Effect of a single dose of a combination injectable contraceptive for treatment of bothersome uterine bleeding in contraceptive implant(s) users: A randomized double-blind placebo-controlled trial.

OBJECTIVES: This study aimed to determine the proportion of participants whose uterine bleeding/spotting was interrupted for at least 7 days during the month after they received a combined hormonal injection. We also evaluated bleeding at 21 days and 12 weeks after the injection. STUDY DESIGN: We conducted a randomized, double-blind, placebo-controlled trial in 46 contraceptive implant users who presented with bothersome uterine bleeding/spotting. A single dose of a combination injectable contraceptive or placebo was administered intramuscularly at enrollment. RESULTS: The proportions of participants whose uterine bleeding/spotting was interrupted for at least 7 days the month after they received a combined hormonal injection were higher in the combination injectable contraception group than in the placebo group (87% vs 48%, p = 0.005). Participants who reported that they were bleeding free at 21 days after treatment were 52% and 35% in the combination injectable contraception group and placebo group, respectively (p = 0.24). At 12 weeks posttreatment, 17% of participants in the combination injectable contraception group and 4% in the placebo group reported cessation of bleeding with no recurrence (p = 0.34). The median days until the first bleeding interruption was shorter in the combination injectable contraception group compared with the placebo group (1 [interquartile range, 1-2] vs 8 [interquartile range, 1-28], p = 0.007). CONCLUSIONS: The combination injectable contraception interrupted bothersome uterine bleeding/spotting in contraceptive implant(s) users compared with placebo. However, this effect was limited only within the month when the treatment was administered. IMPLICATIONS: Bothersome uterine bleeding/spotting is a common side effect leading to contraceptive implant(s) discontinuation. In implant users experiencing these symptoms with no estrogen contraindications, a combined injectable contraception appears to rapidly improve bleeding for the duration of injectable exposure (1 month).

A comparison of the effects of oral dydrogesterone and levonorgestrel-releasing intrauterine device on quality of life and sexual function in patients with abnormal uterine bleeding.

OBJECTIVE: The purpose of this study is to compare the effects of cyclic oral dydrogesterone treatment and levonorgestrel-releasing intrauterine device (LNG_IUD) on quality of life (QoL) and sexual function in patients diagnosed with abnormal uterine bleeding (AUB). STUDY DESIGN: The study was conducted at the University of Health Sciences Turkey Health Istanbul Kanuni Sultan Süleyman Training and Research Hospital, on 171 sexually active patients, aged 18-45, who were under a minimum of 6 months of treatment for AUB. 85 patients were treated with oral cyclic dydrogesterone, and 86 patients received LNG-IUD. Following a minimum of 6 months of treatment, these patients were recruited to the study and were asked to complete a 36-Item Short Form Survey (SF-36) and the Female Sexual Function Index (FSFI). RESULTS: When the FSFI scores of the patients were compared, it was observed that the total FSFI score was significantly higher in the cyclic dydrogesterone group (p < 0.05). Likewise, it was observed that sexual desire, arousal, and lubrication domains were significantly higher in the cyclic dydrogesterone group (p < 0.05). No significant differences were found between the treatment groups in 7 out of the 8 dimensions of SF-36. The energy/vitality dimension was found to be significantly higher in the cyclic dydrogesterone group. CONCLUSION: Total FSFI score, as well as sexual desire, arousal, and lubrication scores, were significantly higher in the cyclic dydrogesterone group compared to the LNG-IUD group indicating that cyclic dydrogesterone has a more positive impact on sexual function when compared to LNG-IUD.

Oral hormonal therapy as treatment option for abnormal uterine bleeding.

BACKGROUND: abnormal uterine bleeding is a very frequent reason for referral to gynaecologists and can deeply influence the quality of life. Once organic causes requiring surgical treatment are ruled out, clinicians should be able to manage these patients conservatively in the most effective way. MATERIALS AND METHODS: a search in PubMed/MEDLINE database was conducted in order to find relevant and recent meaningful sources for this narrative review. RESULTS: LNG-IUS 52 mg is the first-line treatment for non-organic causes. Nevertheless, it could be contraindicated or declined by the patient. Combined oral contraceptives (COC) and progestin-only pills inhibit the hypothalamic-pituitary-ovarian axis, preventing ovulation, and induce endometrial atrophy. Consequently, they are effective in treating AUB. Moreover, brand new pills containing a combination of oestrogens, progestins and GnRH antagonists are now available for the management of AUB related to uterine fibroids. CONCLUSIONS: In daily clinical practice, oral hormonal therapies are convenient and reversible tools to manage AUB when LNG-IUS 52 mg is contraindicated or turn down by the patient. Many oral hormonal therapies are prescribed to treat AUB, but only a few have been approved with this specific indication, therefore further large well-designed studies are necessary in order to compare the efficacy of different pills for treating AUB.

