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Objective: This study aimed to investigate the curative effect of motherwort combined with ethinylestradiol-cyproterone acetate (EE/CPA) on dysfunctional uterine bleeding (DUB)., Methods: Atotal of 68 patients with DUB were divided into a single medication group (treated with EE/CPA) and a combination medication group(treated with motherwort and EE/CPA). The clinical efficacy, uterine hemodynamic parameters, sex hormone levels, coagulation index levels, blood routine test levels, and adverse reactions of patients were evaluated., Results: After three months of treatment, total treatment response rate of the combination medication group was significantly higher than that of the single medication group. Decreased uterine volume, endometrial thickness and resistance index (RI), increased pulsatility index(PI), average flow rate, and uterine artery blood flow, as well asreduced follicle-stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2), progesterone (P), activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen (FIB), thrombin time(TT), platelet count (PLT), red blood cell (RBC), and hemoglobin (Hb)levels were witnessed in patients of the two groups. In thecombination medication group, there exhibited reduced uterine volume, endometrial thickness and RI, elevated PI, average flow rate, and uterine artery blood flow, reduced P, E2, FSH, LH, aPTT, PT, FIB, TT,PLT, RBC, and Hb levels in comparison to the single medication group., Conclusion: The combination of motherwort and EE/CPA is clinically effective in the treatment of DUB.

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)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: COVID-19 vaccines have provided fertile ground for research, especially with the unprecedented spread of misinformation about this disease and its vaccines. Among women, one of the most frequently reported side effects of the vaccine has been menstrual disturbance., Objective: To investigate the perceived impact of COVID-19 vaccines on the menstrual cycle. In addition, the research seeks to identify factors that could predispose certain individuals to experience these effects, thereby contributing to a deeper understanding of the interplay between vaccines and menstrual health., Design: We conducted a retrospective observational cross-sectional study., Methods: Any woman of menstruating age who received at least one dose of the COVID-19 vaccine and currently resides in Saudi Arabia was invited to complete an online questionnaire. The questionnaire compared menstruation characteristics-regularity, volume, intermenstrual bleeding, and dysmenorrhea-before and after receiving the COVID-19 vaccine, taking into consideration possible predisposing factors such as polycystic ovarian syndrome, contraceptives, or period-blocking pills., Results: Women without polycystic ovarian syndrome experienced less change in dysmenorrhea post-vaccine compared to those with polycystic ovarian syndrome (23.88% versus 37.78%, p  = 0.045). Women using hormonal contraceptives were about two times more likely to experience changes in volume compared to those not using contraceptives (odds ratio = 2.09, 95% confidence interval = 1.23-3.57, p  = 0.006). COVID-19 vaccine skeptics were about three times more likely to perceive changes in regularity post-vaccine compared to non-skeptics (odds ratio = 2.96, 95% confidence interval = 1.79-4.90, p  < 0.001). They were also three times more likely to perceive changes in volume post-vaccine (odds ratio = 3.04, 95% confidence interval = 1.95-4.74, p  < 0.001)., Conclusion: Our data suggest significant associations between COVID-19 skepticism, the use of hormonal contraceptives, and the reported post-vaccine menstrual disturbances. This underscores the importance of public education efforts aimed at dispelling misinformation and addressing controversies related to these vaccines.

Emicizumab has been widely used for prophylaxis in patients with hemophilia A (HA) of all ages, with or without factor VIII inhibitors. Data on emicizumab efficacy are certainly significant; however, protection against bleeding is not absolute, and the breakthrough bleeding risk can be approximately equivalent to that of patients with mild HA. This single-center retrospective review aimed to present the rate and management of breakthrough bleeding events in pediatric HA patients with and without inhibitors who are on emicizumab prophylaxis. Fifty-one pediatric patients on emicizumab prophylaxis that were followed up at Birmingham Children's Hospital between March 1, 2018, and May 15, 2021, were included in the current study. Our results showed that 56.8% (29/51) experienced no bleeding events, and 80.3% (41/51) had no major treated bleeds during the follow-up period. A total of 29.4% (15/51) had minor bleeds that resolved spontaneously or with antifibrinolytics. Overall, 19.6% (10/51) of the patients received additional FVIII to prevent or treat breakthrough bleeding. One patient had a major bleeding event in the form of hematuria. However, it resolved without treatment. Both major and minor bleeding episodes occurred in 7.8% (4/51) of patients. None of the patients with inhibitors (5/51) developed breakthrough bleeding. Only a few, mostly minor, breakthrough bleeding episodes were reported in our cohort. The balance between bleeding control and the risk of inhibitor development after episodic factor administration should be considered. Therefore, careful decisions should be made in managing bleeding events.Supplemental data for this article is available online at.

To evaluate the clinical effect of Gongning granules combined with low-dose hormone therapy in pubertal dysfunctional uterine bleeding (PDUB) and its effect on uterine hemodynamics. A total of 164 PDUB patients who were treated in the gynecological outpatient department of our hospital from December 2018 to June 2020 were randomized into study group and control group, with 82 cases each. The control group received estrogen progesterone, and the study group received Gongning granules plus. The clinical efficacy and uterine arterial hemodynamics were compared. The clinical efficacy of the study group was superior to the control group (91.46% vs. 76.83%, P<0.05). The study group yielded shorter bleeding control time and complete hemostasis time than the control group (P<0.05). The amount of menstrual bleeding and duration of menstruation in both groups decreased significantly with time and the study group was significantly lower than the control group (all P<0.05). The endometrial thickness in the study group was significantly thinner than the control group, and the maximum follicle diameter was significantly longer than that in the control group (all P<0.05). After treatment, the platelet count, hemoglobin level of peripheral blood, uterine arterial blood flow and mean flow velocity in the study group were significantly higher than those in the control group (all P<0.05). In addition, there was no significant difference in adverse drug reaction (ADR) between the two groups (P>0.05). In PDUB patients, Gongning granules plus low-dose hormone can significantly relieve bleeding symptoms, improve hemodynamic status and has good safety.

Dysfunctional uterine bleeding is menstrual bleeding in abnormal volume, duration, or time, and it is a common problem in women. A wide range of drug therapies, with varying efficacy, is available for women with dysfunctional uterine bleeding. The use of herbal and traditional medicine is one of the ways to treat this disease, which has fewer side effects than chemical drugs. On the other hand, these medicines have less effect on treatment than chemical drugs. Therefore, increasing their effectiveness in the treatment of diseases has always been important. For this purpose, in this study, a comparison was done between direct use and PLGA nanocapsules containing Tiaojing Zhixue, in the treatment of dysfunctional uterine bleeding. First, PLGA nanocapsules containing Tiaojing Zhixue were synthesized by the electrospray technique. Then 80 women with dysfunctional uterine bleeding were treated with this medicine. These people were divided into two groups of 40 people. The first group was treated with 20mg of Tiaojing Zhixue and the other group was treated with PLGA nanocapsules containing Tiaojing Zhixue for eight months. The duration and frequency of bleeding from one month before the start of treatment and during the eight months after the start of treatment (second, fourth, and eighth month) were assessed in two groups. The two groups were homogeneous in terms of mean frequency of bleeding and mean duration of bleeding before starting treatment. The positive response in the PLGA nanocapsules treatment group (75%) was higher than the direct use drug treatment group (42.5%) (P < 0.01). The rate of side effects was the same in each group. Due to the effectiveness of PLGA nanocapsules in the treatment of dysfunctional uterine bleeding and the lack of side effects, it can be considered as an alternative medicine for the treatment of this disorder.

