OBJECTIVE: Identification of heavy menstrual bleeding (HMB) cases in primary care settings is often done by using pictorial blood assessment charts (PBAC). The study aims to highlight the challenge of assessing blood loss, to develop a standardized method to efficiently customize a patient-reported pictorial chart, to validate the tool produced with our proposed method, and to demonstrate the feasibility of using PBACs in settings where resources are scarce.
METHODS: Using blood samples and feedback from 21 women aged 30-51 years, we followed guidelines suggested in the literature, developed a method to produce PBACs for regular, long and night sizes, and had 9 participants testuse them. Linear regression analysis was performed to determine the correlation between participants\' scores and menstrual blood weight.
RESULTS: The study demonstrated the feasibility of customizing product-sensitive and size-specific pictorial charts by adopting essential steps including collecting menstrual blood with menstrual cups, employing fluid application techniques, and using sanitary pads as icons for easy identification. Linear regression analyses of score versus blood weight showed that the recorded blood weight was around 95% of the scored values (R2 = 0.9428, 0.947, and 0.9508, respectively; p < 0.001).
CONCLUSIONS: Valid patient-reported PBACs created by the proposed method provides an innovative women\'s healthcare solution to assist HMB identification and reduce health expenditure by preventing risks for HMB related complications in varying economic and technological contexts. Women\'s participation in tracking menstrual abnormalities may improve health literacy.

Objective: This study aims to determine the efficacy of the Acacia arabica (Lam.) Willd. and Cinnamomum camphora (L.) J. Presl. vaginal suppository in addressing heavy menstrual bleeding (HMB) and their impact on participants\' health-related quality of life (HRQoL) analyzed using machine learning algorithms. Method: A total of 62 participants were enrolled in a double-dummy, single-center study. They were randomly assigned to either the suppository group (SG), receiving a formulation prepared with Acacia arabica gum (Gond Babul) and camphor from Cinnamomum camphora (Kafoor) through two vaginal suppositories (each weighing 3,500 mg) for 7 days at bedtime along with oral placebo capsules, or the tranexamic group (TG), receiving oral tranexamic acid (500 mg) twice a day for 5 days and two placebo vaginal suppositories during menstruation at bedtime for three consecutive menstrual cycles. The primary outcome was the pictorial blood loss assessment chart (PBLAC) for HMB, and secondary outcomes included hemoglobin level and SF-36 HRQoL questionnaire scores. Additionally, machine learning algorithms such as k-nearest neighbor (KNN), AdaBoost (AB), naive Bayes (NB), and random forest (RF) classifiers were employed for analysis. Results: In the SG and TG, the mean PBLAC score decreased from 635.322 ± 504.23 to 67.70 ± 22.37 and 512.93 ± 283.57 to 97.96 ± 39.25, respectively, at post-intervention (TF3), demonstrating a statistically significant difference (p < 0.001). A higher percentage of participants in the SG achieved normal menstrual blood loss compared to the TG (93.5% vs 74.2%). The SG showed a considerable improvement in total SF-36 scores (73.56%) compared to the TG (65.65%), with a statistically significant difference (p < 0.001). Additionally, no serious adverse events were reported in either group. Notably, machine learning algorithms, particularly AB and KNN, demonstrated the highest accuracy within cross-validation models for both primary and secondary outcomes. Conclusion: The A. arabica and C. camphora vaginal suppository is effective, cost-effective, and safe in controlling HMB. This botanical vaginal suppository provides a novel and innovative alternative to traditional interventions, demonstrating promise as an effective management approach for HMB.

Adenomyosis is one of the structural causes of abnormal uterine bleeding, which often presents as heavy menstrual bleeding. Mostly because of the poor understanding of its pathophysiology, medical management of adenomyosis-induced heavy menstrual bleeding is still a challenge. We have previously reported that glycolysis is crucial to endometrial repair following menstruation and that suppressed glycolysis can cause heavy menstrual bleeding.
This study aimed to test the hypothesis that meclizine, a drug with an excellent safety profile, alleviates heavy menstrual bleeding in mice with induced adenomyosis using a simulated menstruation model.
Adenomyosis was induced in 36 female C57BL/6 mice using endometrial-myometrial interface disruption. Three months after induction, the mice were randomly divided into the following 3 groups: low-dose meclizine, high-dose meclizine, and controls. Treatment with meclizine or vehicle started shortly before the simulated menstruation procedure and ended before progesterone withdrawal. The amount of blood loss was quantified and uterine tissue was harvested for histologic evaluation of the grade of endometrial repair. We performed immunohistochemistry analysis of 4 proteins critically involved in glycolysis: Glut1 (glucose transporter 1), Hk2 (hexokinase 2), Pfkfb3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3), and Pkm2 (pyruvate kinase M2). The extent of tissue fibrosis in both ectopic and eutopic endometria was evaluated using Masson trichrome staining.
In mice with induced adenomyosis, meclizine accelerated endometrial repair in a dose-dependent manner and reduced the amount of menstrual bleeding. Meclizine administration raised endometrial immunoexpression of Hk2 and Pfkfb3 but not of Glut1 or Pkm2. The extent of endometrial fibrosis was reduced following the meclizine administration. Remarkably, these favorable changes were accompanied by the suppression of lesional progression, as evidenced by the dose-dependent reduction in the extent of fibrosis (a surrogate for lesional progression).
These encouraging results, taken together, suggest that glycolysis may be a promising therapeutic target and that meclizine may hold therapeutic potential as a nonhormonal treatment for adenomyosis-induced heavy menstrual bleeding without exacerbating the disease.

