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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 -
Drugs Oct 2022An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo; Myfembree) has been approved for the management of... (Review)
Review
An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo; Myfembree) has been approved for the management of heavy menstrual bleeding associated with uterine fibroids in the USA and management of moderate to severe symptoms of uterine fibroids in the EU. Relugolix is a gonadotropin releasing hormone (GnRH) receptor antagonist that decreases serum estradiol and progesterone concentrations to postmenopausal levels. The addition of estradiol/norethisterone acetate to relugolix ameliorates relugolix-induced bone loss and hot flush. In the two phase 3 LIBERTY trials, relugolix + estradiol/norethisterone substantially decreased menstrual bleeding and improved a range of other uterine fibroid symptoms in women with uterine fibroids-associated heavy menstrual bleeding. The combination was generally well tolerated, with vasomotor symptoms being the most common adverse reaction. Treatment with this combination for over up to 2 years did not induce a clinically meaningful bone loss in the majority of women. Relugolix/estradiol/norethisterone acetate, with its convenient once-daily administration, is a useful addition to current pharmacological treatment options for premenopausal women with symptomatic uterine fibroids.
Topics: Female; Humans; Norethindrone Acetate; Menorrhagia; Uterine Neoplasms; Leiomyoma; Norethindrone; Estradiol; Acetates
PubMed: 36331779
DOI: 10.1007/s40265-022-01790-4 -
Advances in Therapy Jan 2021Up to one-third of women of reproductive age experience heavy menstrual bleeding (HMB). HMB can give rise to iron deficiency (ID) and, in severe cases, iron-deficiency... (Review)
Review
INTRODUCTION
Up to one-third of women of reproductive age experience heavy menstrual bleeding (HMB). HMB can give rise to iron deficiency (ID) and, in severe cases, iron-deficiency anemia (IDA).
AIM
To review current guidelines for the management of HMB, with regards to screening for anemia, measuring iron levels, and treating ID/IDA with iron replacement therapy and non-iron-based treatments.
METHODS
The literature was searched for English-language guidelines relating to HMB published between 2010 and 2020, using the PubMed database, web searching, and retrieval of clinical guidelines from professional societies.
RESULTS
Overall, 55 guidelines mostly originating from North America and Europe were identified and screened. Twenty-two were included in this review, with the majority (16/22) focusing on guidance to screen women with HMB for anemia. The guidance varied with respect to identifying symptoms, the criteria for testing, and diagnostic hemoglobin levels for ID/IDA. There was inconsistency concerning screening for ID, with 11/22 guidelines providing no recommendations for measurement of iron levels and four contrasting guidelines explicitly advising against initial assessment of iron levels. In terms of treatment, 8/22 guidelines provided guidance on iron therapy, with oral iron administration generally recommended as first-line treatment for ID and/or IDA. Four guidelines recommended intravenous iron administration for severe anemia, in non-responders, or before surgery. Three guidelines provided hemoglobin thresholds for choosing between oral or intravenous iron treatment. Four guidelines discussed the use of transfusion for severe IDA.
CONCLUSION
Many of the guidelines for managing HMB recognize the importance of treating anemia, but there is a lack of consensus in relation to screening for ID and use of iron therapy. Consequently, ID/IDA associated with HMB is likely to be underdiagnosed and undertreated. A consensus guidance, covering all aspects of screening and management of ID/IDA in women with HMB, is needed to optimize health outcomes in these patients.
Topics: Anemia, Iron-Deficiency; Europe; Female; Hemoglobins; Humans; Iron; Menorrhagia
PubMed: 33247314
DOI: 10.1007/s12325-020-01564-y -
BMJ Sexual & Reproductive Health Jan 2024Heavy menstrual bleeding affects up to one third of menstruating individuals and has a negative impact on quality of life. The diagnosis of heavy menstrual bleeding is...
BACKGROUND
Heavy menstrual bleeding affects up to one third of menstruating individuals and has a negative impact on quality of life. The diagnosis of heavy menstrual bleeding is based primarily on history taking, which is highly dependent on traditional disposable menstrual products such as pads and tampons. Only tampons undergo industry-regulated testing for absorption capacity. As use of alternative menstrual products is increasing, there is a need to understand how the capacity of these products compare to that of standard products.
METHODS
A variety of commercially available menstrual products (tampons, pads, menstrual cups and discs, and period underwear) were tested in the laboratory to determine their maximal capacity to absorb or fill using expired human packed red blood cells. The volume of blood necessary for saturation or filling of the product was recorded.