Objective: To evaluate whether a short course of tamoxifen decreases bothersome bleeding in etonogestrel contraceptive implant users., Methods: In a 90-day, double-blind randomized control trial, we enrolled etonogestrel implant users with frequent or prolonged bleeding or spotting. A sample size of 40 per group (N=80) was planned to compare 10 mg tamoxifen or placebo twice daily for 7 days after 3 consecutive days of bleeding or spotting no more than once per 30 days (maximum three treatments). Participants then entered a 90-day open-label study where all received tamoxifen if needed every 30 days (maximum three treatments). Participants used text messages to record daily bleeding patterns. Our primary outcome was the total number of consecutive amenorrhea days after the first treatment. Secondary outcomes included time to bleeding or spotting cessation and restart after first treatment, overall bleeding patterns, and satisfaction., Results: From January 2017 to November 2018, 112 women enrolled in the study; 88 (79%) completed 90 days, and 79 (71%) completed 180 days. Participant characteristics did not differ between groups; mean age 24, majority identified as white not Hispanic with at least some college education. After the first treatment, the tamoxifen group reported an average of 9.8 (95% CI 4.6-15.0) more consecutive days of amenorrhea and more total days of no bleeding (amenorrhea or spotting) in the first 90 days (median 73.5 [range 24-89] vs 68 [range 11-81], P=.001). The placebo group showed a similar treatment benefit after first active use of tamoxifen in the open-label phase. At the end of the randomized study (first 90 days), women who received tamoxifen reported higher satisfaction (median 62 mm [range 16-100]) than those treated with placebo (46 mm [range 0-100]; P=.023)., Conclusion: A short course of tamoxifen reduces problematic bleeding and improves satisfaction in users of etonogestrel implants., Clinical Trial Registration: ClinicalTrials.gov, NCT02903121.

Aim: This study is to evaluate whether unacceptable bleeding among the etonogestrel implant user could be better alleviated using combined oral contraceptive pills (COCP) or nonsteroidal anti-inflammation drugs (NSAID)., Methods: This is a prospective randomized study for evaluation of 84 etonogestrel implant (Implanon) users with prolonged or frequent bleeding. They were assigned to either receiving a COCP containing 20 mcg ethinyl estradiol/150 mg desogestrel for two continuous cycle or NSAID; mefenamic acid 500 mg TDS for 5 days, 21 days apart for two cycles. Bleeding pattern during the treatment was recorded and analyzed., Results: A total of 32 women (76.2%) in COCP group and 15 women (35.7%) in NSAID group stop bleeding within 7 days after the initiation of treatment which was statistically significant (P < 0.05). The mean duration of bleeding and spotting days in women treated with COCP was significantly lesser compared to NSAID group (7.29 ± 3.16 vs 10.57 ± 4.14 days (P < 0.05)., Conclusion: We conclude that COCP is more efficient compared to NSAID in managing bleeding irregularities among etonogestrel implant users., (© 2020 Japan Society of Obstetrics and Gynecology.)

Sex matters when it comes to venous thromboembolism (VTE). We defined 5P's - period, pill, prognosis, pregnancy, and postthrombotic syndrome - that should be discussed with young women with VTE. Menstrual blood loss (Period) can be aggravated by anticoagulant therapy. This seems particularly true for direct oral anticoagulants. Abnormal uterine bleeding can be managed by hormonal therapy, tranexamic acid, or modification of treatment. The use of combined oral contraceptives (Pill) is a risk factor for VTE. The magnitude of the risk depends on progestagen types and estrogen doses used. In women using therapeutic anticoagulation, concomitant hormonal therapy does not increase the risk of recurrent VTE. Levonorgestrel-releasing intrauterine devices and low-dose progestin-only pills do not increase the risk of VTE. In young women VTE is often provoked by transient hormonal risk factors that affects prognosis. Sex is incorporated as predictor in recurrent VTE risk assessment models. However, current guidelines do not propose using these to guide treatment duration. Pregnancy increases the risk of VTE by 4-fold to 5-fold. Thrombophilia and obstetric risk factors further increase the risk of pregnancy-related VTE. In women with a history of VTE, the risk of recurrence during pregnancy or post partum appears to be influenced by risk factors present during the first VTE. In most women with a history of VTE, antepartum and postpartum thromboprophylaxis with low-molecular-weight heparin is indicated. Women generally are affected by VTE at a younger age then men, and they have to deal with long-term complications (Post-thrombotic syndrome) of deep vein thrombosis early in life., (© 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)

Dyspareunia, vaginitis and dysfunctional uterine bleeding (DUB) are common problems which, despite their polygenicity, commonly appear idiopathic and treatment-refractory. Mast cell (MC) activation syndrome (MCAS) is a newly-recognised, prevalent, chronic multisystem polymorbidity of general themes of inflammation ± allergic-type phenomena ± aberrant growth/development in assorted tissues. MCs produce significant quantities of heparin, too. As such, MCAS may underlie some cases of chronic dyspareunia, vaginitis or DUB. We report five such patients; all who responded well to MC-targeted treatment. We review aspects of MC biology and pathobiology of potential relevance to otherwise idiopathic persistent inflammatory or coagulopathic genital tract problems. Diagnostic testing for MCAS may be warranted in some patients with chronic dyspareunia, vaginitis or DUB (especially patients whose histories well fit the general profile of MCAS), and prospective therapeutic trials of MC-directed topical and/or systemic therapies may be warranted in such populations. Impact statement What is already known on this subject? Chronic, idiopathic, treatment-refractory female genital tract inflammation or bleeding are common problems for which mast cell (MC) disease, previously generally thought to consist of just rare cases of mastocytosis, and is seldom considered in the differential diagnosis. What do the results of this study add? The substantial prevalence of the newly recognised 'mast cell activation syndrome' (MCAS), featuring chronic inappropriate MC activation with little-to-no MC neoplasia, and its clinical presentation with chronic multisystem inflammation ± allergic-type phenomena ± aberrant growth/development in assorted tissues, raises the possibility that MCAS might underlie the aforementioned genital tract problems, especially in patients whose larger clinical presentations fit the MCAS profile. We report five example patients (among many more we have similarly treated) who enjoyed excellent responses to safe, inexpensive MC-targeted treatments, often given just intravaginally. What are the implications of these findings for clinical practice and/or further research? Our report identifies a potentially significant new MC-focused direction, of relevance to millions of affected women worldwide, for clinical treatment as well as for basic and clinical research, which historically has yielded major advancements disappointingly disproportionate to the scope of the affected population.

Background: Many patients with gynecological disorders seek traditional medicine consultations in Asian countries. This study intended to investigate the utilization of traditional Chinese medicine (TCM) in patients with dysfunctional uterine bleeding (DUB) in Taiwan., Methods: We analyzed a cohort of one million individuals randomly selected from the National Health Insurance Research Database in Taiwan. We included 46,337 subjects with newly diagnosed DUB (ICD-9-CM codes 626.8) from January 1, 1997 to December 31, 2010. The patients were categorized into TCM seekers and non-TCM seekers according to their use of TCM., Results: Among the subjects, 41,558 (89.69%) were TCM seekers and 4,779 (10.31%) were non-TCM seekers. Patients who were younger tended to be TCM seekers. Most of the patients had also taken Western medicine, especially tranexamic acid and non-steroidal anti-inflammatory drugs (NSAIDs). More than half of TCM seekers (55.41%) received combined treatment with both Chinese herbal remedies and acupuncture. The most commonly used TCM formula and single herb were Jia-Wei-Xiao-Yao-San (Bupleurum and Peony Formula) and Yi-Mu-Cao (Herba Leonuri), respectively. The core pattern of Chinese herbal medicine for DUB patients consisted of Jia-Wei-Xiao-Yao-San, Xiang-Fu (Rhizoma Cyperi), and Yi-Mu-Cao (Herba Leonuri)., Conclusions: TCM use is popular among patients with DUB in Taiwan. Further pharmacological investigations and clinical trials are required to validate the efficacy and safety of these items.

