Baseline E2 Research Articles

Abstract PO2-11-06: Anti-Müllerian hormone in Young women with breast CAncer to predict permanent loss of ovarian function after chemotherapy and anti-HER2 therapy (AMYCA): a biomarker analysis of the BETH and KAITLIN trials

Abstract Background: The ability to predict and identify ovarian function loss accurately after anticancer treatment is important for appropriate oncofertility counseling and to aid in therapy decision making for young women with early breast cancer (eBC). Anti-Müllerian hormone (AMH) has been proposed as both a pre- and post-treatment predictor of subsequent permanent loss of ovarian function. The present biomarker analysis conducted within two randomized controlled trials (RCTs) in a large and well-characterized patient population with HER2+ eBC receiving homogeneous treatment aimed to assess AMH use, alone and in combination with other hormonal biomarkers, for predicting loss of ovarian function at 36 months from randomization, i.e. approximately 2 years after end of therapy. Methods: BETH (NCT00625898) and KAITLIN (NCT01966471) were RCTs investigating adjuvant chemotherapy (CT) plus anti-HER2 therapy in high-risk HER2+ eBC patients. For the purpose of the present analysis, only samples of patients receiving currently adopted treatments were used, i.e. cohort 1A (6 cycles of docetaxel/carboplatin+trastuzumab (T)) and cohort 2A (3 cycles of docetaxel plus T followed by 3 cycles of anthracycline- and cyclophosphamide-based CT) of BETH trial, and arm 1 (3-4 cycles of anthracycline- and cyclophosphamide-based CT followed by 3-4 cycles of taxane plus T plus pertuzumab (P)) of KAITLIN trial. Women selected for this analysis were ≤45 years with known premenopausal status, available serum samples at baseline (pre-treatment) and/or end of therapy and 36 months (± 6 months) from randomization (i.e. min of 2 samples in all cases). Selected samples were centrally tested measuring AMH, follicle stimulating hormone (FSH) and estradiol (E2) using Roche Elecsys assays. Permanent ovarian loss was defined as FSH >25 IU/L and E2 < 110 pmol/L at 36 months. Results: Of 194 included patients, 62 were from BETH and 132 from KAITLIN. 139 (71.6%) received both taxane and anthracycline- and cyclophosphamide-based CT and 55 (28.4%) taxane only. Pertuzumab was used in addition to trastuzumab in 132 (68.0%) patients. AMH values declined from baseline median 8.44 pmol/L to undetectable levels in many women at end of therapy (median 0.08 pmol/L), with partial recovery at 36 months (median 0.14 pmol/L). Ovarian loss at 3 years was observed in 56 women with AMH available at baseline (29.5%) and in 52 women with AMH available at end of therapy (29.7%). For prediction of ovarian loss, in ROC analysis, AMH measured at baseline showed AUC 0.784 (internally validated using bootstrap: 0.783). While age influenced risk of ovarian loss, addition to AMH only slightly improved AUC to 0.800 (internal validation: 0.795) while addition of baseline FSH and E2 did not improve prediction. AMH measured at the end of therapy showed AUC 0.741 (internal validation: 0.742), which increased slightly to 0.785(internal validation: 0.781) with addition of age but without improved prediction with the addition of FSH and E2. The combination of AMH at baseline and end of therapy increased prediction slightly to 0.808 (internal validation 0.806) and with addition of age added to 0.820 (internal validation: 0.806). Conclusions: These results support the use of pretreatment measurement of AMH in predicting loss of ovarian function in women withHER2+ eBC aged ≤45 receiving CT and anti-HER2 therapy. Measurement of AMH at end of treatment was comparably valuable to pretreatment and added slightly to the value of pretreatment sampling. Inclusion of ovarian function assessment by measuring AMH before commencing treatment can inform subsequent risk of ovarian function loss with value for fertility preservation counselling and treatment decisions. Further validation is required in larger cohorts. Citation Format: Matteo Lambertini, Deirdre Allegranza, Ruediger Laubender, Nadia Harbeck, Sandra Swain, Charles Geyer, Dennis Slamon, Gabriella Bobba, Chiara Lambertini, Sanne Lysbet De Haas, Eleonora Restuccia, Ines Vaz Luis, David Cameron, Ian Krop, Eric Winer, Richard Anderson. Anti-Müllerian hormone in Young women with breast CAncer to predict permanent loss of ovarian function after chemotherapy and anti-HER2 therapy (AMYCA): a biomarker analysis of the BETH and KAITLIN trials [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-11-06.

Longitudinal Changes in Sex Hormone Binding Globulin (SHBG) and Risk of Incident Diabetes: The Study of Women's Health Across the Nation (SWAN).

To investigate the associations of longitudinal changes in sex hormone binding globulin (SHBG) and testosterone (T) over the menopause transition with the risk of diabetes. We followed 2,952 participants in the Study of Women's Health Across the Nation (SWAN) who were premenopausal or early perimenopausal and diabetes-free at baseline. SHBG,T, and estradiol (E2) levels were measured at up to 13 follow-up visits (over up to 17 years). We used complementary log-log-based discrete-time survival models anchored at baseline. Diabetes developed in 376 women. A 5-unit increase in time-varying SHBG was associated with a 10% reduced risk of diabetes (hazard ratio [HR] 0.91, 95% CI 0.87-0.95), adjusting for covariates, and baseline SHBG,T, and E2 levels. Time-varying T was not associated with diabetes risk. Compared with the lowest quartile for annual rate of change of SHBG since baseline (quartile 1 [Q1] -92.3 to -1.5 nmol/L), all other quartiles were associated with a decreased risk of diabetes adjusting for covariates and baseline SHBG; associations persisted after adjusting for rate of change of T and E2 (Q2 [> -1.5 to -0.2 nmol/L] HR 0.33, 95% CI 0.23-0.48; Q3 [> -0.2 to 1.3 nmol/L] HR 0.37, 95% CI 0.25-0.55; Q4 [>1.3 to 82.0 nmol/L] HR 0.43, 95% CI 0.30-0.63). Increasing levels of SHBG over the menopause transition were associated with a decreased risk of incident diabetes. Stable to increasing rates of change in SHBG were also independently associated with a decreased risk of diabetes compared with decreasing rates of change, suggesting SHBG may affect glucose through a mechanism beyond androgenicity.

Estradiol-to-follicle ratio on human chorionic gonadotropin day is a novel predictor of gestational diabetes mellitus in women receiving fresh embryo transfer.

