Life-threatening vaginal bleeding after starting rivaroxaban treatment.

This is a case report of a 44-year-old premenopausal woman who was admitted to hospital due to uncontrollable and life-threatening vaginal bleeding after starting rivaroxaban treatment for atrial fibrillation. She had a medical history with menorrhagia due to an intrauterine fibroma. She did not respond sufficiently to factor X supplement or other non-surgical medical interventions. The bleeding subsided after bilateral embolization of aa. uterinae.

Clomiphene citrate as a new modality in management of vaginal bleeding with depomedroxyprogesterone acetate (DMPA): A randomized controlled trial.

BACKGROUND: Depo-medroxyprogesterone acetate (DMPA) functions as a contraceptive method by inhibiting the secretion of gonadotropins, which prevents follicular maturation and ovulation, as well as thinning of the endometrium leading to unscheduled vaginal bleeding and subsequent discontinuation of DMPA. Our study aimed to evaluate the efficacy and safety of clomiphene citrate (CC) in stopping bleeding among DMPA users. MATERIALS AND METHODS: We randomly assigned 200 DMPA users using a computer-generated random numbers table in a 1:1 ratio to one of two groups; the study group, which received CC at a dose of 50 mg twice daily for five days (n = 100), and the control group, which received a placebo for five days (n = 100). Our primary outcome measure was the onset and duration of bleeding cessation. Secondary outcomes included endometrial thickness, recurrence of vaginal bleeding, and any reported side effects associated with CC use. RESULTS: Clomiphene citrate significantly resulted in early cessation of vaginal bleeding in 83 % of the patients, which continued for three months of follow-up. In addition, the recurrence of vaginal bleeding was significantly reduced in the CC group compared to the control group (11 % vs. 67 %; p < 0.001). Endometrial thickness was significantly greater in the CC group than in the control group (p < 0.001). Breast tenderness was more frequently reported in the study group, with no difference in dyspareunia between the two groups. CONCLUSIONS: Clomiphene citrate is effective in controlling bleeding among DMPA users. Further studies are encouraged to confirm our findings.

Management of abnormal uterine bleeding on anticoagulation: the patient-clinician perspective.

Bleeding is a well-recognized side effect of anticoagulant therapy, which is used to treat venous thromboembolism (VTE) in individuals of all ages, including those of female sex, who commonly experience VTE as a complication of hormonal therapies and/or pregnancy. Heavy menstrual bleeding (HMB) is also extremely common in reproductive-aged individuals of female sex. Despite these overlapping situations, relatively little attention has been paid to the impact of anticoagulant-associated HMB on treatment strategies and the patient experience. In this review, we summarize incidence and complications of HMB in anticoagulated individuals as well as management strategies for HMB in this population. We also address the patient experience, including the impact of HMB on quality of life and the impact of discontinuing hormonal therapies at the time of VTE diagnosis and anticoagulant initiation. We conclude by highlighting specific gaps related to the patient experience of anticoagulant-associated HMB in both the research and clinical settings.

Abnormal Uterine Bleeding Associated With Hormonal Contraception.

Abnormal uterine bleeding is a common and bothersome symptom in people using hormonal contraception, and it can lead to discontinuation of reliable methods of contraception and unintended pregnancies. Clinicians should counsel individuals about the potential for abnormal bleeding at initiation of the contraceptive method. After considering and excluding other potential causes of abnormal uterine bleeding, clinicians can offer treatment options specific to each hormonal contraceptive method. This article includes algorithms to help clinicians treat abnormal uterine bleeding in people using levonorgestrel intrauterine devices, depo-medroxyprogesterone acetate, progestin implant, progestin-only pills, and combined hormonal contraception. For patients with levonorgestrel intrauterine devices, physicians should first ensure that the device is correctly placed within the uterus, then consider nonsteroidal anti-inflammatory drugs as a first-line treatment for abnormal uterine bleeding; estradiol can be used if nonsteroidal anti-inflammatory drugs are ineffective. For depo-medroxyprogesterone acetate or progestin implant users, combined oral contraceptives or nonsteroidal anti-inflammatory drugs may be considered. For patients using norethindrone progestin-only pills, changing to drospirenone progesterone-only pills may help reduce the bleeding. In people using combined hormonal contraception, it may be helpful to increase estrogen content from 20 mcg to 35 mcg per day, decrease the hormone-free interval (from seven to four or five days) in people using cyclic contraception, or start a trial of low-dose doxycycline. For continuous combined contraception users, adding a hormone-free interval of four or five days can help regulate bleeding patterns.

