Selection and Validation of Reference Genes for RT-qPCR Analysis in Tibetan Medicinal Plant Saussurea Laniceps Callus under Abiotic Stresses and Hormone Treatments.

Real-time quantitative PCR (RT-qPCR) is an important technique for studying gene expression analysis, but accurate and reliable results depend on the use of a stable reference gene. This study proposes to test the expression stability of candidate reference genes in the callus of Saussurea laniceps, a unique Tibetan medicinal plant. Based on the S. laniceps callus transcriptome, eleven candidate reference genes, including TUA2, TUB3, TUB8, TIF3B1, TIF3H1, ELF5A, PP2AA2, UEV1D, UBL5, UBC36, and SKIP1), were validated for RT-qPCR normalization in the callus under abiotic stress (salt, cold, and UV) and hormone treatments (abscisic acid, MeJA, and salicylic acid). The stability of the candidate genes was evaluated in all the samples of S. laniceps. Comprehensive analysis of all samples showed that the best reference genes were UBC36 and UBL5. ELF5A and TIF3B1 were ranked as the most stable genes in the sample sets under abiotic stress. For hormone stimulation, UBC36 and TIF3H1 genes had the best stability. This study provides useful guidelines and a starting point for reference gene selection for expression analysis using RT-qPCR techniques in S. laniceps.

Alternative and non-hormonal treatments to symptoms of menopause.

Ovarian function can start to decline a few years before the eventual cessation of the menstrual cycle. The average age of menopause in the UK is 51 years, and it is a retrospective diagnosis after 12 months of amenorrhoea. Women can experience many symptoms such as vasomotor and vulvovaginal symptoms that impact them physically, psychologically, sexually and thus their overall wellbeing. Women may have medical contraindications to hormonal therapy or may prefer non-hormonal or alternative treatments. This review looks at the evidence, efficacy, and safety of a range of complementary or alternative treatments and non-hormonal pharmacological treatments for the treatment of vasomotor symptoms and vulvovaginal atrophy of menopause.

Melatonin attenuates glucocorticoid effect induced by medroxyprogesterone acetate in rats.

Medroxyprogesterone acetate (MPA) acts on glucocorticoid receptors and, when it is in excess, can cause clinical disorders comparable to hyperadrenocorticism. Melatonin (MEL) is a hormone with potent antioxidant and anti-glucocorticoid activity and it can be beneficial in the excessive activation of glucocorticoid receptors. To evaluate the protective effects of MEL on the glucocorticoid effect of MPA, 34 male Wistar rats were randomized into four groups: CON (control), MEL, MPA, and MPA + MEL. The animals were treated for 28 days, by subcutaneous injection. At the high dose that we used, the MPA caused effects compatible with an excessive activation of glucocorticoid receptors, resulting on a reduction in adrenal size, less weight gain, lower final body weight and feeding efficiency, and fewer lymphocytes compared with the control group. In addition, there was an increase in abdominal fat, cholesterol, very-low-density lipoprotein (VLDL), triglycerides, erythrocytes, hemoglobin, hematocrit, and hepatic vacuolization. We concluded that MEL was effective reducing the mean values of total cholesterol, high-density lipoprotein (HDL), urea, VLDL, triglycerides, hepatic microvacuolization and abdominal fat/weight in rats treated with MPA. These findings indicate that MEL attenuates the harmful effects of MPA.

[The HRT follow-up consultation. What to do in case of breast pain. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]. / La consultation de suivi du THM. Conduite à tenir en cas de syndrome douloureux mammaire. RPC Les femmes ménopausées du CNGOF et du GEMVi.

Breast pain is a concern in perimenopausal and postmenopausal women, quantifiable using validated tools, and may pre-exist or appear after initiation of a HRT. OBJECTIVES: A review of the literature was conducted to evaluate the frequency of breast pain, its evolution with age, its changes under HRT, its link with a possible risk of subsequent breast cancer, and the diagnostic (breast imaging) or therapeutic management modalities (pharmacological or other) in women taking HRT. METHOD: A review of the literature was carried out by consulting Medline, Cochrane Library data and international recommendations in French and English up to the end of 2019. RESULTS: Published data confirm the importance of breast pain in relation to breast cancer risk. Women with breast pain prior to or related to the use of HRT have a significantly increased risk of breast cancer compared to women without breast pain. The risk is increased in cases of moderate to severe breast pain. In the presence of diffuse breast pain without abnormalities on clinical examination, it is not recommended to change the usual indications for screening, whether organized or individual. For focal breast pain, breast imaging (mammography and possibly ultrasound) is recommended. In the absence of abnormalities on breast imaging, a reassuring dialogue has to take place. With regard to HRT, doses of estrogens should be reduced until the breast pain decreases, or even stop the HRT if this symptom persists despite the use of low doses. Wearing a bra brassiere-type can also reduce breast pain.

