Best Practices for Counseling Adolescents about the Etonogestrel Implant.

Among young persons, ease of use, high efficacy, and high acceptability makes the etonogestrel contraceptive implant an important choice for this age group. Adolescent-friendly, patient-centered counseling considers the patient's cognitive development, the influence of friends and family, as well as their own preferences and values. Age-appropriate language, graphics, and models are useful to explain contraceptive options and relevant side effects. Effectiveness, reversibility, safety, noncontraceptive benefits, and side effects are important attributes and should be discussed when teens are choosing a contraceptive method. In this review we describe suggested best practices for counseling adolescents about the etonogestrel implant so they can make informed, prudent decisions about using this contraceptive method.

Diagnosing adenomyosis: an integrated clinical and imaging approach.

BACKGROUND: Adenomyosis is a benign uterine disorder where endometrial glands and stroma are pathologically demonstrated within the uterine myometrium. The pathogenesis involves sex steroid hormone abnormalities, inflammation, fibrosis and neuroangiogenesis, even though the proposed mechanisms are not fully understood. For many years, adenomyosis has been considered a histopathological diagnosis made after hysterectomy, classically performed in perimenopausal women with abnormal uterine bleeding (AUB) or pelvic pain. Until recently, adenomyosis was a clinically neglected condition. Nowadays, adenomyosis may also be diagnosed by non-invasive techniques, because of imaging advancements. Thus, a new epidemiological scenario has developed with an increasing number of women of reproductive age with ultrasound (US) or magnetic resonance imaging (MRI) diagnosis of adenomyosis. This condition is associated with a wide variety of symptoms (pelvic pain, AUB and/or infertility), but it is also recognised that some women are asymptomatic. Furthermore, adenomyosis often coexists with other gynecological comorbidities, such as endometriosis and uterine fibroids, and the diagnostic criteria are still not universally agreed. Therefore, the diagnostic process for adenomyosis is challenging. OBJECTIVE AND RATIONALE: We present a comprehensive review on the diagnostic criteria of adenomyosis, including clinical signs and symptoms, ultrasound and MRI features and histopathological aspects of adenomyotic lesions. We also briefly summarise the relevant theories on adenomyosis pathogenesis, in order to provide the pathophysiological background to understand the different phenotypes and clinical presentation. The review highlights the controversies of multiple existing criteria, summarising all of the available evidences on adenomyosis diagnosis. The review aims also to underline the future perspective for diagnosis, stressing the importance of an integrated clinical and imaging approach, in order to identify this gynecological disease, so often underdiagnosed. SEARCH METHODS: PubMed and Google Scholar were searched for all original and review articles related to diagnosis of adenomyosis published in English until October 2018. OUTCOMES: The challenge in diagnosing adenomyosis starts with the controversies in the available pathogenic theories. The difficulties in understanding the way the disease arises and progresses have an impact also on the specific diagnostic criteria to use for a correct identification. Currently, the diagnosis of adenomyosis may be performed by non-invasive methods and the clinical signs and symptoms, despite their heterogeneity and poor specificity, may guide the clinician for a suspicion of the disease. Imaging techniques, including 2D and 3D US as well as MRI, allow the proper identification of the different phenotypes of adenomyosis (diffuse and/or focal). From a histological point of view, if the diagnosis of diffuse adenomyosis is straightforward, in more limited disease, the diagnosis has poor inter-observer reproducibility, leading to extreme variations in the prevalence of disease. Therefore, an integrated non-invasive diagnostic approach, considering risk factors profile, clinical symptoms, clinical examination and imaging, is proposed to adequately identify and characterise adenomyosis. WIDER IMPLICATIONS: The development of the diagnostic tools allows the physicians to make an accurate diagnosis of adenomyosis by means of non-invasive techniques, representing a major breakthrough, in the light of the clinical consequences of this disease. Furthermore, this technological improvement will open a new epidemiological scenario, identifying different groups of women, with a dissimilar clinical and/or imaging phenotypes of adenomyosis, and this should be object of future research.