Even though LNG-IUS 52 mg is the first-line treatment for abnormal uterine bleeding, oral hormonal therapies should be effectively managed by gynaecologists in case of contraindications or patient's decline. Contraceptive pills are practical, but further studies are necessary to compare their efficacy and to approve them with the specific AUB indication.

LIBERTY randomized withdrawal study: relugolix combination therapy for heavy menstrual bleeding associated with uterine fibroids.

BACKGROUND: In the pivotal LIBERTY 1 and 2 trials and long-term extension study, once-daily relugolix combination therapy (40 mg relugolix, 1 mg estradiol, 0.5 mg norethindrone acetate) reduced menstrual blood loss volume and pain among women with uterine fibroids. Relugolix combination therapy was well tolerated with preservation of bone mineral density through 52 weeks. OBJECTIVE: This study aimed to report the 2-year relugolix combination therapy efficacy and safety results of the phase 3 LIBERTY randomized withdrawal study. STUDY DESIGN: Women with uterine fibroid-associated heavy menstrual bleeding who completed the 24-week LIBERTY 1 or 2 trials, followed by the 28-week long-term extension study (up to 52 weeks total treatment), and who met the responder criteria (menstrual blood loss volume <80 mL and ≥50% reduction from pivotal study baseline at week 48 [week 24 of long-term extension]) were randomized in a 1:1 ratio to either blinded treatment with relugolix combination therapy or placebo for 52 weeks (total treatment period, 104 weeks). For women who had a relapse of heavy menstrual bleeding during the study (menstrual blood loss volume ≥80 mL), open-label relugolix combination therapy was offered. The primary endpoint was the proportion of women who maintained menstrual blood loss volume <80 mL through week 76 (week 24 of randomized withdrawal study). Secondary endpoints included time to menstrual blood loss volume ≥80 mL, proportion of women who maintained a menstrual blood loss volume of <80 mL through week 104 (over the 52-week randomized treatment period), the proportion of women who achieved or maintained amenorrhea at week 76 at the end of treatment, and the change in Uterine Fibroid Symptom-Quality of Life Bleeding and Pelvic Discomfort Scale and symptom severity scores. Analyses were performed for the modified intent-to-treat population, including all randomized women who received ≥1 dose of the study drug. RESULTS: Of the 229 randomized women (relugolix combination therapy, n=115; placebo, n=114), 228 received the study drug and 175 (76.7%) completed the randomized withdrawal study. Through week 76, 78.4% of women on relugolix combination therapy maintained menstrual blood loss volume <80 mL vs 15.1% in the placebo group (difference, 63.4%; 95% confidence interval, 52.9%-73.9%; P<.0001). At week 104, 69.8% of women on relugolix combination therapy maintained menstrual blood loss volume <80 mL vs 11.8% in the placebo group (difference, 58.0%; 95% confidence interval, 47.0%-69.1%; P<.0001). Through week 104, 88.3% of women on placebo relapsed with heavy menstrual bleeding (median time to relapse, 5.9 weeks). Among the 89 women in the placebo group who relapsed and received open-label rescue treatment, 87 women responded to relugolix combination therapy with a menstrual blood loss volume <80 mL. The proportion of women who achieved or maintained amenorrhea were 57.4% vs 13.3% at week 76 (difference, 44.1%; 95% confidence interval, 33.10%-55.1%; P<.0001) and 58.3% vs 10.6% at week 104 (difference, 47.6%; 95% confidence interval, 37.0%-58.3%; nominal P<.0001) for relugolix combination therapy and the placebo group, respectively. Relugolix combination therapy was generally well tolerated; no new safety signals were identified, and the adverse event profile over the second year was consistent with that reported through the first year of treatment. Bone mineral density remained stable in women who received relugolix combination therapy from week 52 to week 104. In women continuously treated with relugolix combination therapy up to 2 years, bone mineral density was generally preserved. CONCLUSION: After 2 years of treatment with relugolix combination therapy, there was evidence of durability of the effect in maintaining low menstrual blood loss volume in women with symptomatic uterine fibroids. Most women had return of heavy menstrual bleeding and associated symptoms after treatment cessation, which improved upon retreatment with relugolix combination therapy. Relugolix combination therapy was well tolerated, the adverse event profile remained consistent, and the mean bone mineral density was generally preserved through 2 years of treatment.

