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.

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.

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.

Epidemiology of uterine myomas and clinical practice in Spain: An observational study.

OBJECTIVE: Characterization of the clinical features of symptomatic uterine myomas in Spanish women visiting the gynaecologist, including impact on quality of life and possible risk factors, description of main therapeutic approaches, and evaluation of symptom and quality of life progression 6 months after inclusion in the study. STUDY DESIGN: This was an observational, epidemiological, non-interventional, multicentre study performed between June 2015 and March 2016. Data were collected at baseline and follow-up visits 6 months apart from women with a diagnosis of uterine myomas and visiting a participating gynaecologist in outpatient units of private clinics or public hospitals in Spain. Data consisted of a gynaecological clinical inspection, an interview with open questions to the patients, and self-administered generic questionnaires. The main outcome measures were socio-demographic data, clinical history, myoma clinical features, symptomatology, data on surgical choices, patient satisfaction, and risk factors associated to myomas. RESULTS: Data were collected from 569 patients (1,022 myomas) at 56 hospitals and private gynaecological offices in Spain. Most patients (85%) presented between 1 and 3 myomas, predominantly intramural and subserosal. Most common symptoms reported heavy menstrual bleeding and pelvic pain, and the mean (±SD) symptom severity score in the UFS-QoL questionnaire (range 0-100) was 50.89 ±â€¯20.85. Up to 60.5% of patients had an indication of surgery (55.8% myomectomies, 40.4% hysterectomies) to treat their uterine myomas and 39.5% followed other therapies, mainly pharmacological. After six months of treatment, all patients had experienced significant reduction in symptoms and improvement of quality of life. CONCLUSIONS: The most frequent symptoms reported by women diagnosed with uterine myomas were heavy menstrual bleeding, pelvic or abdominal pain and dysmenorrhea; QoL was impaired reflecting high symptom distress. We found that surgery was the main therapeutic approach to manage uterine myomas in Spain. Both surgical and non-surgical treatments achieve relevant improvements in symptom severity and quality of life.

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.

Characterization of the population with severe iron deficiency anemia at risk of requiring intravenous iron supplementation.

Iron deficiency anemia is the most frequent cause of anemia world-wide and is a very common disorder in daily medical practice. Heavy menstrual bleeding (menorrhagia) and pregnancy and delivery can cause significant iron loss leading to severe anemia The aim of the present study was to characterize the population requiring intravenous iron and identify whether gynecological and obstetric iron loss are frequent indications for treatment. MATERIAL AND METHODS: Restrospective, single center study performed in a tertiary level university hospital from January 2014 to December 2016. RESULTS: During the 3-year study period, there were 4529 treatments with intravenous iron (45.98% in men vs. 54.02% in women). The population group from 10 to 54 years of age made up 19.33% of the total treatments, with 35.93% in men and 64.01% in women (Fisher exact test, p<0.001). Intravenous iron administration for gynecological and obstetric reasons was required in 20.54% and 24.82% of the total population, respectively, representing >45% of the indications for treatment in this population. CONCLUSIONS: The need for intravenous iron is related to anemia refractory to oral treatment or the need for rapid iron recovery. Our results show that women of fertile age are a population at risk of requiring intravenous iron as compared to a male population of the same age. It is mainly due to blood los related to pregnancy, delivery and puerperium as well as heavy menstrual bleeding.

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.

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.

Hirsutism scoring in polycystic ovary syndrome: concordance between clinicians' and patients' self-scoring.

In a clinical series of 68 women with polycystic ovary syndrome in which the reason for consultation was hirsutism, the mean (standard error of the mean) hirsutism score of the modified Ferriman-Gallwey method was 15.1 (6.8), compared with 12.0 (4.4) for clinicians' scoring. In the multivariable analysis, clinicians' scoring of hirsutism was the only independent variable significantly associated with increased testosterone free index levels.

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.

Raloxifene use in clinical practice: efficacy and safety.