RESULTS
Of the 21 individual menstrual hygiene products tested, a menstrual disc (Ziggy, Jiangsu, China) held the most blood of any product (80 mL). The perineal ice-activated cold pack and period underwear held the least (<3 mL each). Of the product categories tested, on average, menstrual discs had the greatest capacity (61 mL) and period underwear held the least (2 mL). Tampons, pads (heavy/ultra), and menstrual cups held similar amounts of blood (approximately 20-50 mL).
CONCLUSION
This study found considerable variability in red blood cell volume capacity of menstrual products. This emphasises the importance of asking individuals about the type of menstrual products they use and how they use them. Further understanding of capacity of newer menstrual products can help clinicians better quantify menstrual blood loss, identify individuals who may benefit from additional evaluation, and monitor treatment.
Topics: Female; Humans; Menorrhagia; Menstrual Hygiene Products; Hygiene; Quality of Life; Menstruation; Erythrocytes
PubMed: 37550075
DOI: 10.1136/bmjsrh-2023-201895 -
JAMA Pediatrics Feb 2020Heavy menstrual bleeding is a common cause of anemia and reduced quality of life in adolescents. There is a higher prevalence of bleeding disorders in girls with heavy... (Review)
Review
IMPORTANCE
Heavy menstrual bleeding is a common cause of anemia and reduced quality of life in adolescents. There is a higher prevalence of bleeding disorders in girls with heavy menstrual bleeding than in the general population. Pediatricians should be comfortable with the initial evaluation of heavy menstrual bleeding and the indications for referral to subspecialty care.
OBSERVATIONS
The most common cause of heavy menstrual bleeding in adolescents is ovulatory dysfunction, followed by coagulopathies. The most common inherited bleeding disorder is von Willebrand disease, and its incidence in adolescents with heavy menstrual bleeding is high. Distinguishing the etiology of heavy menstrual bleeding will guide treatment, which can include hemostatic medications, hormonal agents, or a combination of both. Among hormonal agents, the 52-mg levonogestrel intrauterine device has been shown to be superior in its effect on heavy menstrual bleeding and is safe and effective in adolescents with bleeding disorders.
CONCLUSIONS AND RELEVANCE
Anemia, need for transfusion of blood products, and hospitalization may be avoided with prompt recognition, diagnosis, and treatment of heavy menstrual bleeding, especially when in the setting of bleeding disorders. Safe and effective treatment methods are available and can greatly improve quality of life for affected adolescents. A multidisciplinary approach to the treatment of girls with bleeding disorders and history of heavy menstrual bleeding is optimal.
Topics: Adolescent; Blood Coagulation Disorders; Diagnosis, Differential; Female; Humans; Menorrhagia
PubMed: 31886837
DOI: 10.1001/jamapediatrics.2019.5040 -
Obstetrics and Gynecology Dec 2022In the LIBERTY 1 and LIBERTY 2 placebo-controlled trials, once-daily relugolix combination therapy reduced menstrual blood loss volume and pain in women with heavy... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
In the LIBERTY 1 and LIBERTY 2 placebo-controlled trials, once-daily relugolix combination therapy reduced menstrual blood loss volume and pain in women with heavy menstrual bleeding associated with uterine leiomyomas and was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks. Here we report the long-term efficacy and safety of relugolix combination therapy treatment for up to 52 weeks.
METHODS
Women with uterine leiomyoma-associated heavy menstrual bleeding who completed any treatment arm in either the LIBERTY 1 or LIBERTY 2 trial were eligible to enroll in a 28-week long-term extension study. All participants received once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) in the extension study. The primary efficacy endpoint was the proportion of women who achieved or maintained a menstrual blood loss volume of less than 80 mL and a 50% or greater reduction in menstrual blood loss volume from LIBERTY study baseline to the last 35 days of treatment (defined as responders ). Analyses were conducted for all three randomized treatment groups from pivotal studies.
RESULTS
Overall, 477 women enrolled, 476 were treated, and 363 (76.1%) completed 52 weeks. Among patients treated with relugolix combination therapy through 52 weeks (n=163), sustained improvement in heavy menstrual bleeding was observed in 87.7% (responders). The least squares mean menstrual blood loss volume reduction was 89.9%, with 70.6% of patients achieving amenorrhea. At week 52, 59.0% of patients with anemia at baseline had improvements in hemoglobin concentration of greater than 2 g/dL. Distress due to uterine leiomyoma-associated symptoms measured by the BPD (Bleeding and Pelvic Discomfort) scale score was reduced by 51.3 points. Sustained reductions in uterine and uterine leiomyoma volume were observed. Bone mineral density was preserved through week 52.