Efficacy of estrogen-progestogen therapy for women with vascular retained products of conception following miscarriage or abortion.

OBJECTIVE: To assess the clinical characteristics and endocrinological background of women with vascular retained products of conception (RPOC) after miscarriage or abortion and evaluate the effect of estrogen-progestogen therapy (EPT) as an initial treatment on this population based on their endocrinological background. MATERIALS AND METHODS: Women with vascular RPOC after miscarriage or abortion at less than 20 weeks of pregnancy who were given EPT (conjugated estrogen and norethisterone) were retrospectively reviewed. Their clinical characteristics, hormonal parameters, ultrasonographic findings, and outcomes were evaluated. RESULTS: Of 35 women with vascular RPOC, 30 (86%) presented with vaginal bleeding at a visit, and 6 (17%) required inpatient management due to heavy bleeding. Among women who presented with vaginal bleeding, serum progesterone levels were significantly lower (0.25 vs. 6.5 ng/mL, p = 0.004) than those in women who did not present with vaginal bleeding. There were no differences in serum hCG levels (10.5 vs. 3.1 mIU/mL) or serum estradiol levels (65.4 vs. 162.3 pg/mL). After withdrawal bleeding following the first course of EPT, vaginal bleeding was stopped in 27 of the 30 women (90%), and 23 (66%) of all women had a thin and linear endometrium. All women could be treated by up to two courses of EPT and did not require additional interventions. The median duration to hCG normalization after the initial EPT was 24.5 (9-88) days. CONCLUSION: Women with vascular RPOC who have no bleeding had significantly higher levels of serum progesterone, indicating that administration of progestogen may have an effect on hemostasis. Endometrial bleeding can be prevented or stopped, and retained tissues can be conservatively expelled by oral administration of EPT, including norethisterone, in women with vascular RPOC.

Malformação arteriovenosa uterina: um relato de caso / Uterine arteriovenous malformation: a case report

O presente estudo tem como objetivo relatar o caso de uma paciente com malformação arteriovenosa uterina, efetivamente tratada com embolização seletiva e com fertilidade preservada. A malformação arteriovenosa uterina é uma alteração vascular rara até então pouco descrita na literatura. A paciente do sexo feminino apresentou quadro de sangramento uterino anormal, com início 30 dias após um abortamento, sem realização de curetagem, de uma gestação resultante de fertilização in vitro. Foram, então, realizados exames de imagem, que levaram ao diagnóstico de malformação arteriovenosa uterina. O tratamento de escolha foi a embolização arterial seletiva, com resolução do caso. Após sete meses, nova fertilização in vitro foi realizada, encontrando-se na 36a semana de gestação. São necessários mais estudos sobre essa malformação a fim de que sejam estabelecidos os métodos mais eficazes para o manejo de casos futuros, especialmente quando há desejo de gestar.

The present study aims to report the case of a patient with uterine arteriovenous malformation, effectively treated with selective embolization and with preserved fertility. Uterine arteriovenous malformation is a rare vascular disorder that has so far been rarely described in the literature. Female patient presented with abnormal uterine bleeding, starting 30 days after an abortion without subsequent curettage, of a pregnancy resulting from in vitro fertilization. Imaging tests were then performed that led to the diagnosis of uterine arteriovenous malformation. The treatment of choice was selective arterial embolization, with successful results. After seven months, a new in vitro fertilization was performed, being in the 36th week of pregnancy. Further studies on this pathology are needed in order to establish the most effective methods for the management of future cases, especially when there is a desire to become pregnant.

Impact of iron supplementation on patient outcomes for women with abnormal uterine bleeding: a protocol for a systematic review and meta-analysis.

