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Fertility and Sterility Oct 2022Iron deficiency (ID) and iron deficiency anemia (IDA) are highly prevalent among women across their life span, especially during the reproductive age. An iron-deficient... (Review)
Review
Iron deficiency (ID) and iron deficiency anemia (IDA) are highly prevalent among women across their life span, especially during the reproductive age. An iron-deficient state has been associated with a number of adverse health consequences, affecting all aspects of the physical and emotional well-being of women. Heavy menstrual bleeding, pregnancy state, and the postpartum period are the major causes of ID/IDA. However, despite the high prevalence and the impact on quality of life, ID/IDA among fertile age women remains underdiagnosed and undertreated. The present Views and Reviews provides an overview on IDA in women's health, describing the background on iron metabolism, heavy menstrual bleeding pathogenetic mechanisms, including a focus on uterine disorders, such as uterine fibroids and adenomyosis. Iron replacement therapies, patient blood management, and treatment options for uterine disorders also are explored.
Topics: Anemia, Iron-Deficiency; Female; Humans; Iron; Iron Deficiencies; Menorrhagia; Pregnancy; Quality of Life; Reproductive Health; Women's Health
PubMed: 36182259
DOI: 10.1016/j.fertnstert.2022.08.850 -
The Medical Journal of Malaysia May 2022Abnormal uterine bleeding (AUB) is one of the commonest complaints of women in reproductive age and non-gravid state that brings them to the attention of the primary...
Abnormal uterine bleeding (AUB) is one of the commonest complaints of women in reproductive age and non-gravid state that brings them to the attention of the primary care doctor or the gynaecologist. Anovulation without any medical illness or pelvic pathology seems to be the common cause. Bleeding due to a wide variation in pathology both inside and outside the reproductive tract can be termed as anovulatory bleeding. Therefore, it is mandatory to elicit a focused menstrual history and appropriate evaluation followed by a pelvic examination. This includes a vaginal speculum examination to differentiate anovulatory bleeding from other causes of bleeding. In contrast, Heavy menstrual bleeding (HMB) is referred to as an ovulatory bleeding exceeding 8 days duration and is often caused by uterine fibroids or adenomyosis, a copper IUD or coagulation disorders. PALM-COEIN classification is a system designed by the Federation Internationale de Gynaecologie et d'Obstetrique to define the precise underlying causes of AUB. Aetiology of AUB can be classified as the following acronym "PALM-COEIN": Polyp, Adenomyosis, Leiomyoma, Malignancy and hyperplasia, Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic and Not yet classified. AUB describes a range of symptoms, such as HMB, intermenstrual bleeding (IMB) and a combination of both heavy and prolonged menstrual bleeding (MB). Dysfunctional uterine bleeding (DUB) and menorrhagia are now better described as AUB. Newborn girls sometimes spot for a few days after birth, due to placental oestrogenic stimulation of the endometrium in utero.
Topics: Adenomyosis; Female; Humans; Infant, Newborn; Leiomyoma; Menorrhagia; Placenta; Pregnancy; Uterine Hemorrhage
PubMed: 35638495
DOI: No ID Found -
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 -
BMJ Clinical Evidence Sep 2015Menorrhagia (also known as heavy menstrual bleeding) limits normal activities, affects quality of life, and causes anaemia in two-thirds of women with objective... (Review)
Review
INTRODUCTION
Menorrhagia (also known as heavy menstrual bleeding) limits normal activities, affects quality of life, and causes anaemia in two-thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia and with heavy bleeding due to fibroids, adenomyosis, or use of intrauterine devices (IUDs). Fibroids have been found in 10% of women with menorrhagia overall and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus.
METHODS AND OUTCOMES
We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of surgical treatments for menorrhagia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review).
RESULTS
At this update, searching of electronic databases retrieved 205 studies. After deduplication and removal of conference abstracts, 102 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 56 studies and the further review of 46 full publications. Of the 46 full articles evaluated, three systematic reviews and five RCTs were added at this update. We performed a GRADE evaluation for 30 PICO combinations.
CONCLUSIONS
In this systematic overview, we categorised the efficacy for three surgical interventions based on information about the effectiveness and safety of dilatation and curettage, endometrial destruction (resection or ablation), and hysterectomy.
