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International Journal of Gynaecology... Dec 2018The International Federation of Gynecology and Obstetrics (FIGO) systems for nomenclature of symptoms of normal and abnormal uterine bleeding (AUB) in the reproductive...
The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions.
BACKGROUND
The International Federation of Gynecology and Obstetrics (FIGO) systems for nomenclature of symptoms of normal and abnormal uterine bleeding (AUB) in the reproductive years (FIGO AUB System 1) and for classification of causes of AUB (FIGO AUB System 2; PALM-COEIN) were first published together in 2011. The purpose was to harmonize the definitions of normal and abnormal bleeding symptoms and to classify and subclassify underlying potential causes of AUB in the reproductive years to facilitate research, education, and clinical care. The systems were designed to be flexible and to be periodically reviewed and modified as appropriate.
OBJECTIVES
To review, clarify, and, where appropriate, revise the previously published systems.
METHODOLOGY AND OUTCOME
To a large extent, the process has been an iterative one involving the FIGO Menstrual Disorders Committee, as well as a number of invited contributions from epidemiologists, gynecologists, and other experts in the field from around the world between 2012 and 2017. Face-to-face meetings have been held in Rome, Vancouver, and Singapore, and have been augmented by a number of teleconferences and other communications designed to evaluate various aspects of the systems. Where substantial change was considered, anonymous voting, in some instances using a modified RAND Delphi technique, was utilized.
Topics: Adolescent; Adult; Classification; Endometrium; Female; Humans; Menstruation Disturbances; Myometrium; Ovulation; Uterine Diseases; Uterine Hemorrhage; Young Adult
PubMed: 30198563
DOI: 10.1002/ijgo.12666 -
Best Practice & Research. Clinical... Jul 2016Abnormal uterine bleeding (AUB) is a common and debilitating condition with high direct and indirect costs. AUB frequently co-exists with fibroids, but the relationship... (Review)
Review
Abnormal uterine bleeding (AUB) is a common and debilitating condition with high direct and indirect costs. AUB frequently co-exists with fibroids, but the relationship between the two remains incompletely understood and in many women the identification of fibroids may be incidental to a menstrual bleeding complaint. A structured approach for establishing the cause using the Fédération International de Gynécologie et d'Obstétrique (FIGO) PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification system will facilitate accurate diagnosis and inform treatment options. Office hysteroscopy and increasing sophisticated imaging will assist provision of robust evidence for the underlying cause. Increased availability of medical options has expanded the choice for women and many will no longer need to recourse to potentially complicated surgery. Treatment must remain individualised and encompass the impact of pressure symptoms, desire for retention of fertility and contraceptive needs, as well as address the management of AUB in order to achieve improved quality of life.
Topics: Adenomyosis; Blood Coagulation Disorders; Female; Humans; Leiomyoma; Leiomyosarcoma; Metrorrhagia; Polyps; Uterine Neoplasms
PubMed: 26803558
DOI: 10.1016/j.bpobgyn.2015.11.012 -
Revista Da Associacao Medica Brasileira... Jun 2019An isthmocele, a cesarean scar defect or uterine niche, is any indentation representing myometrial discontinuity or a triangular anechoic defect in the anterior uterine... (Review)
Review
An isthmocele, a cesarean scar defect or uterine niche, is any indentation representing myometrial discontinuity or a triangular anechoic defect in the anterior uterine wall, with the base communicating to the uterine cavity, at the site of a previous cesarean section scar. It can be classified as a small or large defect, depending on the wall thickness of the myometrial deficiency. Although usually asymptomatic, its primary symptom is abnormal or postmenstrual bleeding, and chronic pelvic pain may also occur. Infertility, placenta accrete or praevia, scar dehiscence, uterine rupture, and cesarean scar ectopic pregnancy may also appear as complications of this condition. The risk factors of isthmocele proven to date include retroflexed uterus and multiple cesarean sections. Nevertheless, factors such as a lower position of cesarean section, incomplete closure of the hysterotomy, early adhesions of the uterine wall and a genetic predisposition may also contribute to the development of a niche. As there are no definitive criteria for diagnosing an isthmocele, several imaging methods can be used to assess the integrity of the uterine wall and thus diagnose an isthmocele. However, transvaginal ultrasound and saline infusion sonohysterography emerge as specific, sensitive and cost-effective methods to diagnose isthmocele. The treatment includes clinical or surgical management, depending on the size of the defect, the presence of symptoms, the presence of secondary infertility and plans of childbearing. Surgical management includes minimally invasive approaches with sparing techniques such as hysteroscopic, laparoscopic or transvaginal procedures according to the defect size.