BACKGROUND: Abnormal uterine bleeding (AUB), which includes heavy menstrual bleeding (HMB), is a common condition placing women at increased risk for developing iron deficiency and iron deficiency anemia (IDA). Depletion of iron stores has negative implications on physical, social, and emotional health, as well as quality of life. Iron supplements are safe, effective, and readily available, while red blood cell (RBC) transfusions have inherent risks including infectious and immune reactions. Despite high prevalence of IDA among women with AUB, there are limited studies on the impact of iron therapies on patient outcomes. This systematic review and meta-analysis will evaluate the impact of iron supplementation on patient outcomes for women with AUB, when compared to combination therapy, no intervention, placebo, or standard of care. METHODS: We will conduct a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the impact of iron interventions on patient outcomes for women with AUB. Systematic literature searches will be conducted in major databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science. Studies assessing the impact of iron interventions on patient outcomes in women experiencing AUB, in comparison to combination therapy, no intervention, placebo, or standard of care, will be included in the review. Independent reviewers will screen for eligibility, assess risk of bias, and abstract data. Overall certainty of evidence for each outcome will be assessed using the GRADE approach. We will meta-analyze outcomes which are sufficiently homogeneous to summarize intervention effects and narratively synthesize nonhomogeneous outcomes. The main outcomes of interest are hemoglobin levels immediately prior to surgery and post-operatively, number of RBC transfusions, and adverse effects. Secondary outcomes will include length of hospital stay, intraoperative blood loss, adverse and side effects, quality of life, and iron indices. DISCUSSION: This review will evaluate the impact of iron interventions on patient outcomes in women with IDA secondary to AUB with focus on changes in hematological and iron indices, red blood cell utilization, quality of life, cost of treatment, and adverse events. The results will inform evidence-based clinical practice for the management of iron deficiency and IDA secondary to AUB. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019137282.

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.

Abnormal Uterine Bleeding during Pubertal Induction with Transdermal Estrogen in Individuals with Turner Syndrome.

STUDY OBJECTIVE: Incidence of abnormal uterine bleeding (AUB) during pubertal induction among individuals with Turner syndrome (TS) has not been described previously. We estimated the incidence and characterized factors associated with AUB among individuals with TS. A secondary objective was to evaluate the management of AUB among this patient population. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: We conducted a retrospective chart review to evaluate individuals with TS undergoing hormone replacement therapy (HRT) for pubertal induction with transdermal estrogen. A total of 45 participants were identified between January 2007 and June 2019. RESULTS: Of the 45 individuals with TS included, 16 (35%) experienced AUB. Individuals with AUB most commonly experienced prolonged (44%), prolonged and heavy (25%), and intermenstrual (19%) bleeding. Individuals who experienced AUB were more likely to experience spontaneous bleeding (69% vs 28%) and a duration of unopposed estrogen greater than 18 months (63% vs 41%), undergo progestin cycling less often than monthly (69% vs 0%), use a micronized progestin dose of less than 200 mg (25% vs 14%), and be noncompliant with HRT (19% vs 0%) compared with those who did not experience AUB. CONCLUSION: There is a relatively high incidence of AUB among individuals with TS undergoing pubertal induction with transdermal estrogen. Care providers should consider the clinical factors examined to guide monitoring and management of individuals with TS on HRT.

Contraceptive Implant-Associated Bleeding in Adolescent/Young Adult Clinical Practice: Associated Factors, Management, and Rates of Discontinuation.

PURPOSE: To identify factors associated with bothersome implant-associated uterine bleeding, and to evaluate the impact of bleeding management on implant discontinuation. METHODS: We analyzed a quality improvement database of implant insertions (n = 825) at three adolescent/young adult programs and described individuals with and without reported bothersome bleeding. We utilized logistic regression to assess for factors associated with bleeding. RESULTS: Implant recipient mean age was 18.9 ± 2.6 years, and 27% reported having subsequent bothersome uterine bleeding. Recipients had increased odds of reporting such bleeding if they had previously irregular menses (odds ratio [OR] = 1.36; 95% confidence interval [CI]: 1.11-1.68 irregular and infrequent, OR = 1.41; 95% CI: 1.07-1.86 irregular and frequent) or sought the implant for menstrual management purposes exclusively (OR = 1.67; 95% CI 1.42-1.96) or in combination with contraceptive need (OR 1.65; 95%: CI 1.57-1.72). Prior use of the progestin injection or implant was associated with lower odds of subsequent bleeding report (OR = 0.63; 95% CI: 0.54-0.73; OR = 0.54; 95% CI: 0.39-0.75, respectively). Medication management of bleeding was associated with the likelihood of implant discontinuation at 1 year compared to those with untreated bleeding (hazard ratio 1.98 times, 95% CI: 1.39-2.81). The implant was continued for 3 years in over 50% of recipients with ever-managed bothersome bleeding. DISCUSSION: Individuals with historically irregular menses and those seeking the implant for menstrual management more often reported bothersome bleeding. Treating such bleeding with medication was associated with higher 1-year discontinuation rates, although many continued implant use for 3 years. Such findings may influence implant preinsertion counseling and/or postinsertion bleeding management.