OBJECTIVE AND METHODS: In this article, we provide an interdisciplinary concise review of the effects of raloxifene on breast, bone, and reproductive organs, as well as the adverse events that may be associated with its use. RESULTS: Raloxifene has been shown to prevent osteoporosis in postmenopausal women (PMW) with low bone mass and prevent vertebral fractures in those with osteoporosis/low bone mass; it has not been shown to reduce the risk of nonvertebral fractures. Raloxifene reduces the risk of invasive breast cancer in PMW with osteoporosis or at high risk of breast cancer. The risk of venous thromboembolism has been consistently shown to be increased with raloxifene, so it should not be used in women at high risk of venous thromboembolism. Although raloxifene does not increase, nor decrease, the risk of coronary or stroke events overall, in the raloxifene trial of PMW at increased risk of coronary events, the incidence of fatal stroke was higher in women assigned raloxifene versus placebo. CONCLUSIONS: Based on its approved indications, it is appropriate to prescribe raloxifene to prevent or treat osteoporosis, as well as to reduce the risk of invasive breast cancer in PMW with osteoporosis or at high risk of breast cancer. Women at increased risk of both fracture and invasive breast cancer are those most likely to receive a dual benefit with raloxifene. Decision making must involve the incorporation of the woman's personal feelings about the risks and benefits of raloxifene therapy, balanced with her interest in reducing risk of fractures and breast cancer through pharmacological intervention.

Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens.

Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p < or = 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p < or = 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal cells from X-ray-treated female rats and that this RIGI enhances the chromosomal damage caused by the chemical agent aphidicolin.

Effectiveness of liquid-based cytology and papanicolaou tests in a low risk population.

OBJECTIVE: To compare sensitivity an effectiveness of ThinPrep vs. Pap Test and determine whether the Hybrid Capture System II (HCII) for detection of human papillomavirus (HPV) could increase the sensitivity and effectiveness of cervical screening in a low risk population. STUDY DESIGN: We present a comparative observer, blind, "split sample" study of ThinPrep and Papanicolaou staining in a population of 2026 consecutive women. RESULTS: Conventional Papanicolaou stain detected lesions in 62 cases (3.06%), including 1 atypical glandular cell of undetermined significance (AGUS), 34 atypical squamous cells of undetermined significance (ASCUS) (1.73% of atypias), 20 (0.99%) low grade squamous intraepithelial lesions (LSIL), and 7 (0.35%) high grade squamous intraepithelial lesions (HSIL). ThinPrep detected lesions in 63 cases (3.11%), including 26 (1.28%) ASCUS, 27 (1.33%) LSIL and 10 (0.49%) HSIL. Despite this overall similarity, only 35 had a coincident cytopathologic result by both methods. The kappa concordance index between ThinPrep and Pap was 0.546. Sensitivity and specificity were 74.6 and 45.0 in ThinPrep and 69.5 and 25.0 in Papanicolaou-stained smears. High risk HPV (HR-HP 17) was positive in 13 of ZOASCUS and in 21 of 22 SIL. CONCLUSION: Technologies now widely available such as Thin Prep and viral detection aim to improve accuracy of screening.

Comparison of the efficacy and tolerability of a new once-a-week matricial estradiol transdermal system (Estrapatch 40 and Estrapatch 60) with a twice week system.

OBJECTIVE: To compare the efficacy and tolerability of three transdermal systems (Estrapatch 40, Estrapatch 60 and Oesclim 50). METHODS: Multicentre, randomized, open, 3 parallel group study on 421 postmenopausal women presenting with at least 35 hot flushes in the week preceding inclusion and treated for six 28-day cycles with either Estrapatch 40 (n = 141) or Estrapatch 60 (n = 140) once a week or Oesclim 50 (n = 140) twice a week, associated to oral NETA (Millligynon 2x 0.6 mg tablets daily) from day 15 to day 28. Hot flushes, mastodynia, bleeding, local skin tolerability and adhesiveness were reported on daily cards. Endometrial thickness and estrogens were measured before and after treatment. RESULTS: Efficacy was clearly established for the three devices as early as after one cycle of treatment, with success rates (% of women with a decrease > or = 50% of the number of hot flushes) over 97% from cycle 2. The three treatments were equivalent on this criteria, except at cycle 1 for Estrapatch 40 which was not equivalent to both other treatments. Incidence and severity of mastodynia, bleeding pattern, endometrial thickness and specific estrogen-related adverse events reflected a significant higher estrogenic stimulation with Oesclim 50. Adhesiveness was very satisfactory for the three systems. CONCLUSIONS: Estrapatch 40 and 60 presents a better benefit/risk ratio compared to Oesclim 50. Thus Estrapach 40 appears to be a good choice for a first-line estrogen replacement therapy with the possibility to increase the dose to Estrapatch 60.