Background: Requests for assistance in menstrual management and menstrual suppression are a common, emotive and sometimes controversial aspect of adolescent disability care., Aims: To review the uptake and outcomes of menstrual suppression among adolescent patients with developmental delay., Methods: A retrospective review of the medical records of adolescent females with intellectual disability referred for menstrual management to the Paediatric and Adolescent Gynaecology Clinic, Children's Hospital at Westmead, Sydney, for the three-year period between January 1, 2010 and January 1, 2013., Results: Eighty adolescent patients with developmental delay were identified. A third (n = 28) of the patients were pre-menarcheal at first review with parent/caregivers seeking anticipatory advice. Of the post-menarcheal patients, the median age of menarche was 12 years (range 10-15 years). First and second line interventions were documented as were reasons for change where applicable. The combined oral contraceptive pill (COCP) was the most frequently used therapy (67%), and 19 patients in total had a levonorgestrel releasing intrauterine system (LNG-IUS) inserted (31%). Our study population differs from similar previously published groups in the marked absence of the use of depot medroxyprogesterone acetate or the subdermal etonogestrel releasing device., Conclusion: As a paediatrician, it is important to address menstrual management issues and allay caregiver concerns with appropriate advice. Our study supports the use of the COCP as sound first line management in achieving menstrual suppression. The LNG-IUS appears to be a favourable second line option. Further investigation into longer-term outcomes and potential complications of device insertion is recommended., (© 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: The etonogestrel (ENG) subdermal implant can cause frequent breakthrough bleeding in some users. The objective of this study was to evaluate whether a short course of tamoxifen reduces bleeding/spotting days compared to placebo in ENG implant users., Study Design: In this double-blind trial, we randomized ENG implant users with frequent or prolonged bleeding or spotting to tamoxifen 10 mg or placebo twice daily for 7 days, to be started after 3 consecutive days of bleeding/spotting. Treatment was repeated as needed up to three times in 180 days. Subjects completed a daily text message bleeding diary. A sample size of 56 provided 80% power to detect a difference of 6 days of bleeding/spotting per 30 days by two-sample t test. Ovulation was monitored by urinary metabolites of progesterone., Results: From March 2014 to February 2015, 56 women enrolled. Fifty-one completed at least 30 days of follow up, and 34 completed 180 days. Compared to women randomized to placebo, women randomized to tamoxifen reported 5 fewer days of bleeding/spotting over 30 days (95% confidence interval [CI] -9.9 to -0.05, p=.05), and 15.2 more continuous bleeding-free days (95% CI 2.8-27.5 days, p=.02) after first use of study drug. Conclusions could not be drawn after 30 days due to higher-than-expected dropout. No ovulation was detected., Conclusion: First use of tamoxifen by ENG implant users reduces bleeding/spotting days and provides a longer cessation of bleeding/spotting than placebo, without compromising ovulation suppression. Further study is needed to determine whether this effect is maintained with repeat use., Implications: Women with frequent ENG implant-related breakthrough bleeding may experience a reduction in bleeding/spotting days and an increase in continuous bleeding-free days in the month following first use of tamoxifen. This short course of tamoxifen was well tolerated with bleeding cessation noted within a median of 5 days., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: This study aims to assess vaginal bleeding patterns and cycle control of oral contraceptives containing estetrol (E4) combined with either drospirenone (DRSP) or levonorgestrel (LNG)., Study Design: An open-label, multicentre, randomised, dose-finding study lasting six cycles in healthy women aged 18-35 years was used. Four treatments (15 mg or 20 mg E4, combined with either 3 mg DRSP or 150 mcg LNG) were administered in a 24/4-day regimen. A marketed dosing regimen of estradiol valerate with dienogest (E2V/DNG) served as reference since it contains (like E4) a natural oestrogen., Results: A total of 396 women were randomised, of whom 389 received study medication, and 316 completed the study. By cycle 6, the frequencies of unscheduled bleeding and/or spotting and absence of withdrawal bleeding were the lowest in the 15 mg E4/DRSP group (33.8% and 3.5%, respectively). In the E2V/DNG reference group, these frequencies were 47.8% and 27.1%, respectively. By cycle 6, the frequency of women with absence of withdrawal bleeding was <20% for all E4 treatment groups: 3.5-3.8% combined with DRSP and 14.0-18.5% combined with LNG. By cycle 6, unscheduled intracyclic bleeding was reported by <20% of women in the 20 mg E4/LNG group (18.9%) and in the 15 mg E4/DRSP group (16.9%)., Conclusion: This study showed that, of the four treatment modalities investigated, the 15 mg E4/DRSP combination has the most favourable bleeding pattern and cycle control., Implications: Due to its favourable bleeding pattern and cycle control, the 15 mg E4/DRSP combination is the preferred combination for further phase III clinical development., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Estimate symptom improvement rate of women with bleeding complaints using the etonogestrel contraceptive implant when started on continuous combined oral contraceptives (COC)., Methods: We conducted a double-blinded randomised controlled trial of women reporting troublesome bleeding related to their etonogestrel contraceptive implant and desiring intervention. Participants received continuous COCs or placebo for four weeks to evaluate self-reported bleeding improvement at four weeks. Participants could continue study treatment or prescribed COCs for another eight weeks if desired. We planned to enroll 130 participants between two sites (80% power to detect a 20% effect size at a 0.05 significance level, with 10% loss to follow up)., Results: We closed the study after enrolling 26 participants due to recruitment futility. All women on COCs and 75% of placebo users reported bleeding improvement at four weeks (p = 0.09), with 92% and 42%, respectively, reporting significant improvement (p = 0.03). The median number of days until bleeding stopped for at least four days in COC and placebo users was 1 day (range 1-9) and 4.5 days (range 1-28), respectively (p = 0.63). Eight (75%) COC and five (42%) placebo users opted to continue study treatment (p = 0.41). Despite bleeding improvement, women who desired implant removal at enrollment were more likely to re-request removal than those who initially considered other interventions (3 of 5 [60%] vs 1 of 17 [6%], p = 0.03)., Conclusion: Although women who have troublesome bleeding while using the contraceptive implant may experience improvement with no treatment over 4 weeks, women using COCs are more likely to report significant improvement. Clinicaltrials.gov registration number: NCT01963403.