Risk factors of heavy uterine bleeding in patients with endometriosis and adenomyosis treated with dienogest.

OBJECTIVE: Dienogest (DNG), a fourth-generation progestin, reduces pain associated with endometriosis and uterine adenomyosis; however, it is associated with irregular uterine bleeding that can cause anemia and poor quality of life. We investigated risk factors for heavy bleeding following DNG administration. MATERIALS AND METHODS: We retrospectively investigated patients who received DNG for risk factors of heavy uterine bleeding, including clinical diagnosis, use of pretreatment gonadotropin-releasing hormone agonist, smoking, cancer antigen 125, and blood hormone levels. We additionally assessed the uterine area in patients with uterine adenomyosis, the major axis of the uterine body, the major axis of myometrial thickness, the site of tumor development, and the site of myoma development in patients with uterine fibroids. RESULTS: Eighty Japanese patients were administered DNG. The median age was 41 (range: 24-51) years. The odds ratio (OR) for moderate-to-severe bleeding according to clinical diagnosis were 0.33 (P = 0.011) for endometrioma and 9.00 (P = 0.049) for uterine adenomyosis. Receiver operating characteristic curve analysis of the uterine area associated with uterine adenomyosis showed an area under the curve (AUC) of 0.909 between those with major and minor bleeding, with an optimal cut-off value of 7388.2 mm2. The uterine body major axis had an AUC of 0.946, with an optimal cut-off value of 78.3 mm. The major axis of myometrial thickness had an AUC of 0.855, with an optimal cut-off value of 46.8 mm. CONCLUSION: Patients with endometrioma treated with DNG were less likely to experience heavy uterine bleeding. Uterine bleeding in patients with uterine adenomyosis and adenomyosis associated with uterine fibroids should be closely monitored while administering DNG.

Abnormal uterine bleeding in anticoagulated patients by drug class: outcomes and management.

BACKGROUND: Although abnormal uterine bleeding is a known adverse effect of anticoagulant drugs, true rates have not been widely studied. Society-backed recommendations and guidelines do not yet exist for prevention and management of abnormal uterine bleeding among anticoagulated patients. OBJECTIVE: This study aimed to describe the incidence of new-onset abnormal uterine bleeding among patients receiving therapeutic anticoagulation by anticoagulant class, and to evaluate gynecologic treatment patterns. STUDY DESIGN: We conducted an institutional review board-waived retrospective chart review of female patients aged 18 to 55 years and prescribed therapeutic anticoagulants, including vitamin-K antagonists, low-molecular-weight heparins, and direct oral anticoagulants, in an urban hospital network from January 2015 through January 2020. We excluded patients with antecedent abnormal uterine bleeding and menopause. Associations between abnormal uterine bleeding, anticoagulant class, and other covariates were evaluated with Pearson chi-square and analysis-of-variance tests. The primary outcome, abnormal uterine bleeding odds by anticoagulant class, was modeled with logistic regression. Age, antiplatelet therapy, body mass index, and race were included in our multivariable model. Secondary outcomes included emergency department visits and treatment patterns. RESULTS: Of the 2479 patients who met the inclusion criteria, 645 were diagnosed with abnormal uterine bleeding after initiating therapeutic anticoagulation. After adjusting for age, race, body mass index, and concurrent use of antiplatelet therapy, those receiving all 3 classes of anticoagulants had higher odds of experiencing abnormal uterine bleeding (adjusted odds ratio, 2.63; confidence interval, 1.70-4.08; P<.001), whereas those taking only direct oral anticoagulants had the lowest odds (adjusted odds ratio, 0.70; confidence interval, 0.51-0.97; P=.032), with vitamin-K antagonists as the reference group. Race other than White was associated with higher odds of abnormal uterine bleeding, as was lower age. The most common hormone therapies used among patients with abnormal uterine bleeding were levonorgestrel intrauterine devices (7.6%; 49/645) and oral progestins (7.6%; 49/645). Sixty-eight patients (10.5%; 68/645) had an emergency department visit for abnormal uterine bleeding; 29.5% (190/645) of patients received a blood transfusion; 12.2% (79/645) began any pharmacologic therapy for bleeding; and 18.8% (121/645) underwent any gynecologic procedure. CONCLUSION: Abnormal uterine bleeding occurs frequently among patients on therapeutic anticoagulation. Incidence in this sample varied considerably by anticoagulant class and race; use of single-agent direct oral anticoagulation carried the lowest risk. Important sequelae such as bleeding-related emergency department visits, blood transfusions, and gynecologic procedures were common. Balancing bleeding and clotting risk in patients on therapeutic anticoagulation requires a nuanced approach and should involve collaborative management between hematologists and gynecologists.

