NOMAC-E2 compares to LNG combined oral contraceptives in women over forty: real-world PRO-E2 study.

OBJECTIVE: To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COCLNG) in users over 40. METHODS: In this large, observational study, new users1 of NOMAC-E2 and COCLNG were recruited in Europe, Australia, and Latin America and followed-up via questionnaires. Incidence of venous thromboembolism (VTE) was expressed as incidence rate (IR; events/104 women-years [WY]). Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 WY). Mood and weight changes were defined as mean changes in mood score and percentage of body weight. RESULTS: Overall, 7,762 NOMAC-E2 and 6,059 COCLNG users over 40 were followed-up. NOMAC-E2 showed no increased VTE risk compared to COCLNG; confirmed events: 5 NOMAC-E2 (IR 5.9; 95% CI, 1.9-13.7) vs 4 COCLNG (IR 5.9; 95% CI, 1.6-15.1). Unintended pregnancy did not differ substantially between cohorts; confirmed events: 4 NOMAC-E2 (PI 0.05; 95% CI, 0.01-0.13) vs 5 COCLNG (PI 0.08; 95% CI, 0.03-0.18). No differential effect on mood and weight was observed between cohorts. CONCLUSIONS: NOMAC-E2 can be considered a valid alternative to COCLNG in perimenopausal women.

NOMAC-E2 shows a better contraceptive effectiveness than LNG combined oral contraceptives in women under 25: real-world PRO-E2 study.

Objective: To investigate unintended pregnancy and changes in mood, acne, and weight in NOMAC-E2 vs levonorgestrel-containing COC (COCLNG) users under 25 years.Methods: In this large, observational study, new users (first-ever users of an eligible COC or restarting with the same or a new eligible COC after a break of at least 2 months) of NOMAC-E2 and COCLNG were recruited in 12 countries in Europe, Australia, and Latin America and followed up via questionnaires for up to 2 years. Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 women-years). Crude (HRcrude) and adjusted hazard ratios (HRadj) were calculated. Mood and acne changes were defined as change of score from baseline. Weight change was defined as percent change of body weight.Results: Overall, 12,829 NOMAC-E2 users and 17,095 COCLNG users under 25 were followed-up. The risk of unintended pregnancy was statistically significantly lower in the NOMAC-E2 cohort; confirmed events: 30 NOMAC-E2 (PI 0.24; 95% CI, 0.16-0.35) vs 94 COCLNG (PI 0.51; 95% CI, 0.41-0.62). The HRcrude for unintended pregnancy comparing NOMAC-E2 to COCLNG was 0.47 (95% CI, 0.31-0.71) and the HRadj was 0.52 (95% CI, 0.34-0.78). No differential effect on acne, mood, and weight was observed between cohorts.Conclusions: NOMAC-E2 shows a significantly better contraceptive effectiveness in young women and has no differential effect on acne, mood, and weight compared to COCLNG.

The HOPE study: evaluating the impact of an online educational resource for heavy menstrual bleeding on the patient-physician dynamic.

The Heavy menstrual bleeding: Evidence-based Learning for best Practice (HELP) Group developed an educational website about heavy menstrual bleeding (HMB). The "HMB improving Outcomes with Patient counseling and Education" (HOPE) project examined the website's impact on women's knowledge, confidence, and consultations with healthcare providers (HCPs). HOPE was a quantitative online survey of gynecologists and women with HMB in Brazil. After an initial consultation, patients had unlimited access to the website and completed a survey. HCPs also completed a survey about the sconsultation. After a second consultation, HCPs and patients completed another survey. HCP surveys assessed their perception of patients' awareness, understanding, and willingness to discuss HMB. Patient surveys assessed their knowledge, experience, and confidence in discussing HMB. Forty HCPs recruited 400 women with HMB. Based on HCP perceptions at the first consultation, 18 percent of patients had "good knowledge" or "very good knowledge" of HMB, increasing to 69 percent after patients had visited the website. Before and after visiting the website, 34 percent and 69 percent of patients, respectively, regarded their HMB knowledge as "goo.d" Additionally, 17 percent of women reported their anxiety as "highest" during the first consultation; this decreased to 7 percent during the second consultation. After visiting the HELP website, patients' knowledge of HMB improved and they were less anxious.