Bleeding profile associated with 1-year use of the segesterone acetate/ethinyl estradiol contraceptive vaginal system: pooled analysis from Phase 3 trials.

OBJECTIVES: To describe bleeding patterns among users of the segesterone acetate (SA) and ethinyl estradiol (EE) contraceptive vaginal system (CVS), and identify factors associated with unscheduled bleeding/spotting (B/S). STUDY DESIGN: We pooled results from two multicenter, single-arm, open-label, pivotal, phase 3 studies of the SA/EE CVS conducted in 17 US and 7 international sites. Participants (age 18-40 years; BMI ≤29 kg/m2) followed a 21/7-day in/out schedule of CVS use for up to 13 cycles and recorded vaginal bleeding daily in paper diaries. Scheduled and unscheduled B/S were summarized by cycle. We used multiple logistic regression to identify factors associated with unscheduled bleeding/spotting, based on the first 4 cycles only. RESULTS: Analysis included data from 2070 participants (16,408 cycles). Ninety-eight percent documented scheduled B/S [mean (SD): 4.9 (1.1) days/cycle)]. Absence of scheduled B/S was 5-8% of women/cycle. Unscheduled B/S ranged from 13.2% to 21.7% of women per cycle. Few women (1.8%) discontinued prematurely due to unacceptable bleeding. Black women were more likely to report unscheduled B/S than White women [Adjusted odds ratio (AOR) = 1.49, 95% confidence interval (CI) = 1.14-1.94]. Women with fewer years of schooling [

Can initial vaginal bleeding patterns in etonogestrel implant users predict subsequent bleeding in the first 2 years of use?

OBJECTIVES: To evaluate if a simple method for characterizing vaginal bleeding patterns in etonogestrel contraceptive implant users can predict subsequent patterns and bleeding-related discontinuation over the first 2 years of use. STUDY DESIGN: We reanalyzed phase 3 study bleeding data for non-breastfeeding participants from the United States, Europe, Russia and Chile during the first 2 years of implant use to characterize and correlate bleeding patterns. We used 90-day reference periods with period 1.1 starting at Day 29 and ending at Day 118. We dichotomized bleeding patterns as "favorable" (amenorrhea, infrequent bleeding and normal frequency bleeding without prolonged bleeding) or "unfavorable' (prolonged and/or frequent bleeding) and tracked user groups based on these bleeding patterns in reference period 1.1 through Year 1 and from Year 1 through Year 2, respectively. RESULTS: We evaluated data from 537 and 428 women with up to 1 and 2 years use, respectively. Of the 325 (60.5%) women with favorable bleeding in reference period 1.1, 275 (84.6%) reported favorable bleeding also in reference period 2, 197 (60.6%) reported favorable bleeding throughout Year 1, and favorable bleeding in 75-85% of reference periods in Year 2. Among 212 (39.5%) women with unfavorable bleeding in reference period 1.1, 118 (55.7%) continued with unfavorable bleeding in reference period 2, while about 40%-50% reported favorable patterns in RP 2, 3 and/or 4. Initial favorable bleeding resulted in lower discontinuation rates than initial unfavorable bleeding in years 1 (3.7% vs 12.7%, p≪.0001) and 2 (2.5% vs 16.5%, p≪.0001). CONCLUSION: Implant users with favorable bleeding in the first reference period are likely to continue with favorable bleeding over the next 2 years. Initial bleeding patterns predict overall continuation rates in years 1 and 2. Implications Statement When evaluating vaginal bleeding in any 90-day reference period over 2 years of etonogestrel implant use, approximately 80% of women with favorable and 40% with unfavorable bleeding patterns will have favorable bleeding in the next reference periods. These findings can facilitate counseling regarding bleeding for women using the etonogestrel implant.

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.

Impact and management of iron deficiency and iron deficiency anemia in women's health.