[Non-hormonal alternatives for the management of menopausal hot flushes. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]. / Alternatives non hormonales de prise en charge des bouffées vasomotrices post-ménopausiques. RPC Les femmes ménopausées du CNGOF et du GEMVi.

One of the major symptoms of climacteric syndrome is hot flushes (HF). They are most often experienced as very disabling. Estrogen therapy is the most effective treatment. However, it may be contraindicated in some women. The aim of this article is to provide a review of the scientific literature on pharmacological and non-pharmacological alternatives in this context. Only randomized trials and meta-analyses of randomized trials were considered. This review shows that some treatments usually used in non-gynecological or endocrinological disease have significant effect in reducing the frequency and/or severity of HF. Hence, some selective serotonin reuptake inhibitors (paroxetine, citalopram and escitalopram), serotonin and norepinephrine reuptake inhibitors (venlafaxine, desvenlafaxine) gabapentin, pregabalin and clonidine have a statistically effect as compared with placebo in reducing, the frequency and/or severity of HF. Some phytoestrogens, such as genistein, may also reduce the frequency of HF. Regarding non-pharmacological interventions, hypnosis, acupuncture or yoga have been analyzed with significant beneficial results, even if their evaluation is difficult by the absence of a good placebo group in most trials. By contrast, other approaches, both pharmacological or non-pharmacological, appear to be ineffective in the management of HT. These include homeopathy, vitamin E, alanine, omega 3, numerous phytoestrogens (red clover, black cohosh…), primrose oil, physical activity. In women suffering from breast cancer, several additional problems are added. On the one hand because all phytoestrogens are contraindicated and on the other hand, in patients using tamoxifen, because the molecules, that interact with CYP2D6, are to be formally avoided because of potential interaction with this anti-estrogen treatment. In conclusion, several pharmacological and non-pharmacological alternatives have significant efficacy in the management of severe HF.

Selection of Reference Genes for qRT-PCR Analysis in Medicinal Plant Glycyrrhiza under Abiotic Stresses and Hormonal Treatments.

Best known as licorice, Glycyrrhiza Linn., a genus of herbaceous perennial legume, has been used as a traditional herbal medicine in Asia and a flavoring agent for tobacco and food industry in Europe and America. Abiotic stresses and hormonal treatments can significantly impact the development and metabolism of secondary metabolites in Glycyrrhiza. To better understand the biosynthesis of the trace-amount bioactive compounds, we first screened for the suitable reference genes for quantitative real-time reverse transcription PCR (qRT-PCR) analysis in Glycyrrhiza. The expression profiles of 14 candidate reference genes, including Actin1 (ACT), Clathrin complex AP1 (CAC), Cyclophilin (CYP), Heat-shock protein 40 (DNAJ), Dehydration responsive element binding gene (DREB), Translation elongation factor1 (EF1), Ras related protein (RAN), Translation initiation factor (TIF1), ß-Tubulin (TUB), Ubiquitin-conjugating enzyme E2 (UBC2), ATP binding-box transpoter 2 (ABCC2), COP9 signal compex subunit 3 (COPS3), Citrate synthase (CS), and R3H domain protein 2 (R3HDM2) from two congeneric species, Glycyrrhiza uralensis F. and Glycyrrhiza inflata B., were examined under abiotic stresses (osmotic and salinity) and hormonal treatments (Abscisic acid (ABA) and methyl jasmonic acid (MeJA)) using a panel of software, including geNorm, NormFinder, BestKeeper, and Delta CT. The overall stability, however, was provided by RefFinder, a comprehensive ranking system integrating inputs from all four algorithms. In G. uralensis, the most stable reference genes under osmotic stress, salt stress, ABA treatment, and MeJA treatment were TIF1, DNAJ, CS, and ABCC2 for leaves and DNAJ, DREB, CAC, and CAC for roots, respectively. In comparison, the top ranked genes were TUB, CAC, UBC2, and RAN for leaves and TIF1, ABCC2, CAC, and UBC2 for roots, respectively, under stress and hormonal treatments in G. inflata. ACT and TIF1, on the other hand, were the least stable genes under the most experimental conditions in the two congeneric species. Finally, our survey of the reference genes in legume shows that EF, ACT, UBC2, and TUB were the top choices for the abiotic stresses while EF, UBC2, CAC, and ABCC2 were recommended for the hormonal treatments in Leguminosae. Our combined results provide reliable normalizers for accurate gene quantifications in Glycyrrhiza species, which will allow us to exploit its medicinal potential in general and antiviral activities in particular.

