and the risk for postmenopausal women remains to be assessed. Trial registration number not applicable

P-578 Oral, Vaginal or Intramuscular Progesterone in Programmed Frozen Embryo Transfer Cyles: A Pilot RCT

Abstract Study question What should be the optimal luteal phase support in programmed frozen embryo transfer (FET) cycles using vitrified-thawed blastocysts? Summary answer 40mg/day oral dydrogesterone, 180mg/day progesterone (P) vaginal gel and 100mg/day im P in oil revealed similar reproductive outcomes in programmed FET cycles. What is known already Luteal phase should be supported either in fresh (Yanushpolsky et al, 2015) or in FET cycles (Pabuccu et al, 2020). Endometrium preparation in FET cycles is outmost important for successful implantation. For this purpose, natural or programmed protocols have been suggested. In programmed FET cycles, exogenous P replacement is of critical importance, as estrogen use will inhibit ovulation and corpus luteum formation.Higher serum P level was associated with increased rates of ongoing pregnancy or live birth in programmed FET cycles (Melo et al 2021). Therefore, lack of a corpus luteum justifies precise and adequate luteal support. Study design, size, duration This was a randomized, parallel, phase IV-pilot RCT (NCT03948022), comparing 3 different luteal support options in programmed FET cycles. A total of 168 women aged between 20-40 years and having available blastocyst(s) were eligible for the study between April-December 2020. After excluding cases, 163 patients were randomly assigned to one of the P arms based on a computer- generated list to administer: 1-oral dydrogesterone 40mg/day (DYD) 2-vaginal %8 P gel 180mg/day (VAG) 3-im 100mg/day P (IM) Participants/materials, setting, methods Estradiol 2 mg TID was started on day 2 or 3 of menstruation for at least 7 days. On day 8, endometrial thickness was assessed. When it was >8 mm, each patient was randomly assigned to one of the intervention arms. After 5 days of P administration, ET was performed on the 6th day preceding serum P measurement. Primary outcome was ongoing pregnancy rate defined as viable healthy pregnancy beyond 20th week of gestation. Main results and the role of chance A total of 151 women out of 163 completed the primary follow-up after randomization. 12 patients were excluded from the final analysis mainly due to protocol violation and discontinuation of intervention. Each patient contributed to a single cycle in the analysis and given data does not include cumulative pregnancies including surplus frozen embryo transfers. Demographic data including; mean woman age, body mass index, serum AMH, TSH and infertility etiologies were comparable among all groups without statistically significance (p > 0.5) Limitations, reasons for caution Lack of a power analysis is the main limitation of this study, potentially coming with type-1 error. Properly designed and powered RCTs are needed. Wider implications of the findings There have been very limited data available for oral progestogen use particularly in FET cycles, unlike many reports for vaginal and im P. Comperable reproductive outcomes with significantly lower side effect profile of oral progestagen merits further attention in programmed FET cycles. Trial registration number NCT03948022

An Update on the General Features of Breast Cancer in Male Patients-A Literature Review.

Male breast cancers are uncommon, as men account for less than 1 percent of all breast carcinomas. Among the predisposing risk factors for male breast cancer, the following appear to be significant: (a) breast/chest radiation exposure, (b) estrogen use, diseases associated with hyper-estrogenism, such as cirrhosis or Klinefelter syndrome, and (c) family health history. Furthermore, there are clear familial tendencies, with a higher incidence among men who have a large number of female relatives with breast cancer and (d) major inheritance susceptibility. Moreover, in families with BRCA mutations, there is an increased risk of male breast cancer, although the risk appears to be greater with inherited BRCA2 mutations than with inherited BRCA1 mutations. Due to diagnostic delays, male breast cancer is more likely to present at an advanced stage. A core biopsy or a fine needle aspiration must be performed to confirm suspicious findings. Infiltrating ductal cancer is the most prevalent form of male breast cancer, while invasive lobular carcinoma is extremely uncommon. Male breast cancer is almost always positive for hormone receptors. A worse prognosis is associated with a more advanced stage at diagnosis for men with breast cancer. Randomized controlled trials which recruit both female and male patients should be developed in order to gain more consistent data on the optimal clinical approach.