Treatment of unfavorable bleeding patterns in contraceptive implant users: a randomized clinical trial of curcumin.

BACKGROUND: Some users of the etonogestrel contraceptive implant experience bothersome bleeding, which can reduce contraceptive satisfaction and continuation. Few strategies exist to manage this bleeding. The exact mechanism of progestin-induced bleeding is unknown, but it is likely multifactorial (eg, impaired angiogenesis, "leaky" fragile vasculature, and inflammation). Curcumin, the active ingredient in turmeric, has anti-inflammatory, antiproliferative, and antiangiogenic properties, which may make it a useful agent for implant-associated bothersome bleeding. OBJECTIVE: This study aimed to evaluate whether curcumin decreases frequent or prolonged bleeding or spotting in contraceptive implant users. STUDY DESIGN: The study was a randomized, double-blind, placebo-controlled trial. Here, etonogestrel implant users with frequent or prolonged bleeding or spotting were enrolled and randomized to either 600-mg Theracurmin HP (Immunovites, Las Vegas, NV) or placebo daily for 30 days. The term "frequent" was defined as ≥2 independent bleeding or spotting episodes, and the term "prolonged" was defined as ≥7 consecutive days of bleeding or spotting in a 30-day interval. Implant use was confirmed by clinical examination and negative gonorrhea and chlamydia and pregnancy tests. Enrolled participants initiated study treatment after 3 consecutive days of bleeding or spotting; if no bleeding or spotting occurred within 30 days of enrollment, the participants were withdrawn from the study. Study treatments were encapsulated to maintain a similar appearance. Participants used text messages to record daily bleeding patterns and study drug compliance. Bleeding was defined as a day that required the use of protection with a pad, tampon, or liner, and spotting was defined as a day with minimal blood loss that did not require the use of any protection. Our primary outcome was the total number of days without bleeding or spotting during the 30 days of study drug or placebo exposure. The secondary outcomes included total number of bleeding-free days, bleeding episodes, and satisfaction. A sample size of 22 per group provided 80% power at an alpha level of .05 to demonstrate a 6-day difference between groups. RESULTS: From February 2021 to November 2022, 58 individuals enrolled in the study with 54 participants (93%) completing 30 days of treatment (26 in the curcumin group and 28 in the placebo group). Of note, 1 individual in the curcumin arm did not experience a qualifying bleeding event and, thus, never initiated treatment and, per protocol, was withdrawn from the study. Participant characteristics did not differ between groups, including length of implant use at study enrollment (placebo, 521±305 days; curcumin, 419±264 days). The study groups did not differ concerning any bleeding-related outcome (mean days without bleeding or spotting: curcumin, 16.7±6.9; placebo, 17.5±4.8; P=.62; mean bleeding-free days: curcumin, 23.4±4.9; placebo, 22.4±4.5; P=.44; bleeding episodes: curcumin, 2.0±0.8; placebo, 2.1±0.8; P=.63). In addition, satisfaction with the implant as contraception and acceptability of bleeding over the study period did not differ by study group (P=.54 and P=.30, respectively). CONCLUSION: Daily use of curcumin did not improve bleeding patterns in users of the etonogestrel contraceptive implant experiencing frequent or prolonged bleeding patterns.