In the treatment of women with abnormal uterine bleeding, once a thorough history, physical examination, and indicated imaging studies are performed and all significant structural causes are excluded, medical management is the first-line approach. Determining the acuity of the bleeding, the patient's medical history, assessing risk factors, and establishing a diagnosis will individualize their medical regimen. In acute abnormal uterine bleeding with a normal uterus, parenteral estrogen, a multidose combined oral contraceptive regimen, a multidose progestin-only regimen, and tranexamic acid are all viable options, given the appropriate clinical scenario. Heavy menstrual bleeding can be treated with a levonorgestrel-releasing intrauterine system, combined oral contraceptives, continuous oral progestins, and tranexamic acid with high efficacy. Nonsteroidal antiinflammatory drugs may be utilized with hormonal methods and tranexamic acid to decrease menstrual bleeding. Gonadotropin-releasing hormone agonists are indicated in patients with leiomyoma and abnormal uterine bleeding in preparation for surgical interventions. In women with inherited bleeding disorders all hormonal methods as well as tranexamic acid can be used to treat abnormal uterine bleeding. Women on anticoagulation therapy should consider using progestin-only methods as well as a gonadotropin-releasing hormone agonist to treat their heavy menstrual bleeding. Given these myriad options for medical treatment of abnormal uterine bleeding, many patients may avoid surgical intervention., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Myrtle (Myrtus communis L.) has been used in the Iranian Traditional Medicine as a treatment for abnormal uterine bleeding-menometrorrhagia. The main aim of this study is to evaluate the effect of myrtle fruit syrup on abnormal uterine bleeding-menometrorrhagia., Methods: A randomized, double-blind, placebo-controlled pilot study was conducted on 30 women suffering from abnormal uterine bleeding-menometrorrhagia. Treatment comprised of giving 15 ml oral myrtle syrup daily (5 ml three times a day) for 7 days starting from the onset of bleeding. The myrtle syrup along with placebo was repeated for 3 consecutive menstrual periods. Menstrual duration and number of used pads were recorded by the Pictorial Blood loss Assessment Chart at the end of each menstrual period. The quality of life was also evaluated using the menorrhagia questionnaire., Results: The mean number of bleeding days significantly declined from 10.6 ± 2.7 days to 8.2 ± 1.9 days after 3 months treatment with the syrup (p = 0.01) and consequently the participants in the intervention group used fewer pads after 3 months (16.4 ± 10.7) compared with the number of pads used at the beginning of the treatment (22.7 ± 12.0, p = 0.01). Bleeding days and number of pads used by the participants in the placebo group did not change significantly. Also significant changes of quality of life scores were observed in the intervention group after 3 months compared to the baseline., Conclusion: Myrtle syrup is introduced as a potential remedy for abnormal uterine bleeding-menometrorrhagia.

Objectives: Excessive menstrual bleeding, the most common complication caused by intrauterine devices (IUDs), often leads to discontinuation of use. Our study investigates the effect of vitamin B1 on menstrual bleeding and spotting after insertion of the TCu380A IUD., Methods: This double-blind, randomised controlled trial involved 110 Iranian women. We recruited women who noted that their menstrual flow (duration, amount, and number of sanitary pads needed) or intermenstrual spotting had increased one month after the insertion of a TCu380A, and randomly assigned them to two groups. The intervention group and the control group received 100 mg of vitamin B1 or a placebo, respectively, daily, for three months. We followed all participants for four months. The Higham scale was used for estimating the volume of menstrual bleeding. The Mann-Whitney test, paired t-test, independent t-test and Repeated Measure test were used for statistical purposes., Results: In the intervention group the duration of menstrual bleeding, the number of sanitary pads and the amount of spotting decreased significantly compared to the control group (p < 0.001)., Conclusion: Vitamin B1 is a safe, natural and cost-effective supplement that is devoid of side effects and reduces menstrual bleeding and spotting caused by a copper bearing-IUD.

Background: Abnormal uterine bleeding is defined as any alteration in the pattern or volume of menstrual blood flow, and it is preferably treated using hysterectomy, endometrial destruction or the levonorgestrel-releasing intrauterine system (Mirena(®) ). Recently, it has been demonstrated that studies of Mirena(®) were generally small and consequently imprecise., Aims: Our study was aimed at assessing the effects of a slow-release levonorgestrel (20 μg/day) intrauterine device in fertile and postmenopausal women experiencing abnormal uterine bleeding that did not respond to traditional medical management., Materials and Methods: A total of 40 women, of whom 24 were of reproductive capacity and 16 were postmenopausal, were enrolled in the trial. Removal of the intrauterine device was required for only 2 of the 24 fertile women and for only 3 of the 16 postmenopausal women. After 6 and 12 months of treatment, the remaining women were clinically evaluated and underwent ultrasound and hysteroscopy using biopsy specimens as a control. The EuroQol Group EQ-5D questionnaire was used for evaluation of quality of life., Results: The device showed good tolerability and efficacy. It resulted in a reduction in the endometrial mucosal thickness with a regression of bleeding and collateral effects, which were more evident after 12 months of treatment. A positive effect of the device on the woman's quality of life was demonstrated., Conclusions: The slow-release levonorgestrel intrauterine device may be a valid therapeutic tool for treating basic symptomatology and increasing quality of life in women with abnormal uterine bleeding., (© 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Bleeding irregularities, such as intermenstrual spotting or heavy or prolonged menstrual bleeding, are common among copper-containing intrauterine device (Cu-IUD) users and are one of the leading reasons for method discontinuation. This review evaluates the evidence for effective therapeutic and preventive treatments for bleeding irregularities during Cu-IUD use., Study Design: We searched the PubMed database for peer-reviewed articles that were published in any language from inception of the database through March 2012 and were relevant to treatments for irregular bleeding during Cu-IUD use. We used standard abstract forms and grading systems to summarize and assess the quality of the evidence., Results: From 1470 articles, we identified 17 articles that met our inclusion criteria. Evidence from two studies of poor quality demonstrated that antifibrinolytic agents or nonsteroidal anti-inflammatory drugs (NSAIDs) have been used for intermenstrual bleeding or spotting among a small number of Cu-IUD users with mixed results. Evidence from 10 studies of fair to poor quality suggested that some NSAIDs may significantly reduce menstrual blood loss or bleeding duration among Cu-IUD users with heavy or prolonged menstrual bleeding. Antifibrinolytic drugs or antidiuretics may also help reduce blood loss. High-dose aspirin was shown to increase blood loss among those with baseline menorrhagia. Evidence from five studies of fair to poor quality suggested that bleeding irregularities among new Cu-IUD users may be prevented with NSAIDs, although one large study of good quality suggested that prophylactic treatment with ibuprofen does not affect continuation of Cu-IUD use. Evidence from two studies of fair to poor quality suggested that antifibrinolytic agents might be helpful in preventing heavy or prolonged menstrual bleeding among new Cu-IUD users., Conclusions: Limited evidence suggests that NSAIDs may be effective treatments for bleeding irregularities associated with Cu-IUD use; antifibrinolytic agents and antidiuretics have also been studied as possible treatments in a small number of subjects, but their safety has not been well documented. NSAIDs and antifibrinolytics may also prevent bleeding irregularities among new CU-IUD users. Preventive NSAID use, however, does not impact Cu-IUD continuation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To assess the efficacy of tranexamic acid or mefenamic acid in the management of the initial "nuisance" bleeding or spotting in the period immediately after placement of the levonorgestrel-releasing intrauterine system., Methods: Women were randomized after levonorgestrel-releasing intrauterine system placement to oral tranexamic acid (500 mg), mefenamic acid (500 mg), or placebo three times daily during bleeding or spotting episodes over a 90-day treatment period. Treatment was initiated from onset of a bleeding or spotting episode and continued until the first day after bleeding or spotting stopped and restarted with a new bleeding or spotting episode. The primary efficacy variable was reduction in the number of bleeding or spotting days. Tranexamic acid and mefenamic acid were compared with placebo using a one-sided Wilcoxon rank-sum test. Bonferroni-Holm adjustment was used to account for multiple testing., Results: A total of 204 women were screened; 187 were randomized to tranexamic acid (n=63), mefenamic acid (n=63), or placebo (n=61). The median number of bleeding or spotting days experienced during treatment was 25, 29, and 33 days in the three groups, respectively. The median number of bleeding or spotting days was reduced by 6 days (95% confidence interval [CI] -14.0 to 1.0, P=.049) with tranexamic acid and by 3 days (95% CI -11.0 to 5.0, P=.229) with mefenamic acid compared with placebo. The relative risk of bleeding or spotting compared with placebo with tranexamic acid and mefenamic acid was 0.82 (95% CI 0.65-1.03) and 0.89 (95% CI 0.71-1.11), respectively. Most women (85% or more) were satisfied with the levonorgestrel-releasing intrauterine system across the groups., Conclusions: Tranexamic acid and mefenamic acid during the first 90 days after levonorgestrel-releasing intrauterine system placement do not alleviate "nuisance" bleeding or spotting., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01295294., Level of Evidence: I.