Therapeutic potential of omega fatty acids in breast cancer. Review / Potencial terapéutico de ácidos grasos omega en cáncer de mama. Revisión

Background: Breast cancer is the second cause of death in women in developed and undeveloped countries, including Colombia. A high percentage of these tumors is estrogen dependent, for which the hormonal treatment is the most used therapy in breast cancer. Currently, the first line treatment for breast tumor in postmenopausal women is the letrozole, an aromatase enzyme inhibitor that avoids the transformation of androgens to estrogens. Since letrozole produced adverse effects on patients, there is a requirement for new alternative treatments. Furthermore, omega fatty acids (ω-FA), essential as they are obtained from the normal diet or from dietary supplements, have demonstrated nutraceutical potential because of their anti-inflammatory or pro-inflammatory activity. Nonetheless, there is controversy in in vitro, in vivo and epidemiologic reports regarding their preventive or inducing activities of carcinogenesis in animals and humans, depending on the structure of the ω-FA. Objectives: This review aims to show the main in vitro, in vivo and epidemiologic evidences of the chemotherapeutic potential of ω-3 and ω-6 FA in different types of neoplasm, particularly in breast cancer, in individual or combined treatments with diverse antineoplastics. Methods: PubMed and Science Direct databases revealed the most representative studies, published during the last two decades, about ω-3 and ω-6 FA, breast cancer and the principal therapeutic strategies for this neoplasm. Findings were presented in separated topics to provide an overview of ω-FA and their potential in treatments for breast cancer. Results: Patients treated with estrogens and progesterone derivate have shown predisposition to develop breast cancer after two years of continued therapy. Furthermore, ω-FA with known nutraceutical potential have demonstrated their potential as adjuvants in the treatment against different neoplasms, like hepatic and colon cancer. Conclusions: Current therapies for breast cancer and their low efficacy in the long term led to explore new alternative treatments with ω-FA. These essential fatty acids in daily consumption could enhance the antineoplastic agent effect. Nevertheless, metabolism of the ω-FA must be considered for this use.

Antecedentes: el cáncer de mama es la segunda causa de muerte de mujeres en países desarrollados y no desarrollados, incluido Colombia. La mayoría de estos tumores son dependientes de estrógeno por esa razón, la terapia más utilizada es la hormonal. Actualmente, el tratamiento de primera línea en mujeres posmenopáusicas es el letrozol, inhibidor de la enzima aromatasa, que evita la conversión de andrógenos en estrógenos. El letrozol causa efectos adversos en las pacientes, lo cual motiva la búsqueda de nuevas alternativas que disminuyan estos efectos. Los ácidos grasos omega, esenciales en la dieta regular o suplementaria, han mostrado su potencial nutracéutico ambivalente, como antiinflamatorios o proinflamatorios. Debido a esto, existe controversia en distintos reportes a nivel in vitro, in vivo y epidemiológicos sobre la actividad preventiva o quimioterapéutica de los ω-3 y ω-6 AGOs. Objetivos: el aporte de este artículo, es mostrar las principales evidencias in vitro, in vivo y epidemiológicas del potencial quimioterapéutico de los AGOs en tratamientos individuales y combinados con antineoplásicos, en distintos tipos de cánceres, particularmente en el cáncer de mama. Métodos: se revisaron las bases de datos PubMed y Science Direct y se seleccionaron los estudios más representativos de las dos últimas décadas sobre ω-3 y ω-6 AGOs y las principales estrategias usadas en el cáncer de mama. Los hallazgos se presentan en temas separados, primero una visión general de los AGOs y luego su potencial bioactivo en tratamientos contra el cáncer de mama. Resultados: la mayoría de los estudios en pacientes con cáncer de mama, tratadas con estrógenos y derivados de progesterona, han mostrado predisposición a desarrollar cáncer de mama después de dos años de terapia continua. De otro lado, los AGOs han demostrado su potencial como adyuvantes en el tratamiento en diferentes cánceres como el de colon y hepático. Conclusiones: las terapias actuales para el cáncer de mama y su baja eficacia a largo plazo exigen explorar nuevas alternativas de terapias, que incluyen los AGOs podrían potenciar fármacos, no obstante, es necesario tener en cuenta, el metabolismo de los AGOs, para uso

No. 164-Consensus Guidelines for the Management of Chronic Pelvic Pain.