Clinical significances of Bishop score and vaginal bleeding to controlled-release dinoprostone delivery system (PROPESS) efficacy for cervical ripening: A retrospective single-center study in Japan.

AIMS: To evaluate the effect of vaginal bleeding on the efficacy of controlled-release dinoprostone delivery system (PROPESS) for cervical ripening and the factors affecting the PROPESS efficacy in a Japanese clinical setting. METHODS: A total of 100 term pregnant women in whom PROPESS was used due to an unfavorable cervix (Bishop score ≤ 6) were enrolled. We retrospectively investigated which factors, including vaginal bleeding, were associated with the success of cervical ripening using logistic regression analysis. Moreover, the effect of vaginal bleeding on vaginal acidity was examined in 24 selected cases (control, 11; rupture of membrane, 4; and vaginal bleeding, 8). RESULTS: A 25 women successfully ripened the cervix (effective group), and 75 were unsuccessful (noneffective group). Bishop score at insertion (adjusted odds ratio: 1.87; 95% confidence interval: 1.23-2.86; p = 0.004), and vaginal bleeding at PROPESS insertion (adjusted odds ratio 6.63; 95% confidence interval 1.21-36.36; p = 0.029) affected cervical ripening success. The cases with vaginal bleeding showed a significantly higher vaginal pH than the control cases (median value: 6.75 and 5.0, respectively). We identified no obvious adverse outcomes, such as tachysystole, fetal heart rate abnormality, or low Apgar/pH, associated with vaginal bleeding at insertion. CONCLUSIONS: Our findings suggest that the PROPESS efficacy depends on Bishop score at insertion and that vaginal bleeding at PROPESS insertion might have a significantly positive effect on cervical ripening in term pregnant women.

Effect of Mirena Intrauterine Device on Endometrial Thickness, Quality of Life Score, and Curative Effect in Patients with Perimenopausal Abnormal Uterine Bleeding.

Objective: To study the effect of Mirena intrauterine device (IUD) on endometrial thickness, life quality score, and curative effect in patients with perimenopausal abnormal uterine bleeding. Methods: Eighty patients with perimenopausal abnormal uterine bleeding cured from January 2020 to December 2021 were enrolled as the object of study. According to random number table, the patients were classified into the study (n = 40) and control (n = 40) groups. The control cases were cured with medroxyprogesterone. The study cases were cured with Mirena IUD. The effective rate of clinical therapies was evaluated after 3 months of treatment. The endometrial thickness, menstrual volume score, and life quality score (WHOQOL-BREF) was measured after 1 month, 2 months, and 3 months of treatment. Results: The effective rate of patients with Mirena IUD for 3 months was higher compared to the control group (P < 0.05). The endometrial thickness and menstrual volume scores of study cohort after 1 month, 2 months, and 3 months following treatment were remarkably lower than those before treatment (P < 0.05) and were considerably lower than those of control cohort (P < 0.05). The hemoglobin level of the studied cases after 1 month, 2 months, and 3 months after therapy was remarkably upregulated (P < 0.05) and was greatly higher compared to the controlled cases (P < 0.05). After 3-month treatment, the WHOQOL-BREF score of the study group was higher compared to the control group (P < 0.05). Conclusion: The Mirena IUD is far more effective in the treatment of perimenopausal abnormal uterine bleeding and is helpful in reducing the thickness of the endometrium. Patients' menstrual flow can be controlled, and anemia can be corrected; thus, patients improve their quality of life and health status and can be considered for further promotion.

Pooled analysis of two phase 3 trials evaluating the effects of a novel combined oral contraceptive containing estetrol/drospirenone on bleeding patterns in healthy women.