COVID-19, gender and estroprogestins, what do we know?

The new coronavirus disease-19 (COVID-19) pandemic has rapidly spread all around the world, eliciting many questions and doubts about the pathogenesis of the disease and treatment. Mortality has been related to a prothrombotic state. Risk factors for the infection and for severe forms of COVID-19 have still to be defined. According to data collected, women appear to be less prone to severe forms of the disease and their mortality was lower than for men. The role of female hormones in the modulation of inflammation may be the reason behind this gender gap.Considering the prothrombotic state activated by the virus, hormone therapies have been placed under investigation as possible increasing risk factors for severe forms. Moreover, new vaccines and their rare thrombotic side effects have increased the concern about this issue.The goal of this review is to go over the mechanisms that lead up to thrombosis during COVID-19, trying to explain the possible reasons why women seem to be naturally protected. The expert opinions about whether to continue/discontinue hormonal therapies are reviewed. Moreover, available data about the so-called 'vaccine induced immune thrombotic thrombocytopaenia' caused by vaccines against COVID-19 are discussed.

The global pandemic and changes in women's reproductive health: an observational study.

OBJECTIVE: The COVID-19 global pandemic has led to the death of millions around the world and impacted the overall health of many people. In this article we aim to compare reproductive health indicators in the first 6 months of 2020 to the prior year, as well as explore stress and quality of life during this time. METHODS: This retrospective observational study examined the menstrual cycles of 1159 women who were using a fertility tracking device to record their menstrual cycle and BBT data. We utilised a supplemental mobile application to administer a supplemental survey to collect data on stress and quality of life. Descriptive analyses were conducted with t-tests for two-group comparisons. RESULTS: Study participants from 15 countries contributed to a total of 13,194 cycles. 23.1% (268/1159) responded to the survey focussed on assessing psychosocial distress. 44.4% (119/268) of the study participants reported that they had noticed a change in their menstrual cycle, temperature curve, or menstruation in the past 12 months. Cycle analysis found the average cycle length and pre-ovulation phase length was longer in the first 6 months of 2019, while the average days of menstruation was slightly longer in 2020. DISCUSSION: Our findings indicate that menstrual cycle indicators changed only slightly in the first 6 months of 2020 but were still statistically significant. We were also able to understand that these study participants had some level of awareness of changes to their menstrual health.

Putting reproductive rights into practice. The profile of the demand in a publicly sponsored ART program for single or female partner women in Catalonia.

PURPOSE: To evaluate the size and characteristics of the demand for a newly established, publicly sponsored, program of assisted reproduction for single women (SW) and women with a female partner (FP) in a European country. MATERIALS AND METHODS: We analysed the application forms received during the first two years and structured interviews with 300 successive non selected applicants. RESULTS: The mean sustained size of the demand was of 52.6 applications per month (sd 14) and corresponded to 0.06 % of the target population. Data from 237 applicants was evaluable. 119 (50.2 %) were SW and 118 (49.8 %) were FP. The median age was 36 years, 36.5 years for SW and 34 years for FP (p < 0.001, Mann-Whitney). Clinically 18.6 % of women presented irregular cycles, and 17.8 % of women had undergone hysterosalpingography (HSG), with a 14.3% prevalence of tubal dysfunction. CONCLUSIONS: A publicly sponsored program for Assisted Reproduction for SWFP should establish clear inclusion criteria, especially as regards to age, ovarian reserve, techniques offered, and the number of cycles to obtain the maximal efficiency. Further research specific for this group is required to ensure that they receive adequate care and ultimately to fulfil their reproductive rights.

Ulipristal acetate for the management of acute heavy menstrual bleeding without fibroids.

Heavy menstrual bleeding is a common condition among women of childbearing age. Although hysterectomy was the usual approach in acute cases in the past, other minimally invasive therapies or pharmacological alternatives, such as the levonorgestrel intrauterine device have shown to be highly effective. This case report presents the case of a pluripathological patient with acute heavy menstrual bleeding and severe anemia, who was successfully managed with ulipristal acetate, a selective progesterone receptor modulator. Bleeding control was achieved in 6 d without side effects, avoiding the need for surgery. This report suggests that ulipristal acetate could be useful in the treatment of acute uterine bleeding even in a structurally normal uterus without fibroids.