Evaluation of the Safety and Efficacy of Ormeloxifene, a Selective Estrogen Receptor Modulator and Medroxyprogesterone Acetate in Women with Non-Structural Abnormal Uterine Bleeding: A Randomized Clinical Trial.

Background and objectives: Abnormal uterine bleeding is a significant clinical and gynaecological concern that necessitates its safe and effective treatment. The present study aims to compare the cost-effectiveness, safety, efficacy, and health-related quality of life of ormeloxifene with medroxyprogesterone acetate in women with non-structural abnormal uterine bleeding. Materials and Methods: A prospective, randomized, single-blinded clinical trial of 367 patients was carried out at a tertiary care hospital for a period of one year from 5 January 2019 to 4 January 2020. Patients were randomized into two groups for administering ormeloxifene and medroxyprogesterone acetate for a 3-month treatment duration and were evaluated by laboratorial investigations like anaemic status, bleeding duration, endometrial thickness, pictorial blood loss assessment chart (PBLAC) score, and patient's medical and medication history. Health-related quality of life was assessed using short form survey-36 (SF-36) questionnaire scale. Cost-effectiveness was determined on the basis of the three-month treatment regimen. Results: The mean duration of bleeding reduced from 16.88 ± 6.46 to 7.76 ± 1.55 in the ormeloxifene group and from 15.91 ± 5.04 to 8.7 ± 1.91 (p < 0.001) in the medroxyprogesterone acetate. Similarly, mean haemoglobin increased from 8.56 ± 0.77 to 10.1 ± 0.087 g/dL and from 8.60 ±0.97 to 9.551 ± 0.90 g/dL (p < 0.001), and endometrial thickness showed a reduction from 8.52 ± 1.61 mm to 6.92 ± 1.68 mm and from 8.40 ± 2.09 mm to 7.85 ± 2.0 mm (p < 0.001) in the ormeloxifene and medroxyprogesterone acetate groups, respectively. PBLAC score reduced from 289.92 ± 42.39 to 128.11 ± 33.10 and from 287.38 ± 40.94 to 123.5 ± 29.57 (p < 0.001) in these groups, respectively. Health-related quality of life improved in the ormeloxifene group more than the medroxyprogesterone group, which was evidenced by SF-36 scale parameters (physical function, energy/fatigue and pain) that changed from 24.39, 12.99, 6.25 to 28.95, 18, 9 and from 25.41, 13.6, 7.1 to 27.02, 16, 8.3 in the ormeloxifene and medroxyprogesterone acetate groups, respectively. Conclusions: The study concludes that both medroxyprogesterone acetate and ormeloxifene are safe and efficacious in controlling abnormal uterine bleeding, but ormeloxifene was the better of the two in terms of cost effectiveness, reduction in pictorial blood loss assessment score, endometrial thickness, bleeding duration (days), increase in haemoglobin concentration (g/dL) and improvement in the quality of life.

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.

Efficacy of Qiancao () and Haipiaoxiao (), a traditional Chinese herb pair, on abnormal uterine bleeding in rats with incomplete abortion.

OBJECTIVE: To investigate the most effective weight ratio of Qiancao () and Haipiaoxiao () used to produce decoction for the treatment of abnormal uterine bleeding (AUB) in rats with incomplete abortion, and to study the possible mechanism. METHODS: The models of AUB were established by incomplete drug abortion with mifepristone and misoprostol in pregnant rats. The therapeutic effects of decoctions made by eight different weight ratios of Qiancao () and Haipiaoxiao () were observed. RESULTS: Statistical analysis revealed that the most effective weight ratio of Qiancao () and Haipiaoxiao () to treat AUB in this study was 2∶1. CONCLUSION: The insights gained from this study would improve understanding of the mechanisms involved in the effect of Qiancao () and Haipiaoxiao () on AUB.