Epidemiologie, Risikofaktoren und Genetik des Endometriumkarzinoms

BackgroundEndometrial cancer (EC) is the fifth most common female malignancy and the most common pelvic malignancy. Effective strategies for early detection, prevention, and genetic assessment are discussed in this article.AimTo review the literature on epidemiology, risk factors, and genetics.Materials and MethodsThis article is based on the current recommendations of the German Society of Obstetrics and Gynecology for the diagnosis and treatment of women with EC. The current literature was summarized based on expert knowledge. Systematic searches in the Medline database and in Cochrane Reviews were performed. The quality of the evidence was rated according to the 2011 Oxford classification. Recommendations and statements were formulated by a representative group using structured consensus methods.ResultsIn Germany, 2.7% of cancer-specific deaths are due to EC. The incidence of EC increases with age and the disease is most often diagnosed in the age group of 75- to 79-year-old women. The lifetime risk of EC is 1.9%. Risk-modulating factors of EC include long-term use of estrogens, progestogen therapy, oral contraceptives, high body mass index, and impaired glucose metabolism. In addition, physical activity and dietary aspects, such as the amount of fat and red meat consumed, as well as soja foods, dietary fibers, vitamins, and specific beverages such as tea and coffee, play an important etiological role. EC also has a genetic component. Immunohistochemical and/or molecular screening is warranted for all patients with EC and has a significant impact on the genetic counselling of affected families as well as on treatment decisions.

Menopause, hysterectomy, menopausal hormone therapy and cause-specific mortality: cohort study of UK Biobank participants.

STUDY QUESTIONWhat is the association between menopausal hormone therapy (MHT) and cause-specific mortality?SUMMARY ANSWERSelf-reported MHT use following early natural menopause, surgical menopause or premenopausal hysterectomy is associated with a lower risk of breast cancer mortality and is not consistently associated with the risk of mortality from cardiovascular disease or other causes.WHAT IS KNOWN ALREADYEvidence from the Women’s Health Initiative randomized controlled trials showed that the use of estrogen alone is not associated with the risk of cardiovascular mortality and is associated with a lower risk of breast cancer mortality, but evidence from the Million Women Study showed that use of estrogen alone is associated with a higher risk of breast cancer mortality.STUDY DESIGN, SIZE, DURATIONCohort study (the UK Biobank), 178 379 women, recruited in 2006–2010.PARTICIPANTS/MATERIALS, SETTING, METHODSPostmenopausal women who had reported age at menopause (natural or surgical) or hysterectomy, and information on MHT and cause-specific mortality. Age at natural menopause, age at surgical menopause, age at hysterectomy and MHT were exposures of interest. Natural menopause was defined as spontaneous cessation of menstruation for 12 months with no previous hysterectomy or oophorectomy. Surgical menopause was defined as the removal of both ovaries prior to natural menopause. Hysterectomy was defined as removal of the uterus before natural menopause without bilateral oophorectomy. The study outcome was cause-specific mortality.MAIN RESULTS AND THE ROLE OF CHANCEAmong the 178 379 women included, 136 790 had natural menopause, 17 569 had surgical menopause and 24 020 had hysterectomy alone. Compared with women with natural menopause at the age of 50–52 years, women with natural menopause before 40 years (hazard ratio (HR): 2.38, 95% CI: 1.64, 3.45) or hysterectomy before 40 years (HR: 1.60, 95% CI: 1.23, 2.07) had a higher risk of cardiovascular mortality but not cancer mortality. MHT use was associated with a lower risk of breast cancer mortality following surgical menopause before 45 years (HR: 0.17, 95% CI: 0.08, 0.36), at 45–49 years (HR: 0.15, 95% CI: 0.07, 0.35) or at ≥50 years (HR: 0.28, 95% CI: 0.13, 0.63), and the association between MHT use and the risk of breast cancer mortality did not differ by MHT use duration (<6 or 6–20 years). MHT use was also associated with a lower risk of breast cancer mortality following natural menopause before 45 years (HR: 0.59, 95% CI: 0.36, 0.95) or hysterectomy before 45 years (HR: 0.49, 95% CI: 0.32, 0.74).LIMITATIONS, REASONS FOR CAUTIONSelf-reported data on age at natural menopause, age at surgical menopause, age at hysterectomy and MHT.WIDER IMPLICATIONS OF THE FINDINGSThe current international guidelines recommend women with early menopause to use MHT until the average age at menopause. Our findings support this recommendation.STUDY FUNDING/COMPETING INTEREST(S)This project is funded by the Australian National Health and Medical Research Council (NHMRC) (grant numbers APP1027196 and APP1153420). G.D.M. is supported by NHMRC Principal Research Fellowship (APP1121844), and M.H. is supported by an NHMRC Investigator Grant (APP1193838). There are no competing interests.TRIAL REGISTRATION NUMBERN/A.