Abnormal uterine bleeding (AUB), which is defined as excessively heavy, prolonged and/or frequent bleeding of uterine origin, is a frequent cause of visits to the Emergency Department and/or health care provider. While there are many etiologies of AUB, the one most likely among otherwise healthy adolescents is dysfunctional uterine bleeding (DUB), which is characterizing any AUB when all possible underlying pathologic causes have been previously excluded. The most common cause of DUB in adolescence is anovulation, which is very frequent in the first 2-3 post-menarchal years and is associated with immaturity of the hypothalamic - pituitary - ovarian axis. Management of AUB is based on the underlying etiology and the severity of the bleeding and primary goals are prevention of complications, such as anemia and reestablishment of regular cyclical bleeding, while the management of DUB can in part be directed by the amount of flow, the degree of associated anemia, as well as patient and family comfort with different treatment modalities. Treatment options for DUB are: combined oral contraceptives (COCs), progestogens, non steroidal anti inflammatory drugs (NSAIDs), tranexamic acid (anti-fibrinolytic), GnRH analogues, Danazol and Levonorgestrel releasing intra uterine system (LNG IUS).

Objective: Endometrial hyperplasia is clinically important, because it can lead to abnormal uterine bleeding (AUB) which itself can precede endometrial cancer. Endometrial carcinoma is the most common malignancy of the female genital tract, occurring in about 75%-85% younger, perimenopausal women as endometrial hyperplasia. The treatment is hysterectomy or hormone therapy with progesterone. The aim of this study was, therefore, to compare the effect of levonorgestrel intrauterine device (LNG-IUD) with medroxyprogesterone acetate (MPA) on simple endometrial hyperplasia for fertility preservation., Materials and Methods: Forty women in reproductive age (22-47 years) with AUB with endometrial biopsies confirming simple hyperplasia, were enrolled in this study and then randomly divided into two groups. All patients presented with designed special checklist which was filled with satisfaction. Complete history and physical examination especially blood pressure (BP), body mass index (BMI), breast examination, bimanual vaginal examination, and transvaginal sonography (to measure the thickness of endometrial and exclude the other pathologic lesions) were performed. In the first group, treatment was performed with MPA (20 mg/daily) for ten days and in other group with LNG-IUD was prescribed. After three months, transvaginal sonography and biopsy of endometrium were done. The status of AUB and side-effects of two methods,along with the rate of satisfactory were evaluated., Result: The findings showed the significant differences in the treatment of simple hyperplasia between two groups (LNG-IUD group vs. MPA group) (p < 0.047). Recovery of AUB in the group LNG was enhanced (p < 0.047). Endometrial thickness was reduced in both groups (p < 0.001), but further reduction in LNG group was seen. Also, LNG was tolerated more than MPA. Side-effects of MPA were more and reached significance (p < 0.003). The rate of satisfaction with LNG was higher than MPA and reached significance (p < 0.048)., Conclusion: The results of this study show that LNG-IUD is more effective than MPA in treatment of simple endometrial hyperplasia and can be helpful in young women who want to preserve their fertilities.

Objective: The aim of the trial was to assess the safety and efficacy of tricholoroacetic acid for the treatment of dysfunctional uterine bleeding using topical versus intrauterine instillation., Study Design: In a pilot prospective randomized clinical trial, seventy women were randomly allocated to one of two groups. In Group I, the patients were subjected to intrauterine instillation of 95% tricholoroacetic acid. Group II underwent dilatation and curettage before topical application of 95% tricholoroacetic acid., Results: The groups were similar regarding baseline clinical characteristics. There was a satisfactory clinical reduction of menstrual flow (amenorrhea, hypomenorrhea and eumenorrhea) at a rate of 97.1% (Group I) and 85.7% (Group II) at 6 months. A significant increase was observed in the mean haemoglobin value at 3 and 6 months in both treatment groups (P<0.05). Group I showed a significant increase in haemoglobin level compared to Group II (P<0.05) and a significant reduction of the endometrial thickness compared to Group II (2.21 ± 0.41 versus 3.03 ± 3.37)., Conclusion: Trichloroacetic acid use for treating dysfunctional uterine bleeding seems to be efficient and safe, especially in women who do not require conception. Trichloroacetic acid intrauterine instillation is associated with longer duration of reduced menstrual bleeding than topical application., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

Erratic, "unscheduled", vaginal bleeding continues to be the greatest disadvantage associated with widespread use of long-acting, progestogen-only methods of contraception. As a consequence, it is also the main reason for premature discontinuation of use of these methods in most cultures. From other perspectives, these methods have high acceptability, very high contraceptive efficacy and a range of valuable, added, non-contraceptive health benefits. There has been widespread awareness of the variability of these vaginal bleeding patterns associated with long-acting methods for several decades and much research has been invested into studying their patterns and implications. Considerable research has also been directed towards trying to understand the underlying mechanisms responsible for the unpredictable bleeding. Much has been clarified about the multiple mechanisms contributing to the appearance of superficial, thin-walled fragile vessels within the endometrium of many of those women with troublesome bleeding, but there is still little understanding of why some women develop these vessels and others have no fragile vessels (and may therefore develop amenorrhea). We now have several medical approaches to reliably stopping a prolonged episode of troublesome bleeding, but no good therapy to produce long-lasting relief from recurrence of erratic bleeding in predisposed women. Future understanding of the variability in individual endometrial responses in different women may be a key to solving this frustrating symptom.

Introduction: Heavy menstrual bleeding (HMB) and the spotting and bleeding (S/B) associated with the use of hormonal contraceptives are distinct entities affecting endometrial vasculature and hemostasis., Materials and Methods: An overview of the major etiologies and potential treatments for each condition is provided., Results: HMB is potentially caused by several different hemostatic dysfunctions. Combination oral contraceptives, levonorgestrel-releasing intrauterine system, non-steroidal anti-inflammatory drugs, and anti-fibrinolytics all have been shown to have some degree of efficacy in treating HMB. The basic cause of HMB is unknown in the majority of cases. Endometrial S/B related to hormonal contraceptives is a common occurrence and may well have a common etiology in altered angiogenesis resulting in abnormal blood vessels with fragile vessel walls. There is no effective treatment for this problem., Conclusions: Medical therapy for HMB is limited and effective for reducing blood loss during menstruation. There is no effective treatment for the S/B associated with hormonal contraceptives.