Topics: Cesarean Section; Cicatrix; Female; Humans; Hysteroscopy; Metrorrhagia; Risk Factors; Uterine Diseases
PubMed: 31166450
DOI: 10.1590/1806-9282.65.5.714 -
Drugs Jul 2022Estetrol/drospirenone is a combined oral contraceptive (COC) with a plant-synthesised foetal oestrogen (estetrol) and a well-established progestin (drospirenone). In... (Review)
Review
Estetrol/drospirenone is a combined oral contraceptive (COC) with a plant-synthesised foetal oestrogen (estetrol) and a well-established progestin (drospirenone). In preclinical models, estetrol has lower binding affinity for the oestrogen receptor-α (ER-α) in contrast to estradiol and has antagonistic properties against membrane ER-α in several tissues, including the breast, while retaining agonistic activity on receptors located in the nucleus. The low oestrogenicity of estetrol may potentially contribute to reduced thrombotic risk. Estetrol/drospirenone was an effective contraceptive in phase II and III clinical trials, with regular and predictable bleeding cycles maintained in the majority of women. Estetrol/drospirenone was generally well-tolerated with metrorrhagia reported as the most common treatment-related adverse event, which is consistent with other COCs. Cases of migraines with aura (or severe migraines), deep vein thrombosis, hyperkalaemia and depression were rarely reported during the phase III trials. Overall, estetrol/drospirenone is an effective and generally well-tolerated COC, with a potentially reduced risk of thrombosis.
Topics: Androstenes; Clinical Trials, Phase III as Topic; Contraceptives, Oral, Combined; Estetrol; Female; Humans
PubMed: 35781795
DOI: 10.1007/s40265-022-01738-8 -
Acta Medica Portuguesa Mar 2021Abnormal uterine bleeding is the most common complaint that motivates female adolescents to seek medical advice. Abnormal uterine bleeding has a significant impact on... (Review)
Review
Abnormal uterine bleeding is the most common complaint that motivates female adolescents to seek medical advice. Abnormal uterine bleeding has a significant impact on quality of life, promoting school absenteeism and limitations in social life. Moreover, episodes can vary from mild to life threatening events if not recognized and treated promptly. Healthcare providers should be able to distinguish between a normal and abnormal menstrual pattern, as this may provide early diagnosis of a potential health concern. The PALM-COEIN classification system should be used in the evaluation. Anovulation is the most frequent cause, frequently due to immaturity of the hypothalamic-pituitary-ovarian axis. A careful history and physical examination are crucial in the differential diagnosis. Management is based on both the underlying cause and the severity of bleeding. Most patients improve with pharmacological treatment, frequently requiring a multidisciplinary approach. First line treatment consists of hormonal therapy. Surgery is rarely needed. Although the prevalence of abnormal uterine bleeding is higher in adolescents compared to adults, most recommendations are not specific for this age, which makes the diagnosis and management challenging. The literature reveals lack of standardized care for adolescents and regimens vary widely. Future studies on efficacy and safety of treatments specifically in adolescents are needed.