The Association Between Route of Post-menopausal Estrogen Administration and Blood Pressure and Arterial Stiffness in Community-Dwelling Women.

BackgroundPostmenopausal hormone therapy (HT) is associated with increased cardiovascular risk. Although the route of estrogen administration may play a role in mediating risk, previous studies have not controlled for concomitant progestin use.ObjectiveTo investigate the association between the route of estrogen therapy (oral or non-oral) HT use, without concomitant progestin, and blood pressure and arterial stiffness in postmenopausal women.MethodsSystolic blood pressure [SBP], diastolic blood pressure [DBP]), arterial stiffness (aortic pulse wave velocity [aPWV] and augmentation index at 75 beats per minute [AIx]) were measured using a validated automated brachial cuff-based oscillometric approach (Mobil-O-Graph) in a community-dwelling sample of 328 women.ResultsFifty-five participants (16.8%) were ever users (current and past use) of estrogen-only HT (oral [n = 16], transdermal [n = 20], vaginal [n = 19]), and 223 were never HT users (control). Ever use of oral estrogen was associated with increased SBP and DBP (Oral: SBP: 137 ± 4 mmHg, DBP: 79 ± 2 mmHg) compared to use of non-oral estrogen (transdermal: SBP: 118 ± 2 mmHg, DBP: 73 ± 1 mmHg; p < 0.01 & p = 0.012, respectively; vaginal: SBP: 123 ± 2 mmHg DBP: 73 ± 2 mmHg; p = 0.02 & p = 0.01, respectively.) and controls (SBP: 124 ± 1 mmHg, DBP: 74 ± 1 mmHg, p = 0.03, p = 0.02, respectively) after adjustment for covariates. aPWV was higher in oral estrogen ever users (9.9 ± 1 m/s) compared to non-oral estrogen (transdermal: 8.6 ± 0.3 m/s, p < 0.01; vaginal: 8.8 ± 0.7 m/s, p = 0.03) and controls (8.9 ± 0.5 m/s, p = 0.03) but these associations were no longer significant after adjustment for covariates. AIx was higher in oral estrogen (29 ± 2 %) compared to non-oral estrogen (transdermal: 16 ± 2 %; vaginal: 22 ± 1.7 %) but this association was no longer significant after adjustment for covariates (p = 0.92 vs. non-oral; p = 0.74 vs. control).ConclusionEver use of oral estrogen was associated with increased SBP and DBP compared to non-oral estrogen use and no use. Given the cardiovascular risk associated with both menopause and increased blood pressure, further studies are required exploring the potential benefits of non-oral estrogen in postmenopausal women.

Exogenous Hormones and Breast Cancer Risk: Contraception, Menopausal Hormone Therapy, and Breast Cancer Survivors.

The use of exogenous estrogen and progesterone/progestin medications spans the reproductive and postreproductive lives of millions of women providing control over pregnancy timing, management of premenopausal and postmenopausal symptoms, and prevention of disease, including endometrial and ovarian cancer. These same hormones can also increase the risk of breast cancer in some settings and their use in breast cancer survivors may increase the risk of breast cancer recurrence. Given both the benefits and risks of these exogenous hormones, a detailed understanding of the available scientific evidence is imperative to help counsel individuals in their use across various settings.

Estrogen May Enhance Toll-Like Receptor 4-Induced Inflammatory Pathways in People With HIV: Implications for Transgender Women on Hormone Therapy.

