Gene expression associated with unfavorable vaginal bleeding in women using the etonogestrel subdermal contraceptive implant: a prospective study.

To evaluate gene expression associated with unfavorable vaginal bleeding in users of the Etonogestrel (ENG) contraceptive implant. Prospective study involving 100 women who intended to use the ENG implant. Exclusion criteria included abnormal uterine bleeding, inability to attend a 1-year follow-up, and implant removal for reasons unrelated to vaginal bleeding or loss of follow-up. We obtained endometrial biopsies before implant placement and assessed the expression of 20 selected genes. Users maintained a uterine bleeding diary for 12 months post-implant placement. For statistical analysis, we categorized women into those with or without favorable vaginal bleeding at 3 and 12 months. Women with lower CXCL1 expression had a 6.8-fold increased risk of unfavorable vaginal bleeding at 3 months (OR 6.8, 95% CI 2.21-20.79, p < 0.001), while those with higher BCL6 and BMP6 expression had 6- and 5.1-fold increased risks, respectively. By the 12-month follow-up, women with lower CXCL1 expression had a 5.37-fold increased risk of unfavorable vaginal bleeding (OR 5.37, 95% CI 1.63-17.73, p = 0.006). Women with CXCL1 expression < 0.0675, BCL6 > 0.65, and BMP6 > 3.4 had a higher likelihood of experiencing unfavorable vaginal bleeding at 3 months, and CXCL1 < 0.158 at 12 months. Users of ENG contraceptive implants with elevated BCL6 and BMP6 expression exhibited a higher risk of breakthrough bleeding at the 3-month follow-up. Conversely, reduced CXCL1 expression was associated with an elevated risk of bleeding at both the 3 and 12-month follow-ups.

Assessment of quality of life, psychological aspects, and sexual function of women with endometriosis according to pain and infertility: a cross sectional study.

PURPOSE: To evaluate the quality of life, sexual function, anxiety, and depression of women with endometriosis according to pain symptoms and infertility. METHODS: This cross-sectional multicenter study included 229 women with endometriosis followed up at a tertiary hospital in Campinas, a tertiary hospital in São Paulo, and a reproductive medicine clinic in Campinas from 2018 to 2021. The women were divided into four groups according to the presence of pain symptoms and infertility. The Endometriosis Health Profile Questionnaire, Female Sexual Function Index, Beck Depression Inventory, and Beck Anxiety Index were applied to assess quality of life, sexual function, depression, and anxiety of women with endometriosis. RESULTS: The women were grouped as follows: group 1 (45 women without infertility and without pain), group 2 (73 women without infertility and with pain), group 3 (49 women with infertility and without pain), and group 4 (62 women with infertility and pain). Of the women with infertility, the majority had primary infertility. Most women had deep endometriosis (p = 0.608). Women with pain had higher anxiety and depression scores and worse quality of life than women without pain (p < 0.001). Regarding sexual function, all the groups were at risk for sexual dysfunction (p = 0.671). The group of women with pain and infertility have worse anxiety scores (25.31 ± 15.96) and depression (18.81 ± 11.16) than the other groups. CONCLUSION: Pain symptoms worsen anxiety, depression, and quality of life of women with endometriosis and when associated with infertility, greater impairment of psychological aspects may occur.

Gene expression associated with vaginal bleeding in women using the 52-mg levonorgestrel hormonal intrauterine device: A prospective study.

OBJECTIVE: To evaluate gene expression associated with vaginal bleeding in the 52-mg hormonal intrauterine device (IUD) users. MATERIALS AND METHODS: We conducted a prospective study involving 100 women seeking to use the 52-mg hormonal IUD for contraception. We excluded women with a history or current condition of abnormal uterine bleeding and who were unable to attend a 1-year follow up. Women who expelled the device, removed it for reasons unrelated to vaginal bleeding, or were lost to follow up were discontinued. We collected endometrial biopsies immediately before IUD placement and assessed 20 selected genes using reverse transcription quantitative polymerase chain reaction. Users maintained a uterine bleeding diary for 12 months following IUD insertion. For statistical analysis, participants were categorized into groups with or without vaginal bleeding at 3 and 12 months. RESULTS: Women with elevated CXCL9 expression had an 8.15-fold higher likelihood of experiencing vaginal bleeding at 3 months (odds ratio [OR] 8.15, 95% confidence interval [CI] 2.24-29.61, P = 0.001). At 12 months of follow up, women with increased TIMP1 expression had a 2.74-fold higher chance of experiencing vaginal bleeding (OR 2.74, 95% CI 1.08-6.95, P = 0.033). CXCL9 ≥ 1.5 and IL17A ≥ 0.68 were associated with a higher probability of vaginal bleeding at 3 months, while TIMP1 levels ≥0.943 were linked to an increased risk of bleeding at 12 months. CONCLUSION: Users of the 52-mg hormonal IUD with elevated relative CXCL9 expression face an increased risk of vaginal bleeding at 3-month follow up, whereas those with heightened TIMP1 expression are more likely to experience vaginal bleeding at 12 months.

Usefulness of Left Atrial Remodeling in Predicting CardiacToxicity During Trastuzumab Therapy for Breast Cancer.