[Anti-inflammatory and hemostatic effects of total extract, saponins, and flavonoids of Clinopodium chinense in female rats with abnormal uterine bleeding and mechanism].

This study aims to explore the anti-inflammatory and hemostatic effects of the total extract of Clinopodium chinense(TEC), total saponins of C. chinense(TSC), and total flavonoids of C. chinense(TFC) in female rats with abnormal uterine bleeding(AUB), and the possible mechanism. Mifepristone(i.g., 12.4 mg·kg~(-1)) and misoprostol(i.g., 130 µg·kg~(-1)) were used to induce AUB in SD female rats conceiving on the same day. Then the AUB rats were randomized into model group, TEC group, TSC group, TFC group, Yimucao Granules(LG) group, and estradiol valerate(EV) group, with 8 rats in each group. Another 8 non-pregnant female rats were selected as normal group. During the experiment, each group was given the corresponding drug by gavage once a day for 7 days. After the administration, blood and uterine tissue were collected. The uterine bleeding volume was measured by ultraviolet spectrophotometry and the pathological changes of endometrium were observed based on hematoxylin-eosin(HE) staining. In addition, the microvessel density of endometrium was determined by immunohistochemistry, and the content of thromboxane B2(TXB2), 6-keto-PGF_(1α), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in plasma and levels of lutenizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E_2), and progesterone in serum were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein expression of estrogenreceptor α(ERα), progesterone receptor(PR), matrix metalloproteinase(MMP)-2, MMP-9, and vascular endothelial growth factor(VEGF) in uterine tissue was determined by Western blot. Compared with the model group, TEC, TSC, and TFC can reduce uterine bleeding volume, alleviate the pathological damage of endometrium, and increase the microvessel density in endometrium. Moreover, TEC and TSC can significantly raise plasma TXB2 level and ratio of TXB2 to 6-keto-PGF_(1α), and TEC and TFC can significantly reduce the levels of IL-6 and TNF-α. In addition, TEC significantly elevated serum progesterone level and TFC significantly increased serum levels of E_2, FSH, and LH. TSC can significantly raise serum progesterone and FSH levels. In addition, TEC can significantly down-regulate the protein expression of PR, MMP-2, and VEGF and TSC significantly reduced the expression of MMP-9. TFC significantly decreased the expression of PR, MMP-9, and VEGF, and up-regulated the expression of ERα. In conclusion, TEC, TSC, and TFC all show therapeutic effects on AUB, particularly TEC. TSC exerts the effects by enhancing the coagulation function and promoting endometrial repair, and TFC by regulating estrogen levels and reducing inflammatory response. This study reveals the mechanism of C. chinense against AUB and also explains the holistic characteristics of Chinese medicine.

Uterine volume, menstrual patterns, and contraceptive outcomes in users of the levonorgestrel-releasing intrauterine system: A cohort study with a five-year follow-up.

OBJECTIVE: The aim of our study was to evaluate the effects of the LNG-IUS on uterine volume, bleeding patterns, and LNG-IUS-related outcomes among women using the device to treat abnormal uterine bleeding caused by fibroids, adenomyosis, HMB (without structural cause), or contraception. STUDY DESIGN: This was a 5-year cohort study with LNG-IUS users. We selected 147 women, who were allocated to four groups: a) control (contraception indication); b) fibroids; c) adenomyosis; d) HMB. The visits for clinical and ultrasound evaluations were made at baseline and at 3, 6, 12, 24, 36, 48, and 60 months postinsertion. All data are expressed as mean and standard deviation (SD) or absolute and relative (%) frequency. Differences among groups were established by using the χ2 (chi-square) test and Fisher's exact tests for categorical outcomes, as well as the Mann-Whitney and the Kruskal-Wallis tests and Friedman's ANOVA for continuous variables. We used the 5% significance level as an indication of statistical significance. Logistic regression analyses were performed to study the association between predictors and outcomes. Results are expressed as odds ratios (ORs) with a 95% confidence interval (CI 95%). RESULTS: Although all groups had real rates of bleeding patterns, troublesome bleeding appeared to be more frequent in the fibroid group (∼15%). Also, along the 60 months of follow-up, uterine volume slightly decreased in the groups of HMB, adenomyosis, and fibroids, but not in the contraception group. However, the isolated volume of fibroids remained unchanged. In this cohort, we observed high continuation rates among LNG-IUS users. The uterine volume ≥200 cm3 was the main predictor of hysterectomy or IUS expulsion in the adenomyosis and fibroid groups. CONCLUSION: The LNG-IUS may control uterine menstrual bleeding as well as uterine volume in adenomyosis, fibroids, and HMB. An initial uterine volume smaller than 200 cm3 is an important predictor of adherence to treatment and better outcomes.

