Estrogen Users Research Articles

Experiences With Genitourinary Syndrome of Menopause and Barriers to Vaginal Estrogen Usage Reported by a National Sample of 1500 Women

ObjectiveTo investigate women’s experiences with genitourinary syndrome of menopause (GSM) and vaginal estrogen therapy (VET), including barriers, awareness, and knowledge, and to report current trends and findings on GSM and VET to address barriers to care. MethodsA survey on GSM and VET was posted on the ResearchMatch website. Eligible participants were women ≥ 40 years of age. Demographic information, menopausal status, current knowledge, prior experiences, and barriers associated with VET and GSM were queried. Satisfaction with their care on a 5-point Likert scale (3 coded to the neutral value with 5 being high) was assessed. ResultsRespondents (n=1,505) had a mean age of 57.6 years (SD 10.8).The majority (87%) were white, 13.7% were perimenopausal, and 872 (57.9%) were post-menopausal. 999 (69%) of women reported at least one genitourinary symptom associated with menopause. Of the 323 women who received a prescription 13% did not use it due to cost and 38.4% for fear of side effects. Among current VET users, moderate to severe concern for risks listed on the package insert were reported for breast cancer (31.4%), endometrial cancer (27.2%), and cardiovascular issues (32.1%). ConclusionThe vast majority of survey respondents reported at least one symptom of GSM. VET usage was lower than reported GSM symptoms. Patient barriers to using VET include cost and fear of side effects. A quarter of women reported their symptoms were not adequately addressed by their provider. The majority of women using VET reported symptomatic improvement and that treatment was well-tolerated.

5158 Estrogen for Feminizing Gender Affirming Hormone Therapy: Understanding the Influence of Route of Administration and Dose on Serum Estradiol and Testosterone Levels

Abstract Disclosure: D.J. Slack: None. A. Di Via Ioschpe: None. M. Saturno: None. S. Kihuwa-Mani: None. U. Amakiri: None. S. Karim: None. D. Guerra: None. J.D. Safer: None. For feminizing gender affirming hormone therapy (GAHT), the Endocrine Society and WPATH SOC 8 suggest targeting testosterone (T) levels below 50 ng/dL and estradiol (E2) levels in the range of 100-200 pg/mL. Exogenous estrogen may be given via several routes of administration (ROA) and at a variety of doses, but little is known about how ROA and dose influence T and E2 levels. We sought to investigate the relationship between estrogen dosage, ROA, and hormonal profiles in trans feminine individuals. We conducted a chart review of patients in the Mount Sinai Health System and included all patients who had active prescriptions for feminizing GAHT with both T and E2 levels recorded (n = 585), excluding those with a history of orchiectomy. For oral (PO) estrogen, there was a negative correlation between dose and serum T (p < .01), LH (p < .05), and FSH (p < .05), but no correlation with E2. For transdermal (TD) estrogen, dose did not correlate with serum T, E2, LH, or FSH. For intramuscular (IM) estrogen, there was a positive correlation with serum E2 (p < .05), LH (p < .05), and FSH (p < .01), but no correlation with T. Individuals were then stratified into groups of T and E2 ranges that were determined via bell-curve frequency distributions. Within each group, the relative proportion of users of a given ROA, their mean dose of estrogen given via that ROA, and their resulting mean T and E2 levels were calculated. For users of IM estrogen, a significantly higher proportion of individuals had T < 50 ng/dL as opposed to T >= 50 ng/dL. IM users also much more frequently exhibited E2 >= 200 pg/mL than E2 < 200 pg/mL. For users of PO estrogen, a higher proportion of individuals had T >= 100 ng/dL compared to T < 50 ng/dL, with the proportion of those with T 50-99 ng/dL not differing from either group. A higher proportion of users of PO estrogen had E2 50 - 199 pg/mL compared to E2 < 25 ng/dL and E2 > 200 pg/mL, with the proportion of those with E2 25-49 pg/mL not differing significantly from either. For users of TD estrogen, there was a higher proportion of those with T 50 - 99 ng/dL compared to < 50 ng/dL and >= 200 ng/dL, with the proportion of those with T 100 - 199 ng/dL not differing from either group. A higher proportion of users of TD estrogen had E2 25 - 49 pg/mL compared to E2 100 - 199 pg/mL and E2 > 300 pg/mL, while the frequency of those with E2 < 25 pg/mL, 50 - 99 pg/mL, or 200 - 299 pg/mL did not differ significantly. Our results indicate a propensity for users of IM estrogen to achieve T suppression and to overshoot E2 targets, while users of PO estrogen were most likely to have E2 levels at-target but less likely to achieve T suppression. Users of TD estrogen appear least likely to achieve either target. While further research is needed to confirm and expand upon our findings, our data are an important step forward in providing clinicians with some predictive capability as to the serum E2 and T levels they might expect with the use of exogenous estrogen at a given dose and ROA. Presentation: 6/2/2024