BackgroundTransgender women (TW) are at increased risk for both human immunodeficiency virus (HIV) and cardiovascular disease (CVD). Antiretroviral therapy-treated HIV has been associated with a two-fold increased risk of CVD, potentially due to dysregulated Toll-like receptor (TLR)-induced immune activation. Use of estrogens in feminizing hormone therapy (FHT) may enhance inflammatory responses and the risk of cardiovascular mortality in TW. Despite this, the immunomodulatory effects of estrogen use in TW with HIV have been inadequately explored.MethodsAs an in vitro model for FHT, cryopreserved PBMCs (cryoPBMCs) from HIV negative (HIV-), HIV+ ART-suppressed (HIV+SP), and HIV+ ART-unsuppressed (HIV+USP) cisgender men were cultured overnight in the presence of 17-β estradiol or 17-α ethinylestradiol with and without the TLR4 agonist LPS or the TLR8 agonist ssPolyU. Monocyte activation (CD69, HLA-DR, CD38) was assessed by flow cytometry. Cytokine levels (IL-6, TNF-α, IL-1β, and IL-10) were measured in cell culture supernatants by Legendplex. Levels of phosphorylated TLR signaling molecules (JNK, MAPK p38) were assessed by Phosflow. Plasma levels of immune activation biomarkers (LPS-binding protein, monocyte activation markers sCD14 and sCD163, and inflammatory molecules IL-6 and TNF-α receptor I) were measured by ELISA.ResultsPBMCs from people with HIV (PWH) produced greater levels of inflammatory cytokines following exposure to LPS or ssPolyU compared to levels from cells of HIV- individuals. While estrogen exposure alone induced mild changes in immune activation, LPS-induced TLR4 activation was elevated with estrogen in cisgender men (CM) with HIV, increasing monocyte activation and inflammatory cytokine production (IL-6, TNF-α). Interestingly, testosterone inhibited LPS-induced cytokine production in CM regardless of HIV status. Plasma markers of immune activation and microbial translocation (e.g., sCD14, sCD163, LPS-binding protein) were generally higher in PWH compared to HIV- CM, and these markers were positively associated with in vitro responsiveness to estrogen and LPS in CM with HIV.ConclusionsOur in vitro data suggest that estrogen exposure may enhance innate immune activation in PWH. Further examination is needed to fully understand the complex interactions of FHT, HIV, and CVD in TW, and determine optimal FHT regimens or supplementary treatments aimed at reducing excess immune activation.

A case-control study of healthcare disparities in sex and gender minority patients with breast cancer.

6517 Background: Disparities in the quality of diagnosis and treatment of breast cancer in sex and gender minority (SGM) populations are largely undefined. Only 24% of studies funded by the National Cancer Institute capture data on sexual orientation, while only 10% capture data on gender identity. To address this gap, the National Academies 2020 Report calls for adding sexual orientation and gender identity (SOGI) to ongoing data collection efforts. This case-control study matching SGM patients with breast cancer to cisgender heterosexual controls is the result of linking SOGI data to the Stanford University Healthcare (SHC) Oncoshare breast cancer database, which integrates data from the electronic medical record (EMR) and California Cancer Registry. Methods: An initial database query across the SHC EMR was performed for charts containing SOGI terms in patients with breast cancer seen in SHC Oncology. 686 charts were identified for manual review and after eliminating false positives, the sample was reduced to 92 SGM patients, who were then matched by year of diagnosis, age, stage, ER-status, and HER-2 status to cisgender heterosexual controls within Oncoshare. Additional data on demographics, diagnosis, treatment, and relapse were then manually abstracted from the EMR. Results: The SGM cohort was comprised of 80% lesbians, 13% bisexuals and 6% transgender men. The median age at diagnosis across both groups was 49. SGM patients were 72% white, 4% Asian, 12% Black or Latinx 6% other compared to 63% white, 24% Asian, 6% Black or Latinx, 6% other in the controls (p = 0.0006). Thirteen percent and 32% of SGM patients engaged in risky alcohol and illicit drug use respectively, compared to 3% and 6% of controls (p = 0.028; p &lt; 0.0001). Estrogen exposure risk factors including median age of menarche, first delivery, menopause, and use of exogenous estrogens were balanced between the two groups, but SGM patients had fewer children (median 0 vs 2, p &lt; 0.0001). There was a delay in time to diagnosis from symptom onset in SGM patients versus controls (median 64 days vs 37 days, p = 0.043). There was no difference in surgical approach, use of post-lumpectomy radiation, or use of neoadjuvant chemotherapy for stage III disease. However, SGM patients were less likely to undergo chest reconstruction (55% vs 82%, p = 0.0098) and if ER+, to complete ≥5 years of ER-directed therapy (53% vs 72%, p = 0.048). SGM patients used more alternative medicine (46% vs 29%, p = 0.033) and had a higher rate of documented refusal of recommended oncologic treatments (38% vs 21%, p = 0.0088). Correspondingly, SGM patients experienced a higher recurrence rate (31% vs 14%, p = 0.0124). Conclusions: To our knowledge, this is the first study to examine quality of diagnosis and treatment of breast cancer in SGM patients. Several novel potential healthcare disparities are identified, which should be further evaluated in population-based studies to inform interventions.