Effect of Tiaojingzhixue Fang on the expression of sex hormone and endometrial tissue mRNA in perimenopausal patients with abnormal uterine bleeding.

This study aimed to investigate the effect of Tiaojingzhixue decoction on the expression of sex hormone and endometrial mRNA in perimenopausal patients with abnormal uterine bleeding. For this purpose, 84 patients with perimenopausal abnormal uterine bleeding who were treated in our hospital from January 2018 to January 2019 were divided into study group and control group, the control group was treated with mifepristone for six months, the clinical efficacy, time of symptom relief and disappearance, endometrial thickness, menstrual volume, adverse events, expression of sex hormone (ER), Progesterone receptor (PR), Lutropin (LH), Follicle-stimulating hormone (FSH), Estradiol (e2) and Vascular endothelial growth factor in endometrial tissue were compared between the two groups. The results showed that the clinical efficacy of the study group (97.61%) was significantly higher than the control group (80.95%) (P<0.05). There was no significant difference in endometrial thickness between the two groups before treatment, but after treatment for 1 month, 3 months and 6 months, endometrial thickness was thinner in the study group (P<0.05). There was no significant difference in menstrual volume between the two groups before treatment (P <0.05), but it was lower in the study group (P <0.05). The incidence of adverse reactions in the study group was 11.90% lower than in the control group (26.19%). The expression levels of ER, PR, LH, FSH and E2 were almost the same before treatment and there was no significant difference between the two groups (P>0.05), but they were lower in the study group after treatment (P<0.05). Before treatment, there was no significant difference in the level of VEGF between the two groups (P>0.05); after treatment, the level of Vegf in the study group was lower than the control group (P<0.05). After treatment, the level of Vegf in both groups was significantly higher than before treatment (P<0.05). In general, Tiaojingzhixue decoction can decrease the level of sex hormone and increase the expression of VEGF in patients with perimenopausal abnormal uterine bleeding.

Medroxyprogesterone Acetate for Abnormal Uterine Bleeding Due to Ovulatory Dysfunction: The Effect of 2 Different-Duration Regimens.

BACKGROUND Abnormal uterine bleeding (AUB) lowers the quality of life of women. This study attempted to determine which treatment protocol of medroxyprogesterone acetate (MPA), 15 vs 10 day-administration in a luteal phase, provides better outcomes in women with ovulatory dysfunction-related AUB (AUB-O). MATERIAL AND METHODS The study included a total of 52 patients with AUB-O: Women in Group A were given MPA between days 11 and 25 of the menstrual cycle (15-day protocol), whereas women in Group B were given MPA between days 16 and 25 (10-day protocol). Outcomes were compared between the 2 groups. RESULTS Women in group B, compared with those in group A, more often showed regular menstrual cycles and decrement of AUB. In group B, 3 cycles of treatment were sufficient to achieve AUB-stop (p<0.05). Post-treatment hemogram parameters and surgical treatment requirements were not different between the 2 groups. CONCLUSIONS In the second half of the cycle/predicted luteal phase, 10-day cyclic use of MPA (the group B) better regulated the menstrual cycle and more frequently stopped AUB-O.

The association of maternal vaginal bleeding and progesterone supplementation in early pregnancy with offspring outcomes: a prospective cohort study.