Abnormal uterine bleeding associated with ovulatory dysfunction (AUB-O) is a typical gynecological disease that can affect women of various ages. Being able to identify women at risk of AUB-O could allow physicians to take timely action. This study aimed to identify the influencing factors of AUB-O in Chinese women, and then develop and validate a predictive model.
In this multicenter case-control study, 391 women with AUB-O and 838 controls who came from nine hospitals in Zhejiang province were recruited between April 2019 and January 2022. All the participants completed a structured questionnaire including general characteristics, lifestyle and habits, menstrual and reproductive history, and previous diseases. The predictive model was developed on a group of 822 women and validated on a group of 407 women. Logistic regression was adopted to investigate the influencing factors and develop the model, and validation was then performed.
The independent predictive factors of AUB-O were age (OR 1.073, 95% CI 1.046-1.102, P < 0.001), body mass index (OR 1.081, 95% CI 1.016-1.151, P = 0.015), systolic blood pressure (OR 1.016, 95% CI 1.002-1.029, P = 0.023), residence (OR 2.451, 95% CI 1.727-3.478, P < 0.001), plant-based diet (OR 2.306, 95% CI 1.415-3.759, P < 0.001), fruits eating (OR 1.887, 95% CI 1.282-2.776, P = 0.001), daily sleep duration (OR 0.819; 95% CI 0.708-0.946, P = 0.007), multiparous (parity = 1, OR 0.424, 95% CI 0.239-0.752, P = 0.003; parity > 1, OR 0.450, 95% CI 0.247-0.822, P = 0.009), and history of ovarian cyst (OR 1.880, 95% CI 1.305-2.710, P < 0.001). The predictive ability (area under the curve) in the development group was 0.77 (95% CI 0.74-0.81), while in the validation group it was 0.73 (95% CI 0.67-0.79). The calibration curve was in high coincidence with the standard curve in the development group, and similar to the validation group. A tool for AUB-O risk calculation was created.
Nine influencing factors and a predictive model were proposed in this study, which could identify women who are at high risk of developing AUB-O. This finding highlights the importance of early screening and the lifelong management of ovulatory disorders for women.

What role, if any, does histone deacetylase 3 (HDAC3) play in adenomyosis-associated heavy menstrual bleeding (HMB)?
Seventy-two women with adenomyosis-associated HMB were recruited. Of these, 37 women reported moderate/heavy bleeding (MHB) and the remaining 35 women reported excessive bleeding (EXB). The stiffness of adenomyotic lesions and neighbouring endometrial-myometrial interface (EMI) was measured by transvaginal elastosonography, and full-thickness uterine tissue columns were processed for Masson trichrome staining and immunohistochemistry analyses. The protein expression levels of HDAC3 in endometrial cells cultured on substrates of different stiffnesses, and the protein concentrations of nuclear factor-κB (NF-κB) p65 subunit with HDAC3 suppression were evaluated. Mouse experiments were performed to assess the effect of adenomyosis on Hdac3 expression, endometrial repair and bleeding, and to evaluate the effect of HDAC3 inhibition on endometrial repair.
Compared with controls, the endometrial staining of HDAC3 was significantly lower in women with adenomyosis-associated HMB, concomitant with a greater extent of fibrosis. The stiffness of lesions and neighbouring EMI was significantly higher in the EXB group compared with the MHB group, as was the extent of fibrosis in lesions, their neighboring EMI and endometrium. Expression of HDAC3 was reduced significantly when endometrial epithelial cells were cultured in stiff substrates. Suppression of HDAC3 abrogated the activation and signalling of NF-κB. Mice with induced adenomyosis exhibited reduced Hdac3 staining and elevated fibrosis in endometrium, concomitant with disrupted endometrial repair and more bleeding. Hdac3 inhibition resulted in botched inflammation and increased bleeding.
Lesional fibrosis results in reduced endometrial HDAC3 expression and subsequent disruption in NF-κB signalling and inflammation, leading to adenomyosis-associated HMB.