To assess the predictive value of estradiol (E2) related parameters on the incidence of gestational diabetes mellitus (GDM) in women undergoing fresh embryo transfer. A Post-hoc analysis of a prospective cohort study. We identified an optimal E2/follicle (E2/F) ratio threshold of 246.03 pg/ml on the day of human chorionic gonadotropin (hCG) administration. Women with an E2/F ratio exceeding this threshold had significantly lower rates of GDM (12.75% vs. 20.41%, P < 0.001) and ovarian hyperstimulation syndrome (OHSS) (11.75% vs. 15.48%, P = 0.03). Additional E2 parameters were also evaluated: baseline E2, E2 on hCG day, E2 increase, and E2 fold change. Lower GDM rates were observed in women with baseline E2 above 31.50 pg/ml (13.51% vs. 19.42%, P <0.01), E2 on hCG day above 3794.50 pg/ml (12.26% vs. 19.32%, P < 0.001), and E2 increase above 3771.50 pg/ml (12.24% vs. 19.28%, P < 0.001). There were no significant differences in OHSS rates for these additional E2 parameters. After adjusting for confounders, lower E2/F ratio (OR: 1.626, 95% CI: 1.229-2.150, P <0.01), E2 on hCG day (OR: 1.511, 95% CI: 1.133-2.016, P = 0.01), and E2 increase (OR: 1.522, 95% CI: 1.141-2.031, P <0.01) were identified as risk factors for GDM. This study demonstrates that an E2/F ratio over 246.03 pg/ml is significantly associated with a reduced risk of both GDM and OHSS in women undergoing fresh embryo transfer, highlighting the E2/F ratio as a superior predictive biomarker compared to other E2-related parameters.

Effects of letrozole on serum estradiol and estrone in postmenopausal breast cancer patients and tolerability of treatment: a prospective trial using a highly sensitive LC–MS/MS (liquid chromatography–tandem mass spectrometry) method for estrogen measurement

PurposeTo analyze serum estradiol (E2) and estrone (E1) during letrozole treatment and their association to Quality of Life (QoL) and side-effects.MethodsPostmenopausal breast cancer patients starting adjuvant letrozole were eligible. Serum samples were taken at baseline, three, and 12 months. E2 and FSH were measured with routine chemiluminescent immunoassays. E2 and E1 were analyzed after trial completion with a highly sensitive liquid chromatography-tandem mass spectrometry method (LC–MS/MS) with lower limits of quantification (LLOQ) of 5 pmol/L. QoL was measured at baseline and at 12 months with the EORTC QLQ-C30 and QLQ-BR23 and the Women’s Health questionnaires, and menopause-related symptoms with the modified Kupperman Index.ResultsOf 100 screened patients 90 completed the trial. Baseline mean LC–MS/MS E2 and E1 were 12 pmol/L (range < 5–57) and 66 pmol/L (< 5–226), respectively. E2 levels measured by immunoassay and LC–MS/MS showed no correlation. E2 and E1 were completely suppressed by letrozole except for one occasion (E1 11 pmol/L at 3 months). Pain, side effects of systemic therapy, vasomotor symptoms, joint and muscle aches, and vaginal dryness increased during letrozole treatment. A high baseline E2 was significantly associated with increased aching joints and muscles, but not with the other side effects.ConclusionsLetrozole supresses E2 and E1 completely below the LLOQ of the LC–MS/MS in postmenopausal women. High pre-treatment E2 levels were associated with more joint and muscle pain during letrozole. Automated immunoassays are unsuitable for E2 monitoring during letrozole therapy due to poor sensitivity.

Testosterone and luteinizing hormone predict semen parameter improvement in infertile men treated with anastrozole

To identify patient factors associated with a clinically significant improvement in semen parameters among infertile men treated with the aromatase inhibitor anastrozole. Multi-institutional retrospective cohort study. Two Tertiary Academic Medical Centers. A total of 90 infertile men treated at 2 tertiary academic medical centers who met inclusion criteria and obtained pretreatment and posttreatment semen analyses. Prescription of anastrozole (median 3 mg/wk). Upgrade in the World Health Organization sperm concentration category (WHO-SCC). Univariate logistic regression, multivariable logistic regression, and partitioning analyses were performed to identify statistically significant patient factors capable of predicting treatment response. With anastrozole treatment, 46% (n = 41/90) of men responded favorably with a WHO-SCC upgrade, and 12% (n = 11/90) experienced a downgrade. Responders exhibited lower pretreatment levels of luteinizing hormone (LH, 4.7 vs. 8.3 IU/L) and follicle-stimulating hormone (4.7 vs. 6.7 IU/mL), higher pretreatment levels of testosterone (T, 356 vs. 265 ng/dL), and similar baseline level of estradiol (E2, 73% vs. 70% with detectible level). Baseline semen parameters differed, with anastrozole responders demonstrating higher baseline semen concentration (3.6 vs. 0.3 M/mL) and higher total motile sperm counts (3.7 vs. 0.1 M). Anastrozole therapy converted 29% (n = 26/90) of the cohort to normozoospermia and enabled intrauterine insemination access in 31% (n = 20/64) of previously ineligible patients. Interestingly, neither body mass index nor the baseline E2 level or E2-T ratio was associated with WHO-SCC upgrade. Multivariable logistic regression revealed the T-LH ratio (odds ratio: 1.02, 95% confidence interval: 1.00-1.03) and baseline nonazoospermia (odds ratio: 9.4, 95% confidence interval: 1.1-78.9) to be statistically significant predictors of WHO-SCC upgrade (area under receiver operating characteristic curve: 0.77). The final user-friendly partitioning model consisting of the T-LH ratio ≥100 and baseline non-azoospermia was 98% sensitive and 33% specific for WHO-SCC upgrades (area under the curve: 0.77). Anastrozole therapy decreases serum E2 levels, increases serum gonadotropins, and clinically improves semen parameters in half of men with idiopathic infertility. Nonazoospermic infertile men with T-LH ratios ≥100 are likely to benefit from anastrozole treatment irrespective of baseline E2 level or E2-T ratio. Men with azoospermia rarely respond to anastrozole and should be counseled on alternative treatments.

