The new LNG-releasing IUS: a new opportunity to reduce the burden of unintended pregnancy.

Unintended pregnancies still remain a worldwide public health problem. They have received much attention in adolescents given the strong impact they have on their present and future lives. On the other side, as women join the labour market, young women wishing to delay maternity are also especially vulnerable. Studies have revealed a pattern of use of contraceptive methods that is likely to increase this risk. Methods of long-acting reversible contraception (LARC), among which cooper and levonorgestrel-releasing intrauterine devices (IUD and IUS) are the most common, have been widely recommended to avoid unintended pregnancy at any age. Despite this, the use of these devices is very limited. Several barriers to their wide spread use have been identified, which specially affect a higher use by nulliparous women. A new levonorgestrel-releasing IUS containing only 13.5 mg of levonorgestrel (IUS12), recently marketed as Jaydess® in Europe, which provides a smaller size, a shorter duration of action, and a lower hormonal content compared to Mirena®, along with a similar efficacy and safety profile, may offer a long-term option that better addresses the needs of nulliparous women. Evidence on the risk of unintended pregnancies in young women –with a special emphasis in Europe—, barriers associated with a lower-than-desirable use of LARC methods –especially intrauterine devices (IUD and IUS)—, and the potential benefits of the new IUS12 including changes in bleeding pattern, safety and user satisfaction –especially with respect to nulliparous and adolescents— are reviewed here. Evidence supports that IUS12 may offer a LARC option that better addresses the needs of these women.pre-print332 K

SARS-CoV-2 vertical transmission; permanent doubt in COVID-19

La reciente definición de la COVID-19 como nueva enfermedad causada por el coronavirus SARS-CoV-2 ha provocado diversos cambios en algunos tratamientos hormonales en ginecología 3 , pero aún permanece sin aclarar si existe TV como forma efectiva de contagio para el feto. Seguramente condicionados por los hechos concernientes al VIH (virus de inmunodeficiencia humana), que asoló el mundo al final del pasado siglo causando más de 35 millones de fallecidos 4 y decenas de miles de fetos infectados durante la gestación, obstetras de todo el mundo debaten aún hoy si será similar la situación en la COVID-19. Es objetivo principal de este artículo especial revisar la escasa casuística publicada en relación con la posible TV de SARS-CoV-2, así como debatir distintos supuestos de esta importante cuestión en relación con esas publicaciones.2019-2

Biomarkers in Ovarian Pathology: From Screening to Diagnosis. Review of the Literature.

Background: Ovarian cancer has a low incidence, but high mortality due to a habitual diagnosis in advanced cancer stages. Currently, used biomarkers have good sensitivity, but low specificity. Aim: To determine the usefulness of the biomarkers and algorithms used up to now in the screening, diagnosis, response to treatments and identification of recurrence in patients with ovarian masses. Methodology: Systematic search of publications in English in the Medline-PubMed database with the terms: “biomarkers”, “tumour”, “tumour biomarkers”, “marker”, “tumour marker”, “ovarian cancer”, “ovarian”, “Neoplasms”, “cancer”, CA-125 Antigen; Human Epididymis-specific Protein E4; Risk of Malignancy Index (RMI); Risk of Ovarian Malignancy Algorithm (ROMA); Ovarian Neoplasms. Original articles, clinical trials, reviews, systematic reviews and meta-analyses, published between January 2000 and November 2020, were selected to determine the usefulness (among others) of CA 125 and HE4 antigen in ovarian cancer. Results: Finally, 39 transcendental publications were selected to write this article to determine the usefulness of tumour markers and algorithms in ovarian cancer. Conclusions: The usefulness of the tumour markers antigen CA125 and antigen HE4 individually or as a basis for decision-making algorithms has low specificity; however, there is little evidence that confirms their usefulness as markers in ovarian cancer screening.post-print723 K

Disability-adjusted-life-years losses in postmenopausal women with osteoporosis: a burden of illness study

To estimate the disability-adjusted life years (DALY) in a nationwide representative sample of postmenopausal women with osteoporosis. The effects of drug-based therapy and risk factors for osteoporotic bone fractures on DALY losses were also explored. DALY were estimated based on participant's clinical characteristics and Health-Related Quality-of-Life (HRQoL) data obtained from a cross-sectional, epidemiological one-visit study (the GINERISK study). The study enrolled postmenopausal women (at least 12-months after their last menstrual period) with osteoporosis, above 18-years old, who attended Spanish outpatient Gynaecology clinics. HRQoL was assessed using the generic SF-12v2 questionnaire, which was used to derive disutility values. Mortality rates were extracted from the Spanish national statistics database. Factors explored to be associated with DALY losses were examined using ANOVA, ANCOVA and MANCOVA models

Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns.This study was funded by Faes Farma, S.A. and Bruno Farmaceutici S.p.A. The authors wish to thank the study participants, research staff, the secondary investigators of the Osteoferol study group, the home nursing staff (Emibet), and Faes Farma clinical research team: Paula Arranz Gutiérrez, Lorena Elgezabal González, Mariana Frau Usoz, and Iñigo Saez Riesco. Medical writing support was provided by Francisco López de Saro (Trialance SCCL), funded by Faes Farma, S.A

Myths and realities of combined hormonal contraception.