CONCLUSION
Improvements in heavy menstrual bleeding and anemia and reduction of uterine leiomyoma-associated symptom burden were sustained through up to 52 weeks of treatment with relugolix combination therapy in women with uterine leiomyomas. No new safety concerns were identified, and BMD was maintained.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov , NCT03049735; NCT03103087; NCT03412890.
FUNDING SOURCE
Myovant Sciences GmbH.
Topics: Female; Humans; Leiomyoma; Menorrhagia; Pyrimidinones; Uterine Neoplasms
PubMed: 36357960
DOI: 10.1097/AOG.0000000000004988 -
British Journal of Sports Medicine Sep 2020To explore athletes' past and current experiences and perceptions of the menstrual cycle in relation to its impact on sporting performance.
OBJECTIVES
To explore athletes' past and current experiences and perceptions of the menstrual cycle in relation to its impact on sporting performance.
METHODS
15 international female rugby players participated in individual semi-structured interviews (age: 24.5±6.2 years). All interviews were recorded and transcribed , resulting in 37 376 words of text for descriptive and thematic analysis. Inter-rater reliability checks resulted in a concordance of agreement of 83%.
RESULTS
Almost all athletes (93%) reported menstrual cycle-related symptoms. Thirty-three per cent perceived heavy menstrual bleeding and 67% considered these symptoms impaired their performances. Two-thirds of athletes self-medicated to alleviate symptoms. Thematic analysis generated 262 meaning units, 38 themes, 10 categories and 4 general dimensions. The four general dimensions were: (1) symptoms: physiological and psychological menstrual cycle-related symptoms such as dysmenorrhoea, flooding, reduced energy levels, worry, distraction, fluctuating emotions and reduced motivation; (2) impact: perceived impact of menstruation on different aspects of daily lives and performance including negative and neutral responses; (3) resolution: the methods/approaches in dealing with menstruation-related concerns including accepting, or adapting and managing symptoms with self-medication or expert treatment; (4) support: available support and comfortability in discussing menstrual cycle-related issues.
CONCLUSIONS
This study provides the first in-depth insight into athlete's experiences of the menstrual cycle and perceived impact on training and competition. It highlights individual responses to menstrual 'issues' and emphasises the need for clinicians and support staff to undertake menstrual cycle profiling, monitoring and continue to develop awareness, openness, knowledge and understanding of the menstrual cycle.
Topics: Activities of Daily Living; Adult; Athletic Performance; Competitive Behavior; Emotions; Female; Football; Humans; Menorrhagia; Menstrual Cycle; Menstruation; Motivation; Perception; Physical Conditioning, Human; Young Adult
PubMed: 32349965
DOI: 10.1136/bjsports-2019-101486 -
The New England Journal of Medicine Jul 2020Uterine fibroids, the most common type of tumor among women of reproductive age, are associated with heavy menstrual bleeding, abdominal discomfort, subfertility, and a... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Uterine fibroids, the most common type of tumor among women of reproductive age, are associated with heavy menstrual bleeding, abdominal discomfort, subfertility, and a reduced quality of life. For women who wish to preserve their uterus and who have not had a response to medical treatment, myomectomy and uterine-artery embolization are therapeutic options.
METHODS
We conducted a multicenter, randomized, open-label trial to evaluate myomectomy, as compared with uterine-artery embolization, in women who had symptomatic uterine fibroids and did not want to undergo hysterectomy. Procedural options included open abdominal, laparoscopic, or hysteroscopic myomectomy. The primary outcome was fibroid-related quality of life, as assessed by the score on the health-related quality-of-life domain of the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire (scores range from 0 to 100, with higher scores indicating a better quality of life) at 2 years; adjustment was made for the baseline score.
RESULTS
A total of 254 women, recruited at 29 hospitals in the United Kingdom, were randomly assigned: 127 to the myomectomy group (of whom 105 underwent myomectomy) and 127 to the uterine-artery embolization group (of whom 98 underwent embolization). Data on the primary outcome were available for 206 women (81%). In the intention-to-treat analysis, the mean (±SD) score on the health-related quality-of-life domain of the UFS-QOL questionnaire at 2 years was 84.6±21.5 in the myomectomy group and 80.0±22.0 in the uterine-artery embolization group (mean adjusted difference with complete case analysis, 8.0 points; 95% confidence interval [CI], 1.8 to 14.1; P = 0.01; mean adjusted difference with missing responses imputed, 6.5 points; 95% CI, 1.1 to 11.9). Perioperative and postoperative complications from all initial procedures, irrespective of adherence to the assigned procedure, occurred in 29% of the women in the myomectomy group and in 24% of the women in the uterine-artery embolization group.