INTRODUCTION: Iron deficiency and iron deficiency anemia are highly prevalent among women throughout their lives. Some females are particularly vulnerable to iron deficiency/iron deficiency anemia, including those with heavy menstrual bleeding (HMB) and pregnant/postpartum women. Despite the high prevalence of iron deficiency/iron deficiency anemia in women, the condition is still underdiagnosed and therefore undertreated, with serious clinical consequences. Areas covered: The following review examines the impact of iron deficiency and iron deficiency anemia on clinical outcomes and quality of life in women from adolescence to post-menopause, paying particular attention to guidelines and current recommendations for diagnostic tests and management. Expert commentary: There are numerous adverse health consequences of an iron-deficient state, affecting all aspects of the physical and emotional health and well-being of women. Guidelines must be developed to help clinicians better identify and treat women at risk of iron deficiency or iron deficiency anemia, particularly those with HMB, or who are pregnant or postpartum. Replacement therapy with oral or intravenous iron preparations is the mainstay of treatment for iron deficiency/iron deficiency anemia, with red blood cell transfusion reserved for emergency situations. Each iron therapy type is associated with benefits and limitations which impact their use.

Potentially effective therapy of heavy menstrual bleeding with an oestradiol-nomegestrol acetate oral contraceptive: a pilot study.

BACKGROUND: Heavy menstrual bleeding (HMB) exceeding 80 mL per cycle leads to considerable adverse impact on a woman's iron metabolism, incidence of iron deficiency and anaemia, as well as her functioning in society. The objective of the study is to determine the potential efficacy of a Monophasic oestradiol-17ß-nomegestrol acetate (E2/Nomac) combined oral contraceptive pill on measured menstrual blood loss as a pilot study in 12 women with objectively demonstrated HMB (>80 mL per cycle). The pilot study aimed to recruit 20 women. METHOD: Consented women completed the HMB questionnaire. The blood was taken for haemoglobin, transferrin, iron saturation, TIBC, serum iron and ferritin. Women were given verbal and written detailed instructions for MBL collection for three control cycles and four treatment cycles. RESULTS: Forty-three women were enrolled, but 31 were ineligible and withdrawn (mainly for failure to meet eligibility criteria). Twelve women entered the treatment phase and commenced the E2/nomegestrol acetate (NOMAC) 24/4 combined pill treatment on the first day of their fourth cycle. All women with complete MBL measurements had >50% reduction in MBL on treatment (exact 95% confidence interval for proportion with MBL reduction >50%: 69 to 100%). The mean percent reduction in MBL between pretreatment and during treatment was 76.9%, and the median was 79% with a range of 53.7 to 100%. CONCLUSIONS: This pilot study indicates that the E2/NOMAC COC will provide a useful potential option for treating HMB in women with FIGO classification AUB-E (primary endometrial causes) but requires a larger placebo-controlled study for confirmation.

Cultural aspects and mythologies surrounding menstruation and abnormal uterine bleeding.

The objective of this chapter is to present an overview of how menstruation, a normal bodily function, was and is perceived in various ethnic groups and cultures in the world, from ancient mythology, historical, or traditional practices to contemporary belief systems. Mythical tales about menstruation abound in the legends and prehistory of ancient cultures. These tales characterize menstrual blood variously as sacred, a gift from the gods, or a punishment for sin, but it is almost always magical and powerful. In contrast, most world religions view menstruation, with varying degrees of severity, as a major problem, a sign of impurity and uncleanliness, and therefore, menstruating women are isolated, prohibited from polluting the holy places, and shunned. Many of these myths and cultural misperceptions persist to the present day, reflected in a wide range of negative attitudes toward menstruation, which can have serious and direct implications for reproductive health. In view of the increasingly globalized nature of current clinical practice, it is crucial that health care providers are familiar with existing cultural and social views and attitudes toward the menstrual function. The ultimate goal is to be able to provide women culturally sensitive and medically appropriate therapies for their menstrual disorders. This biocultural approach to menstruation management is desirable in contemporary medical practice.

Effect of perceptions of menstrual blood loss and menstrual pain on women's quality of life.