ANTECEDENTES: La anticoncepción ha cambiado el devenir histórico de muchas mujeres, además de permitir su desarrollo personal, sin ligarse a los embarazos sucesivos sin planificación. Hace muchas décadas que la eficacia clínica de la anticoncepción hormonal está fuera de duda, incluso por parte de la población general. Persisten, sin embargo, demasiados mitos acerca de su seguridad y sobre determinadas circunstancias de su empleo que condicionan las decisiones profesionales de la salud y de usuarias potenciales. METODOLOGÍA: Ensayo retrospectivo consistente en la búsqueda de artículos originales y revisiones sistemáticas publicados en los últimos diez años en la base de datos de PubMed, específicamente relacionados con temas de anticoncepción hormonal. Las palabras de búsqueda (MeSH) fueron: hormonal contraception, oral contraceptives, myths about oral contraceptives y otros. Se seleccionaron los artículos de mayor nivel de evidencia; se analizaron más de 50 documentos y, de éstos, se ubicaron los más relevantes en cuanto a los mitos y las realidades en torno a la anticoncepción hormonal. CONCLUSIONES: A pesar del cambio personal y social que la anticoncepción hormonal ha supuesto en los pasados 50 años, persisten aún demasiados mitos acerca de su seguridad y relación con los sangrados regulares, que condicionan negativamente la información proporcionada a las posibles usuarias y las decisiones de la mujer que requiere anticoncepción segura y confortable.post-print255 K

La anticoncepción del siglo XXI; desde la prevención de embarazos no deseados a la mejora integral de la calidad de vida.

post-print153.00 K

Calcifediol (25OHD) Deficiency and Its Treatment in Women’s Health and Fertility

Currently, there is abundant scientific evidence showing that the vitamin D endocrine system (VDES) is a highly complex endocrine system with multiple actions in different regions of the body. The unequivocal presence of vitamin D receptors in different tissues related to fertility, and to specific aspects of women’s health such as pregnancy, undoubtedly implies functions of this steroid hormone in both male and female fertility and establishes relationships with different outcomes of human gestation. In order to review the role of the VDES in human fertility, we evaluated the relationships established between 25-hydroxyvitamin D (calcifediol) deficiency and in vitro fertilization, as well as aspects related to ovarian reserve and fertility, and commonly diagnosed endocrinopathies such as polycystic ovary disease. Likewise, we briefly reviewed the relationships between calcifediol deficiency and uterine fibroids, as well as the role that treatment may have in improving human fertility. Finally, the best scientific evidence available on the consequences of calcifediol deficiency during pregnancy is reviewed in relation to those aspects that have accumulated the most scientific literature to date, such as the relationship with the weight of the newborn at the time of delivery, the appearance of preeclampsia, and the risk of developing gestational diabetes and its final consequences for the pregnancy. To date, there is no definitive consensus on the necessary dose for treatment of calcifediol deficiency in the therapeutic management of infertility or during pregnancy. Large prospective clinical intervention studies are needed to clarify the benefits associated with this supplementation and the optimal dose to use in each situation. Although most intervention studies to date have been conducted with cholecalciferol, due to its much longer history of use in daily care, the use of calcifediol to alleviate 25-hydroxyvitamin D deficiency seems safe, even during pregnancy. The unequivocal presence of vitamin D receptors in very different tissues related to human fertility, both male and female, as well as in structures typical of pregnancy, allows us to investigate the crucial role that this steroid hormone has in specific aspects of women’s health, such as pregnancy and the ability to conceive. Well-designed clinical studies are needed to elucidate the necessary dose and the best form of treatment to resolve the very common calcifediol deficiency in women of reproductive age

Calcifediol in the management of vitamin D deficiency-related skeletal and extraskeletal diseases: overview and clinical cases

As well as being essential for musculoskeletal health, vitamin D is involved in numerous other physiological processes. Poor vitamin D status is linked to a wide range of diseases, including cardiovascular disease, autoimmune conditions, pulmonary disorders and upper respiratory tract infections. While optimal target concentrations of serum 25-hydroxyvitamin D (25(OH)D) for health maintenance or therapeutic purposes are still the subject of debate, there is reasonable agreement that serum 25(OH)D levels <50 nmol/L (20 ng/mL) constitute vitamin D deficiency and that severe deficiency states (serum 25(OH)D levels <25-30 nmol/L ≈ 10-12 ng/ mL) should be avoided. Main strategies to maintain or improve vitamin D status are food supplementation and therapeutic use of medicinal forms of vitamin D. In this review, we examine evidence that implicates vitamin D deficiency in diverse conditions in the clinical settings of endocrinology, rheumatology, pneumology and reproductive health. Cholecalciferol (vitamin D3) is the most frequently used vitamin D supplement worldwide, though calcifediol (25-hydroxyvitamin D3) has recently become more widely available. Calcifediol is one step closer than cholecalciferol in the metabolic pathway to biologically active vitamin D. Pharmacokinetic differences between these vitamin D metabolites confer putative advantages for calcifediol in certain clinical situations. The clinical use of calcifediol is explored more closely through case studies, which illustrate its adjunctive role in the treatment of several vitamin D deficiency-related skeletal and extraskeletal diseases

Disability-adjusted-life-years losses in postmenopausal women with osteoporosis: a burden of illness study

To estimate the disability-adjusted life years (DALY) in a nationwide representative sample of postmenopausal women with osteoporosis. The effects of drug-based therapy and risk factors for osteoporotic bone fractures on DALY losses were also explored. DALY were estimated based on participant's clinical characteristics and Health-Related Quality-of-Life (HRQoL) data obtained from a cross-sectional, epidemiological one-visit study (the GINERISK study). The study enrolled postmenopausal women (at least 12-months after their last menstrual period) with osteoporosis, above 18-years old, who attended Spanish outpatient Gynaecology clinics. HRQoL was assessed using the generic SF-12v2 questionnaire, which was used to derive disutility values. Mortality rates were extracted from the Spanish national statistics database. Factors explored to be associated with DALY losses were examined using ANOVA, ANCOVA and MANCOVA models