Dietary genistein and 17β-estradiol implants differentially influence locomotor and cognitive functions following transient focal ischemia in middle-aged ovariectomized rats at different lengths of estrogen deprivation

Genistein possesses estrogenic activity and has been considered a potential replacement for estrogen replacement therapy after menopause. In the current study, we investigated the neuroprotective effects of dietary genistein at varied lengths of estrogen deprivation in middle-aged ovariectomized Sprague-Dawley rats under ischemic conditions. Two weeks of treatment with dietary genistein at 42 mg/kg but not 17β-estradiol implants improved cognitive flexibility (Morris water maze test) after short-term estrogen deprivation (2 weeks) but not long-term estrogen deprivation (12 weeks). 17β-estradiol implants but not dietary genistein improved locomotor asymmetry (cylinder test) after long-term but not short-term estrogen deprivation. Dietary genistein but not 17β-estradiol implant improved early phase motor learning (rotarod test) after long-term estrogen deprivation. Neither 17β-estradiol implant nor dietary genistein reduced infarct size after either short-term or long-term estrogen deprivation. Genistein, however, reduced ionized calcium-binding adaptor molecule-1 (Iba1) expression, a marker of brain inflammation, at the ipsilateral side of stroke injury after short-term but not long-term estrogen deprivation. This study suggests that the neuroprotective effects of dietary genistein on motor and cognitive functions are distinctly influenced by the length of estrogen deprivation following focal ischemia. SignificanceThere is an increasing postmenopausal population opting for homeopathic medicines for the management of menopausal symptoms due to the perceived distrust in estrogen use as hormone replacement. Basic and clinical studies support the notion that early, but not delayed, hormone replacement after menopause is beneficial. Furthermore, evidence suggests that delaying hormone replacement augments the detrimental, rather than the beneficial effects of estrogens. Because of the active consideration of soy isoflavones including genistein as alternatives to estrogen replacement, it is necessary to understand the ramifications of soy isoflavones use when their administration is begun at various times after menopause.

Reference range of serum uric acid and prevalence of hyperuricemia: a cross-sectional study from baseline data of ELSA-Brasil cohort

BackgroundMost of the few studies that have established reference ranges for serum uric acid (SUA) have not taken into account factors which may interfere with its levels and followed rigorous laboratory quality standards. The aim of this study was to establish reference ranges for SUA and determine the prevalence of hyperuricemia.MethodCross-sectional study including 15,100 participants (all sample) aged 35 to 74 years from baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicentric cohort of volunteer civil servants from five universities and one research institute located in different regions of Brazil. It was established a reference sample excluding participants with factors that directly influence SUA levels: glomerular filtration rate lower than 60 ml/min, excessive alcohol intake, use of diuretics, aspirin, estrogen or urate-lowering therapy. SUA was measured using the uricase method and following rigorous international quality standards. Reference ranges were defined as values between percentiles 2.5 (P2.5) and 97.5 (P97.5) of SUA distribution in the reference sample, stratified by sex. Hyperuricemia was defined as SUA ≥ 7 mg/100 ml in the all sample.ResultsThe reference sample was composed of 10,340 individuals (55.3% women, median age 50 years). Reference ranges (P2.5 to P97.5) for SUA were: 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Sex was a major determinant for SUA levels (median [IQR], mg/100 ml: 6.1 [5.3–7.0] for men versus 4.5 [3.9–5.3] for women, p < 0.001). Higher levels of SUA were found in patients with higher BMI. Higher age had (a modest) influence only for women. The prevalence of hyperuricemia for all sample (N = 15,100) was 31.9% (95% confidence interval [CI] 30.8–33.0%) in men and 4.8% (95% CI 4.3–5.3%) in women.ConclusionSUA reference ranges were 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Prevalence of hyperuricemia was 31.9% in men and 4.8% in women. Updated SUA reference ranges and prevalence of hyperuricemia are higher nowadays and might be used to guide laboratories and the screening for diseases related to SUA.

Urethral prolapse mimicking a uterine prolapse in an eight-year-old girl: A case report.