The effect of rifampin on serum etonogestrel concentrations and biomarkers of ovulation among contraceptive implant users: A pharmacokinetic and pharmacodynamic study

ObjectivesRifampin, a strong CYP3A inducer, is the gold standard for evaluating CYP3A-mediated drug-drug interactions. We aimed to evaluate the pharmacokinetic and pharmacodynamic effects of a short course (2 weeks) of rifampin on serum etonogestrel (ENG) concentrations and serologic measures of ovarian activity (endogenous estradiol [E2] and progesterone [P4]) among ENG implant users. Study designWe enrolled healthy females using ENG implants for 12 to 36 months. We measured baseline serum ENG concentrations using a validated liquid chromatography mass-spectrometry assay and baseline E2 and P4 concentrations using chemiluminescent immunoassays. After 2 weeks of rifampin 600 mg daily, we repeated ENG, E2, and P4 measurements. We compared pre- and post-rifampin serum measurements using paired Wilcoxon signed-rank tests. ResultsFifteen participants completed all study procedures. Participants’ median age was 28.2 years (range 21.8–34.1), median body-mass index was 25.2 kg/m2 (range 18.9–37.3), and median duration of implant use was 22 months (range 12–32). All participants experienced significant decreases from baseline ENG concentrations (median 164.0 pg/mL [range 94.4–265.0]) to post-rifampin measurements (median 47.8 pg/mL [range 24.7–82.8]) (p < 0.001). Serum E2 concentrations also significantly increased with rifampin exposure (median 73 pg/mL vs 202 pg/mL, p = 0.003); increases in serum P4 concentrations were not statistically significant (p = 0.19). Three participants (20%) experienced increased luteal activity, with one presumptively ovulating post-rifampin (P4 = 15.8 ng/mL). ConclusionsWith only short exposure to a strong CYP3A inducer, ENG implant users experienced clinically significant decreases in serum ENG concentrations that led to changes in biomarkers indicative of waning suppression of ovulation. ImplicationsEven a short, 2-week course of treatment with rifampin places etonogestrel contraceptive implant users at risk for decreased contraceptive efficacy. Clinicians should counsel patients using etonogestrel implants considering any duration of rifampin therapy on the need for backup nonhormonal contraception or the use of an intrauterine device to avoid unintended pregnancies.

Associations of Estradiol With Mortality and Health Outcomes in Patients Undergoing Hemodialysis: A Prospective Cohort Study

Background: Both lower and higher estradiol (E2) levels have been associated with increased mortality among women with kidney failure. However, robust data are still lacking. Objective: We investigated the interaction of diabetes and age on linear and nonlinear associations between E2 levels, adverse outcomes, and health-related quality of life (HRQOL) in Canadian women undergoing hemodialysis (HD). Design: Population-based cohort study; data from Canadian Kidney Disease Cohort Study (CKDCS). Setting &amp; patients: A total of 427 women undergoing HD enrolled in the CKDCS. Measurements: Baseline E2 (in pmol/L) and E2 tertiles (&lt;38 pmol/L, 38-95 pmol/L, &gt;95 pmol/L). Methods: Cox-proportional hazards used for all-cause and cardiovascular disease (CVD) mortality. Fine-Gray models used for incident CVD. Mixed models used for Health Utilities Index Mark 3 (HUI3), Kidney Disease Quality of Life Physical Component Scores (KDQOL12-PCS), and Mental Component Scores (KDQOL12-MCS). Results: Over a median follow-up of 3.6 (interquartile range [IQR]: 1.6-7.5) years, 250 (58.6%) participants died; 74 deaths (29.6%) were CV-related. Among 234 participants without prior CV events, 80 (34.2%) had an incident CVD event. There were no significant linear associations between E2 and all-cause mortality, CVD mortality, and incident CVD. However, E2 showed a significant concave association with all-cause mortality, but not with CVD mortality and incident CVD. Among patients aged ≥63 years, higher E2 levels were associated with lower HUI3 scores, mean difference (MD) = –0.062 per 1 – SD pmol/L, 95% confidence interval (CI) = –0.112 to –0.012, but the opposite was observed in younger patients (&lt;63 years) in whom higher E2 levels were associated with higher HUI3 scores (MD = 0.032 per 1 – SD pmol/L, 95% CI = 0.008-0.055), Pinteraction = .045. No associations were observed among E2, KDQOL12-PCS (MD = –0.15 per 1 – SD pmol/L, 95% CI = –1.15 to 0.86), and KDQOL12-MCS (MD = –0.63 per 1 – SD pmol/L, 95% CI = –1.82 to 0.57). Limitations: Unmeasured confounding and small sample size. Conclusions: The association between E2 and all-cause mortality may be nonlinear, while no association was observed for CVD mortality, incident CVD, KDQOL12-PCS, and KDQOL12-MCS. Furthermore, the association between serum E2 and HUI3 was modified by age: Higher levels were associated with higher utility among women aged &lt;63 years and the converse observed among older women.

Baseline anxiety-sensitivity to estradiol fluctuations predicts anxiety symptom response to transdermal estradiol treatment in perimenopausal women – A randomized clinical trial

BackgroundThe menopausal transition (perimenopause) is associated with an increased risk of major depression, characterized by anxiety and anhedonia phenotypes. Greater estradiol (E2) variability predicts the development of perimenopausal depression, especially within the context of stressful life events (SLEs). While transdermal E2 (TE2) reduces perimenopausal depressive symptoms, the mechanisms underlying TE2 efficacy and predictors of TE2 treatment response remain unknown. This study aimed at determining relationships between E2 fluctuations, mood symptoms, and physiologic stress-reactivity (cortisol and interleukin-6) and whether differences in mood-sensitivity to E2 fluctuations predict mood responses to TE2 treatment. MethodsThis randomized, double-blind, placebo-controlled trial investigated medically healthy women (46–60 years) in the early or late menopause transition. Baseline E2-sensitivity strength was calculated from eight weekly individual correlations between week-to-week E2 change and index week anxiety (State-Trait Anxiety Inventory) and anhedonia (Snaith-Hamilton Pleasure Scale). Women then received eight weeks of TE2 or transdermal placebo. ResultsAnalyses included 73 women (active TE2 n = 35). Greater baseline E2 fluctuations predicted greater anhedonia (p = .002), particularly in women with more SLEs. Greater E2 fluctuations also predicted higher cortisol (p = .012) and blunted interleukin-6 (p = .02) stress-responses. Controlling for baseline symptoms, TE2 was associated with lower post-treatment anxiety (p < .001) and anhedonia (p < .001) versus placebo. However, the efficacy of TE2 for anxiety (p = .007) and also for somatic complaints (p = .05) was strongest in women with greater baseline E2 sensitivity strength. ConclusionsTE2 treatment reduced perimenopausal anxiety and anhedonia. The ability of baseline mood-sensitivity to E2 fluctuations to predict greater TE2 efficacy has implications for individualized treatment of perimenopausal anxiety disorders.