5158 Estrogen for Feminizing Gender Affirming Hormone Therapy: Understanding the Influence of Route of Administration and Dose on Serum Estradiol and Testosterone Levels

Abstract Disclosure: D.J. Slack: None. A. Di Via Ioschpe: None. M. Saturno: None. S. Kihuwa-Mani: None. U. Amakiri: None. S. Karim: None. D. Guerra: None. J.D. Safer: None. For feminizing gender affirming hormone therapy (GAHT), the Endocrine Society and WPATH SOC 8 suggest targeting testosterone (T) levels below 50 ng/dL and estradiol (E2) levels in the range of 100-200 pg/mL. Exogenous estrogen may be given via several routes of administration (ROA) and at a variety of doses, but little is known about how ROA and dose influence T and E2 levels. We sought to investigate the relationship between estrogen dosage, ROA, and hormonal profiles in trans feminine individuals. We conducted a chart review of patients in the Mount Sinai Health System and included all patients who had active prescriptions for feminizing GAHT with both T and E2 levels recorded (n = 585), excluding those with a history of orchiectomy. For oral (PO) estrogen, there was a negative correlation between dose and serum T (p < .01), LH (p < .05), and FSH (p < .05), but no correlation with E2. For transdermal (TD) estrogen, dose did not correlate with serum T, E2, LH, or FSH. For intramuscular (IM) estrogen, there was a positive correlation with serum E2 (p < .05), LH (p < .05), and FSH (p < .01), but no correlation with T. Individuals were then stratified into groups of T and E2 ranges that were determined via bell-curve frequency distributions. Within each group, the relative proportion of users of a given ROA, their mean dose of estrogen given via that ROA, and their resulting mean T and E2 levels were calculated. For users of IM estrogen, a significantly higher proportion of individuals had T < 50 ng/dL as opposed to T >= 50 ng/dL. IM users also much more frequently exhibited E2 >= 200 pg/mL than E2 < 200 pg/mL. For users of PO estrogen, a higher proportion of individuals had T >= 100 ng/dL compared to T < 50 ng/dL, with the proportion of those with T 50-99 ng/dL not differing from either group. A higher proportion of users of PO estrogen had E2 50 - 199 pg/mL compared to E2 < 25 ng/dL and E2 > 200 pg/mL, with the proportion of those with E2 25-49 pg/mL not differing significantly from either. For users of TD estrogen, there was a higher proportion of those with T 50 - 99 ng/dL compared to < 50 ng/dL and >= 200 ng/dL, with the proportion of those with T 100 - 199 ng/dL not differing from either group. A higher proportion of users of TD estrogen had E2 25 - 49 pg/mL compared to E2 100 - 199 pg/mL and E2 > 300 pg/mL, while the frequency of those with E2 < 25 pg/mL, 50 - 99 pg/mL, or 200 - 299 pg/mL did not differ significantly. Our results indicate a propensity for users of IM estrogen to achieve T suppression and to overshoot E2 targets, while users of PO estrogen were most likely to have E2 levels at-target but less likely to achieve T suppression. Users of TD estrogen appear least likely to achieve either target. While further research is needed to confirm and expand upon our findings, our data are an important step forward in providing clinicians with some predictive capability as to the serum E2 and T levels they might expect with the use of exogenous estrogen at a given dose and ROA. Presentation: 6/2/2024

Efficacy and Safety of Intravaginal Estrogen in the Treatment of Atrophic Vaginitis: A Systematic Review and Meta-Analysis.

Postmenopausal females often experience genitourinary symptoms like vulvovaginal dryness due to estrogen decline. Hormone replacement therapy is effective in alleviating vaginal atrophy and genitourinary syndrome in this population. Evaluate local estrogen's safety and effectiveness for alleviating postmenopausal vaginal symptoms, including endometrial thickness, dyspareunia, vaginal pH, and dryness. We searched Google Scholar, Cochrane Library, ClinicalTrial.Gov, PubMed, and ScienceDirect databases until July 2023. All randomized controlled trials (RCTs) linking intravaginal estrogen supplementation to vaginal atrophy or vaginitis were included. The risk of bias was evaluated with RoB 2, and publication bias was assessed using Egger and Beggs analysis. All evidence pertains to females. Eighteen studies (n = 4,723) compared estrogen with placebo. Patients using estrogen showed a significant increase in superficial cells (mean differences [MD]: 19.28; 95% confidence intervals [CI]: 13.40 to 25.16; I² = 90%; P < 0.00001) and a decrease in parabasal cells (MD: -24.85; 95% CI: -32.96 to -16.73; I² = 92%; P < 0.00001). Vaginal pH and dyspareunia significantly reduced in estrogen users (MD: -0.94; 95% CI: -1.05 to -0.84; I² = 96%) and (MD: -0.52; 95% CI: -0.63 to -0.41; I² = 99%), respectively. Estrogen did not significantly affect vaginal dryness (MD: -0.04; 95% CI: -0.18 to 0.11; I² = 88%). Adverse events like vulvovaginal pruritis, mycotic infection, and urinary tract infection were reported, but the association was insignificant (risk ratio: 0.95; 95% CI: 0.88 to 1.02; I² = 0%). Our meta-analysis of 18 RCTs suggests promising potential for intravaginal estrogen therapy in alleviating vaginal atrophy and vaginitis in postmenopausal females.