Background: Increased matrix metalloproteinase (MMP) activity in the endometrium is a predisposing factor for bleeding with depot medroxy progesterone acetate (DMPA) injectable contraception. Doxycycline (DOX) has been proven in vitro to inhibit MMP-mediated degradation of stromal matrix. The current study examined the effect of DOX compared to placebo in treating a current bleeding episode during DMPA use., Study Design: A double-blinded randomized controlled trial was conducted in Assiut, Egypt. DMPA users with current bleeding episode were counseled to participate. Women who agreed to participate were randomly assigned to receive 100 mg DOX twice daily for 5 days (34 patients) or an identical placebo (34 patients). All participants were asked to report bleeding and spotting days in a menstrual diary. All participants were followed for 3 months after treatment. This trial was registered (NCT01254799)., Results: The relative risk to stop a bleeding episode within 10 days of starting treatment was 0.88 (confidence interval 0.64-1.21) in the treatment group compared to the control. DOX treatment caused no significant difference compared to placebo in the number of bleeding and/or spotting days in the 3 months following the treatment., Conclusion: Doxycycline as MMP inhibitor is not effective in stopping a current attack of bleeding with DMPA. It also does not improve the bleeding characteristics of women for the subsequent 3 months following the treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Evaluation of: Gemzell-Danielsson K, Schellschmidt I, Apter D. A randomized, Phase II study describing the efficacy, bleeding profile, and safety of two low-dose levonorgestrel-releasing intrauterine contraceptive systems and Mirena. Fertil. Steril. 97(3), 616-622.e3 (2012). A randomized, open-label, Phase II study was conducted in 37 centers in five European countries to assess the optimal dose for a new contraceptive levonorgestrel intrauterine system (LNG-IUS). Overall, 742 parous or nulliparous women aged 21-40 years were allocated to receive a LNG-IUS that initially releases 12 µg/day (LNG-IUS(12)) or 16 µg/day (LNG-IUS(16)) in vitro or the currently available device that releases 20 µg/day (LNG-IUS(20)). The two new devices are shorter than the current one. Pearl Indices of 0.17, 0.82 and 0.00 for the LNG-IUS(12), LNG-IUS(16) and LNG-IUS(20), respectively, reflect the contraceptive efficacy of these devices. The mean number of bleeding and spotting days decreased in all three groups; however, this decrease was more significant in LNG-IUS(20) users. Placement of the new shorter devices was considered simple by providers, while patients reported significantly less pain with the two new devices compared with the current one. This study provided further insight into the development of two new LNG-IUS devices as contraceptives, with the additional possibility of using them to treat heavy menstrual bleeding or as endometrial protection during estrogen therapy.

Abnormal uterine bleeding is one of the most common reasons that reproductive-aged women seek health care. The causes are varied, depending in large part on the age and life stage of the woman. Thus, diagnosis requires a systematic approach that is driven by a thorough health history and review of presenting symptoms. In recent years, the treatment of abnormal uterine bleeding has moved away from surgical procedures in favor of more conservative, yet effective, hormonal therapy such as combined contraceptives and the levonorgestrel-releasing intrauterine system. Clinicians must be knowledgeable about the various abnormal uterine bleeding treatment options and partner with women to develop appropriate, individualized treatment plans. The purpose of this article is to synthesize the current literature to describe the contributing etiologies, common presentations, diagnosis, evaluation, and management of abnormal uterine bleeding., (© 2012 by the American College of Nurse-Midwives.)

Background: Unscheduled bleeding is the main side effect of continuous oral contraceptive pills (OCPs) and has been correlated with the up-regulation of matrix metalloprotineases (MMPs). The study objective was to determine if prophylactic administration of doxycycline (an MMP inhibitor at low subantimicrobial doses) would prevent unscheduled bleeding during the initiation of a continuous OCP., Study Design: Subjects using cyclic hormonal contraceptives (combined OCPs, patch or ring) without unscheduled bleeding were switched to continuous OCPs (20 mcg ethinyl estradiol/100 mcg levonorgestrel). They were randomized to receive daily doxycycline [sustained-release subantimicrobial dose (40 mg daily)] or placebo for the first 84 days and then observed for an additional 28 days on the continuous OCP alone. The number of bleeding/spotting days and the time in days it took to achieve amenorrhea were compared using a t test., Results: Sixty-five subjects were randomized. Although the use of doxycycline did not significantly decrease the number of mean bleeding/spotting days in the first 84 days of the study [doxycycline 14.75 (SE 2.30), placebo 17.78 (2.31), p=.36], women who received doxycycline had a significantly earlier onset of amenorrhea [mean last day of bleeding/spotting doxycycline 61.7 (7.7), placebo 85.2 (6.7), p=.03]., Conclusion: The coadministration of subantimicrobial-dose doxycycline during initiation of continuous OCPs results in a significant reduction in the length of time needed to achieve amenorrhea., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women who are initiating the levonorgestrel-releasing intrauterine system., Study Design: We conducted a randomized controlled trial of naproxen, estradiol, or placebo that was administered over the first 12 weeks of levonorgestrel-releasing intrauterine system use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis., Results: There were 129 women who were assigned randomly to naproxen (n = 42 women), estradiol (n = 44 women), or placebo (n = 43 women). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared with placebo (42.9% vs 16.3%; P = .03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (adjusted relative risk, 0.90; 95% confidence interval, 0.84-0.97) compared with placebo. More frequent bleeding and spotting was observed in the estradiol group (adjusted relative risk, 1.25; 95% confidence interval, 1.17-1.34)., Conclusion: The administration of naproxen resulted in a reduction in bleeding and spotting days compared with placebo., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: To observe the clinical treatment of supplementing qi and nourishing yin recipe and progestogen., Method: One group was treated using traditional Chinese medicine decoction, which was made of Danshen, Shenghuangqi, Wuweizi, Baishao, Nvzhenzi, Hanliancao and Wuzeigu, and the other group was medroxyprogesterone acetate (depogeston)., Result: After 3 menstrual cycles of treatment, the recovery rate of the treatment group was 43.42%, with 27.63% of marked effectiveness,18.42% of positive effects, and 10.53% of inefficiency. The total effective rate was 89.47%. The recovery rate of the control group was 23%, with 47% of marked effectiveness, 20% of positive effects, and 10% of inefficiency. The total effective rate was 90.00%. With statistically comparison, there was no obvious difference. The treatment group was higher than the control group on the Chinese symptom, the two groups were significantly different (P < 0.05). The treatment group and the control group was no obvious difference on Hb, PLT, PT, APTT. The treatment group and the control group was no obvious difference on FSH, LH, E2, P., Conclusion: Traditional Chinese medicine decoction should be recommended for its better therapeutic efficacy and stable clinical effects such as high recovery rate, significant improvement of symptom and no side effect and no adverse reaction.