OBJECTIVE: To evaluate the bleeding patterns of a new combined oral contraceptive containing estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg in a 24/4-day regimen. STUDY DESIGN: We pooled bleeding data from two parallel, open-label, 13-cycle phase 3 trials that enrolled participants 16 to 50 years old with body mass index (BMI) ≤35 kg/m2. Participants reported vaginal bleeding/spotting in daily diaries. For this bleeding analysis, we included participants with at least one evaluable cycle. We calculated mean frequencies of scheduled and unscheduled bleeding/spotting episodes and median duration of bleeding/spotting episodes, and assessed associations between treatment compliance, BMI and recent hormonal contraceptive use on bleeding/spotting outcomes. RESULTS: We included 3409 participants with 33,815 cycles. Scheduled bleeding/spotting occurred in 87.2% to 90.4% of participants/cycle, with a median duration of 4 to 5 days. Unscheduled bleeding/spotting decreased from 27.1% in Cycle 1 to 20.6% in Cycle 2 to ≤17.5% from Cycle 5 onwards. Most (66.5%) unscheduled bleeding/spotting episodes were spotting-only. Between 5.8% and 7.8% of users/cycle experienced absence of any scheduled or unscheduled bleeding/spotting. Missing one or more active pills resulted in a higher occurrence of unscheduled bleeding/spotting (adjusted odds ratio [aOR] 2.13 [95% confidence interval 1.68-2.70]) and absence of scheduled bleeding/spotting (aOR 2.36 [1.82-3.07]). Participants with a BMI ≥30 kg/m2 reported more absence of scheduled bleeding/spotting (aOR 1.68 [1.37-2.05]). Switchers and starters reported similar frequencies of unscheduled bleeding/spotting (aOR 0.94 [0.83-1.07]) and absence of scheduled bleeding/spotting (aOR 1.00 [0.85-1.19]). Three percent of participants discontinued for a bleeding-related adverse event. CONCLUSION: E4/DRSP use results in a predictable bleeding pattern with limited unscheduled bleeding/spotting. Noncompliance and BMI affect bleeding patterns. IMPLICATIONS STATEMENT: Most estetrol/drospirenone users experience a predictable and regular bleeding pattern. Providers can educate patients about the expected bleeding patterns and should advise users that they may infrequently experience no scheduled bleeding/spotting. This information may improve user acceptability and continuation of this new oral contraceptive.

Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism.

Preliminary data and clinical experience have suggested an increased risk of abnormal uterine bleeding (AUB) in women of reproductive age treated with anticoagulants, but solid data are lacking. The TEAM-VTE study was an international multicenter prospective cohort study in women aged 18 to 50 years diagnosed with acute venous thromboembolism (VTE). Menstrual blood loss was measured by pictorial blood loss assessment charts at baseline for the last menstrual cycle before VTE diagnosis and prospectively for each cycle during 3 to 6 months of follow-up. AUB was defined as an increased score on the pictorial blood loss assessment chart (>100 or >150) or self-reported AUB. AUB-related quality of life (QoL) was assessed at baseline and the end of follow-up using the Menstrual Bleeding Questionnaire. The study was terminated early because of slow recruitment attributable to the COVID-19 pandemic. Of the 98 women, 65 (66%) met at least one of the 3 definitions of AUB during follow-up (95% confidence interval [CI], 57%-75%). AUB occurred in 60% of women (36 of 60) without AUB before VTE diagnosis (new-onset AUB; 95% CI, 47%-71%). Overall, QoL decreased over time, with a mean Menstrual Bleeding Questionnaire score increase of 5.1 points (95% CI, 2.2-7.9), but this decrease in QoL was observed only among women with new-onset AUB. To conclude, 2 of every 3 women who start anticoagulation for acute VTE experience AUB, with a considerable negative impact on QoL. These findings should be a call to action to increase awareness and provide evidence-based strategies to prevent and treat AUB in this setting. This was an academic study registered at www.clinicaltrials.gov as #NCT04748393; no funding was received.