Topics: Dilatation and Curettage; Endometrial Ablation Techniques; Endometrium; Female; Humans; Menorrhagia; Treatment Outcome
PubMed: 26382038
DOI: No ID Found -
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 -
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 -
BMJ Clinical Evidence Jan 2012Menorrhagia limits normal activities, and causes anaemia in two-thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may... (Review)
Review
INTRODUCTION
Menorrhagia limits normal activities, and causes anaemia in two-thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia, and with heavy bleeding due to fibroids, adenomyosis, or use of intrauterine devices (IUDs). Fibroids have been found in 10% of women with menorrhagia overall, and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments for menorrhagia? What are the effects of surgical treatments for menorrhagia? What are the effects of endometrial thinning before endometrial destruction in treating menorrhagia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations, such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 39 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following medical interventions: combined pill, danazol, etamsylate, gonadorelin analogues, intrauterine progesterone, non-steroidal anti-inflammatory drugs (NSAIDs), progestogens, and the following surgical interventions: dilatation and curettage, endometrial destruction, and hysterectomy.
Topics: Administration, Oral; Danazol; Dilatation and Curettage; Endometrial Ablation Techniques; Female; Humans; Intrauterine Devices, Medicated; Menorrhagia; Progestins
PubMed: 22305976
DOI: No ID Found -
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 -
BMJ Clinical Evidence Sep 2008Menorrhagia limits normal activities, and causes anaemia in two thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may... (Review)
Review
INTRODUCTION
Menorrhagia limits normal activities, and causes anaemia in two thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia, and with heavy bleeding due to fibroids, adenomyosis, or use of intrauterine devices (IUDs). Fibroids have been found in 10% of women with menorrhagia overall, and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments for menorrhagia? What are the effects of surgical treatments for menorrhagia? What are the effects of endometrial thinning before endometrial destruction in treating menorrhagia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 39 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following medical interventions: combined pill, danazol, etamsylate, gonadorelin analogues, intrauterine progesterone, non-steroidal inflammatory drugs (NSAIDs), progestogens, and the following surgical interventions: dilatation and curretage, endometrial destruction, and hysterectomy.
Topics: Administration, Oral; Danazol; Endometrium; Female; Humans; Incidence; Menorrhagia; Progestins; Treatment Outcome
PubMed: 19445802
DOI: No ID Found -
The Cochrane Database of Systematic... May 2022Heavy menstrual bleeding (HMB) is excessive menstrual blood loss that interferes with women's quality of life, regardless of the absolute amount of bleeding. It is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding (HMB) is excessive menstrual blood loss that interferes with women's quality of life, regardless of the absolute amount of bleeding. It is a very common condition in women of reproductive age, affecting 2 to 5 of every 10 women. Diverse treatments, either medical (hormonal or non-hormonal) or surgical, are currently available for HMB, with different effectiveness, acceptability, costs and side effects. The best treatment will depend on the woman's age, her intention to become pregnant, the presence of other symptoms, and her personal views and preferences.
OBJECTIVES
To identify, systematically assess and summarise all evidence from studies included in Cochrane Reviews on treatment for heavy menstrual bleeding (HMB), using reviews with comparable participants and outcomes; and to present a ranking of the first- and second-line treatments for HMB.
METHODS
We searched for published Cochrane Reviews of HMB interventions in the Cochrane Database of Systematic Reviews. The primary outcomes were menstrual bleeding and satisfaction. Secondary outcomes included quality of life, adverse events and the requirement of further treatment. Two review authors independently selected the systematic reviews, extracted data and assessed quality, resolving disagreements by discussion. We assessed review quality using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool and evaluated the certainty of the evidence for each outcome using GRADE methods. We grouped the interventions into first- and second-line treatments, considering participant characteristics (desire for future pregnancy, failure of previous treatment, candidacy for surgery). First-line treatments included medical interventions, and second-line treatments included both the levonorgestrel-releasing intrauterine system (LNG-IUS) and surgical treatments; thus the LNG-IUS is included in both groups. We developed different networks for first- and second-line treatments. We performed network meta-analyses of all outcomes, except for quality of life, where we performed pairwise meta-analyses. We reported the mean rank, the network estimates for mean difference (MD) or odds ratio (OR), with 95% confidence intervals (CIs), and the certainty of evidence (moderate, low or very low certainty). We also analysed different endometrial ablation and resection techniques separately from the main network: transcervical endometrial resection (TCRE) with or without rollerball, other resectoscopic endometrial ablation (REA), microwave non-resectoscopic endometrial ablation (NREA), hydrothermal ablation NREA, bipolar NREA, balloon NREA and other NREA.