Letrozole ovulation regimen for frozen-thawed embryo transfer in women with polycystic ovary syndrome: study protocol for a randomized controlled trial

BackgroundWomen with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the frozen-thawed embryo transfer (FET) during their IVF/ICSI treatment. The programmed regimen permits flexible scheduling of embryo transfer but requires long-term usage of exogenous estrogen and higher dosages of luteal support while the letrozole ovulation regimen needs lower dosages of luteal support only. Recently, multiple studies have shown that the letrozole ovulation regimen can improve pregnancy outcomes of FET in women with PCOS compared with the programmed regimen. However, most of these studies are retrospective, and prospective studies are urgently needed the evidence from the perspective study is insufficient.Methods/designWe are undertaking a multicentre, randomized, controlled clinical trial of an endometrial preparation regimen for FET in women with PCOS. The eligible women are randomly assigned to either the letrozole ovulation regimen or the programmed regimen for endometrial preparation. The primary outcome is the clinical pregnancy rate.DiscussionThe results of this study will provide evidence for whether the letrozole ovulation regimen for endometrial preparation could improve pregnancy outcomes in PCOS women undergoing FET.Trial registrationChinese Clinical Trial Registry ChiCTR2200062244. Registered on 31 July 2022.

Three-year outcomes of a randomized clinical trial of perioperative vaginal estrogen as adjunct to native tissue vaginal apical prolapse repair

As the muscular and connective tissue components of the vagina are estrogen responsive, clinicians may recommend vaginal estrogen to optimize tissues preoperatively and as a possible means to reduce prolapse recurrence, but long-term effects of perioperative intravaginal estrogen on surgical prolapse management are uncertain. This study aimed to compare the efficacy of perioperative vaginal estrogen vs placebo cream in reducing composite surgical treatment failure 36 months after native tissue transvaginal prolapse repair. This was an extended follow-up of a randomized superiority trial conducted at 3 tertiary US sites. Postmenopausal patients with bothersome anterior or apical vaginal prolapse were randomized 1:1 to 1-g conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally twice weekly for ≥5 weeks preoperatively and continued twice weekly for 12 months postoperatively. All participants underwent vaginal hysterectomy (if the uterus was present) and standardized uterosacral or sacrospinous ligament suspension at the surgeon's discretion. The primary report's outcome was time to failure by 12 months postoperatively, defined by a composite outcome of objective prolapse of the anterior or posterior walls beyond the hymen or the vaginal apex descending below one-third the total vaginal length, subjective bulge symptoms, and/or retreatment. After 12 months, participants could choose to use-or not use-vaginal estrogen for atrophy symptom bother. The secondary outcomes included Pelvic Organ Prolapse Quantification points, subjective prolapse symptom severity using the Patient Global Impression of Severity and the Patient Global Impression of Improvement, and prolapse-specific subscales of the 20-Item Pelvic Floor Distress Inventory and the Pelvic Floor Impact Questionnaire-Short Form 7. Data were analyzed as intent to treat and "per protocol" (ie, ≥50% of expected cream use per medication diary). Of 206 postmenopausal patients, 199 were randomized, and 186 underwent surgery. Moreover, 164 postmenopausal patients (88.2%) provided 36-month data. The mean age was 65.0 years (standard deviation, 6.7). The characteristics were similar at baseline between the groups. Composite surgical failure rates were not significantly different between the estrogen group and the placebo group through 36 months, with model-estimated failure rates of 32.6% (95% confidence interval, 21.6%-42.0%) and 26.8% (95% confidence interval, 15.8%-36.3%), respectively (adjusted hazard ratio, 1.55; 95% confidence interval, 0.90-2.66; P=.11). The results were similar for the per-protocol analysis. Objective failures were more common than subjective failures, combined objective and subjective failures, or retreatment. Using the Patient Global Impression of Improvement, 75 of 80 estrogen participants (94%) and 72 of 76 placebo participants (95%) providing 36-month data reported that they were much or very much better 36 months after surgery (P>.99). These data included reports from 51 of 55 "surgical failures." Pelvic Organ Prolapse Quantification measurements, Patient Global Impression of Severity scores, and prolapse subscale scores of the 20-Item Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire-Short Form 7 all significantly improved for both the estrogen and placebo groups from baseline to 36 months postoperatively without differences between the groups. Of the 160 participants providing data on vaginal estrogen usage at 36 months postoperatively, 40 of 82 participants (49%) originally assigned to the estrogen group were using prescribed vaginal estrogen, and 47 of 78 participants (60%) assigned to the placebo group were using vaginal estrogen (P=.15). Adjunctive perioperative vaginal estrogen applied ≥5 weeks preoperatively and 12 months postoperatively did not improve surgical success rates 36 months after uterosacral or sacrospinous ligament suspension prolapse repair. Patient perception of improvement remained very high at 36 months.