What do TSECs provide in the menopausal hormone therapy?

Tissue-selective estrogen complex (TSEC) is projected as a progestogen-free option for the treatment of estrogen deficiency symptoms in postmenopausal, non-hysterectomized women. TSEC combines the benefits of estrogen with a selective estrogen receptor modulator (SERM), in this case bazedoxifene acetate (BZA), which has an antagonistic effect on the endometrium, thus avoiding the use of progestins. The authorized TSEC combination (conjugated estrogens [CE] 0.45 mg/BZA 20 mg) for the alleviation of vasomotor symptoms has been demonstrated in randomized clinical trials compared with placebo or menopausal hormone therapy (MHT). In addition, TSEC has shown improvements in quality of life and vaginal atrophy. In respect to MHT using progestins, the benefits of TSEC are found mainly in the bleeding pattern, amenorrhea rate, and reduction in mammary repercussion (i.e., breast tenderness and radiological density). The objective of this guide will be to analyze the efficacy and safety of TSEC consisting of CE/BZA in postmenopausal women.

Weight decrease improves live birth rates in obese women undergoing IVF: a pilot study.

Obese women have lower pregnancy rates than normal-weight women undergoing assisted reproductive treatment. We conducted a pilot study to evaluate whether a 12-week diet and exercise intervention before an IVF cycle would influence pregnancy rates in obese women. Forty-one patients were enrolled in this study. They were randomly allocated to two groups: an intervention group (n = 21), who underwent an individualized diet and physical exercise programme supervised by a dietician, and a control group (n = 20), who started IVF with no previous intervention. The primary outcome was clinical pregnancy rate after a single treatment cycle. Mean weight loss in the study group after the intervention was 5.4 kg (range 1.1-14.6 kg). The study and control groups had similar total FSH consumption, number of oocytes and embryos obtained, and number and quality of embryos transferred. There was a non-significant trend towards a higher clinical pregnancy rate after fresh embryo transfer (66.7% versus 41.2%). The intervention group had a significantly higher cumulative live birth rate (61.9% versus 30%, P = 0.045) (odds ratio for intervention group, 3.8; 95% confidence interval, 1.03 to 13.9) The data suggest that weight loss resulted in a significantly increased cumulative live birth rate.

Pituitary response profile following metoclopramide administration in women with different forms of hyperprolactinemia.

AIMS: To test the hypothesis that macroprolactinemia is an extra-pituitary phenomenon by showing that the pituitary production of prolactin in patients with hyperprolactinemia due to macroprolactin is comparable to that in normoprolactinemic women and different from that in women with monomeric hyperprolactinemia. METHODS: Twenty-five women were studied: eight with macroprolactin hyperprolactinemia, eight with monomeric hyperprolactinemia, and nine controls. Prolactin levels were measured before and after precipitation with polyethylene glycol at baseline and at 5, 10,15, 30, and 60 min after metoclopramide administration (10 mg i.v.) in the three groups. RESULTS: The response profile of total and monomeric prolactin following the administration of metoclopramide was similar in women with monomeric hyperprolactinemia and normoprolactinemia but different in women with macroprolactinemia. The areas under the curve for total and monomeric prolactin were higher in patients with macroprolactinemia than in the other two groups (p < 0·0001). The maximal concentration of monomeric prolactin was reached before that of total prolactin in macroprolactinemic patients but the differences were not significant. DISCUSSION: Our findings support the hypothesis that prolactin secretion is comparable in women with macroprolactinemia and in normoprolactinemic women. The dynamics of the secretion suggest that the formation of prolactin complexes is an extra-pituitary process.

Effect of changes to cost and availability of emergency contraception on users' profiles in an emergency department in Catalunya.