Introduction and importanceA urethral prolapse is a rare condition occurring most likely in prepubertal girls and post-menopausal women. The cause of this condition is not well known but an under-laying low level of estrogen is thought to have a role.Case presentationThis is an 8-year-old girl diagnosed with urethral prolapse, who was successfully managed by excision of the prolapsed urethral mucosa circumferentially. A three-month following up did not notice any particular challenge.Clinical discussionThe most common presenting sign is genital bleeding and the vaginal doughnut sign. Treatment of urethral prolapse should begin with medical therapy in most patients before resorting to surgical management. However, in case of bigger size, severe genital hemorrhage, and prolapsed mucosa with an appearance suggestive of vascular compromise, surgical management is the first-line option. We estimate a severe prolapse mimicking a uterine prolapse must be included in surgical management as a first-line option.ConclusionSurgical excision may be the first-line option in certain urethral prolapses given its association with quick recovery versus the effectiveness of the long-time required for estrogen use, as well as the low likelihood of successful resolution linked to estrogen use.

PD44-12 VAGINAL ESTROGEN THERAPY FOR GENITOURINARY SYNDROME OF MENOPAUSE (GSM) IN WOMEN WITH A PERSONAL HISTORY OF BREAST CANCER - A CLAIMS DATABASE ANALYSIS

You have accessJournal of UrologyCME1 May 2022PD44-12 VAGINAL ESTROGEN THERAPY FOR GENITOURINARY SYNDROME OF MENOPAUSE (GSM) IN WOMEN WITH A PERSONAL HISTORY OF BREAST CANCER - A CLAIMS DATABASE ANALYSIS Kathryn Dumas, Sajya Singh, Jaden R. Kohn, Taylor P. Kohn, and Marisa Clifton Kathryn DumasKathryn Dumas More articles by this author , Sajya SinghSajya Singh More articles by this author , Jaden R. KohnJaden R. Kohn More articles by this author , Taylor P. KohnTaylor P. Kohn More articles by this author , and Marisa CliftonMarisa Clifton More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002605.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Systemic therapies for breast cancer - selective estrogen receptor modulators (SERM), aromatase inhibitors (AI), and chemotherapies - can result in genitourinary syndrome of menopause (previously recognized as vulvovaginal atrophy) for up to 70% of postmenopausal breast cancer survivors. While systemic estrogen therapy is often avoided in these women, vaginal estrogen can be safely used to treat GSM symptoms. Our objective is to assess the use of vaginal estrogen for women with a diagnosis of GSM and a personal history of breast cancer using a large US claims database. METHODS: The TriNetX Diamond network database was queried: a US health research network of 190 million patients, encompassing healthcare encounters and prescriptions between 2009-2021. Females with a diagnosis of postmenopausal atrophic vaginitis or atrophy of the vulva (ICD-10 N95.2, N90.5) were included. Of these, women with breast cancer (C50 or Z86.000) were included if the diagnosis was at least 1 month prior to VVA diagnosis. Estrogen receptor status was collected when available (ICD-10 Z17.0, Z17.1). Prescriptions for treatment of GSM were included if prescribed the day of VVA diagnosis up to 1 year after index diagnosis. Incidence of vaginal estrogen use in patients with a history of breast cancer was determined for 2013-2015, 2016-2018, and 2019 to present. RESULTS: A total of 2,159,766 women with GSM were identified; of whom, 4.8% (n=104,327) had a personal history of breast cancer. Vaginal estrogen prescriptions were less frequent in women with history of breast cancer compared to women without (11% vs 22%, p<0.01, Table 1). Incidence rate of vaginal estrogen prescriptions for women with GSM and history of breast cancer remained stable around 10-11% from 2013 to present. 25,410 women with GSM and history of breast cancer had positive estrogen receptor status (ER+) and 4,893 had negative estrogen receptor status (ER-). There was no difference in vaginal estrogen prescribing between ER+ and ER- patients (7.4% vs 8.4%). CONCLUSIONS: While vaginal estrogen can be safely used in women with GSM and personal history of breast cancer, it is prescribed for few eligible patients. Barriers to use of vaginal estrogen in this population should be explored to optimize patient’s quality of life. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e712 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kathryn Dumas More articles by this author Sajya Singh More articles by this author Jaden R. Kohn More articles by this author Taylor P. Kohn More articles by this author Marisa Clifton More articles by this author Expand All Advertisement PDF DownloadLoading ...

Menopausal Hormone Therapy and Breast Cancer.