Prediagnostic use of menopausal hormone therapy and long-term survival of localized epithelial ovarian cancer: The Extreme study.

Use of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long-term MHT use, especially estrogen therapy (ET), was associated with improved long-term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long-term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000-2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo-values, 5- and 10-year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5-year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10-year survival. Use of MHT was not significantly associated with an improved 5- or 10-year survival in women with localized EOC (5-year relative survival probability = 0.95, 95% CI: 0.89-1.02; 10-year relative survival probability = 0.92, 95% CI: 0.84-1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long-term survival of localized EOC.

Effect of menopausal hormonal therapy on cardiovascular risks in Korean postmenopausal women: A nationwide cohort study.

To evaluate the association between menopausal hormonal therapy (MHT) and the risk of cardiovascular disease (CVD), according to various regimens, dosages, routes of administration and starting ages of MHT. A population-based cohort study using the Korean National Health Insurance Services database. Nationwide health insurance database. Women who reported entering menopause at an age of ≥40 years with no history of CVD in the national health examination. The study population comprised 1 120 705 subjects enrolled between 2002 and 2019, categorised according to MHT status (MHT group, n = 319 007; non-MHT group, n = 801 698). Incidence of CVD (a composite of myocardial infarction and stroke). The incidence of CVD was 59 266 (7.4%) in the non-MHT group and 17 674 (5.5%) in the MHT group. After adjusting for confounding factors, an increased risk of CVD was observed with the administration of tibolone (hazard ratio, HR 1.143, 95% CI 1.117-1.170), oral estrogen (HR 1.246, 95% CI 1.198-1.295) or transdermal estrogen (HR 1.289, 95% CI 1.066-1.558), compared with the non-MHT group; the risk was based on an increased risk of stroke. The risk trends were consistent regardless of the age of starting MHT or the physicians' specialty. Among tibolone users, a longer period from entering menopause to taking tibolone and the use of any dosage (1.25 or 2.5 mg) were linked with a higher risk of CVD, compared with non-MHT users. This nationwide cohort study demonstrated an increased risk of CVD, driven mainly by an increased risk of stroke, among tibolone and oral or transdermal estrogen users, compared with that of non-MHT users.

Association between C10X polymorphism in the CARD8 gene and inflammatory markers in young healthy individuals in the LBA study

BackgroundThe Caspase activation and recruitment domain 8 (CARD8) protein is a component of innate immunity as a negative regulator of NF- ĸB, and has been associated with regulation of proteins involved in inflammation. Expression of CARD8 mRNA and protein has been identified in human atherosclerotic lesions, and the truncated T30A variant (rs2043211) of CARD8 has been associated with lower C-reactive (CRP) and MCP-1 levels in myocardial infarction patients. The present study examines the role of a genetic variation in the CARD8 gene in relation to a selection of markers of inflammation.MethodsIn a cross-sectional study of young healthy individuals (18.0–25.9 yrs, n = 744) the association between the rs2043211 variant in the CARD8 gene and protein markers of inflammation was assessed. Genotyping of the CARD8 C10X (rs2043211) polymorphism was performed with TaqMan real time PCR on DNA from blood samples. Protein levels were studied via Olink inflammation panel (https://olink.com/). Using linear models, we analyzed men and two groups of women with and without estrogen containing contraceptives separately, due to previous findings indicating differences between estrogen users and non-estrogen using women. Genotypes were analyzed by additive, recessive and dominant models.ResultsThe minor (A) allele of the rs2043211 polymorphism in the CARD8 gene was associated with lower levels of CCL20 and IL-6 in men (CCL20, Additive model: p = 0.023; Dominant model: p = 0.016. IL-6, Additive model: p = 0.042; Dominant model: p = 0.039). The associations remained significant also after adjustment for age and potential intermediate variables.ConclusionsOur data indicate that CARD8 may be involved in the regulation of CCL20 and IL-6 in men. No such association was observed in women.These findings strengthen and support previous in vitro data on IL-6 and CCL20 and highlight the importance of CARD8 as a factor in the regulation of inflammatory proteins. The reason to the difference between sexes is however not clear, and the influence of estrogen as a possible factor important for the inflammatory response needs to be further explored.