OBJECTIVE: Vilaprisan is a highly potent selective progesterone receptor modulator shown to reduce heavy menstrual bleeding, induce amenorrhea, and diminish uterine fibroid volume in phase 2 studies. The objective of ASTEROID 3 was to demonstrate the superiority of vilaprisan compared with placebo in the treatment of heavy menstrual bleeding in women with uterine fibroids.
METHODS: Randomized, double-blind, placebo-controlled, multicenter phase 3 study.
METHODS: Hospitals and medical centers.
METHODS: Women with ≥1 uterine fibroid of ≥3 cm and heavy menstrual bleeding of >80 mL/cycle.
METHODS: Women were randomly assigned to 1 of 4 treatment arms, which were planned to comprise 2 treatment periods of 12 weeks, each with vilaprisan (2 mg/d) or placebo that were continuous or separated by a break of one bleed.
METHODS: Amenorrhea (primary end point; <2 mL in the last 28 days of treatment) and heavy menstrual bleeding response (key secondary end point; <80 mL/cycle and >50% reduction in bleeding from baseline) were measured with the alkaline hematin method. Change in volume of the 3 largest fibroids from baseline to end of treatment was assessed by ultrasound. Safety was monitored throughout the study.
RESULTS: Overall, 75 women completed the first 12 weeks of treatment. Statistically significant and clinically meaningful differences were observed between the vilaprisan- and placebo-treated groups in both the full analysis and per-protocol sets. In the per-protocol set (n = 36 and n = 12 for the vilaprisan and placebo groups, respectively), amenorrhea was observed more frequently in women treated with vilaprisan than in those who received placebo (83.3% vs. 0%, P<.0001), with a median time to onset of 3 days in the vilaprisan group. Similarly, more vilaprisan- than placebo-treated women achieved a response in heavy menstrual bleeding (91.7% vs. 25.0%, P<.0001). Serious adverse events were reported for 22 (27.8%) of 79 women and were evenly distributed among the 4 groups receiving vilaprisan and/or placebo. None of these events led to study discontinuation or were related to the liver, and no new safety findings were identified compared with the earlier phase 2 ASTEROID studies.
CONCLUSIONS: Vilaprisan is efficacious and well tolerated over 12 weeks in the treatment of heavy menstrual bleeding associated with uterine fibroids. Further investigations of the long-term efficacy and safety of vilaprisan are warranted.
BACKGROUND: NCT03400943 (ClinicalTrials.gov).

The Heavy menstrual bleeding: Evidence-based Learning for best Practice (HELP) Group developed an educational website about heavy menstrual bleeding (HMB). The \"HMB improving Outcomes with Patient counseling and Education\" (HOPE) project examined the website\'s impact on women\'s knowledge, confidence, and consultations with healthcare providers (HCPs). HOPE was a quantitative online survey of gynecologists and women with HMB in Brazil. After an initial consultation, patients had unlimited access to the website and completed a survey. HCPs also completed a survey about the sconsultation. After a second consultation, HCPs and patients completed another survey. HCP surveys assessed their perception of patients\' awareness, understanding, and willingness to discuss HMB. Patient surveys assessed their knowledge, experience, and confidence in discussing HMB. Forty HCPs recruited 400 women with HMB. Based on HCP perceptions at the first consultation, 18 percent of patients had \"good knowledge\" or \"very good knowledge\" of HMB, increasing to 69 percent after patients had visited the website. Before and after visiting the website, 34 percent and 69 percent of patients, respectively, regarded their HMB knowledge as \"goo.d\" Additionally, 17 percent of women reported their anxiety as \"highest\" during the first consultation; this decreased to 7 percent during the second consultation. After visiting the HELP website, patients\' knowledge of HMB improved and they were less anxious.

Widely viewed as an enigmatic disease, adenomyosis is a common gynecological disease with bewildering pathogenesis and pathophysiology. One defining hallmark of adenomyotic lesions is cyclic bleeding as in eutopic endometrium, yet bleeding is a quintessential trademark of tissue injury, which is invariably followed by tissue repair. Consequently, adenomyotic lesions resemble wounds. Following each bleeding episode, adenomyotic lesions undergo tissue repair, and, as such, platelets are the first responder that heralds the subsequent tissue repair. This repeated tissue injury and repair (ReTIAR) would elicit several key molecular events crucial for lesional progression, eventually leading to lesional fibrosis. Platelets interact with adenomyotic cells and actively participate in these events, promoting the lesional progression and fibrogenesis. Lesional fibrosis may also be propagated into their neighboring endometrial-myometrial interface and then to eutopic endometrium, impairing endometrial repair and causing heavy menstrual bleeding. Moreover, lesional progression may result in hyperinnervation and an enlarged uterus. In this review, the role of platelets in the pathogenesis, progression, and pathophysiology is reviewed, along with the therapeutic implication. In addition, I shall demonstrate how the notion of ReTIAR provides a much needed framework to tether to and piece together many seemingly unrelated findings and how it helps to make useful predictions.