Topics: Adolescent; Adult; Blood Coagulation Disorders; Female; Humans; Menorrhagia; Metrorrhagia; Quality of Life; Uterine Diseases; Uterine Hemorrhage
PubMed: 34214420
DOI: 10.20344/amp.12829 -
Fertility and Sterility Oct 2022To synthesize the published literature to better understand the association between cesarean scar defects (CSDs) and abnormal uterine bleeding (AUB). In particular, we... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To synthesize the published literature to better understand the association between cesarean scar defects (CSDs) and abnormal uterine bleeding (AUB). In particular, we aimed to evaluate the risk and pattern(s) of CSD-associated AUB in addition to exploring the relationship between defect morphology with bleeding symptoms.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENTS
Patients with CSD and reports of uterine bleeding as an outcome were identified in 60 studies from database searches.
INTERVENTIONS
Studies that investigated CSD (as defined by investigators) and reported uterine bleeding, menstrual bleeding, or AUB as an outcome were included.
MAIN OUTCOME MEASURES
The prevalence and risk of AUB (intermenstrual, postmenstrual, and unscheduled bleeding) in patients with confirmed CSD.
RESULTS
Nine studies reported on the prevalence of AUB in patients with a confirmed CSD. Patients with CSD were more likely to experience AUB, compared with those without CSD (relative risk, 3.47; 95% confidence interval [CI], 2.02-5.97; 6 studies, 1,385 patients; I = 67%). In a population of patients with at least 1 cesarean delivery, the prevalence of AUB in those with CSD was 25.5% (95% CI, 14.7-40.5; 6 studies, 667 patients, I = 93%). However, symptom prevalence was much higher in patients presenting for imaging for a gynecologic indication where the prevalence of AUB in the presence of a CSD was 76.4% (95% CI, 67.8-83.3; 5 studies, 505 patients; I = 71%). The mean menstrual duration in symptomatic patients with CSD was 13.4 days (95% CI, 12.6-14.2; 19 studies, 2,095 patients; I = 96%), and the mean duration of early-cycle intermenstrual bleeding was 6.8 days (95% CI, 5.7-7.8 days; 9 studies, 759 patients; I = 93%). The most common descriptor of CSD-associated AUB was "brown discharge". Patients with larger CSD experienced more bleeding symptoms.
CONCLUSION
There is a strong and consistent association between patients with CSD and AUB. These patients experience a unique bleeding pattern, namely prolonged menstruation and early-cycle intermenstrual bleeding. These data should provide impetus for including CSD as a distinct entity in AUB classification systems. High heterogeneity in our results calls for standardization of nomenclature and outcome reporting for this condition.
Topics: Cesarean Section; Cicatrix; Female; Humans; Metrorrhagia; Pregnancy; Uterine Diseases; Uterine Hemorrhage
PubMed: 35985862
DOI: 10.1016/j.fertnstert.2022.06.031 -
Contraception Sep 2021To assess efficacy, cycle control, and safety of an oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg.
OBJECTIVE
To assess efficacy, cycle control, and safety of an oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg.
STUDY DESIGN
Women aged 16 to 50 years with a body mass index ≤35 kg/m enrolled in this multicenter, open-label, 13-cycle, phase 3 trial evaluating E4/DRSP in a 24-active/4-placebo regimen. Follow-up was scheduled at Cycles 2, 4, 7, and 10 and within 3 weeks of completing Cycle 13. Participants used daily diaries to record pill use and vaginal bleeding. We evaluated efficacy outcomes in women 16 to 35 years and bleeding patterns and safety (adverse events [AEs]) in all participants. We assessed overall and method-failure pregnancy rates using the Pearl index (PI) and life-table analysis. Scheduled bleeding included spotting or bleeding starting during the 4-day placebo period or first 3 days of the next cycle.
RESULTS
We enrolled 1864 women of whom 1674 were 16 to 35 years. Women 16 to 35 years had a PI of 2.65 (95% CI 1.73-3.88), method-failure PI of 1.43 (95% CI 0.7-2.39) and 13-cycle life-table pregnancy rate of 2.1%. Scheduled bleeding occurred in 82.9% to 87.0% of women per cycle; median duration was 4.5 days. Unscheduled bleeding decreased from 30.3% in Cycle 1 to 21.3% to 22.1% during Cycles 2 to 4 and remained stable (15.5% to 19.2%) thereafter. The most frequently reported AEs were headache (5.0%) and metrorrhagia (4.6%). One-hundred thirty-two (7.1%) women discontinued the study early for an AE, most commonly for metrorrhagia (0.9%) and menorrhagia (0.8%). No thromboembolic events occurred.