OBJECTIVE: Emergency contraception (EC) accessibility has evolved differently in Catalunya as compared with other autonomous communities in Spain. Free-of-charge access within the Public Health System was authorised in 2004, and over-the-counter (OTC) access was implemented in 2009. The aim of the study is to assess the impact of these measures on demand and users' profiles at our institution. METHODS: A retrospective study, in our Emergency Department, was conducted to evaluate EC requests in relationship to accessibility modifications. The age of women and which days of the week they attended were analysed. RESULTS: The number of EC requests, the distribution by age and the demand over the week remained stable after access to EC became free of charge. However, requests sharply decreased following OTC access implementation. Distribution by age also changed, with a significant increase in requests from women under 25 years (72% vs 56%, p < 0.001). Demand was greatest on Sunday and Monday, and this distribution persisted over the study period. CONCLUSION: EC requests remained unchanged following free-of-charge access to EC, but decreased after OTC implementation. Women currently seeking EC at no cost at our institution are more likely to be younger and to request it on a Monday.

The modern management of uterine fibroids-related abnormal uterine bleeding.

Uterine fibroids (UFs) are the most common female benign pelvic tumors, affecting >60% of patients aged 30-44 years. Uterine fibroids are asymptomatic in a large percentage of cases and may be identified incidentally using a transvaginal ultrasound or a magnetic resonance imaging scan. However, in approximately 30% of cases, UFs affect the quality of life and women's health, with abnormal uterine bleeding and heavy menstrual bleeding being the most common complaints, along with iron deficiency (ID) and ID anemia. Medical treatments used for UFs-related abnormal uterine bleeding include symptomatic agents, such as nonsteroidal antiinflammatory drugs and tranexamic acid, and hormonal therapies, including combined oral contraceptives, gonadotropin-releasing hormone agonists or antagonists, levonorgestrel intrauterine systems, selective progesterone receptor modulators, and aromatase inhibitors. Nevertheless, few drugs are approved specifically for UF treatment, and most of them manage the symptoms. Surgical options include fertility-sparing treatments, such as myomectomy, or nonconservative options, such as hysterectomy, especially in perimenopausal women who are not responding to any treatment. Radiologic interventions are also available: uterine artery embolization, high-intensity focused ultrasound or magnetic resonance-guided focused ultrasound, and radiofrequency ablation. Furthermore, the management of ID and ID anemia, as a consequence of acute and chronic bleeding, should be taken into account with the use of iron replacement therapy both during medical treatment and before and after a surgical procedure. In the case of symptomatic UFs, the location, size, multiple UFs, or coexistent adenomyosis should guide the choice with a shared decision-making process, considering long- and short-term treatment goals expected by the patient, including pregnancy desire or wish to preserve the uterus independently of reproductive goals.

Effects of SARS-COVID-19 lockdown on menstrual patterns: A transversal large sample survey.

OBJECTIVE: To elucidate the presence, importance, and characteristics of menstrual changes related to stressful circumstances during the COVID-19 lockdown in Spain. STUDY DESIGN: An online survey was administered in Spain to menstruating women aged 15-55 who had not contracted COVID-19. It collected information on activities during the lockdown, sexual activity, perceptions of emotional status, any changes in menstrual characteristics, and impact on quality of life. The analysis of menstrual changes was limited to responders who did not use hormonal contraception. RESULTS: A total of 6449 women answered the survey, and 4989 surveys were valid for the final analysis. 92.3% of women had at least one menstruation period during the lockdown, while 7.7% had amenorrhea. Quality of life (QoL) associated with menstruation worsened in 19% of women, did not change in 71.7%, and improved in 1.6%. For 50.1% of the women, global QoL worsened during the lockdown; 41.3% remained about the same and 8.7% reported improvement. Sexual activity during the lockdown decreased in 49.8% of the respondents, remained unchanged in 40.7%, and increased in 9.5%. As far the menstrual changes are concerned, there were no statistically significant differences in amenorrhea incidence, regularity of the menstrual cycle, or the amount or duration of menstrual bleeding in non-hormonal contraceptive users when evaluated by the length and characteristics of isolation, the perception of exposure to COVID-19 and the economic or employment situation. Conversely, we found statistically significant differences according to the intensity of changes in emotional status due to lockdown stressors and changes in regularity, duration, and heaviness of menstruation. CONCLUSION: Changes in emotional status, but not the length and intensity of the isolation or exposure to the disease, significantly influenced menstrual disturbances during the COVID-19 lockdown.