P-695 Anti-muellerian Hormone (AMH) and Plasminogen Activator Inhibitor (PAI-1) are robust follicular-fluid (FF) biomarkers predictive of follicle maturity and oocyte quality in women undergoing IVF cycles

Abstract Study question Is AMH the in-vivo trigger that correlates with PAI-1 in the follicular-fluid micro-milieu to influence maturity and quality of oocytes derived in vitro during IVF? Summary answer Lower FF-AMH levels correlate with top quality oocytes whereas Lower FF-PAI-1 levels correlate with follicle-maturity as reflected in mature MII oocytes retrieved in IVF cycles What is known already Ovulation is a time-coordinated tightly regulated proteolytic event. PAI-1, primarily produced by granulosa cells, is a major form of PAI in FF of human preovulatory follicles, allowing localized degradation and regulating ovulation.While ovulation process is rendered redundant in IVF cycles; nevertheless FF PAI-1 concentration may influence maturity of oocyte within the follicle. AMH is exclusively produced by granulosa cells of pre-antral &amp; early-antral ovarian follicles in the adult female and secreted into FF. Although AMH is widely accepted as an ovarian-reserve marker, very few studies have explored direct putative correlation of FF-AMH with oocyte quality in stimulated IVF cycles. Study design, size, duration Prospective study of n = 1150 (Power of study &amp;gt;85%) women (mean age 30.22±4.25 years, BMI 23.97±4.53, W/H ratio 0.88±0.06) undergoing antagonist stimulation protocol with r-FSH (September 2015-December 2018). On day of ovum pick-up, original aspirate per follicle was pooled per patient. AMH and PAI-1 were evaluated in pooled FF by ELISA method using diagnostic kits. These protein-biomolecules were expressed as ratio of total protein content. SerumE2, LH, P on d/hCG trigger were also estimated by RadioImmunoAssay. Participants/materials, setting, methods Elderly women (age&amp;gt;35 years), women with polycystic-ovaries, endometriosis were excluded. Embryo-transfer (ET) was done either on Day3 or day5. Luteal-phase was supported with micronized progesterone. All cycles were divided into Low FF-AMH (≤1.72 ng/mg protein), High FF-AMH (&amp;gt;1.72ng/mg protein) and Low FFPAI-1 (≤592.1 ng/mg protein), High FFAI-1 (&amp;gt;592.1 ng/mg protein) groups. Oocyte quality was graded as poor, average and top based on morphological assessment of COC-complex, zona-pellucida (thickness, regularity) and cytoplasm (granularity, vacuolation, refractile bodies). Main results and the role of chance Mean Age, Baseline D3-Serum AMH, E2 d/hCG and number of eggs retrieved did not differ significantly between low vs. High FF AMH groups as well as Low vs. High FF-PAI-1 groups. Low FF AMH group displayed significantly higher percent of top-quality oocytes (70.38±11.5 vs. 52.16±8.3;p&amp;lt;0.0001) and higher fertilization rates (88.68±10.7 vs. 72.5±9.2%; p = 0.004) compared to High FF AMH group. Incidences of total fertilization failure were significantly higher in high FF AMH (3.25% vs. 1.1%, p = 0.0002) compared to Low-FFAMH group. FF-AMH correlated with oocyte-quality (Pearsonr=0.48); lower-levels increased the odds of top-quality oocytes. Thresholds of FF-AMH for top quality oocytes was &amp;lt;1.8 ng/mg protein;ROCAUC:85%) Low FF PAI-1 group had significantly higher Percentage of MII oocytes (93.55 vs. 74.8%; p &amp;lt; 0.0001), Rates of Fertilization (86.35 vs. 71.04, p = 0.008) and cleavage (79.19 vs. 69.85;p=0.03) compared to High FF-PAI-1 group. FF-PAI-1 correlated with oocyte-maturity (Pearsonr=0.51), lower-levels increased the odds of obtaining MII-oocytes. Cutoff of FF PAI-1 for mature MII oocytes was &amp;lt;504.4 ng/mg protein;ROCAUC:76%). FF-AMH showed strong positive correlation with FF-PAI-1 (Pearsonr=0.66) Limitations, reasons for caution Several other molecules in the follicular-fluid milieu may be responsible for maturity status and quality of oocytes. Although these are apparently the most plausible of markers; role of other factors cannot be ruled out. Also, it may be better to study mono-follicular aspirates rather than pooled FF for each patient. Wider implications of the findings FF-levels of AMH and PAI-1 as non-invasive endogenous biomarkers of oocyte maturity and quality in-vitro may facilitate better understanding of the physiological pathway governing in-vivo ovulation process. This study reiterates ‘Follicle-maturation’ is the rate-determining step that sets off a cascade mechanism triggering oocyte-maturation and quality further influencing fertilization, embryo development. Trial registration number In patients with polycystic ovarian syndrome (PCOS), are serum androgen levels (total and free testosterone) associated with the risk of endometrial hyperplasia or cancer?

P-704 Post trigger progesterone levels as a predictor of oocyte recovery rate

Abstract Study question Do progesterone (P) levels the day after trigger for oocyte maturation impact the oocyte recovery rate? Summary answer A progesterone cutoff value of ≤ 5.0 ng/ml the day after trigger for oocyte maturation is associated with a lower oocyte recovery rate. What is known already Oocyte maturation and embryo development are controlled by intra-ovarian factors such as steroid hormones. P exists in the follicular fluid, and it is known to mediate some luteinizing hormone (LH)- initiated periovulatory events through autocrine/paracrine mechanisms that help mediate granulasa cell luteinization and oocyte maturation. More importantly, a rise in P levels is associated with an adequate follicular rupture. To date, no study has evaluated if lower P levels after oocyte maturation induction are a reflection of impaired physiological periovulatory mechanisms required for the oocyte release from the follicular wall. Study design, size, duration This monocentric retrospective analysis from January 2017 to December 2021 included 435 controlled ovarian hyperstimulation cycles for in vitro fertilization (IVF)/ egg freezing. Serum P, estradiol (E2), bHCG, and LH levels were measured the day after trigger for oocyte maturation to assure adequate luteinization. Participants/materials, setting, methods Women &amp;lt;4O years, that underwent controlled ovarian hyperstimulation with a GnRH antagonist protocol and final oocyte maturation (when ≥2 follicles reached ≥18 mm in diameter) induction with dual trigger (Leuprolide acetate and hCG) were segregated into two groups: Group 1: progesterone cutoff value of ≤ 5.0 ng/ml the day after trigger; Group 2: progesterone cutoff value of ≥ 5.1 ng/ml the day after trigger. Main results and the role of chance 147 cycles in Group 1 were compared with 288 cycles on Group 2. No significant differences were noted in mean patient’s age, BMI, baseline FSH, AMH, baseline antral follicle count, serum P and E2 levels the day of trigger, total dose of gonadotropins, day of trigger as well as serum E2, LH, and bHCG levels the day after trigger among cohorts. A total of 5765 oocytes were retrieved: 1703 corresponding to group 1 and 4692 to group B. Women with progesterone levels higher than ≥5.1 ng/ml the day after trigger had a greater number of oocytes retrieved compared to women with a progesterone cutoff value of ≤ 5.0 ng/ml (16.3 ± 9.1 versus 11.5 ± 7.4, p = &amp;lt; 0.0001). The oocyte/follicle rate was also significantly higher in women in Group 2 vs Group 1 (80.3% vs 63.7%, p = 0.003) However, the mature oocyte (MII) rate was comparable among cohorts (Group 1: 78.0 ± 20.2% vs Group 2: 78.8 ± 17.7%, p = 0.38). Limitations, reasons for caution The retrospective nature of the study, small sample size, selected progesterone cutoff value, and progesterone assay techniques compared to other ART centers may limit the external validity of our findings. Wider implications of the findings Our findings suggest for the first time that lower progesterone levels after final oocyte maturation induction may be a result of compromised mechanisms associated with the release of the oocyte from the follicular wall as demonstrated by a lower oocyte recovery rate. Trial registration number NA