Excessive menstrual bleeding reflects aberrant angiogenesis, generally due to submucosal myomas and endometrial polyps, although it is also frequently observed with long-term progestin-only contraception, impaired haemostasis and hormonal disorders. Surgery (hysterectomy, endometrial ablation) is used too frequently. Uterine artery embolisation is also an option for myomas. Medical treatments include combined oral contraception, progestins and levonorgestrel-releasing Intrauterine System. Gonadotropin-releasing hormone agonists provide significant improvements in bleeding for myomas, but also decrease estrogen secretion (e.g. hot flushes, decreased bone mass). Progestins, although used widely, remain poorly effective as they promote myoma cell growth. Recently, Selective Progesterone Receptor Modulators (SPRMs) have been shown to induce amenorrhea whilst maintaining endogenous estrogen secretion. Phase II studies have also demonstrated decreased fibroid size in SPRM-treated women. Although the mechanism of amenorrhea observed after SPRM treatment is still poorly understood, they may control uterine bleeding via a direct effect on endometrial blood vessels. Suppression of bleeding in women with uterine fibroids receiving SPRMs is associated with moderate reductions in uterine artery blood flow, without major changes in angiogenic factors and extracellular matrix composition; a clear difference to modifications observed with progestins. These data suggest major progress in the treatment of excessive menstrual bleeding.

Pharmacological therapies for the treatment of abnormal uterine bleeding are effective and generally well tolerated. This review presents an evidence-based approach to medical therapy. Selection depends on the etiology and amount of bleeding, need for contraception or preservation of fertility, perimenopause status, and medication efficacy and adverse effects.Available nonhormonal agents include nonsteroidal anti-inflammatory agents, which reduce bleeding by 25% to 35% and improve dysmenorrhea through reduced prostaglandin levels; tranexamic acid, which inhibits plasminogen activator with a 40% to 60% reduction in menstrual blood loss; and intranasal desmopressin, which is an antifibrinolytic for women with an underlying bleeding disorder (eg, von Willebrand disease).Hormonal regimens cause the inhibition of endometrial growth. Cyclic progestogen therapy for 21 days results in a significant reduction in menstrual blood loss. Limited data suggest that oral contraceptives reduce menstrual blood loss by 40% to 50% with decreased breast tenderness and dysmenorrhea and a reduction in risk of uterine and ovarian cancer. The progestin-releasing intrauterine devices are effective up to 97% by 6 months and provide relief of dysmenorrhea and contraception. Long-acting progestogen injections produce amenorrhea and provide contraception but are associated with irregular spotting and reversible bone loss. Danazol leads to endometrial atrophy with a reduced menstrual loss; androgenic adverse effects may be lessened with lower doses or vaginal use. Gonadotrophin agonists lead to ovarian suppression and are used to shrink fibroids or the endometrium preoperatively but are limited by hypoestrogenic adverse events. Emergency use of parenteral conjugated estrogens has a 70% chance of stopping abnormal bleeding but an increased risk of thrombosis., (© 2011 by The North American Menopause Society)

Objective: To review the literature for economic and health-related quality of life outcomes data associated with the use of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the management of heavy menstrual bleeding., Methods: We searched the MEDLINE and EMBASE databases simultaneously using the Ovid interface to review the literature in a systematic manner for economic and health-related quality of life outcomes data associated with the use of the LNG-IUS in women with heavy menstrual bleeding. Articles were then selected for further review based on the relevance of their titles and/or abstracts. We identified 17 articles for inclusion in this review., Results: Treating heavy menstrual bleeding with the LNG-IUS was found to be cost-effective in various countries and settings. Moreover, irrespective of the measuring instrument used, health-related quality-of-life outcomes were found to be improved to a degree similar to that achieved with endometrial ablation or hysterectomy. In some cases, the LNG-IUS appeared to be more effective and less costly than the surgical options., Conclusion: The LNG-IUS is a cost-effective treatment option for heavy menstrual bleeding when pharmacologic treatment is indicated., (Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: To compare the cost and effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) versus combined oral contraception (COC) and progestogens (PROG) in first-line treatment of dysfunctional uterine bleeding (DUB) in Spain., Study Design: A cost-effectiveness and cost-utility analysis of LNG-IUS, COC and PROG was carried out using a Markov model based on clinical data from the literature and expert opinion. The population studied were women with a previous diagnosis of idiopathic heavy menstrual bleeding. The analysis was performed from the National Health System perspective, discounting both costs and future effects at 3%. In addition, a sensitivity analysis (univariate and probabilistic) was conducted., Results: The results show that the greater efficacy of LNG-IUS translates into a gain of 1.92 and 3.89 symptom-free months (SFM) after six months of treatment versus COC and PROG, respectively (which represents an increase of 33% and 60% of symptom-free time). Regarding costs, LNG-IUS produces savings of € 174.2-309.95 and € 230.54-577.61 versus COC and PROG, respectively, after 6 months-5 years. Apart from cost savings and gains in SFM, quality-adjusted life months (QALM) are also favourable to LNG-IUS in all scenarios, with a range of gains between 1 and 2 QALM compared to COC and PROG., Conclusions: The results indicate that first-line use of the LNG-IUS is the dominant therapeutic option (less costly and more effective) in comparison with first-line use of COC or PROG for the treatment of DUB in Spain. LNG-IUS as first line is also the option that provides greatest health-related quality of life to patients., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

In this study the clinical data of all girls who visited the ambulance for paediatric and adolescent gynaecology at the university clinic for gynaecology and obstetrics in Vienna between 2001 and 2008 because of menstrual cycle abnormalities were used (n = 255). Most frequently, the girls suffered from dysmenorrhoea (29%), tempoanomaly (24%) and metrorrhagia (19%). For 57%, it was possible to find an underlying cause, mainly (24%) a hormonal one. The therapy was in 54% of all cases hormonal. In a second step, the study analyses matches between the age at menarche and the development of menstrual cycle abnormalities. Girls with primary amenorrhoea were excluded (n = 219). The study shows that every age of menarche has its special kind of menstrual cycle abnormality. Only if the menarche had set in at the age of 16, two kinds were named with equal frequency.

Objective: To investigate the effect and hemostatic mechanism of Shenqi Guchong Recipe (SGR) in treating peri-menopausal anovulatory dysfunctional uterine bleeding (ADUB) of qi deficiency blood stasis syndrome type (QDBS)., Methods: Patients of ADUB-QDBS were assigned to two groups, the 47 patients in the treated group administering orally with SGR and the 31 in the control group treated with Kunning Oral Liquid. The hemostatic effect, and the changes before and after treatment of 6-ketoprostaglandin 1alpha (6-K-PGF1 alpha), thromboxane B2(TXB2), T-lymphocyte subsets (CD3 and CD8, CD4/CD8 ratio) in menstrual blood, and serum calcium level in patients were observed., Results: The hemostatic effect in the treated group [85.1% (40/47)] was better than that in the control group [51.6% (16/31)], significant difference was shown between groups (P < 0.05). Changes of 6-K-PGF1 alpha TXB2, and 6-K-PGF1 alph/TXB2 ratio in the treated group were significant after treatment and showed significant difference as compared with those in the control group (P < 0.05 or P < 0.01). Meantime, serum Ca2+ level was increased and parameters of T-lymphocyte subsets improved significantly in the treated group (P < 0.05 or P < 0.01), also statistically different to those in the control group (P < 0.05)., Conclusion: SGR shows obvious hemostatic effect in treating patients with ADUB of QDBS type, and the mechanism may be related to its actions for improving microcirculation, enhancing immune function, and improving uterine local micro-environment, etc.