OBJECTIVES: The aim of the study was to explore Australian women's experiences of menstruation and effect on quality of life (QoL). METHODS: A representative sample of women recruited through a commercial social research sampling organisation completed a detailed online questionnaire about menstruation. Specific detailed questions were asked about perceptions of heavy menstrual bleeding (HMB) and menstrual pain. RESULTS: The questionnaire was completed by 1575 women aged 20-39 years. Most perceived their bleeding to be light (11.6%) or moderate (60.5%); 363 (22.5%) perceived it to be heavy and 86 (5.3%) very heavy. Women who experienced severe or very severe menstrual pain were significantly more likely to report periods as heavy or very heavy (p < .001). The prevalence ratios for being confined to bed during menstruation for women experiencing severe or very severe menstrual pain were 12.02 (95% CI: 5.71-25.31) and 15.93 (95% CI: 7.51-33.78), respectively, compared with women experiencing no pain. The prevalence ratios for being confined to bed were 1.58 (95% CI: 1.11-2.24) and 1.53 (95% CI: 1.04-2.25) for women with heavy or very heavy bleeding, respectively. Women who experienced severe or very severe menstrual pain associated with their HMB were >12 times more likely to be confined to bed for 0.5-1 day during menstruation than if they reported HMB without pain. CONCLUSION: Severe menstrual pain with HMB has a much more profound effect on all aspects of women's QoL than HMB alone; it accounts for more days in bed and for loss of productivity.

Medical Therapies for Uterine Fibroids - A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Uterine fibroids are common, often symptomatic and a third of women need repeated time off work. Consequently 25% to 50% of women with fibroids receive surgical treatment, namely myomectomy or hysterectomy. Hysterectomy is the definitive treatment as fibroids are hormone dependent and frequently recurrent. Medical treatment aims to control symptoms in order to replace or delay surgery. This may improve the outcome of surgery and prevent recurrence. PURPOSE: To determine whether any medical treatment can be recommended in the treatment of women with fibroids about to undergo surgery and in those for whom surgery is not planned based on currently available evidence. STUDY SELECTION: Two authors independently identified randomised controlled trials (RCT) of all pharmacological treatments aimed at the treatment of fibroids from a list of references obtained by formal search of MEDLINE, EMBASE, Cochrane library, Science Citation Index, and ClinicalTrials.gov until December 2013. DATA EXTRACTION: Two authors independently extracted data from identified studies. DATA SYNTHESIS: A Bayesian network meta-analysis was performed following the National Institute for Health and Care Excellence-Decision Support Unit guidelines. Odds ratios, rate ratios, or mean differences with 95% credible intervals (CrI) were calculated. RESULTS AND LIMITATIONS: A total of 75 RCT met the inclusion criteria, 47 of which were included in the network meta-analysis. The overall quality of evidence was very low. The network meta-analysis showed differing results for different outcomes. CONCLUSIONS: There is currently insufficient evidence to recommend any medical treatment in the management of fibroids. Certain treatments have future promise however further, well designed RCTs are needed.

Nerve Bundles and Deep Dyspareunia in Endometriosis.

The etiology of deep dyspareunia in endometriosis is unclear. Our objective was to determine whether nerve bundle density in the cul-de-sac/uterosacrals (zone II) is associated with deep dyspareunia in women with endometriosis. We conducted a blinded retrospective immunohistochemistry study (n = 58) at a tertiary referral center (2011-2013). Patients were stringently phenotyped into a study group and 2 control groups. The study group (tender endometriosis, n = 29) consisted of patients with deep dyspareunia, a tender zone II on examination, and an endometriosis lesion in zone II excised at surgery. Control group 1 (nontender endometriosis, n = 17) consisted of patients without deep dyspareunia, a nontender zone II on examination, and an endometriosis lesion in zone II excised at surgery. Control group 2 (tender nonendometriosis, n = 12) consisted of patients with deep dyspareunia, a tender zone II on examination, and a nonendometriosis lesion (eg, normal histology) in zone II excised at surgery. Protein gene product 9.5 (PGP9.5) immunohistochemistry was performed to identify nerve bundles (nerve fibers surrounded by perineurium) in the excised zone II lesion. PGP9.5 nerve bundle density (bundles/high powered field [HPF]) was then scored by a pathologist blinded to the group. We found a significant difference in PGP9.5 nerve bundle density between the 3 groups (analysis of variance, F2,55 = 6.39, P = .003). Mean PGP9.5 nerve bundle density was significantly higher in the study group (1.16 ± 0.56 bundles/HPF [±standard deviation]) compared to control group 1 (0.65 ± 0.36, Tukey test, P = .005) and control group 2 (0.72 ± 0.56, Tukey test, P = .044). This study provides evidence that neurogenesis in the cul-de-sac/uterosacrals may be an etiological factor for deep dyspareunia in endometriosis.

Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome.

BACKGROUND: Reproductive disorders and infertility are associated with the risk of obstetric complications and have a negative impact on pregnancy outcome. Affected patients often require assisted reproductive technologies (ART) to conceive, and advanced maternal age is a further confounding factor. The challenge is to dissect causation, correlation and confounders in determining how infertility and reproductive disorders individually or together predispose women to poor pregnancy outcomes. METHODS: The published literature, to June 2015, was searched using PubMed, summarizing all evidences concerning the perinatal outcome of women with infertility and reproductive disorders and the potential mechanisms that may influence poor pregnancy outcome. RESULTS: Reproductive disorders (endometriosis, adenomyosis, polycystic ovary syndrome and uterine fibroids) and unexplained infertility share inflammatory pathways, hormonal aberrations, decidual senescence and vascular abnormalities that may impair pregnancy success through common mechanisms. Either in combination or alone, these disorders results in an increased risk of preterm birth, fetal growth restriction, placental pathologies and hypertensive disorders. Systemic hormonal aberrations, and inflammatory and metabolic factors acting on endometrium, myometrium, cervix and placenta are all associated with an aberrant milieu during implantation and pregnancy, thus contributing to the genesis of obstetric complications. Some of these features have been also described in placentas from ART. CONCLUSIONS: Reproductive disorders are common in women of childbearing age and rarely occur in isolation. Inflammatory, endocrine and metabolic mechanisms associated with these disorders are responsible for an increased incidence of obstetric complications. These patients should be recognized as 'high risk' for poor pregnancy outcomes and monitored with specialized follow-up. There is a real need for development of evidence-based recommendations about clinical management and specific obstetric care pathways for the introduction of prompt preventative care measures.

The importance of pelvic nerve fibers in endometriosis.

Several lines of recent evidence suggest that pelvic innervation is altered in endometriosis-affected women, and there is a strong presumption that nerve fibers demonstrated in eutopic endometrium (of women with endometriosis) and in endometriotic lesions play roles in the generation of chronic pelvic pain. The recent observation of sensory C, sensory A-delta, sympathetic and parasympathetic nerve fibers in the functional layer of endometrium of most women affected by endometriosis, but not demonstrated in most women who do not have endometriosis, was a surprise. Nerve fiber densities were also greatly increased in myometrium of women with endometriosis and in endometriotic lesions compared with normal peritoneum. Chronic pelvic pain is complex, and endometriosis is only one condition which contributes to this pain. The relationship between the presence of certain nerve fibers and the potential for local pain generation requires much future research. This paper reviews current knowledge concerning nerve fibers in endometrium, myometrium and endometriotic lesions, and discusses avenues of research that may improve our knowledge and lead to enriched understanding and management of endometriotic pain symptoms.

Use of hormonal therapy is associated with reduced nerve fiber density in deep infiltrating, rectovaginal endometriosis.