OBJECTIVE: To improve the understanding of chronic pelvic pain (CPP) and to provide evidence-based guidelines of value to primary care health professionals, general obstetricians and gynaecologists, and those who specialize in chronic pain. BURDEN OF SUFFERING: CPP is a common, debilitating condition affecting women. It accounts for substantial personal suffering and health care expenditure for interventions, including multiple consultations and medical and surgical therapies. Because the underlying pathophysiology of this complex condition is poorly understood, these treatments have met with variable success rates. OUTCOMES: Effectiveness of diagnostic and therapeutic options, including assessment of myofascial dysfunction, multidisciplinary care, a rehabilitation model that emphasizes achieving higher function with some pain rather than a cure, and appropriate use of opiates for the chronic pain state. EVIDENCE: Medline and the Cochrane Database from 1982 to 2004 were searched for articles in English on subjects related to CPP, including acute care management, myofascial dysfunction, and medical and surgical therapeutic options. The committee reviewed the literature and available data from a needs assessment of subjects with CPP, using a consensus approach to develop recommendations. VALUES: The quality of the evidence was rated using the criteria described in the Report of the Canadian Task Force on the Periodic Health Examination. Recommendations for practice were ranked according to the method described in that report (Table 1). RECOMMENDATIONS: The recommendations are directed to the following areas: (a) an understanding of the needs of women with CPP; (b) general clinical assessment; (c) practical assessment of pain levels; (d) myofascial pain; (e) medications and surgical procedures; (d) principles of opiate management; (f) increased use of magnetic resonance imaging (MRI); (g) documentation of the surgically observed extent of disease; (h) alternative therapies; (i) access to multidisciplinary care models that have components of physical therapy (such as exercise and posture) and psychology (such as cognitive-behavioural therapy), along with other medical disciplines, such as gynaecology and anesthesia; G) increased attention to CPP in the training of health care professionals; and (k) increased attention to CPP in formal, high-calibre research. The committee recommends that provincial ministries of health pursue the creation of multidisciplinary teams to manage the condition.

No 164 - Directive clinique de consensus pour la prise en charge de la douleur pelvienne chronique.

OBJECTIF: Améliorer La compréhension de la douleur pelvienne chronique (DPC) et fournir des directives cliniques factuelles qui bénéficieront aux fournisseurs de soins de santé primaires, aux obstétriciens-gynécologues et aux spécialistes de la douleur chronique. FARDEAU DE LA SOUFFRANCE: La DPC est une pathologie débilitante courante qui affecte les femmes. Elle est à l'origine d'importantes souffrances personnelles et de dépenses de santé considérables associées aux interventions, dont de multiples consultations et un grand nombre de traitements médicaux et chirurgicaux. Puisque la pathophysiologie sous-jacente de cet état pathologique complexe est mal comprise, ces traitements n'ont obtenu que des taux de réussite variables. ISSUES: Efficacité des options diagnostiques et thérapeutiques (y compris l'évaluation du dysfonctionnement myofascial); soins multidisciplinaires; un modèle de réadaptation mettant l'accent sur l'obtention d'un fonctionnement supérieur malgré la présence d'une certaine douleur (plutôt que de chercher à obtenir une guérison totale); et utilisation appropriée des opiacés pour le soulagement de la douleur chronique. PREUVES: Des recherches ont été menées dans Medline et la base de données Cochrane en vue d'en tirer les articles de langue anglaise, publiés entre 1982 et 2004, portant sur des sujets liés à la DPC, dont la gestion des soins actifs, le dysfonctionnement myofascial et les options thérapeutiques médicales et chirurgicales. Les membres du comité ont analysé la littérature pertinente, ainsi que les données disponibles tirées d'une évaluation des besoins des personnes présentant une DPC; ils ont fait appel à une approche de consensus pour l'élaboration des recommandations. VALEURS: La qualité des résultats a été évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur l'examen médical périodique. Les recommandations visant la pratique ont été classées conformément à la méthode décrite dans ce rapport (Tableau 1). RECOMMANDATIONS: Les recommandations visent ce qui suit : (a) compréhension des besoins des femmes présentant une DPC ; (b) évaluation clinique générale ; (c) évaluation pratique des niveaux de douleur ; (d) douleur myofasciale ; (e) médicaments et interventions chirurgicales ; (f) principes de la gestion des opiacés; (g) utilisation accrue de l'imagerie par résonance magnétique (IRM) ; (h) documentation de l'étendue de La maladie constatée au moyen de la chirurgie ; (i) thérapies non conventionnelles; (j) accès à des modèles de soins multidisciplinaires faisant appel à des composantes de physiothérapie (comme l'exercice et la posture) et de psychologie (comme La thérapie cognitivo- comportementale), conjointement avec d'autres disciplines médicales, telles que La gynécologie et l'anesthésie ; (k) attention accrue portée à La DPC dans La formation des professionnels de La sante ; et (l) attention accrue portée à la DPC dans le domaine des recherches officielles et de haut calibre. Le comité recommande que les ministères provinciaux de La Sante prennent des mesures en faveur de la création d'équipes multidisciplinaires pouvant assurer La prise en charge de cette pathologie. Chapitre 2 : Portee et definition de La douleur pelvienne chronique Chapitre 3 : Anamnese, examen physique et évaluation psychologique Chapitre 4 : Explorations Chapitre 5 : Sources de douleur pelvienne chronique Chapitre 6 : Causes urologiques et gastro-intestinales de La douleur pelvienne chronique Chapitre 7 : Dysfonctionnement myofasclal Chapitre 8 : Therapie medicale - résultats en matiere d'efficacite Chapitre 9 : Chirurgie - résultats en matiere d'efficacite Chapitre 11 : Prise en charge multidisciplinaire de La douleur chronique Chapitre 14 : Orientations futures.