Trastuzumab is a key therapy for patients with human epidermal growth factor receptor 2 positive breast cancer (BC). However, it may cause left ventricular dysfunction, resulting in withdrawal of therapy. Left atrium (LA) enlargement has proven to cue subclinical ventricular dysfunction in various clinical setting. Aim of the study was to investigate the association between LA volume index (LAVI) change over time and the development of Cancer Therapeutics Related Cardiac Dysfunction (CTRCD). Consecutive human epidermal growth factor receptor 2 positive BC patients were retrospectively included. Transthoracic echocardiography was performed before starting Trastuzumab and at every 3 up to 12 months. LA volume was measured using the modified Simpson's rule and indexed for body surface area. Ninety patients formed the study population. All patients had a complete 12 months follow-up. Mean baseline LAVI was 27 ± 8 ml/m2 and it was dilated (≥34 ml/m2) in 10 patients (11%). During follow-up, CTRCD occurred in 19 (21%) patients and there was modest LAVI enlargement, with a mean increase of 3 ± 2 ml/m2 (p = 0.0002 vs. baseline). LAVI dilation was significantly higher in patients with CTRCD (average increase at the time of CTRCD vs. baseline: 7 ± 6 ml/m2, p = 0.008), versus patients without CTRCD (average increase at 12 months of follow-up 2±1, p = 0.02), p for comparison = 0.004. LAVI dilatation over time predicted CTRCD independently from baseline LAVI values and the presence of systemic arterial hypertension (OR for 5 ml/m2 dilation was 1.56 [95%CI 1.09 to 2.37], p = 0.01). Trastuzumab related CTRCD is associated with significant LAVI morphological remodeling in BC patients.

Left atrial volume in patients with HER2-positive breast cancer: One step further to predict trastuzumab-related cardiotoxicity.

BACKGROUND: Trastuzumab (TZ) therapy requires careful monitoring of left ventricular (LV) ejection fraction (LVEF) because it can be potentially cardiotoxic. However, LVEF is an imperfect parameter and there is a need to find other variables to predict cardiac dysfunction early. Left atrium (LA) enlargement has proven to be a powerful predictor of adverse outcomes in several disease entities. HYPOTHESIS: Baseline LA volume enlargement might predict TZ-related LV dysfunction. METHODS: HER2-positive breast cancer patients receiving TZ and undergoing transthoracic echocardiography at baseline and at follow-up every 3 months were retrospectively recruited. One-hundred sixty-two patients formed the study population. RESULTS: Baseline LAVI was dilated in 14 patients (8.6%). Mean follow-up was 14 ± 4 months. Cardiotoxicity occurred in 24 patients (14.8%). LAVI was an independent predictor of TZ-induced LV dysfunction in a clinical model, after adjustment for age and hypertension (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.03-1.82, P = 0.03); and in a hemodynamic model, including ventricular sizes and systolic blood pressure level (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.01-1.81, P = 0.04). The predicted probability of developing cardiotoxicity increased progressively, in parallel with LAVI values. CONCLUSIONS: Baseline LA dilatation emerges as a condition associated with the development of cardiotoxicity in HER2-positive breast cancer patients treated with TZ.

Left ventricular end-diastolic volume as early indicator of trastuzumab-related cardiotoxicity in HER2+ breast cancer patients: results from a single-center retrospective study.

BACKGROUND: Adjuvant trastuzumab therapy increases survival rates in patients with early HER2-positive breast cancer, although it can be potentially cardiotoxic. The aim of this study was to evaluate the prevalence of left ventricular (LV) systolic dysfunction; and the relationship between the presence of cardiovascular risk factors, cardiac therapy and/or echocardiographic parameters of systolic function at baseline and the development of cardiotoxicity in such patients. METHODS: A total of 227 patients were retrospectively reviewed. Cardiotoxicity was defined as a decrease in LV ejection fraction (EF) below 50% or an absolute decrease of >10 points below the baseline value or any indication of heart failure. Each patient underwent echocardiography at baseline and at follow-up every three months. RESULTS: The prevalence of cardiotoxicity was 17.6% (15.4% asymptomatic, 2.2% symptomatic). Patients developing LV dysfunction presented hypertension (P=0.041) and diabetes (P=0.01) and used cardiac therapy at baseline more frequently. Smoke habit, age >50 and use of angiotensin-converting enzyme (ACE)-inhibitors, were independent predictors of cardiac damage. Furthermore, patients with LV dysfunction showed baseline LV end-diastolic volume (EDV) higher than those who did not and baseline EDV (OR=1.02; 95% CI: 1.00-1.04; P=0.027) independently predicted cardiotoxicity with 58 mL/m2 as best cut-off point (AUC=0.65, 95% CI: 0.55-0.75]). CONCLUSIONS: The prevalence of trastuzumab-related cardiotoxicity in patients with HER2-positive early breast cancer is relatively frequent, although asymptomatic in most cases. Baseline EDV resulted as independent predictor of cardiotoxicity suggesting that EDV may be more reliable than LVEF to identify patients at higher risk of developing cardiac damage.