Heavy Menstrual Bleeding-Visual Analog Scale, an Easy-to-Use Tool for Excessive Menstrual Blood Loss That Interferes with Quality-of-Life Screening in Clinical Practice.

Background: Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss that interferes with quality of life (QoL). The methods for assessing HMB are not suited for clinical practice. We analyzed the validity of a combined visual analog scale (VAS) tool assessing the intensity of menstrual bleeding (VASInt) and its impact on activities of daily living (VASImp) to identify women with HMB. Materials and Methods: Analysis conducted in the data set used to validate the Spanish HMB screening tool SAMANTA questionnaire. A logistic regression analysis was used to construct the model. Reference standard was the pictorial blood loss assessment chart (PBAC). The performance of the HMB-VAS and the SAMANTA questionnaire was compared. Correlation with SAMANTA questionnaire, PBAC, and other QoL measurements was assessed. Results: The resulting function (HMB-VAS score = 10.86 × VASInt score +2.48 × VASImp score) showed a slightly lower accuracy versus the SAMANTA questionnaire (86.8% vs. 87.9%) but a similar area under the curve: 0.9396 versus 0.943, respectively (p = 0.6605). The cutoff point was established as 700. After rounding the regression coefficients, the resulting function (11 × VASInt +2 × VASImp) showed 87.6% accuracy. The correlation of HMB-VAS with the SAMANTA questionnaire was strong (r: 0.79819; p < 0.0001), whereas the correlation was moderate to strong with the PBAC (0.59299; p < 0.0001) and weak with the QoL (EuroQoL five dimensions five levels questionnaire [EQ-5D-5L]) and well-being (Psychological General Well-Being Index [PGWBI]) scales (EQ-5D-5L VAS and Index: -0.20332 and -0.24384; PGWBI: -0.21680; p < 0.0001 for both). Conclusion: The HMB-VAS shows good performance for HMB screening, providing an easy-to-use alternative to other psychometric tools.

Heavy menstrual bleeding and its detection in clinical practice. / Sangrado menstrual abundante y su detección en la práctica clínica.

Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss that interferes with quality of life. It is an under-diagnosed and under-treated disorder due to the poor correlation between patient perception and objective menstrual blood loss, as well as the scarcity of validated diagnostic tools. Anaemia caused by HMB is a common problem, underestimated on many occasions and with consequences that go beyond the scope of gynaecology. Despite the condition's negative effect on quality of life, most of the tools validated to detect HBM do not take this into account. The aim of this paper is to review the main instruments available to detect HMB, their advantages and disadvantages, their applicability in routine clinical practice, and to recommend those with the best characteristics.

Validation of the Spanish version of the Uterine Fibroid Symptom and Quality of Life (UFS-QoL) questionnaire in women with uterine myomatosis. / Validación de la versión española del cuestionario Síntomas y Calidad de Vida en los Miomas Uterinos en mujeres con miomatosis uterina.

AIM: To validate the Spanish version of the Uterine Fibroid Symptom and Quality of Life (UFS-QoL) questionnaire in women with uterine myomatosis, in order to assess severity of symptoms, and their impact on health-related quality of life. MATERIALS AND METHODS: The participants were recruited in gynaecology clinics. The UFS-QoL questionnaire comprises 37 items, 8 of which assess severity of symptoms, and the remaining 29 assess health-related quality of life in 6 subscales. Internal consistency, concurrent and discriminant validity, test-retest reliability, and the scale's sensitivity to change were evaluated. RESULTS: A total of 619 patients with uterine myomatosis, and 57 women without myomatosis, took part in the study. Cronbach's alpha was 0.97, and the test-retest reliability was 0.90 for the overall scale. The UFS-QoL not only discriminated between patients and healthy controls but also between patients with different degrees of uterine myomatosis. The scale responded to changes after treatment with an effect size of 1.2. CONCLUSIONS: The Spanish version of the UFS-QoL questionnaire, used in a sample of the Spanish population, proved a valid and reliable tool to differentiate patients with uterine myomatosis and different grades of symptoms, and to evaluate the impact of the severity of these symptoms on health-related quality of life. In addition, the UFS-QoL proved sensitive to the changes generated by myomatosis treatment.