CONCLUSIONS
Among women with symptomatic uterine fibroids, those who underwent myomectomy had a better fibroid-related quality of life at 2 years than those who underwent uterine-artery embolization. (Funded by the National Institute for Health Research Health Technology Assessment program; FEMME Current Controlled Trials number, ISRCTN70772394.).
Topics: Adult; Female; Humans; Hysteroscopy; Intention to Treat Analysis; Intraoperative Complications; Laparoscopy; Leiomyoma; Length of Stay; Menorrhagia; Middle Aged; Ovarian Reserve; Postoperative Complications; Quality of Life; Reoperation; Uterine Artery Embolization; Uterine Myomectomy; Uterine Neoplasms; Uterus
PubMed: 32726530
DOI: 10.1056/NEJMoa1914735 -
American Journal of Obstetrics and... Dec 2022The 52-mg levonorgestrel-releasing intrauterine system is an established, long-acting contraceptive option with approved use for up to 7 years.
BACKGROUND
The 52-mg levonorgestrel-releasing intrauterine system is an established, long-acting contraceptive option with approved use for up to 7 years.
OBJECTIVE
The Mirena Extension Trial evaluated the efficacy and safety of the 52-mg levonorgestrel-releasing intrauterine system during extended use beyond 5 and up to 8 years.
STUDY DESIGN
This was a multicenter, single-arm study in the United States, enrolling existing users of the 52-mg levonorgestrel-releasing intrauterine system, aged 18 to 35 years, who have had the system for 4.5 to 5 years. We assessed the contraceptive efficacy (Pearl Index) and cumulative failure rate (using the Kaplan-Meier method) of the 52-mg levonorgestrel-releasing intrauterine system during extended use. We also evaluated bleeding outcomes and adverse events.
RESULTS
Of the 362 participants starting year 6, 243 entered and 223 completed 8 years of 52-mg levonorgestrel-releasing intrauterine system use. Just more than half the participants were parous. The mean (standard deviation) age was 29.2 (±2.9) years, and all participants were aged ≤36 years at the end of year 8. Two pregnancies occurred, both with the device in situ. The year 6 pregnancy was of undetermined location and resolved spontaneously. The pregnancy in year 7 was ectopic and resolved with methotrexate treatment. In both cases, the 52-mg levonorgestrel-releasing intrauterine system was removed and the participants left the trial. For years 6 to 8, the 3-year Pearl Index (95% confidence interval) was 0.28 (0.03-1.00) with a 3-year cumulative failure rate of 0.68% (0.17-2.71). Pearl Indexes for years 6, 7, and 8 were 0.34 (0.01-1.88), 0.40 (0.01-2.25), and 0.00 (0.00-1.90), respectively. The 3-year (years 6-8) ectopic pregnancy Pearl Index was 0.14 (0.00-0.77). We found treatment-emergent adverse events in 249 of 362 participants (68.8%), with 65 (18.0%) events considered to be related to the 52-mg levonorgestrel-releasing intrauterine system. The discontinuation rate was 38.4% (139/362), most commonly because of desire for pregnancy (12.2%, 44/362). During extended use beyond 5 years and up to 8 years, participants reported a decrease in the mean number of bleeding or spotting days with approximately half of the women experiencing amenorrhea or infrequent bleeding. We did not enroll a sufficient number of women using the 52-mg levonorgestrel-releasing intrauterine system for contraception and heavy menstrual bleeding to assess extended use for that indication. At the end of year 8, most (98.7%, 220/223) of the participants who completed the study remained satisfied with the continued use of the 52-mg levonorgestrel-releasing intrauterine system. Of the 31 women who discontinued early because of desire for pregnancy with evaluable data for return-to-fertility analysis, 24 reported a posttreatment pregnancy within 1 year, giving a 12-month return-to-fertility rate of 77.4%.
CONCLUSION
The 52-mg levonorgestrel-releasing intrauterine system, initially approved for 5 years, maintains high contraceptive efficacy, user satisfaction, and a favorable safety profile through 8 years of use. Participants reported 26 posttreatment pregnancies in total, of which 24 occurred in women who had discontinued the 52-mg levonorgestrel-releasing intrauterine system because of a desire for pregnancy. Of note, among women who elected to continue use through 8 years, bleeding patterns remained highly favorable. These findings support continued 52-mg levonorgestrel-releasing intrauterine system use for up to 8 years in women who wish to continue treatment.
Topics: Pregnancy; Female; Humans; Levonorgestrel; Intrauterine Devices, Medicated; Contraceptive Agents, Female; Menorrhagia; Metrorrhagia
PubMed: 36096186
DOI: 10.1016/j.ajog.2022.09.007