CONCLUSION
E4/DRSP is an effective oral contraceptive with a predictable bleeding pattern for most women and low AE rates.
IMPLICATIONS STATEMENT
A new oral contraceptive with a novel estrogen, estetrol, combined with drospirenone has efficacy and safety within the range of other available oral contraceptives. Large phase 4 studies will be needed to confirm if this combination is associated with an improved adverse event profile or lower thrombosis risk.
Topics: Androstenes; Contraceptives, Oral, Combined; Estetrol; Estrogens; Ethinyl Estradiol; Female; Humans; North America; Pregnancy
PubMed: 34000251
DOI: 10.1016/j.contraception.2021.05.002 -
Fertility and Sterility Mar 2022To evaluate the efficacy and safety of 40-mg relugolix (REL) compared with those of leuprorelin (LEU) in women with endometriosis-associated pain. (Randomized Controlled Trial)
Randomized Controlled Trial
Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain compared with leuprorelin in Japanese women: a phase 3, randomized, double-blind, noninferiority study.
OBJECTIVE
To evaluate the efficacy and safety of 40-mg relugolix (REL) compared with those of leuprorelin (LEU) in women with endometriosis-associated pain.
DESIGN
Phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled study in Japanese patients.
SETTING
Hospitals and clinics.
PATIENT(S)
Women aged ≥20 years with regular menstrual cycles (25-38 days) experiencing endometriosis or ovarian endometrioma and reporting pelvic pain.
INTERVENTION(S)
In the REL group, 40 mg of REL was orally administered once a day for 24 weeks. In the LEU group, 3.75 or 1.88 mg of LEU was subcutaneously injected every 4 weeks for 24 weeks.
MAIN OUTCOME MEASURE(S)
The primary endpoint was the change in the maximum visual analog scale score for pelvic pain from baseline until 28 days before the end of treatment.
RESULT(S)
Changes in the maximum visual analog scale score were -52.6 ± 1.3 for REL and -57.5 ± 1.4 for LEU. Ovarian endometrioma decreased by 12.26 ± 17.52 cm for REL and 14.10 ± 18.81 cm for LEU. Drug-related treatment emergent adverse events with an incidence of >10% for both groups were hot flush, metrorrhagia, headache, and genital hemorrhage. Discontinuations from treatment emergent adverse events were 2.9% for REL and 4.3% for LEU.
CONCLUSION(S)
Relugolix was noninferior to LEU for treating endometriosis-associated pelvic pain. Safety profiles of both medications were comparable, although menses returned earlier in patients taking REL, a huge benefit for women who plan to conceive after treatment.
CLINICAL TRIAL REGISTRATION NUMBER
ClinicalTrials.gov: NCT03931915.
Topics: Administration, Oral; Adult; Double-Blind Method; Endometriosis; Female; Fertility Agents, Female; Follow-Up Studies; Hormone Antagonists; Humans; Japan; Leuprolide; Pain Measurement; Pelvic Pain; Phenylurea Compounds; Pyrimidinones; Receptors, LHRH
PubMed: 34895700
DOI: 10.1016/j.fertnstert.2021.11.013 -
Acta Obstetricia Et Gynecologica... Dec 2019Approximately 100 million women currently use combined oral contraceptives. Combined oral contraceptives use is associated with increased risk of venous thromboembolic...
INTRODUCTION
Approximately 100 million women currently use combined oral contraceptives. Combined oral contraceptives use is associated with increased risk of venous thromboembolic events and cardiovascular disease. Progestin-only pills do not increase the risk of venous thromboembolic events, stroke and myocardial infarction but are associated with a poor cycle control. A novel estrogen-free pill containing only drospirenone (DRSP) was developed to improve bleeding pattern, tolerability and acceptance without increasing venous thromboembolic events risks in contraception.