Intramuscular testosterone cypionate vs subcutaneous testosterone enanthate: Comparing the outcomes in hypogonadal men

ABSTRACT Introduction Intramuscular testosterone cypionate (IM-TC) is the conventional treatment option for hypogonadal men with baseline serum total testosterone (TT) less than 300 ng/dL; however, significant peaks in testosterone cause adverse effects including polycythemia and rise in estradiol (E2). Subcutaneous testosterone enanthate-autoinjectors (SCTE-AI) were designed with a lower testosterone peak-to-trough ratio of 1.8. Objective This dual-institutional study compared the TT, hematocrit (HCT), E2, and prostate-specific antigen (PSA) response to treatment with IM-TC versus SCTE-AI. Methods 263 hypogonadal men were treated with testosterone replacement therapy (TRT) via IM-TC or SCTE-AI. TT, HCT, E2, and PSA levels were obtained at baseline and 6- to 12-weeks post-treatment. Significant differences in baseline and post-treatment levels were identified by univariate analysis. Linear regression models determined whether treatment modality was independently associated with post-TRT levels of TT, HCT, E2, and PSA. Results Patients treated with SCTE-AI were significantly younger, had higher baseline TT levels, and lower baseline E2 levels (Table 1). Post-TRT, the SCTE-AI cohort had significantly lower HCT and E2, while TT and PSA levels were not significantly different between the treatment arms. After adjusting for significant differences with linear regression, SCTE-AI was associated with a 14% greater increase in trough TT levels compared to IM-TC (p=0.027) (Table 2a). Furthermore, SCTE-AI was independently associated with 41% and 26.5% lower post-therapy HCT (p&amp;lt;0.001) and E2 (p&amp;lt;0.001) levels, respectively, when compared to IM-TC (Table 2b-c). Neither TRT modality was associated with post-therapy elevation of PSA (p=0.691). TT: Total Testosterone; HCT: Hematocrit; E2: Estradiol; PSA: prostate-specific antigen Conclusions While IM-TC and SCTE-AI provide a significant increase in testosterone, SCTE-AI is associated with lower levels of post-therapy HCT and E2 compared to IM-TC after adjusting for significant covariates. SCTE-AI is an effective testosterone delivery system with a preferable safety profile over IM-TC. Disclosure Work supported by industry: no. A consultant, employee (part time or full time) or shareholder is among the authors (Antares Pharma, Clarus Therapeutics, Coloplast, Promescent, Viome).

Impact of Surgical Management of Endometrioma on Ovarian Reserve

Objective: The aim of this study was to explore the outcome of surgical removal of endometriotic cyst on ovarian reserve.&#x0D; Materials and methods: This prospective observational study was carried out in Infertility Care and Research Centre, Dhaka, Bangladesh between January 2011 and December 2018. One hundred and fifty-five patients, who had an ultrasonographic diagnosis of endometrioma measuring ³3 cm and underwent surgical excision due to subfertility were the candidates for this study. The exclusion criteria were a) previous ovarian cystectomy, b) removal of one ovary, c) irregular menstrual cycle, d) polycystic ovarian syndrome e) endocrine disorder, f) low AMH (&lt;1ng/ml), g) history of taking medication for endometriosis that could affect ovarian function, e.g., GnRH analogues or oral contraceptives during the 6 months preceding scheduled surgery. To investigate the effect of surgery on ovarian reserve, their FSH, E2 and AMH were measured before and after surgery. Tests were done before surgery and repeated after 3 months and 6 months of surgery. A value of &lt; 0.05 was considered significant.&#x0D; Results: Mean age of the patients was 31.72 ±2.77 years. The baseline FSH, E2 and AMH were within normal limit. In 63.88% of the cases the cysts were unilateral and 83.22% of the cases the size of the cysts were within 10 cm. To assess the change of ovarian reserve FSH, E2 and AMH were measured in 3 and 6 months after surgery. There was marked declining of AMH level from baseline to both 3 months and 6 months after surgery p is &lt;0.0001. There was no significant change of FSH and AMH between 3 months and 6 months after surgery.&#x0D; Conclusion: Cystectomy in ovarian endometrioma significantly reduces ovarian reserve, which is menifested by reduced level of AMH.&#x0D; Bangladesh J Obstet Gynaecol, 2020; Vol. 35(2): 96-101

Abstract P2-07-04: Analysis of host inflammatory and estrogen biomarkers in JAKEE: A phase II trial of the JAK inhibitor ruxolitinib in combination with exemestane for estrogen receptor-positive metastatic breast cancer