Evaluation of the Efficacy and Adverse Reactions of Mirena Combined with Hysteroscopic Surgery When Treating AUB: Based on a Retrospective Cohort Study.

Objective: A case-control study was performed to explore the efficacy and adverse reactions of Mirena combined with hysteroscopy when treating AUB. Methods: 108 patients with perimenopausal AUB treated in our hospital from June 2019 to December 2021 were enrolled, and their clinical data were collected and analyzed retrospectively. According to the mode of treatment, the patients were assigned into control group (54 cases) and study group (54 cases). The therapeutic effects were compared. Visual analog score (VAS) was adopted to evaluate the degree of incision pain, Barthel index score was adopted to evaluate the ability of daily living, quality of life scale was adopted to investigate the quality of life before and after treatment, and the changes of sex hormone levels, endometrial thickness, and menstruation were detected before and after treatment. The incidence of adverse reactions was calculated. Results: In terms of the therapeutic effects, 46 cases were cured, 6 cases were effective, and 2 cases were ineffective in the study group, and the effective rate was 96.30%; in the control group, 32 cases were cured, 10 cases were effective, and 12 cases were ineffective, and the effective rate was 77.78%; the effective rate of the study group was higher than that of the control group (P < 0.05). In terms of VAS score, the VAS score decreased after treatment, and the VAS score in the study group was significantly lower than that in the control group at 1 week, 2 weeks, 1 month, and 3 months after treatment. With regard to the Barthel index scores after treatment, the Barthel index scores increased, and the Barthel index scores of the study group at 1 week, 2 weeks, 1 month, and 3 months after treatment were higher compared to the control group (P < 0.05). In terms of the Barthel index scores after treatment, the Barthel index scores increased, and the Barthel index scores of the study group at 1 week, 2 weeks, 1 month, and 3 months after treatment were higher compared to the control group (P < 0.05). Compared with those before treatment, the levels of FSH, LH, and E2 in both groups decreased remarkably (all P < 0.05). In terms of the changes of endometrium and menstruation, the endometrial thickness, menstrual time, and menstrual volume were significantly improved after treatment (P < 0.05). After treatment, the endometrial thickness, menstrual time, and menstrual volume in the study group were better than those in the control group (P < 0.05). With regard to the scores of qualities of life, the scores of qualities of life decreased after treatment. Compared between the two groups, the scores of physiological function, psychological function, social function, and health self-cognition in the study group were lower compared to the control group. Regarding the incidence of adverse reactions, in the study group, there were 1 case of breast pain, 2 cases of vaginal bleeding, and no dizziness and nausea, and the incidence of adverse reaction was 5.56%; In the control group, there were 1 case of dizziness, 2 cases of breast pain, 4 cases of nausea, and 3 cases of vaginal bleeding, and the incidence of adverse reactions in the study group was 18.52%. The incidence of adverse reactions in the study group was lower compared to the control group (P < 0.05). Conclusion: Hysteroscopy combined with Mirena when treating perimenopausal AUB can remarkably enhance the related symptoms, regulate the level of sex hormones, and remarkably reduce the amount of menstrual bleeding. The curative effect is better than hysteroscopy combined with dydrogesterone tablets, which is worth popularizing in clinic.

Efficacy of Uterine Artery Embolization for Treatment of Anticoagulant-Associated Abnormal Uterine Bleeding.