Development and Psychometric Validation of a Screening Questionnaire to Detect Excessive Menstrual Blood Loss That Interferes in Quality of Life: The SAMANTA Questionnaire.

Background: Heavy menstrual bleeding (HMB) affects up to 35% of women at some point in their lives, and has an important impact on their quality of life (QoL). Current techniques to assess and quantify menstrual blood loss are inconvenient and the correlation between actual and perceived blood loss is poor. This study aimed to develop and validate a screening questionnaire in Spanish to identify HMB in women of reproductive age. Methods: The study consisted of two phases: the conceptual development of a set of items to discriminate between women with and without HMB and the assessment of the sensitivity and specificity of these items. Correlation of the screening tool with women's perception of the intensity of bleeding and the interference in their daily life activities was also assessed. Results: An initial set of 46 items were identified, from which 21 items were selected following the cognitive interviews. For the psychometric validation phase, 389 patients were enrolled, of whom 364 were assessable: 211 cases with Pictorial Blood loss Assessment Chart-confirmed excessive menstrual loss (EML) and 153 controls. Six items met entry criteria in the model and together yielded a sensitivity of 86.7% and specificity of 89.5% to identify cases and controls. These items were weighted according to their contribution to the final model to yield a tool that can be scored from 0 to 10 being 3 the cutoff point to diagnose EML that interferes in QoL. Conclusions: The 6-item SAMANTA questionnaire represents a valid screening tool to easily identify women with EML that interfere with QoL.

Status of human assisted reproduction in Spain: results from the new registry of Catalonia.

The FIVCAT. NET database in Catalonia is the only official obligatory registry of human assisted reproduction practitioners in Spain. The present study assessed the effectiveness and outcomes of assisted reproduction over the period 2001-2005 relative to other established worldwide registries. The data analysed were derived from all centres conducting assisted reproduction in Catalonia, and included users of the services (resident and non-resident); all cycles performed; descriptive characteristics of the assisted reproduction procedures; and sociodemographic characteristics of the women. Effectiveness of assisted reproduction was measured by standard indicators such as rates of pregnancy and rates of live births per pregnancy. The results indicated that the preferred number of embryos for transfer changed from three to two over this period. Pregnancies per transfer improved from 33.2% to 37.1% (from 36.9% to 40.2% using fresh embryos and from to 18.4% to 27.0% with frozen embryos). Multiple births decreased from 50.1% to 38.6%, premature births from 37.5% to 28.3% and low-birth-weight infants from 38.0% to 25.6%. It is concluded that the conduct of assisted reproduction in Catalonia has improved considerably and compares favourably with other countries, not only with respect to the level of activity, but also the effectiveness and outcomes achieved, although the quality of the sociodemographic information requires improvement.

Prevalence and predictors of abnormal glucose metabolism in Mediterranean women with polycystic ovary syndrome.

Impaired glucose tolerance (IGT) and Type 2 diabetes mellitus (DM) are common in women with polycystic ovary syndrome (PCOS) in American studies. However, whether rates are similar in other countries with a lower frequency of insulin resistance is not clear. Our purpose was to investigate the prevalence of abnormal glucose metabolism (AGM) in women with PCOS and asses the ability of clinical data and biochemical tests to predict these abnormalities within our population. One hundred and three PCOS women undergo a 75-g oral glucose tolerance test. Glucose tolerance was categorised according to World Health Organisation criteria. Glucose tolerance was abnormal in 18.5% of women: 10.7% had IGT and 7.7% had DM. Women with DM were older than those with IGT or normal glucose tolerance. Women with AGM were more obese, had a higher waist/hip ratio and free testosterone levels than normal glucose metabolism patients. QUICKI was the best predictor of AGM. Receiver operating characteristics analysis suggested a threshold value of 0.31 in quantitative insulin-sensitivity check index (QUICKI) (94.1% sensitivity, 86% specificity, 57.1 positive predictive value and 98.6 negative predictive value) for the prediction of AGM. In conclusion, Mediterranean women with PCOS are at lower risk of AGM than that published from other countries; however, the incidence is still high compared with populations of women without PCOS. We recommend that PCOS patients undergo periodic metabolic screening for AGM using QUICKI.