MAIN RESULTS
We included nine systematic reviews published in the Cochrane Library up to July 2021. We updated the reviews that were over two years old. In July 2020, we started the overview with no new reviews about the topic. The included medical interventions were: non-steroidal anti-inflammatory drugs (NSAIDs), antifibrinolytics (tranexamic acid), combined oral contraceptives (COC), combined vaginal ring (CVR), long-cycle and luteal oral progestogens, LNG-IUS, ethamsylate and danazol (included to provide indirect evidence), which were compared to placebo. Surgical interventions were: open (abdominal), minimally invasive (vaginal or laparoscopic) and unspecified (or surgeon's choice of route of) hysterectomy, REA, NREA, unspecified endometrial ablation (EA) and LNG-IUS. We grouped the interventions as follows. First-line treatments Evidence from 26 studies with 1770 participants suggests that LNG-IUS results in a large reduction of menstrual blood loss (MBL; mean rank 2.4, MD -105.71 mL/cycle, 95% CI -201.10 to -10.33; low certainty evidence); antifibrinolytics probably reduce MBL (mean rank 3.7, MD -80.32 mL/cycle, 95% CI -127.67 to -32.98; moderate certainty evidence); long-cycle progestogen reduces MBL (mean rank 4.1, MD -76.93 mL/cycle, 95% CI -153.82 to -0.05; low certainty evidence), and NSAIDs slightly reduce MBL (mean rank 6.4, MD -40.67 mL/cycle, -84.61 to 3.27; low certainty evidence; reference comparator mean rank 8.9). We are uncertain of the true effect of the remaining interventions and the sensitivity analysis for reduction of MBL, as the evidence was rated as very low certainty. We are uncertain of the true effect of any intervention (very low certainty evidence) on the perception of improvement and satisfaction. Second-line treatments Bleeding reduction is related to the type of hysterectomy (total or supracervical/subtotal), not the route, so we combined all routes of hysterectomy for bleeding outcomes. We assessed the reduction of MBL without imputed data (11 trials, 1790 participants) and with imputed data (15 trials, 2241 participants). Evidence without imputed data suggests that hysterectomy (mean rank 1.2, OR 25.71, 95% CI 1.50 to 439.96; low certainty evidence) and REA (mean rank 2.8, OR 2.70, 95% CI 1.29 to 5.66; low certainty evidence) result in a large reduction of MBL, and NREA probably results in a large reduction of MBL (mean rank 2.0, OR 3.32, 95% CI 1.53 to 7.23; moderate certainty evidence). Evidence with imputed data suggests hysterectomy results in a large reduction of MBL (mean rank 1.0, OR 14.31, 95% CI 2.99 to 68.56; low certainty evidence), and NREA probably results in a large reduction of MBL (mean rank 2.2, OR 2.87, 95% CI 1.29 to 6.05; moderate certainty evidence). We are uncertain of the true effect for REA (very low certainty evidence). We are uncertain of the effect on amenorrhoea (very low certainty evidence). Evidence from 27 trials with 4284 participants suggests that minimally invasive hysterectomy results in a large increase in satisfaction (mean rank 1.3, OR 7.96, 95% CI 3.33 to 19.03; low certainty evidence), and NREA also increases satisfaction (mean rank 3.6, OR 1.59, 95% CI 1.09 to 2.33; low certainty evidence), but we are uncertain of the true effect of the remaining interventions (very low certainty evidence).
AUTHORS' CONCLUSIONS
Evidence suggests LNG-IUS is the best first-line treatment for reducing menstrual blood loss (MBL); antifibrinolytics are probably the second best, and long-cycle progestogens are likely the third best. We cannot make conclusions about the effect of first-line treatments on perception of improvement and satisfaction, as evidence was rated as very low certainty. For second-line treatments, evidence suggests hysterectomy is the best treatment for reducing bleeding, followed by REA and NREA. We are uncertain of the effect on amenorrhoea, as evidence was rated as very low certainty. Minimally invasive hysterectomy may result in a large increase in satisfaction, and NREA also increases satisfaction, but we are uncertain of the true effect of the remaining second-line interventions, as evidence was rated as very low certainty.
Topics: Amenorrhea; Antifibrinolytic Agents; Child, Preschool; Female; Humans; Menorrhagia; Network Meta-Analysis; Progestins; Quality of Life; Systematic Reviews as Topic
PubMed: 35638592
DOI: 10.1002/14651858.CD013180.pub2