Lower levels of the neuroprotective tryptophan metabolite, kynurenic acid, in users of estrogen contraceptives

Changes in kynurenine metabolites are reported in users of estrogen containing contraception. We have assessed kynurenines, vitamin B6, vitamin B2 and the inflammation markers, C-reactive protein (CRP) and neopterin, in healthy, never-pregnant women between 18 and 40 years (n = 123) and related this to their use of hormonal contraception. The population included 58 women, who did not use hormonal contraceptives (non-users), 51 users of estrogen-containing contraceptives (EC-users), and 14 users of progestin only contraceptives (PC-users). EC-users had significantly lower plasma kynurenic acid (KA) and higher xanthurenic acid (XA) levels compared to non-users. Serum CRP was significantly higher and negatively associated with both vitamin B6 and B2 status in EC-user compared to non-users. No significant differences in any parameters were seen between PC-users and non-users (p > 0.1). The low KA and high XA concentration in users of estrogen containing contraception resemble the biochemical profile observed in vitamin B6 deficiency. The hormonal effect may result from interference with the coenzyme function of vitamin B6 and B2 for particular enzymes in the kynurenine metabolism. KA has been suggested to be neuroprotective and the significantly reduced concentration in EC-users may be of importance in the observed increased risk of mood disorders among users of oral contraceptives.

The Relationship Between Myocardial Infarction and Estrogen Use: A Literature Review.

This thorough literature evaluation was prompted by significant research into the complex interactions between estrogen use and myocardial infarction (MI). Estrogenhas fascinated researchers because of its possible cardioprotective benefits and its impact on cardiovascular health. In order to clarify the connection between estrogen use and the risk of MI, this review critically examines the body of prior evidence. This review focuses on estrogen and its pivotal role in cardiovascular health, concentrating on lipid metabolism, vasodilation, inflammation, and endothelial function. It examines contentious data about estrogen therapy's heart-protective effects, taking into account age, initiation timing, dosage, and dosage of administration. Genetic and epigenetic influences on MI risk among estrogen users highlight intricate, personalized estrogen effects. The conclusion summarizes the main findings and emphasizes the need for an all-encompassing strategy for initiating and managing estrogen medication. It is crucial to consider patient-specific traits and risk factors to successfully customize treatment regimens. This review sheds vital light on the potential directions for better cardiovascular treatment for postmenopausal women by shedding light on the complex link between estrogen use and myocardial infarction. The review also identifies research gaps and future objectives in this area, highlighting the demand for novel medicines and individualized strategies to improve cardiovascular outcomes.

Wealth of Knowledge and Passion: Patient Perspectives on Vaginal Estrogen as Expressed on Reddit

To qualitatively analyze the knowledge, attitudes, and beliefs of women regarding genitourinary syndrome of menopause (GSM) and vaginal estrogen therapy as expressed on Reddit, a public, anonymous internet forum for discussion and information sharing. "r/menopause," a Subreddit with >30,000 subscribers, was queried for "vaginal estrogen" to collect postings related to vaginal estrogen in October 2022. Posts were analyzed qualitatively by 2 independent researchers. The principles of grounded theory were applied, and preliminary themes were generated. These themes were used to derive emergent concepts. Sixty-seven unique posts with 1101 responses were analyzed. Qualitative analysis revealed 5 preliminary themes: (1) questions regarding medication usage, (2) medication side effects, (3) medication alternatives, (4) frustration with the medical system, and (5) seeking validation for symptoms and experiences. Three emergent concepts were derived: (1) women experience bothersome side effects from menopause, and they desire compassionate and effective medical treatment; (2) women are engaged and active participants in their health and health care decisions; and (3) women perceive that their concerns are not taken seriously and seek validation for their medical conditions. Peri- and post-menopausal women have many questions and concerns about the condition of GSM and vaginal estrogen as treatment. They also have a broad range of frustrations including access to health care and questions about the usage of vaginal estrogen. By better understanding patient perspectives, physicians can better meet women's needs and improve care for GSM.