OBJECTIVE: This study aimed to investigate whether the use of levonorgestrel intrauterine devices (LNG-IUD) in the perspective of traditional Chinese medicine (TCM) can improve the body constitution deviations and quality of life (QoL) in patients with chronic pelvic pain (CPP) and heavy menstrual bleeding (HMB).
METHODS: To understand the TCM body constitution differences between patients, patients with CPP from a gynecology clinic were first compared to a healthy control group from the Academia Sinica Taiwan Biobank (TWB). Patients with CPP were also compared with patients with pelvic diseases from the TWB. Patients with CPP and HMB, some who under LNG-IUD treatment, underwent tests for physical consistency. After 6-8 months, the TCM body constitution and QoL of patients who received LNG-IUD treatment were reanalyzed. The questionnaires used included the Self-Assessment Chart of Menstrual Bleeding, the Taiwanese version of the Pictorial Blood Loss Assessment Chart, the TCM Body Constitution Questionnaire, the 6-point Behavior Rating Scale, and the Taiwanese version of the Short Form-36 Health Survey. All data were analyzed using Wilcoxon\'s signed-rank test in SAS 9.4 software.
RESULTS: In total, 2932 healthy women and 724 women with pelvic diseases were present in the TWB project. Moreover, 376 patients with CPP were admitted to a gynecology clinic, of whom 42 received LNG-IUD treatment. After LNG-IUD treatment, the primary endpoint was regarded as an improvement in Yang-Xu (lack of energy), Yin-Xu (lack of material), and phlegm stasis (accumulation of pathological products). These findings indicated an improvement in menstrual blood loss, pelvic pain, physical functioning, physical problems, body pain, general health, and emotional problems (p < 0.05).
CONCLUSIONS: LNG-IUD treatment improves body constitution deviations in TCM and QoL in patients with CPP and HMB. Our results provide a valuable reference for the use of modern medicine and TCM in treating CPP and HMB.

The occurrence of heavy menstrual bleeding (HMB) induced by pharmacological agents has been reported in young adult women. This study aimed to investigate a possible association between the occurrence rates of HMB and different treatment methods such as antidepressant agents alone and in combination with other pharmacological agents. The examined cohort included young women (age 18-35 years, n = 1,949) with bipolar disorder (BP) or major depressive disorder (MDD). Menstruation history for 24 months was recorded and evaluated according to pictorial blood loss assessment charts of HMB. Multivariate analyses were conducted to determine odds ratios (ORs) and 95% confidence intervals. The examined antidepressant agents had varying ORs for patients with BP vs. those with MDD. For example, the ORs of venlafaxine-induced HMB were 5.27 and 4.58 for patients with BP and MDD, respectively; duloxetine-induced HMB, 4.72 and 3.98; mirtazapine-induced HMB, 3.26 and 2.39; fluvoxamine-induced HMB, 3.11 and 2.08; fluoxetine-induced HMB, 2.45 and 1.13; citalopram-induced HMB, 2.03 and 1.25; escitalopram-induced HMB, 1.85 and 1.99; agomelatine-induced HMB, 1.45 and 2.97; paroxetine-induced HMB, 1.19 and 1.75; sertraline-induced HMB, 0.88 and 1.13; reboxetine-induced HMB, 0.45 and 0.45; and bupropion-induced HMB, 0.33 and 0.37, in each case. However, when antidepressant agents were combined with valproate, the OR of HMB greatly increased, with distinct profiles observed for patients with BP vs. those with MDD. For example, the ORs of HMB induced by venlafaxine combined with valproate were 8.48 and 6.70 for patients with BP and MDD, respectively; for duloxetine, 5.40 and 4.40; mirtazapine, 5.67 and 3.73; fluvoxamine, 5.27 and 3.37; fluoxetine, 3.69 and 4.30; citalopram, 5.88 and 3.46; escitalopram, 6.00 and 7.55; agomelatine, 4.26 and 5.65; paroxetine, 5.24 and 3.25; sertraline, 4.97 and 5.11; reboxetine, 3.54 and 2.19; and bupropion, 4.85 and 3.46, in each case. In conclusion, some antidepressant agents exhibited potential risks of inducing HMB. Therefore, a combined prescription of antidepressant agents and valproate should be carefully considered for young women with HMB.