STUDY OBJECTIVE: Data regarding uterine artery embolization (UAE) to specifically treat anticoagulant-associated iatrogenic abnormal uterine bleeding (AUB-I) are sparse. This manuscript aimed to quantify the effectiveness of UAE in treating this subset of patients. DESIGN: Retrospective case series. SETTING: Academic hospital serving a large minority-majority population. PATIENTS: Twenty-four patients with AUB-I that was provoked or aggravated by the initiation of anticoagulation therapy. INTERVENTIONS: Treatment of anticoagulant-associated AUB-I that failed medical management or was acute with UAE rather than inferior vena cava filter placement and hysterectomy. MEASUREMENTS AND MAIN RESULTS: An imaging database search was performed to identify patients who underwent UAE for anticoagulant-associated AUB-I from May 2011 to July 2020. Medical and radiologic records were reviewed. Short- and long-term outcomes were obtained to date, ranging from 10 months to 10 years after the procedure. In total, 24 patients were identified, ranging in age from 35 to 54 (mean 44.9) years. Venous thromboembolic disease was the most common (92%) indication for anticoagulation. At presentation, 14 patients (58%) were anticipated to require lifelong anticoagulation. Most UAE procedures (54%) occurred within 10 days of anticoagulation initiation. Before UAE, 17 patients (71%) attempted and failed medical management, myomectomy, or endometrial ablation to control bleeding. After UAE, 21 patients (88%) experienced substantial improvement or resolution of AUB and continued anticoagulation therapy. Three patients (14%) did not experience improvement and were treated with hysterectomy. Amenorrhea immediately after UAE occurred in 1 patient at age 45. CONCLUSION: UAE was an effective tool in the management of anticoagulant associated AUB-I in this cohort, resulting in decreased bleeding while allowing the continuation of anticoagulation therapy, with high rates of uterine preservation and preserved menses.

Exposure of pregnant rats to stress and/or sertraline: Side effects on maternal health and neurobehavioral development of male offspring.

AIMS: Sertraline (SE) is one of the most prescribed medications for treating gestational depression, anxiety and stress. However, little is known about its effects on nervous-system development in offspring. Therefore, this study investigated the somatic, reflex and neurobehavioral development of rats exposed to SE during pregnancy, associated or not with stress. MAIN METHODS: Pregnant Wistar rats were assigned to the following groups (n = 10-8 rats/group): CO - control animals administered filtered water by gavage; SE - animals administered 20 mg/kg SE by gavage; ST - animals subjected to restraining stress and administered filtered water; ST/SE - animals subjected to restraining stress and administered 20 mg/kg SE. The treatment was administered between gestational days (GD) 13 to 20. Somatic and reflex developments were investigated in the male offspring from postnatal day (PND) 1 to 21. The elevated plus maze was performed on PND 25 and 80. The open field and light/dark box test were performed on PND 90 and 100, respectively. KEY FINDINGS: Body weight reduction and vaginal bleeding were observed in pregnant rats exposed to SE. The male offspring of the SE group showed delay in incisor eruption, fur development and negative geotaxis. In addition, the SE group was less exploratory (anxious personality) compared to the CO and ST groups. SIGNIFICANCE: The results obtained in the present study demonstrate that sertraline not only impairs maternal health, but also, associated or not with stress, can compromise the somatic, reflex and neurobehavioral development of male rats.

Overall and bleeding-related discontinuation rates of a new oral contraceptive containing 4 mg drospirenone only in a 24/4 regimen and comparison to 0.075 mg desogestrel.

OBJECTIVES: Progestin-only pills do not increase the risk of venous thromboembolism, stroke, and myocardial infarction but are associated with poor cycle control. A novel estrogen-free pill containing only drospirenone (DRSP) to improve bleeding patterns and tolerability and reduce discontinuation rates has been introduced into the market. The present study aims to describe the improvement in the acceptability of this DRSP-only pill, e.g. regarding the bleeding profile and the reduction in discontinuation rates due to unacceptable bleeding compared to desogestrel (DSG). STUDY DESIGN: Double-blind, double-dummy prospective phase III study in healthy women aged 18-45 years evaluating a total of 858 women with 6691 DRSP and 332 women with 2487 DSG treatment cycles. RESULTS: Overall, 82 (9.6%) women in the DRSP group and 44 (13.3%) women in the DSG group experienced treatment-emergent adverse events (TEAEs) leading to premature termination of the trial meaning that 32% more women in the DRSP group finished the trial in comparison to the DSG group (based on the AUC of Kaplan-Meier's curves). Discontinuation rates due to abnormal bleeding were 3.7% for DRSP and 7.3% for DSG users. This is a 55.7% lower discontinuation rate in the DRSP group compared to the DSG group. CONCLUSIONS: This report describes the improvement in acceptability and bleeding profile of women using the new DRSP-only oral contraceptive compared to DSG, providing a better quality of life and adherence to the contraceptive method as demonstrated by lower discontinuation rates of women using the estrogen-free DRSP-only pill.