BACKGROUND: Progesterone is widely used to improve the adverse pregnancy outcomes related to vaginal bleeding during early pregnancy. However, the evidence of its effectiveness is equivocal. METHODS: Six thousand six hundred fifteen mother-infant pairs from Tongji Maternal and Child Health Cohort (TMCHC) were involved in the study. Information on vaginal bleeding, progesterone administration in early pregnancy were obtained at enrolment. Birth outcomes were obtained from the hospital notes. Body weight of the infants at 12 months of age was collected by telephone interview. Multivariable logistic regression was conducted to estimate the effect of vaginal bleeding and progesterone administration in early pregnancy on birth outcomes and weight status of infants at 12 months of age. RESULTS: 21.4% (1418/6615) participants experienced bleeding in early pregnancy, and 47.5% (674/1418) of them were treated with progesterone. There were no significant associations between progesterone supplementation in early pregnancy and offspring outcomes. Compared to women without bleeding or any therapy, women with bleeding and progesterone therapy experienced increased risk of preterm (OR 1.74, 95% CI 1.21-2.52), and delivering a small-for-gestational-age (SGA) (OR 1.46, 95% CI 1.07-1.98) or low birth weight (LBW) (OR 2.10, 95% CI 1.25-3.51) neonate, and offspring of them had an increased risk of weight for age z-score (WAZ) < -1 at 12 months of age (OR 1.79, 95%CI 1.01-3.19). CONCLUSIONS: Offspring of mothers with bleeding and progesterone therapy were more likely to be a premature, SGA or LBW neonate, and had lower weight at 12 months of age. Progesterone supplementation may have no beneficial effect on improving adverse offspring outcomes related to early vaginal bleeding. TRIAL REGISTRATION: TMCHC was registered at clinicaltrials.gov as NCT03099837 on 4 April 2017.

Predicting the likelihood of successful medical treatment of early pregnancy loss: development and internal validation of a clinical prediction model.

STUDY QUESTION: What are clinical predictors for successful medical treatment in case of early pregnancy loss (EPL)? SUMMARY ANSWER: Use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start are predictors for successful medical treatment in case of EPL. WHAT IS KNOWN ALREADY: Success rates of medical treatment for EPL vary strongly, between but also within different treatment regimens. Up until now, although some predictors have been identified, no clinical prediction model has been developed yet. STUDY DESIGN, SIZE, DURATION: Secondary analysis of a multicentre randomized controlled trial in 17 Dutch hospitals, executed between 28 June 2018 and 8 January 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with a non-viable pregnancy between 6 and 14 weeks of gestational age, who opted for medical treatment after a minimum of 1 week of unsuccessful expectant management. Potential predictors for successful medical treatment of EPL were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques. MAIN RESULTS AND THE ROLE OF CHANCE: 237 out of 344 women had a successful medical EPL treatment (68.9%). The model includes the following variables: use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start. The model shows a moderate capacity to discriminate between success and failure of treatment, with an AUC of 67.6% (95% CI = 64.9-70.3%). The model had a good fit comparing predicted to observed probabilities of success but might underestimate treatment success in women with a predicted probability of success of ∼70%. LIMITATIONS, REASONS FOR CAUTION: The vast majority (90.4%) of women were Caucasian, potentially leading to less optimal model performance in a non-Caucasian population. Limitations of our model are that we have not yet been able to externally validate its performance and clinical impact, and the moderate accuracy of the prediction model of 0.67. WIDER IMPLICATIONS OF THE FINDINGS: We developed a prediction model, aimed to improve and personalize counselling for medical treatment of EPL by providing a woman with her individual chance of complete evacuation. STUDY FUNDING/COMPETING INTEREST(S): The Triple M Trial, upon which this secondary analysis was performed, was funded by the Healthcare Insurers Innovation Foundation (project number 3080 B15-191). TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT03212352.

Long-acting reversible contraceptives effects in abnormal uterine bleeding, a review of the physiology and management.

Around two-thirds of women who are of reproductive age use some type of contraception. Two of the most effective long-acting reversible contraceptives (LARC) are the intrauterine device (IUD) and the subdermal contraceptive implant (SCI). Despite their effectiveness, women often report abnormal uterine bleeding as the reason for discontinuation. In this review, we analyze key aspects regarding the mechanisms of action of IUDs (both copper-containing and levonorgestrel-releasing) and SCIs, as well as how they change the intrauterine environment in order to provide effective contraception at a physiological level. Additionally, we introduce the pathophysiology of different types of abnormal intrauterine bleeding provoked by the mentioned LARCs. These three contraceptive methods work in diverse ways, thus, the etiology of abnormal uterine bleeding is different and multifactorial according to each LARC. This review intends to provide information in order to better our understanding of bleeding induced by these contraceptive methods, as well as introduce current and potential new therapies. Furthermore, this review intends to provide updated and concise information that could be available firsthand not only to health care providers but scientists who are innovating and revolutionizing this field. In 2013, the American College of Obstetricians and Gynecologists published a management of abnormal uterine bleeding, however, there is limited updated data regarding the physiology and pathophysiology of abnormal uterine bleeding and its treatment based on different LARCs (hormonal and non-hormonal).