OBJECTIVE: To study the density of nerve fibers in cases of deep infiltrating endometriosis (DIE) of the rectovaginal septum in relation to various clinical factors. DESIGN: A research laboratory-based study. SETTING: A tertiary center together with a research laboratory. METHODS: Archived DIE tissue samples from 45 women operated upon for rectovaginal septum DIE were re-examined histologically, and by immunohistochemistry. MAIN OUTCOME MEASURES: The effect of progestogens or combined oral contraceptives on the density of nerve fibers, and the expression of nerve growth factor (NGF) and its high-affinity receptor (tyrosine kinase receptor A, Trk-A). RESULTS: The use of hormonal therapy was associated with reduced densities of sympathetic, parasympathetic and sensory nerve fibers in DIE lesions. Density of total nerve fibers (with pan-neuronal marker PGP9.5) was significantly lower (p < 0.05) in lesions collected from hormone-treated women (8.6/mm², 4.2-20.8/mm²; median density, from 25th to 75th quartiles) compared with that in lesions from untreated women (24.9/mm², 11.2-34.9/mm²). DIE lesions stained strongly for NGF and its receptor Trk-A. Expression of NGF, but not of Trk-A, was significantly reduced during use of hormonal therapy. CONCLUSIONS: Use of hormonal therapy was associated with significantly reduced nerve fiber density in DIE lesions. This may be an important mechanism of action of hormonal therapy for controlling DIE pain symptoms. The expression of estrogen-regulated NGF and its receptor was only partially suppressed during the use of hormonal therapy, suggesting that local estrogen action is often maintained during conventional hormonal therapy in cases of DIE.

Medical management of heavy menstrual bleeding: a comprehensive review of the literature.

IMPORTANCE: Heavy menstrual bleeding (HMB) is a common complaint among reproductive-aged women, which negatively affects their health as well as their social, professional, and family lives. Modern medical management usually provides effective control of HMB irrespective of the underlying cause. Surgical interventions should be reserved for women with significant pelvic pathology and those unresponsive to medical therapy. OBJECTIVE: The aim of this review was to provide a comprehensive summary of the efficacy and safety of available medical treatments of HMB. EVIDENCE ACQUISITION: A comprehensive MEDLINE and EMBASE literature search was undertaken using selected terms associated with HMB to identify clinical studies published before March 20, 2013, that reported changes in menstrual blood loss in women receiving medical intervention. RESULTS: The effectiveness of treatments to reduce HMB due to endometrial dysfunction in descending order was as follows: (1) the levonorgestrel-releasing intrauterine system (LNG-IUS) (initial release rate of 20 µg of LNG per 24 hours), (2) combined hormonal contraceptives (oral or transvaginal), (3) tranexamic acid, and (4) long-course oral progestogens (≥3 weeks per cycle). The LNG-IUS was found to reduce HMB due to some structural causes (leiomyomas and adenomyosis). The reduction in menstrual blood loss achieved with nonsteroidal anti-inflammatory drugs and short-course oral progestogens (≤14 days per cycle) is less impressive but may be sufficient for women who have marginally increased blood loss. CONCLUSIONS AND RELEVANCE: For women not seeking pregnancy, the LNG-IUS is the first-line medical therapy for HMB, with combined hormonal contraceptives as second choice. For other women, fewer effective options exist.

Prevalence of heavy menstrual bleeding and experiences of affected women in a European patient survey.

OBJECTIVE: To examine the prevalence and impact of heavy menstrual bleeding (HMB) among women in Europe, and their experience of HMB assessment and management. METHODS: An internet-based survey was conducted among women (aged 18-57 years) in five European countries between January and February 2012. The prevalence of HMB among the general population was determined in a short survey, and women who had been diagnosed with HMB were then asked to complete an extended survey about their diagnosis and symptoms. RESULTS: Overall, 4506 women responded, of whom 1225 (27.2%) had experienced two or more predefined HMB symptoms within the previous year. Of these women, 564 (46.0%) had never consulted a physician. Among 330 women who completed the detailed survey, 208 (63.0%) had ever been diagnosed with iron deficiency or iron-deficiency anemia. Symptoms associated with iron deficiency were used to help confirm a diagnosis in 83 (39.9%) women. Only 152 (46.1%) of the 330 patients with confirmed HMB had received prescription medication for iron deficiency. CONCLUSION: Many women affected by HMB do not seek medical help, and few of those who do consult physicians report that they have received appropriate treatment. HMB continues to be underdiagnosed and poorly treated.