Associations of estrogen-alone and estrogen plus progestin with breast cancer incidence and related mortality are reviewed from observational studies (The Collaborative Group on Hormonal Factors in Breast Cancer and The Million Women Study, 2019) and the Women's Health Initiative's (2020) two randomized trials evaluating conjugated equine estrogen alone, for women with prior hysterectomy or with medroxyprogesterone acetate. Findings are generally concordant for estrogen plus progestin use with both observational and randomized studies reporting higher breast cancer incidence. Findings are discordant for estrogen-alone use where, in the WHI randomized trial, a lower incidence and lower breast cancer mortality was seen. In contrast, in the observational studies, estrogen-alone use was associated with higher breast cancer incidence and higher breast cancer mortality. Although these discordant findings are difficult to fully reconcile, we conclude with a discussion of public health implications of the available evidence on menopausal hormone therapy and breast cancer.

Correction of menopausal disorders: new possibilities of menopausal hormone therapy

Determining the role of menopausal hormone therapy in the era of covid infection is an urgent task. The reasons for the lower rate of severe outcomes in women against the background of covid infection compared to men are currently being discussed. This is suggestive of the idea that the female body has the protection that accounts for this advantage. that Scientific literature data were reviewed to select the best combination of estrogen and progesterone when used as menopausal hormone therapy in the present setting. During the analysis of the literature on the use of estrogens and progestins as menopausal hormone therapy published in recent years, we used the following sources: PubMed, E-libary, Scopus. The body of material, which we studied, led us to a conclusion about the preference for the gestagen component when menopausal hormone therapy was prescribed. Gestagen should have the lowest risks in the development of thrombosis, as well as level the pronounced symptoms of peri- and postmenopause. According to the sources we studied and the authors’ own clinical experience, levonorgestrel-containing menopausal hormone therapy preparations have a high safety profileImproving physicians’ literacy about the criteria for prescribing menopausal hormone therapy, including drugs containing two components, estrogen and levonorgestrel in a cyclic regimen, will allow the use of hormone therapy in a wider range of patients in the perimenopausal and postmenopausal periods.

CRP levels are significantly associated with CRP genotype and estrogen use in The Lifestyle, Biomarker and Atherosclerosis (LBA) study

BackgroundThe C-reactive protein (CRP) is an important biomarker for atherosclerosis and single nucleotide polymorphisms (SNPs) in the CRP locus have been associated with altered CRP levels and associated with risk for cardiovascular disease. However, the association between genetic variations in the CRP gene, estrogen use and CRP levels or early signs of atherosclerosis in young healthy individuals is not fully characterized. We aimed to evaluate the influence of five genetic variants on both plasma CRP levels and carotid intima-media thickness (cIMT) values, including aspects on estrogen containing contraceptive use in females.MethodsGenotyping was performed with TaqMan real time PCR and compared with high sensitivity CRP serum levels in 780 Swedish young, self-reported healthy individuals. Haplotypes of the SNPs were estimated with the PHASE v 2.1. The cIMT was measured by 12 MHz ultrasound. The contraceptive use was self-reported.ResultsStrong associations between CRP and genotype were observed for rs3091244, rs1800947, rs1130864, and rs1205 in women (all p < 0.001). In men, only rs1800947 was associated with CRP (p = 0.029). The independent effect of genotypes on CRP remained significant also after adjustment for established risk factors. Female carriers of the H1/ATGTG haplotype had higher CRP than non-carriers. This was specifically pronounced in the estrogen-using group (p < 0.001), and they had also higher cIMT (p = 0.002) than non-carriers but with a small cIMT difference between the haplotype groups (0.02 mm). In parallel, a significant correlation between CRP and cIMT in the estrogen using group was observed (r = 0.194; p = 0.026).ConclusionsEstrogen use, genotypes and haplotypes in the CRP locus are significantly associated with CRP levels. Based on an observed interaction effect between sex/estrogen use and the H1/ATGTG haplotype on CRP, and a marginally thicker cIMT in the estrogen using group, our data suggest that both genotypes and estrogen usage could be involved in arterial wall structural differences. The causality between CRP levels and cIMT remains unclear, and the observed difference in cIMT is not clinically relevant in the present state. Future larger and longitudinal studies may shed further light on the role of more long-term estrogen use and early atherosclerosis.