Abstract Background: Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor outcomes and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) metastatic breast cancer (MBC). We previously presented clinical outcomes of JAKEE, a single arm, phase II, Simon two-stage clinical trial that tested Ruxolitinib (Rux), an oral selective inhibitor of JAK1/2, and exemestane (EXE) in 25 participants (pts) with HR+ MBC that relapsed/progressed on non-steroidal AI (NSAI); specifically, the primary endpoint of safety was met, but there were no complete or partial responses and 6/25 (24%) achieved stable disease (SD) for ≥6 cycles. We investigated whether host circulating inflammatory markers, IL-6 genotypes, and estrogen levels were associated with differential response to therapy.Methods: Responders (R) were defined as having achieved SD≥6 cycles. Flow cytometry was performed on baseline and on-treatment peripheral blood samples to assess downstream CD3+ T-cell phosphoSTAT3 inhibition by Rux. Serum concentrations of C-reactive protein (CRP), IL-6, serum amyloid A (SAA), Estrone (E1) and Estradiol (E2) were measured at baseline and serially on treatment. Sanger sequencing was performed to assess for three functional variants of the IL-6 promoter: −572G&amp;gt;C (rs1800796), −597G&amp;gt;A (rs1800797), and −174G&amp;gt;C (rs1800795), with high-risk polymorphisms being -597G/G and/or -174G/G. Non-parametric median testing was employed to test for differences in circulating markers by response groups given non-normal distribution, with a two-sided alpha of 0.05.Results: The cohort was heavily pre-treated: 28% received ≥2 lines of chemotherapy for MBC and 20% had CNS disease at enrollment. Among 17/25 pts with samples for pharmacodynamic assessment, Rux exhibited a 25% median inhibition (range 0-77%) of phosphoSTAT3. There was no differential effect in R vs non-responders (NR) (median inhibition 20% vs 29%, p=0.15). Frequency of high-risk IL-6 genotypes and distribution of baseline serum CRP, IL-6, SAA, E1 and E2 are depicted in the table. 15/25 (60%) harbored a high-risk IL-6 promoter polymorphism, with no significant difference in frequency between R and NR (50% vs 63%, p=0.65). 19 pts had samples for inflammatory biomarker analysis. 16/19 had baseline CRP≥10mg/L. While median levels of baseline CRP, SAA, and IL-6 were above upper limit of normal, there was no difference between R and NR (table). The proportion of pts with baseline undetectable E1 and E2 were similar between R and NR (E1: 36.9% vs 33.3%, p=1.0, E2: 52.6% vs 50%, p=1.0); notably, a significantly lower proportion with high-risk IL-6 genotype had undetectable baseline E1 (20% vs 60%, p=0.041), while no difference was noted for baseline E2, nor in the % change in E1 or E2 levels from baseline to cycle 4 by responder status.Conclusions: The JAKEE cohort represents an inflamed population with elevated circulating inflammatory markers and a high proportion with high-risk IL-6 genotypes. Examination of host inflammatory markers, IL-6 genotypes and estrogen levels did not reveal a differential response to the combination of Rux and EXE in patients with HR+ MBC that had progressed on prior NSAI. At tolerable dosing, Rux exhibited only a modest inhibition of phosphoSTAT3. Further work is needed to optimize strategies for targeting inflammation and JAK/STAT signaling in HR+ MBC. IL-6 GenotypeFrequencyFrequency by ResponderSignificanceHigh-Risk -174G/G and/or -597G/G15/25 (60%)Non-responder12/19 (63.2%)Responder3/6 (50%)p-value0.56Pretreatment Inflammatory Biomarkers [Upper limit of normal]Median (Range)Median Level by Responder GroupSignificanceCRP [8mg/L]SAA [10mg/L]IL-6 [2pg/mL]24.0 (0.2-146.8)12.8 (2.8-162.5)4.2 (1.8-11.5)Non-responder23.219.84.5Responder24.7 12.42.7p-value0.510.150.15Baseline Estrogen BiomarkersMedian (Range)Non-responderResponderp-valueEstrone (E1) (pg/mL)Estradiol (E2) (pg/mL)79.5.0 (0.2-1039.0)0.2 (0.2-44.1)79.8 0.247.8 4.20.410.91 Citation Format: Igor Makhlin, Nicholas McAndrew, E. Paul Wileyto, Amy Clark, Robin Holmes, Lisa N Bottalico, Grace R Jeschke, Kevin R Fox, Susan M Domcheck, Jennifer M Matro, Angela R Bradbury, Natalie Shih, Michael D Feldman, Elizabeth O Hexner, Jacqueline F Bromberg, Angela DeMichele. Analysis of host inflammatory and estrogen biomarkers in JAKEE: A phase II trial of the JAK inhibitor ruxolitinib in combination with exemestane for estrogen receptor-positive metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-07-04.

Association Between Sex Hormones and Visual Field Progression in Women With Primary Open Angle Glaucoma: A Cross-Sectional and Prospective Cohort Study.

Purpose: We evaluated the level of sex hormones in female patients with primary open angle glaucoma (POAG) to determine whether they are associated with the onset and/or progression of POAG.Methods: The cross-sectional study enrolled 63 women with POAG and 56 healthy women as normal control subjects. Furthermore, 57 women with POAG were included and followed-up for at least 2 years in the cohort study. All subjects were evaluated for serum concentration of sex hormones [prolactin (PRL), luteinizing hormone (LH), testosterone (TESTO), follicle-stimulating hormone (FSH), progesterone (PROG), and estrogen (E2)] and underwent visual field (VF) examination. In the cross-sectional study, Spearman analysis, linear regression analysis, and logistic regression analysis were performed to assess risk factors for POAG in women. In the cohort study, Cox regression analyses and Kaplan–Meier survival analysis were performed to identify factors associated with VF progression in women with POAG.Results: In the cross-sectional study, the level of E2 was significantly lower in the POAG group than in the normal group (p < 0.05). Multiple logistic regression showed that the decreased level of E2 was a risk factor of POAG (OR = 0.27, 95% CI = 0.09–0.78, p < 0.05), especially in premenopausal subjects. In the cohort study, there were 29 non-progression subjects and 28 progression subjects. Patients in the progression group had significantly lower levels of E2 than those in the no progression group (p < 0.01). The decreased level of E2 at baseline was associated with POAG progression (HR = 0.08, 95% CI = 0.02–0.46, p < 0.05), especially in premenopausal subjects. Patients with POAG and with lower baseline E2 levels had significantly lower VF non-progression rates than patients with higher E2 levels (log-rank test p < 0.001), especially premenopausal subjects (log-rank test p < 0.05). Additionally, logistic regression analyses, Cox regression analyses, and Kaplan–Meier survival analysis showed that PROG, LH, FSH, and TESTO were risk factors of POAG and/or significantly associated with POAG progression.Conclusion: A decreased E2 level is a POAG risk factor and is associated with VF progression in women with POAG, especially in premenopausal subjects. Additionally, other sex hormones (PROG, LH, FSH, and TESTO) might also play a role in POAG pathogenesis.