Objective: To estimate whether doxycycline, a matrix metalloproteinase inhibitor, would decrease unscheduled bleeding associated with initiation of a continuous oral contraceptive pill., Methods: Participants initiating a continuous oral contraceptive pill (20 micrograms of ethinyl estradiol/90 micrograms of levonorgestrel) were randomly assigned to receive either doxycycline (100 mg orally twice daily) or placebo taken for 5 days at the onset of each bleeding or spotting episode during the first 84 days of the study period. For the final 28 days of the study, participants were observed on the oral contraceptive pill alone. The primary outcome was the number of bleeding and spotting days. A sample size of 66 (33 in each arm) was calculated to detect a 50% reduction in bleeding (beta=0.80, alpha=0.05) and accounted for a 30% dropout rate., Results: Sixty-six women were randomly assinged (33 in each study group). There were no significant differences during the 84-day treatment in bleeding or spotting days (doxycycline [mean {standard error}, placebo, P=.32) or the length of the longest bleeding or spotting episode (doxycycline, placebo, P=.70) between study groups. Similarly, no significant differences in bleeding patterns existed between groups during the final 28 days., Conclusion: Doxycycline, administered once bleeding has started, does not decrease unscheduled bleeding or shorten episodes of unscheduled bleeding in continuous oral contraceptive pill users., Level of Evidence: I.

Objective: To evaluate the efficacy of mifepristone to reduce intermenstrual bleeding in levonorgestrel intrauterine system (LNG-IUS) users., Method: In this prospective, open-label, comparative study, 36 women using the LNG-IUS for menorrhagia received 100mg of mifepristone every 30 days for 3 months (group 1). Fifty age-matched LNG-IUS users who did not receive any drugs were used as the comparison group (group 2). Menstrual bleeding days, pictorial blood loss assessment chart (PBAC) score, and intermenstrual bleeding/spotting days were compared between the 2 groups at 3 months (during treatment) and at 6 months (3 months post treatment)., Results: Baseline characteristics were comparable between the groups. At 3 months, median duration and episodes of intermenstrual bleeding/spotting were significantly lower in group 1 compared with group 2 (6 vs 12.5 days, P=0.01; 2.5 vs 3, P=0.05, respectively). More women were satisfied with the LNG-IUS in the mifepristone group compared with the control group (75% vs 44%; P=0.004). At 6 months, the median duration of intermenstrual bleeding/spotting was significantly lower in group 1 compared with group 2 (6 vs 15 days; P=0.008)., Conclusion: Mifepristone was effective in reducing the number of episodes and duration of intermenstrual bleeding/spotting in LNG-IUS users., (Copyright 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: The vaginal route is more effective than the other drug delivery routes for some specific indications., Aim: To compare the efficacy of a vaginal progesterone preparation with that of oral dydrogesterone., Methods: A total of 69 women with irregular dysfunctional uterine bleeding were randomly assigned into one of two groups: oral dydrogesterone group (n = 35) and vaginal progesterone group (n = 34). At the end of a three-month treatment period, the women were re-evaluated. The endometrial histology findings and menstrual cycle characteristics were used as primary outcome measures. Pearson chi-square and Fisher's exact test were used for data analysis., Results: Findings from 54 eligible women were evaluated. There was no statistically significant difference in both menstrual recordings and endometrial histology results between the groups., Conclusions: Vaginal micronised progesterone could be an alternative to oral preparations in the treatment of dysfunctional uterine bleeding. This needs to be further evaluated in adequately controlled randomised trials against other effective treatments.

Background: Pilot data have indicated that both doxycycline alone and mifepristone combined with ethinyl estradiol (EE) are effective in stopping episodes of bleeding in Implanon users with troublesome bleeding. We compared four treatments against a placebo in Implanon users and tested whether repeated treatment improved subsequent bleeding patterns., Method: Implanon users aged 18-45 years were randomized to treatment with (i) mifepristone 25 mg given twice on day 1 followed by 4 days of EE 20 microg; (ii) doxycycline 100 mg twice daily for 5 days; (iii) mifepristone 25 mg given twice on day 1 plus doxycycline 100 mg twice daily for 5 days; (iv) doxycycline 100 mg twice daily with EE 20 microg daily; and (v) placebo twice daily for 5 days. The primary end-point was the number of days of bleeding/spotting immediately following initiation of the first 5-day course of each therapy, compared with placebo., Results: There were 204 women assigned to treatment. Mifepristone in combination with either EE or doxycycline was significantly more effective in stopping an episode of bleeding (mean 4.0 days (CI 3.5-4.6) and 4.4 days (CI 3.8-5.2), respectively) than doxycycline alone or in combination with EE, or placebo (6.4 days (CI 4.4-9.2), 6.4 days (CI 4.8-8.6) and 6.4 days (CL 5.1-8.0), respectively)., Conclusion: Mifepristone combined with either EE or doxycycline was significantly more effective than placebo in terminating an episode of bleeding in Implanon users. However there was no improvement in subsequent bleeding patterns., Trial Registration Number: ACTR # 012605000206628.

Objective: To evaluate the efficacy of levonorgestrel intrauterine systems (LNG-IUS) in obese women with AUB on anticoagulant therapy., Design: Prospective observational case series (Canadian Task Force Classification II-3)., Setting: University affiliated teaching hospital., Patients: Premenopausal women on Warfarin therapy., Interventions: From January 2002 through January 2007, 10 women were identified from the senior author's clinical practice (G.A.V.). After clinical assessment, including Papanicolaou smear, endometrial biopsy, and pelvic sonography, the LNG-IUS was placed to treat their AUB., Measurements and Main Results: The median and range of age, parity, and body mass index were 45 years (34-49), 1 (0-4), and 38 kg/m(2) (26-52), respectively. All women were receiving warfarin therapy (4-12.5 mg/d) for previous venous thromboembolism. Some patients had additional comorbid conditions and were at high risk for traditional medical or surgical therapies. After placement of the LNG-IUS, all women reported menstrual reduction at 3 and 6 months. By 12 months, 1 woman with large fibroids expelled the LNG-IUS and was treated with transfemoral uterine artery embolization. Two women had amenorrhea, and 7 had hypomenorrhea. At 2 to 5 years, 1 woman expelled the LNG-IUS and hysterectomy indicated extensive adenomyosis in a 195-g uterus, and 1 woman had hysteroscopic endometrial ablation, 4 were menopausal, 2 had amenorrhea, and 1 had hypomenorrhea. In the 5 women with uterine fibroids measuring 4.2 to 147 cm(3), the fibroids were reduced in volume by approximately 75% in 2, were no longer detectable in 1, were subsequently shown to be adenomyoma in 1, and required uterine artery embolization in 1., Conclusion: In properly assessed and selected obese, premenopausal women with AUB receiving warfarin therapy and at high risk for traditional therapies, the LNG-IUS was an effective treatment in 70% of patients.

Background: Endometrial spotting and/or bleeding (ESB) occurs in levonorgestrel subcutaneous implant (LNG SI) users. Matrix metalloproteinases (MMPs) may play a role in ESB., Study Design: Women between 18 and 40 years with regular menstrual cycles had a baseline evaluation followed by LNG SI insertion and randomization to doxycycline (DOX; 20 mg) or placebo (PL) twice a day. MMP-2, MMP-9 and tissue inhibitor of MMP-1 (TIMP-1) in serum and the endometrium were estimated at baseline and at 1, 3 and 6 months after insertion., Results: LNG increased serum MMP-9, while DOX decreased MMP-9 levels compared to PL after 1 month (p<.05). DOX decreased endometrial MMP-9 at 1 and 6 months compared to baseline and PL (p<.05). DOX increased endometrial TIMP-1 at 6 months compared with baseline and PL (p<.05). MMP-2 levels were unchanged., Conclusion: LNG SI increased serum MMP-9 and TIMP-1 levels, while DOX decreased both serum and endometrial MMP-9 levels.