[Management of dysmenorrhea]. / Prise en charge des dysménorrhées.

Dysmenorrhea is one of the most common reasons for consultation in gynecology. The social and economic burdens are important. Dysmenorrhea may therefore be considered as a major public health issue. Its management is not yet optimal as dysmenorrhea still affects the quality of life of many patients. Primary dysmenorrhea, with no underlying organic cause, results from myometrial hyper contractility, arteriolar vasoconstriction, and tissue hypoxia. Secondary dysmenorrhea may involve the pathophysiological mechanisms of primary dysmenorrhea, but is mainly the expression of an underlying gynecological pathology. Although the pathophysiology of primary dysmenorrhea is well established, studies are now focusing on treatments to improve the management of these patients, who are often young. Nonsteroidal anti-inflammatory drugs and oral contraception remain the recommended firstline drugs, but their effectiveness can be enhanced by complementary therapy such as local heat application or regular exercise. Studies on other unconventional complementary therapies, such as ginger consumption, are very encouraging and need to be reinforced to incorporate recommendations for the management of primary dysmenorrhea.

Les dysménorrhées représentent un des motifs de consultation les plus fréquents en gynécologie. Les répercussions sociales et économiques qu'elles engendrent en font un phénomène de santé publique. Leur prise en charge n'est pas encore optimale et les dysménorrhées altèrent toujours la qualité de vie de nombreuses patientes. Les dysménorrhées primaires, sans cause organique sous-jacente, sont le résultat d'une hyper contractilité myométriale, d'une vasoconstriction artériolaire et d'une hypoxie tissulaire. Les dysménorrhées secondaires peuvent faire intervenir les mécanismes physiopathologiques des dysménorrhées primaires mais sont surtout l'expression d'une pathologie gynécologique sous-jacente. Si la physiopathologie des dysménorrhées primaires est de mieux en mieux connue, les études s'intéressent à présent aux options thérapeutiques pour améliorer la prise en charge de ces patientes souvent jeunes. Les antiinflammatoires non stéroïdiens et la contraception orale restent les molécules recommandées en première intention mais leur efficacité peut être potentialisée par des traitements complémentaires comme l'application locale de chaleur ou la pratique régulière d'exercices physiques. Des premiers résultats concernant d'autres thérapies complémentaires non conventionnelles, comme la consommation de gingembre, sont très encourageants et doivent être renforcés pour intégrer les recommandations de la prise en charge des dysménorrhées primaires.

[Medical treatment for the management of painful endometriosis without infertility: CNGOF-HAS Endometriosis Guidelines]. / Traitement médical de l'endométriose douloureuse sans infertilité, RPC Endométriose CNGOF-HAS.