Age-Dependent Female Survival Advantage in Hepatocellular Carcinoma: A Multicenter Cohort Study

Hepatocellular carcinoma (HCC) has a higher incidence in males, but the association of sex with survival remains controversial. This study aimed to examine the effect of sex on HCC survival and its association with age. Among 33,238 patients with HCC from 12 Chinese tertiary hospitals, 4175 patients who underwent curative-intent hepatectomy or ablation were analyzed. Cancer-specific survival (CSS) was analyzed using Cox regression and Kaplan-Meier methods. Two propensity score methods and multiple mediation analysis were applied to mitigate confounding. To explore the effect of estrogen, a candidate sex-specific factor that changes with age, female participants' history of estrogen use, and survival were analyzed. There were 3321 males and 854 females included. A sex-related disparity of CSS was present and showed a typical age-dependent pattern: a female survival advantage over males appeared at the perimenopausal age of 45 to 54 years (hazard risk [HR], 0.77; 5-year CSS, 85.7% vs 70.6%; P= .018), peaked at the early postmenopausal age of 55 to 59 years (HR, 0.57; 5-year CSS, 89.8% vs 73.5%; P= .015), and was not present in the premenopausal (<45 y) and late postmenopausal groups (≥60 y). Consistent patterns were observed in patients after either ablation or hepatectomy. These results were sustained with propensity score analyses. Confounding or mediation effects accounted for only 19.5% of sex survival disparity. Female estrogen users had significantly longer CSS than nonusers (HR, 0.74; 5-year CSS, 79.6% vs 72.5%; P= .038). A female survival advantage in HCC depends on age, and this may be associated with age-dependent, sex-specific factors.

(014) Testosterone Therapy in Females Is Not Associated with Increased Cardiovascular Risk – A US Claims Database Analysis

Abstract Introduction Testosterone therapy (TT) has been shown to improve libido in females with sexual dysfunction; however, utilization of TT has been limited in part due to concern for increased cardiovascular risk. Objective Our objective was to assess the association of TT in females with major adverse cardiac events (MACE) using a large claims database. Methods A US-based claims database (TriNetX Diamond Network) of over 200 million patients was queried from 2009 to 2022. Our study cohort included adult (18+) females with three or more injectable or topical testosterone prescriptions excluding those with heart failure (ICD-10 I50), unstable angina (I20.0), intersex surgery female to male (CPT 55980), personal history of sex reassignment (Z87.890), and gender identity disorders (F64). Our control cohort excluded females with any testosterone prescriptions, heart failure, intersex surgery female to male, personal history of sex reassignment, gender identity disorder, unstable angina, polycystic ovary syndrome (E28.2), or androgen excess (E28.1). Propensity-matching between the cohorts was performed for age, ethnicity, race, estrogen usage (HS300), family history of cardiovascular disease (Z82.4), tobacco usage (Z72.0), type 2 diabetes (E11), hyperlipidemia (E78), hypertensive diseases (I10-16), and utilization of outpatient (1013626), inpatient (1013659), or emergency department services (1013711). MACE was defined as heart attack (I21, I22), stroke (I60, I61, I62, I63), or death within three years of the index event. We evaluated the association of TT to MACE, upper or lower emboli or DVT (I82.4, I82.6), pulmonary embolism (PE) (I26), breast neoplasm (C50), and hirsutism (L68.0). A sub-analysis by age-based stratification (18-55-year-old and &amp;gt;55-year-old) was also conducted. Results Adult females with ≥3 testosterone prescriptions (n=8,457) were compared to an equivalent number of propensity-score matched controls (Table 1). Compared to matched controls, those with testosterone prescriptions had similar odds of MACE (odds ratio (OR) 0.80 [95% CI 0.60, 1.07]) and PE (OR 0.77 [0.41, 1.46]); significantly lower odds of upper or lower emboli or DVT (OR 0.59 [0.35, 0.99]) and breast neoplasm (OR 0.43 [0.32, 0.59]); and higher odds of hirsutism (OR 2.34 [1.28, 4.29]). This trend remained in the age 18-55 years group (n=5,951): MACE (OR 0.67 [0.37, 1.21]), breast neoplasm (OR 0.41 [0.24, 0.70]), and hirsutism (OR 1.45 [0.79, 2.64]) (Table 2). A similar trend was observed amongst &amp;gt;55-year-olds (n=2,582): MACE (OR 1.18 [0.81, 1.72]), upper or lower emboli or DVT (OR 0.89 [0.45, 1.75]), and breast neoplasm (OR 0.49 [0.33, 0.72]) (Table 2). Odds ratios could not be calculated for any patient counts less than 10 (Table 2). Conclusions In this large claims-based analysis, we showed systemic TT in women does not increase the odds of MACE or PE, and is protective against upper and lower emboli or DVTs and breast neoplasm. Our results suggest that TT in women may be safe, enabling physicians to provide appropriate therapy to women with sexual dysfunction. Disclosure No

(011) Female Sexual Dysfunction Associated with Decreased Cardiovascular Risk – A US Claims Database Analysis