Risk of Severe Abnormal Uterine Bleeding Associated with Rivaroxaban Compared with Apixaban, Dabigatran and Warfarin.

INTRODUCTION: There have been reports of clinically relevant uterine bleeding events among women of reproductive age exposed to rivaroxaban. OBJECTIVE: The aim of this study was to compare the risk of severe abnormal uterine bleeding (SAUB) resulting in transfusion or surgical intervention among women on rivaroxaban versus apixaban, dabigatran and warfarin. METHODS: We conducted a retrospective cohort study in the FDA's Sentinel System (10/2010-09/2015) among females aged 18+ years with venous thromboembolism (VTE), or atrial flutter/fibrillation (AF) who newly initiated a direct oral anticoagulant (DOAC; rivaroxaban, apixaban, dabigatran) or warfarin. We followed women from dispensing date until the earliest of transfusion or surgery following vaginal bleeding, disenrollment, exposure or study end date, or recorded death. We estimated hazard ratios (HRs) using Cox proportional hazards regression via propensity score stratification. Four pairwise comparisons were conducted for each intervention. RESULTS: Overall, there was an increased risk of surgical intervention with rivaroxaban when compared with dabigatran (HR 1.19; 95% CI 1.03-1.38), apixaban (1.23; 1.04-1.47), and warfarin (1.34; 1.22-1.47). No difference in risk for surgical intervention was observed for dabigatran-apixaban comparisons. Increased risk of transfusion was observed for rivaroxaban compared with dabigatran (1.49; 1.03-2.17) only. For patients with no gynecological history, rivaroxaban was associated with risk of surgical intervention compared with dabigatran (1.22; 1.05-1.42), apixaban (1.25; 1.04-1.49), and warfarin (1.36; 1.23-1.50). CONCLUSION: Our study found increased SAUB risk with rivaroxaban use compared with other DOACs or warfarin. Increased risk with rivaroxaban was present among women without underlying gynecological conditions. Women on anticoagulant therapy should be aware of a risk of SAUB.

Development of endometrial cancer after long-term usage of the levonorgestrel-releasing intrauterine system.

A 52-year-old long-term user of the levonorgestrel-releasing intrauterine system (LNG-IUS) presented with vaginal bleeding. Endometrial biopsy was performed and revealed endometrioid adenocarcinoma. The patient had a laparoscopic hysterectomy and bilateral salpingo-oophorectomy. Endometrial cancer is rare in women with LNG-IUS as only seven cases have been published in the literature. Although scientific evidence shows LNG-IUS has a protective effect on the endometrium from developing cancer, our report highlights the importance of clinicians to be vigilant in cases of women with LNG-IUS who develop intermittent vaginal bleeding.

Taking Call.

Telehealth proves to be more than just a stopgap in providing support to patients.

Office hysteroscopy safety and feasibility in women receiving anticoagulation and anti-platelet treatment.

OBJECTIVES: More than 60,000 hysteroscopies are performed every year in the UK for common reasons such as heavy menstrual bleeding (HMB) or postmenopausal bleeding. A significant number of women requiring hysteroscopy receive oral anticoagulants and there is often a reluctance to perform these procedures due to bleeding concerns. STUDY DESIGN: We are presenting the first proof of concept cohort of patients undergoing minor hysteroscopic procedures while on anticoagulant or antiplatelet medication. A variety of minor procedures such as cervical dilatation, targeted endometrial biopsies, Pipelle endometrial biopsies and insertion or removal of intrauterine contraceptive devices were performed alongside hysteroscopy. RESULTS: Completion of planned procedures was feasible in all women due to minimal bleeding despite the ongoing anticoagulation or anti-platelet treatment. CONCLUSION: More research is needed to establish the safety of performing diagnostic and operative hysteroscopies without bridging or interrupting anticoagulation or antiplatelet treatment.