THE EFFECT OF OOCYTE MATURITY INDEX ON BLASTOCYST RATE AND PREGNANCY OUTCOMES

To determine the effect of oocyte maturity index on pregnancy outcomes in fresh and frozen embryo transfers All autologous day 5, non-PGT embryo transfers (ET) from 2017 to 2021 at a single academic fertility center were included. Both fresh and frozen ETs were evaluated based on oocyte maturity index (OMI), defined as the ratio of M2 to total oocytes retrieved. Primary outcomes studied were blastocyst rate (BR) (number of blastocysts per total number of 2PN) in the fresh cycle, clinical pregnancy (CPR), and live birth (LBR) rates. Cycle characteristics collected included: age, BMI, AMH, infertility diagnosis, days of stimulation, baseline E2, E2 and P4 at trigger, endometrial thickness, trigger medication, total oocytes retrieved, number of embryos transferred, and number of embryos cryopreserved. A total of 196 fresh and 480 frozen ETs were included in this study. In fresh ETs, 46 cycles had OMI ≤70% and 150 cycles had OMI >70%. Cycles with OMI ≤70% had a higher baseline E2 (p=0.04), higher E2 at trigger (p=0.04), and a greater number of oocytes retrieved (p=0.0004). Multiple logistic regression controlling for age and significant variables was performed, and CPR were higher in patients with OMI >70% (p=0.005). A prediction model was created using logistic regression assessing all variables associated with positive pregnancy outcome in the fresh cycle. AMH was inversely correlated with ongoing pregnancy rate (OR 0.931, 95% CI 0.861-0.995). Sub-analysis of OMI ≤70%, 71-80% (N=50), 81-90% (N=49), and 91-100% (N=51) showed that OMI is also inversely related to E2 at trigger (p=0.04) and total oocytes (p<0.0001). Additionally, OMI ≤70% had the highest baseline E2 (p=0.01). Between these groups, there were no statistical difference in BR, CPR, or LBR. In frozen ETs, 129 cycles had OMI ≤70% and 351 cycles had OMI >70%. OMI ≤70% had significantly higher BMI (p=0.01), AMH (p=0.002), E2 at trigger (p=0.001), and total oocytes retrieved (p<0.0001). In cycles that were able to proceed to a frozen transfer, OMI ≤70% had higher utilization of leuprolide-only trigger (p=0.03). Between these groups, there were no difference in CPR or LBR. In the sub-analysis, AMH, frequency of HCG trigger, E2 at trigger, and total oocytes retrieved were all inversely related to OMI. Many patients measure their success of IVF stimulation based on the number of oocytes retrieved. Markers of increased ovarian response include higher AMH, E2 at trigger, and number of oocytes retrieved. However, OMI were significantly decreased in cycles with these parameters. Despite these findings, OMI had no effect on blastocyst rate and only had an effect on CPR in the fresh cycle. Although supraphysiologic levels of steroid hormones may negatively affect implantation, this may be overcome by improved OMI. These negative effects also may also be overcome in frozen ETs where OMI did not impact CPR.

MP36-20 INTRAMUSCULAR TESTOSTERONE CYPIONATE VS SUBCUTANEOUS TESTOSTERONE ENANTHATE: COMPARING THE OUTCOMES IN HYPOGONADAL MEN

You have accessJournal of UrologySexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II (MP36)1 Sep 2021MP36-20 INTRAMUSCULAR TESTOSTERONE CYPIONATE VS SUBCUTANEOUS TESTOSTERONE ENANTHATE: COMPARING THE OUTCOMES IN HYPOGONADAL MEN Edward Choi, Perry Xu, Farouk El-Khatib, Faysal Yafi, and Parviz Kavoussi Edward ChoiEdward Choi More articles by this author , Perry XuPerry Xu More articles by this author , Farouk El-KhatibFarouk El-Khatib More articles by this author , Faysal YafiFaysal Yafi More articles by this author , and Parviz KavoussiParviz Kavoussi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002045.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intramuscular testosterone cypionate (IM-TC) is the conventional treatment option for hypogonadal men with baseline serum total testosterone (TT) less than 300 ng/dL; however, significant peaks in testosterone cause adverse effects including polycythemia and rise in estradiol (E2). Subcutaneous testosterone enanthate-autoinjectors (SCTE-AI) were designed with a lower testosterone peak-to-trough ratio of 1.8. This dual-institutional study compared the TT, hematocrit (HCT), E2, and prostate-specific antigen (PSA) response to treatment with IM-TC versus SCTE-AI. METHODS: 263 hypogonadal men were treated with testosterone replacement therapy (TRT) via IM-TC 100 mg weekly or SCTE-AI 100 mg weekly. TT, HCT, E2, and PSA levels were obtained at baseline and 6- to 12-weeks post-treatment. Significant differences in baseline and post-treatment levels were identified by univariate analysis. Linear regression models determined whether treatment modality was independently associated with post-TRT levels of TT, HCT, E2, and PSA. RESULTS: Patients treated with SCTE-AI were significantly younger, had higher baseline TT levels, and lower baseline E2 levels. Post-TRT, both cohorts had significant increases in trough TT compared to their respective baseline levels (IM-TC: 313.6 ng/dL to 536.4 ng/dL, p<0.001; SCTE-AI: 249.6 ng/dL to 540.4 ng/dL, p<0.001). When comparing between cohorts, the SCTE-AI cohort group had significantly lower HCT and E2, while TT and PSA levels were not significantly different between the treatment arms. After adjusting for significant differences with linear regression, SCTE-AI was associated with a 14% greater increase in trough TT levels compared to IM-TC (p=0.027). Furthermore, SCTE-AI was independently associated with 41% and 27% lower post-therapy HCT (p<0.001) and E2 (p<0.001) levels, respectively, when compared to IM-TC (Table 2b-c). Neither TRT modality was associated with significant post-therapy elevation of PSA (p=0.691). CONCLUSIONS: While IM-TC and SCTE-AI provide a significant increase in TT levels, SCTE-AI is associated with lower levels of post-therapy HCT and E2 compared to IM-TC after adjusting for significant covariates. SCTE-AI is an effective testosterone delivery system with a potentially preferable safety profile over IM-TC. Source of Funding: n/a © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e643-e644 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Edward Choi More articles by this author Perry Xu More articles by this author Farouk El-Khatib More articles by this author Faysal Yafi More articles by this author Parviz Kavoussi More articles by this author Expand All Advertisement Loading ...

The effect of prophylactic bilateral salpingectomy on ovarian reserve in patients who underwent laparoscopic hysterectomy