Abstract Introduction Erectile dysfunction can be a harbinger of underlying cardiovascular (CVD) risk factors in men. Despite the higher prevalence of sexual dysfunction among women than men, the association between vascular impairment and female sexual dysfunction (FSD) as well as the pathophysiology of FSD remains understudied. Objective Our objective was to assess the association of FSD with major adverse cardiac events (MACE) using a large claims database. Methods A US-based claims database network (TriNetX Diamond Network) was queried from 2009 to 2022 to create our cohorts. Our study cohort included adult (age 18+) females diagnosed with FSD (ICD-10 F52) excluding those with heart failure (I50) or unstable angina (I20.0). Our control cohort excluded females diagnosed with FSD, heart failure, or unstable angina. Propensity-matching between the cohorts for age, ethnicity, race, BMI, family history of CVD (Z82.4), tobacco usage (Z72.0), type 2 diabetes (E11), hyperlipidemia (E78), hypertension (I10), and utilization of inpatient (1013659), outpatient (1013626), or emergency services (1013711) was conducted. MACE was defined as heart attack (I21, I22), stroke (I60, I61, I62, I63), or death within five years of FSD diagnosis. A sub-analysis by age (18-40 years, 41-55 years, and &amp;gt;55 years) was conducted. Amongst the &amp;gt;55 years cohort, the effect of ≥3 vaginal estrogen prescriptions on MACE was evaluated. Results All results are reported for our study cohorts in comparison to an equivalent number of propensity-matched controls. Adult females diagnosed with FSD (n=65,265) had significantly lower odds of heart attack (odds ratio (OR) 0.26 [95% CI 0.22 – 0.30]), stroke (OR 0.29 [0.26 – 0.32]), death (OR 0.46 [0.41 – 0.51]), and any MACE event (OR 0.32 [0.30 – 0.34]) (Table 1). This trend remained in females aged 18-40 years (n=18,473) and diagnosed with FSD (Table 2); they had significantly lower odds of heart attack (OR 0.31 [0.16 – 0.59]), stroke (OR 0.27 [0.18 – 0.39]), death (OR 0.36 [0.21 – 0.63]), and any MACE event (OR 0.30 [0.22, 0.39]). Among 41–55-year-olds (n=21,648) with FSD, (Table 2) we found our study cohort to have significantly lower odds of heart attack (OR 0.21 [0.15 – 0.29]), stroke (OR 0.26 [0.22 – 0.32]), death (OR 0.39 [0.30 – 0.50]), and any MACE event (OR 0.28 [0.24 – 0.32]) (Table 2). Finally, the population of individuals aged &amp;gt; 55 years (n=25,144) were found to have significantly lower odds of heart attack (OR 0.30 [0.25 – 0.36]), stroke (OR 0.35 [0.31 – 0.39]), death (OR 0.54 [0.47 – 0.62]), and any MACE event (OR 0.38 [0.36 – 0.42]). There was no difference in the odds of MACE event by vaginal estrogen usage in this age-group (OR 0.66 [0.31 – 1.38]). Conclusions In this large claims-based analysis, we demonstrated that females diagnosed with FSD had lower odds of MACE. Though screening for CV risk should be discussed with all patients, our results suggest that vascular impairment may not have a role in the pathophysiology of FSD. Disclosure No

PD20-04 TRENDS IN PROSTATE CANCER DIAGNOSIS IN TRANSGENDER WOMEN: A NATIONAL STUDY

You have accessJournal of UrologyCME1 Apr 2023PD20-04 TRENDS IN PROSTATE CANCER DIAGNOSIS IN TRANSGENDER WOMEN: A NATIONAL STUDY Farnoosh Nik-Ahd, Amanda De Hoedt, Christi Butler, Jennifer T. Anger, Peter R. Carroll, Matthew R. Cooperberg, and Stephen J. Freedland Farnoosh Nik-AhdFarnoosh Nik-Ahd More articles by this author , Amanda De HoedtAmanda De Hoedt More articles by this author , Christi ButlerChristi Butler More articles by this author , Jennifer T. AngerJennifer T. Anger More articles by this author , Peter R. CarrollPeter R. Carroll More articles by this author , Matthew R. CooperbergMatthew R. Cooperberg More articles by this author , and Stephen J. FreedlandStephen J. Freedland More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003286.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Little is known about prostate cancer (CaP) screening and diagnosis in transgender women (TW). To date, only 10 case reports have been published on CaP in this population. In this study, we sought to understand the clinical characteristics and CaP screening history at prostate cancer diagnosis among TW. METHODS: This is a retrospective study of all patients ages 18 and older across the entire Veterans Affairs Health System (VAHS) in the United States from January 2000-February 2022 with both an ICD code for CaP and at least one ICD code related to transgender identity. Detailed chart review was performed to stratify patients by gender-affirming hormone usage. Data abstracted included PSA at diagnosis, consistency of PSA screening, clinical stage, bilateral orchiectomy status, biopsy grade group, and primary treatment modality. Consistent PSA screening was defined as screening at least every 2 years between ages 55-69, as per American Urological Association screening guidelines. RESULTS: After detailed chart review, 133 TW with CaP were identified. After stratification by use of estrogen for gender-affirming hormone therapy, 99 had no prior estrogen use, 15 were formerly on estrogen but had stopped prior to diagnosis, and 19 were actively on estrogen at diagnosis. Only 25-33% of TW were undergoing consistent guideline-based PSA screening regardless of estrogen usage. Median duration of estrogen use was 44 months and 11 months, respectively, for those formerly on estrogen and those actively on estrogen at diagnosis. Among all patients, PSA, PSA density, and grade group were highest among those on estrogen at diagnosis followed by those formerly on estrogen. CONCLUSIONS: This is the largest study of CaP in TW to date. Nonetheless, our study population of 133 CaP patients was much lower than expected given the estimated TW population within the VAHS. The degree to which this represents the effects of estrogen therapy on CaP diagnosis and/or dramatic underdiagnosis due to limited guideline-based PSA screening even among those with CaP requires further study. Future work should aim to understand the incidence and long-term outcomes of CaP in this population and establish guidelines for CaP screening for those on gender-affirming hormone therapy. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e584 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Farnoosh Nik-Ahd More articles by this author Amanda De Hoedt More articles by this author Christi Butler More articles by this author Jennifer T. Anger More articles by this author Peter R. Carroll More articles by this author Matthew R. Cooperberg More articles by this author Stephen J. Freedland More articles by this author Expand All Advertisement PDF downloadLoading ...