Management of Contraception in Adolescent Females With Hormone-Related Venous Thromboembolism

PurposeManagement of contraception in adolescent females with hormone-related venous thromboembolism (VTE) is challenging. We examined the characteristics of this patient population and outcomes, including recurrent VTE, heavy menstrual bleeding, and pregnancy. MethodsWe performed a single-institution retrospective cohort study of adolescents with a new diagnosis of VTE and concurrent use of estrogen- and/or progestin-containing medication (N = 89). We collected data on additional risk factors for thrombosis, management of hormone therapy, and anticoagulation. We compared outcomes between patients with prescribed contraception within the year after their VTE diagnosis (n = 52) with those without (n = 37). ResultsAt least one additional risk factor for thrombosis was identified in 92% of patients, and 73% had two or more. The most common additional thrombosis risk factors were obesity (35%), family history (33%), and recent immobility (33%). Ninety-seven percent of patients were receiving combined hormonal medications, and 42% of patients had their medication stopped and not replaced with an alternative. Heavy menstrual bleeding was reported while on anticoagulation in 46% of patients with a documented menstrual history. Recurrent VTE occurred in 9.0% of patients. The group without prescribed contraception had a significantly higher rate of pregnancy in the two years after VTE diagnosis (18% vs. 1.9%, p = .04). Two pregnancies occurred while on warfarin. DiscussionEarly assessment of contraceptive needs and menstrual bleeding symptoms are needed after diagnosis of hormone-related VTE in adolescent females. Access to contraceptive methods associated with low thrombosis risk is important for the prevention of unplanned pregnancy in this patient population.

Vaginal estrogen: An option to be considered for postmenopausal women

The author reviews the use of vaginal estrogen for postmenopausal women affected by the genitourinary syndrome of menopause, explaining that it is safe and effective for most and that women’s health nurse practitioners are well positioned to recognize the need for vaginal estrogen, educate the patient on safety concerns, and prescribe it when indicated.

Measurement of the vaginal wall thickness by transabdominal and transvaginal ultrasound of women with vaginal laxity: a cross-sectional study.

An objective diagnostic method to understand vaginal laxity (VL) is still missing. The aim of our study is to determine whether vaginal wall thickness (VWT) measured by ultrasound may differ according to the abdominal or vaginal techniques and to assess whether clinical variables are associated with vaginal measurements of women with VL. A cross-sectional study conducted at a tertiary hospital included 82 women aged ≥ 18 years with VL complaints assessed by the Vaginal Laxity Questionnaire. Women who reported severe comorbidities or vulvovaginal disorders, previous treatment for VL, and use of vaginal estrogen in the last 6 months were excluded. Participants reporting VL underwent transabdominal (TAUS) and transvaginal ultrasound (TVUS) and physical examination and answered validated questionnaires. Descriptive data were given as mean and standard deviation, median (range), and absolute and relative frequency. The significance level adopted for this study was 5%. Sample size calculation was not performed for the present study. Mean age was 41.20 ± 8.64 years, and most participants were multiparous, with previous vaginal delivery and having vaginal intercourse. A statistically significant difference (up to 3 mm) between TAUS and TVUS measurements of the VWT was found in the proximal, middle-third, and distal compartments. A significant correlation was found between VWT and TAUS or TVUS in the mid-third and distal compartments. A significant correlation was found between the VWT measurements in TVUS and TAUS. Our findings might give the health professional more possibilities for investigating VWT according to patient characteristics.

Urinary Tract Infection in Parkinson's Disease.

Urinary tract infection (UTI) is a common precipitant of acute neurological deterioration in patients with Parkinson’s disease (PD) and a leading cause of delirium, functional decline, falls, and hospitalization. Various clinical features of PD including autonomic dysfunction and altered urodynamics, frailty and cognitive impairment, and the need for bladder catheterization contribute to an increased risk of UTI. Sepsis due to UTI is a feared consequence of untreated or undertreated UTI and a leading cause of morbidity in PD. Emerging research suggests that immune-mediated brain injury may underlie the pathogenesis of UTI-induced deterioration of PD symptoms. Existing strategies to prevent UTI in patients with PD include use of topical estrogen, prophylactic supplements, antibiotic bladder irrigation, clean catheterization techniques, and prophylactic oral antibiotics, while bacterial interference and vaccines/immunostimulants directed against common UTI pathogens are potentially emerging strategies that are currently under investigation. Future research is needed to mitigate the deleterious effects of UTI in PD.