BackgroundBilateral salpingectomy has been proposed to reduce the risk of ovarian cancer, but it is not clear whether the surgery affects ovarian reserve. This study compares the impact of laparoscopic hysterectomy for benign disease with or without prophylactic bilateral salpingectomy on ovarian reserve.MethodsRecords were reviewed for 373 premenopausal women who underwent laparoscopic hysterectomy with ovarian reserve for benign uterine diseases. The serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and three-dimensional antral follicle count (AFC) were assessed before surgery and 3 and 9 months postoperatively to evaluate ovarian reserve. Patients were divided into two groups according to whether they underwent prophylactic bilateral salpingectomy. The incidence of pelvic diseases was monitored until the ninth month after surgery.ResultsThere was no significant difference between the two surgery groups in terms of baseline AMH, E2, FSH, LH, and AFC (all P > 0.05). There was no difference in potential bias factors, including patient age, operative time, and blood loss (all P > 0.05). There was also no significant difference between the two groups 3 months after surgery with respect to AMH (P = 0.763), E2 (P = 0.264), FSH (P = 0.478), LH (P = 0.07), and AFC (P = 0.061). Similarly, there were no differences between groups 9 months after surgery for AMH (P = 0.939), E2 (P = 0.137), FSH (P = 0.276), LH (P = 0.07) and AFC (P = 0.066). At 9 months after the operation, no patients had malignant ovarian tumors. The incidences of benign ovarian tumors in the salpingectomy group were 0 and 2.68 % at 3 and 9 months after surgery, respectively, and the corresponding values in the control group were 0 and 5.36 %. The incidences of pelvic inflammatory disease in the salpingectomy group were 10.72 and 8.04 % at 3 and 9 months after surgery, respectively, while corresponding values in the control group were 24.13 and 16.09 %.ConclusionsProphylactic bilateral salpingectomy did not damage the ovarian reserve of reproductive-age women who underwent laparoscopic hysterectomy. Prophylactic bilateral salpingectomy might be a good method to prevent the development of ovarian cancer. Larger clinical trials with longer follow-up times are needed to further evaluate the risks and benefits.

Determinants of attained estradiol levels in response to oral estradiol plus progesterone therapy

Objectives Among postmenopausal women taking hormone therapy (HT), the estradiol (E2) dose and E2 levels were differentially associated with change in metabolic measures. We evaluated determinants of attained E2 levels in response to HT. Methods Postmenopausal women from the REPLENISH trial tested four formulations of oral combined E2 and progesterone compared with placebo. Mixed-effects linear models assessed characteristics associated with E2 levels among women with ≥80% HT compliance, adjusted for E2 dose and baseline E2 level. Results Among 1173 postmenopausal women with mean (standard deviation) age 55 (4.3) years and 5.2 (4.8) years since menopause, higher treated E2 levels were significantly related to younger age, more recent menopause, and current alcohol use, while lower E2 levels were related to current smoking. Both age and time since menopause were significantly inversely associated with E2 levels; time since menopause had a stronger association with E2 levels. In the final multivariable model, E2 levels were positively associated with current alcohol use, and inversely associated with time since menopause and current smoking. Conclusion Adjusting for E2 dose and baseline E2 level, on-trial E2 levels were significantly associated with time since menopause, current smoking, and current alcohol use. Practitioners should consider these factors in individual women to achieve a desirable E2 level during HT.

Factors Associated With Serum Estradiol Levels Among Postmenopausal Women Using Hormone Therapy.

To identify factors associated with serum estradiol (E2) levels among healthy postmenopausal women using hormone therapy (HT). This is an unplanned post hoc analysis of data from ELITE (Early versus Late Intervention Trial with Estradiol), a randomized controlled trial of 1 mg oral E2 with or without vaginal progesterone in healthy early compared with late (<6 years compared with 10 or more years since menopause) postmenopausal women. We included results from visits when women reported at least 80% compliance with HT. Mixed-effects linear models identified factors associated with serum E2 levels while participants were taking HT, assessed every 6 months over a median follow-up of 4.8 years and adjusted for baseline E2 level, visit, and reduced E2 dose. Possible correlates evaluated included demographics, clinical characteristics, medication use, and biomarkers of liver and kidney metabolic function. The analysis included 2,160 E2 measurements in 275 postmenopausal women. Mean±SD age was 55.4±3.9 vs 64.4±5.5 years, and mean±SD time since menopause was 3.6±1.8 vs 16.0±5.6 years for early vs late postmenopausal women. Adjusted for pretreatment E2 level, visit, and reduced dose indicator, higher serum E2 levels were associated with higher body mass index (BMI), higher weight, surgical menopause, alcohol use, and antihypertensive medication use. Current and past smoking and antifungal medication use were associated with lower serum E2 levels. In the multivariable model, higher BMI and alcohol use were associated with higher serum E2 levels, whereas current and past smoking were associated with lower serum E2 levels. These factors were similar between early and late postmenopausal women. Factors associated with serum E2 levels among postmenopausal women taking HT include BMI, alcohol use, and smoking. As serum E2 levels relate to HT effect, achievement of desirable E2 levels may be maximized through personalized intervention. ClinicalTrials.gov, NCT00114517.

Association Between 17-β-Estradiol and Interleukin-8 and Visual Field Progression in Postmenopausal Women with Primary Angle Closure Glaucoma

To investigate an association between sex hormones and inflammatory cytokines, and to determine whether baseline 17-β-estradiol (E2) and interleukin-8 (IL-8) are associated with visual field (VF) progression in postmenopausal women with primary angle closure glaucoma (PACG). A prospective cross-sectional and cohort study. The cross-sectional study enrolled 200 postmenopausal women with PACG and 151 healthy postmenopausal women as normal control subjects. A total of 105 postmenopausal women with PACG were included and followed up for ≥2 years in the cohort study. All participants were evaluated for levels of baseline sex hormones (follicle-stimulating hormone, prolactin, progesterone, testosterone, luteinizing hormone, and E2) and inflammatory cytokines (IL-1, IL-2, IL-6, IL-8, IL-10, and C-reactive protein) and underwent VF examinations. The cross-sectional study was conducted to establish risk factors for postmenopausal women with PACG using logistic regression analysis. The cohort study was designed to identify factors that could be used to predict VF progression in postmenopausal women with PACG using multivariate Cox regression analyses. The main outcome measures included factors associated with VF progression over time. Decreased E2 (odds ratio 0.88 [95% confidence interval {CI} 0.78-0.99], P= .007) and increased IL-8 (odds ratio 1.12 [95% CI 1.01-1.23], P < .001) levels were risk factors in postmenopausal women with PACG. A significant negative correlation was observed between IL-8 levels and E2 (r=-0.21, P= .02). Multivariable regression analyses revealed a significant correlation between E2 levels and visual field mean deviation (MD) (B=-0.16, P= .04 [95% CI-.09 to-.003) and between IL-8 levels and MD (B= 0.36, P < .001 [95% CI 0.01-0.02]). During follow-up, 48 (45.71%) patients showed VF progression. Lower baseline E2 (hazard ratio 0.85 [95% CI 0.82-0.88], P= .04) and higher baseline IL-8 levels (hazard ratio 1.01 [95% CI 1.00-1.02], P= .004) were associated with progression of glaucoma. Patients with lower E2 levels had a significantly higher rate of PACG progression (log-rank test P < .001), similar to those with higher IL-8 levels (log-rank test P= .04). Decreased E2 and increased IL-8 levels at baseline are significant predictors of VF progression in postmenopausal women with PACG.