Pulmonary embolism in menopausal hormone therapy: a population-based register study

Objective Oral but not transdermal menopausal hormone therapy (MHT) increases the risk of venous thromboembolism. There is no evidence regarding the risk of the serious complication pulmonary embolism (PE). The aim was to investigate the risk of PE in women using MHT depending on administration route, type of progestin and treatment duration. Method The population-based case-control study covered 1,771,253 women aged 40–69 years, during 2006–2015. Diagnoses of PE (n = 13,974) and drug dispensations were received from national validated registers. Results Current MHT users had a higher risk of PE than non-users (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.05–1.26). First ever users had the highest risk (OR 2.07, 95% CI 1.23–3.50). Transdermal administration was not associated with increased risk of PE. The OR was slightly but non-significantly higher with estrogen combined with medroxyprogesterone acetate than with norethisterone acetate. Discussion The risk of PE was significantly increased in users of oral but not transdermal MHT, with the highest risk in first ever users of oral estrogen combined with medroxyprogesterone acetate. The risk was considerably lower in women with recurrent treatment, probably because of the healthy user effect. Conclusion PE was most common close to initiation of oral treatment. Transdermal MHT did not increase the risk of PE.

The relationship between using estrogen and/or progesterone and the risk of mammary gland hyperplasia in women: a meta-analysis

Background As reported that the usage of estrogen and/or progesterone increases the risk of mammary gland hyperplasia (MGH) with conflicting results. Therefore, we conducted a meta-analysis to higher elucidate the relationship between hormones and MGH. Method PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, and Wan-fang database were searched for studies until April 28, 2021. Results Nine related studies were included in the present meta-analysis. We found that the usage of estrogen and/or progesterone had a significant association with increasing the risk of MGH (RR = 1.56, 95% CI: 1.13–2.15, p = .000). The subgroup results showed that the risk of MGH increased in the Mix population (RR = 1.72, CI: 1.58–1.88, p < .001) but no significant difference in the Asian population. Meanwhile, as for using estrogen plus progesterone (EPP) and postmenopausal women the risk of MGH, respectively, increased (RR = 1.74, CI: 1.22–2.47, p = .002) and (RR = 1.75, CI: 1.24–2.47, p = .001) but no significant different for using estrogen alone and premenopausal women. Conclusions This study findings indicated that using estrogen and/or progesterone might increase the risk of MGH in premenopausal and postmenopausal women.

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.

Continuing perioperative estrogen therapy does not increase venous thromboembolic events in transgender patients: a systematic review and meta-analysis.

The aim of this study is to compare the risk of venous thromboembolic events (VTE) between patients suspending and continuing estrogen therapy perioperatively, in male to female gender-affirming surgery (vaginoplasty). The authors conducted a systematic review and meta-analysis of existing research on male to female gender-affirming study, which compared the risk of VTE among the usage of estrogen perioperatively. A total of 209 studies were identified as potentially eligible among PubMed, Embase, and Cochrane library databases. Among the studies, 191 studies were excluded due to their abstract inappropriateness. Out of the remaining 18 studies, only 3 articles were eligible and were finally included. Meta-analysis was performed and showed odds ratio of 0.77 (95% CI: 0.04, 14.01). Perioperative estrogen therapy does not increase VTE risk on male to female gender-affirming surgery. Therefore, estrogen therapy may be continued perioperatively in vaginoplasty. More prospective studies are needed.