MATERIAL AND METHODS
Two prospective, multicenter Phase III studies in healthy women aged 18-45 years were performed to demonstrate the efficacy and safety of a drospirenone-only pill in a regimen of 24 days of 4 mg of drospirenone tablets followed by 4 days of placebo. A total of 1571 women (14 329 exposure cycles) were analyzed: 713 patients in the 13-cycle study 1 with 7638 exposure cycles and 858 patients in the 9-cycle study 2 with 6691 exposure cycles. The primary endpoint was the overall Pearl index, calculated for each study separately, and for both pooled. As main secondary efficacy endpoint, the "method failure Pearl index" including all pregnancies during "perfect medication cycles" was evaluated. EudraCT registration numbers: 2010-021787-15 & 2011-002396-42.
RESULTS
Calculations on pooled studies 1 and 2 with 1571 patients gave an overall Pearl index (based on 14 329 cycles) of 0.7258 (95% CI 0.3133 to 1.4301). No single case of deep vein thrombosis or pulmonary embolism and only one case of hyperkalemia were reported. Additional information such as laboratory parameters, body mass index, bodyweight, heart rate and blood pressure showed no statistically significant changes due to the treatment.
CONCLUSIONS
This is the first report of a new drospirenone-only oral contraceptive providing clinical efficacy similar to combined oral contraceptives, with a good safety profile, and favorable cycle control.
Topics: Adult; Androstenes; Contraceptives, Oral; Female; Humans; Hyperkalemia; Metrorrhagia; Pregnancy; Pregnancy Rate; Prospective Studies; Pulmonary Embolism; Treatment Failure; Venous Thrombosis; Young Adult
PubMed: 31321765
DOI: 10.1111/aogs.13688 -
BJOG : An International Journal of... Jan 2022To assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg.
OBJECTIVES
To assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg.
DESIGN
Multicenter, open-label, phase 3 trial.
SETTING
Sixty-nine sites in Europe and Russia.
POPULATION
Sexually active women aged 18-50 years with regular menstrual cycles and body mass index ≤35 kg/m .
METHODS
E4/DRSP was administered in a 24 active/4 placebo regimen for up to 13 cycles. Visits were scheduled during Cycles 2, 4, 7 and 10 and after completing treatment during which adverse events (AEs) were collected. Participants recorded medication intake, vaginal bleeding/spotting, use of other contraceptive methods and sexual intercourse on a daily diary.
MAIN OUTCOME MEASURES
Pearl Index (PI) for women 18-35 years (overall and method-failure), bleeding pattern and AEs.
RESULTS
A total of 1553 women aged 18-50 years, including 1353 from 18 to 35 years old, received the study medication. PI was 0.47 pregnancies/100 woman-years (95% CI 0.15-1.11); method failure PI was 0.29 pregnancies/100 woman-years (95% CI 0.06-0.83). Scheduled bleeding/spotting occurred in 91.9-94.4% of women over Cycles 1 to 12 and lasted a median of 4-5 days per cycle. The percentage of women with unscheduled bleeding/spotting episodes decreased from 23.5% in Cycle 1 to <16% from Cycle 6 onwards. The most common AEs were headache (7.7%), metrorrhagia (5.5%), vaginal haemorrhage (4.8%) and acne (4.2%). One treatment-related serious AE was reported, a lower extremity venous thromboembolism. One-hundred and forty-one (9.1%) women discontinued study participation because of treatment-related adverse events.
CONCLUSION
E4/DRSP provides effective contraception, a predictable bleeding pattern and a favourable safety profile.
TWEETABLE ABSTRACT
A phase 3 trial with E4/DRSP shows high contraceptive efficacy, a predictable bleeding pattern and favourable safety profile.
Topics: Adolescent; Adult; Contraceptives, Oral, Combined; Estetrol; Europe; Female; Humans; Metrorrhagia; Middle Aged; Russia; Young Adult
PubMed: 34245666
DOI: 10.1111/1471-0528.16840