OBJECTIVE: To provide clinical practice guidelines for the management of painful endometriosis in women without infertility. METHODS: Systematic review of the literature literature since 2006, level of evidence rating, external proofreading and grading of the recommendation grade by an expert group according to HAS methodology. RESULTS: Combined hormonal contraceptives (COP) and the levonorgestrel-releasing intra-uterin system (LNG-IUS) are recommended as first-line hormonal therapies for the treatment of painful endometriosis (grade B). Second-line therapy relies on oral desogestrel microprogestative, etonogestrel-releasing implant, GnRH analogs (GnRHa) and dienogest (grade C). It is recommended to use add-back therapy containing estrogen in association with GnRHa (grade B). After endometriosis surgery, hormonal treatment relying on COP or LNG-IUS is recommended to prevent pain recurrence (grade B). COP is recommended to reduce the risk of endometrioma recurrence after surgery (grade B) but the prescription of GnRHa is not recommended (grade C). Continuous COP is recommended in case of dysmenorrhea (grade B). GnRHa is not recommended as first line endometriosis treatment for adolescent girl because of the risk of bone demineralization (grade B). The management of endometriosis-induced chronic pain requires an interdisciplinary evaluation. Physical therapies improving the quality of life such as yoga, relaxation or osteopathy can be proposed (expert agreement). Promising medical alternatives are currently under preclinical and clinical evaluation.

Estrategias no farmacológicas para el manejo de los síntomas vasomotores en la menopausia

Los síntomas vasomotores afectan a gran número de mujeres en la peri y posmenopausia, impactando notablemente en la calidad de vida; por otro lado, su duración en el tiempo es incierta y muchas veces prolongada. Si bien la terapia hormonal de la menopausia (THM) constituye el tratamiento más efectivo para los síntomas climatéricos en su conjunto, en algunos casos existen contraindicaciones para su uso. Por lo tanto, ofrecer estrategias de tratamiento en las mujeres con contraindicación al tratamiento hormonal resulta mandatorio. Contamos con una amplia gama de opciones no hormonales, tanto farmacológicas como no farmacológicas. Dentro de estas últimas se incluyen las terapias alternativas o naturales (isoflavonas y cimicifuga racemosa), las modificaciones sobre el estilo de vida y las terapias complementarias. Las terapias alternativas presentaron resultados controvertidos en cuanto a la efectividad sobre los síntomas climatéricos y, por otro lado, debido a que su mecanismo de acción involucra a los receptores estrogénicos, están contraindicadas en las pacientes con antecedentes personales de cánceres hormonodependientes. Las modificaciones del estilo de vida impactan positivamente la salud general de la mujer, más allá de los síntomas climatéricos. En cuanto a las terapias complementarias, las únicas recomendadas son la terapia cognitiva conductual y la hipnosis. Se debe individualizar en cada caso la mejor opción terapéutica, teniendo en cuenta los antecedentes, interacciones medicamentosas, estado cognitivo, entre otros, ya que el objetivo final es mejorar la calidad de vida de nuestras pacientes.

Vasomotor symptoms affect a large number of women in the peri and post menopause with significant impact on quality of life; the duration of these symptoms is uncertain and often prolonged. Although menopausal hormone therapy is the most effective treatment for climacteric symptoms, there are some contraindications for its use. Therefore, it is mandatory to offer other treatment strategies for women with contraindication to hormonal treatment. We have a wide range of non-hormonal options available, both pharmacological and non-pharmacological. Among the latter, we include alternative or natural therapies (isoflavones and cimicifuga racemosa), lifestyle changes, and complementary therapies. Alternative therapies show controversial results regarding effectiveness on climacteric symptoms, and their mechanism of action involves estrogen receptors; they are contraindicated in patients with a personal history of hormone-dependent cancers. Lifestyle modifications have a positive impact on women's general health, beyond the climacteric symptoms. The only complementary therapies recommended are cognitive behavioral therapy and hypnosis. In each case, the best therapeutic option should be individualized, taking into account the patient's clinical history, drug interactions and cognitive status, since the ultimate goal is to improve quality of life.

Update on the management of abnormal uterine bleeding.

Abnormal uterine bleeding (AUB) is a common complaint that affects large numbers of women from puberty to menopause. It negatively affects health by causing anemia, and impacts the quality of life of women affected. AUB also has an economic impact for both women and society. Therefore, it should not be under- or overestimate and diagnosis, investigations and treatment should be proposed, taking into account the scientific data available in the current state of medical knowledge. Using the new terminology and etiologic classification of AUB is essential to communicate properly around the subject. The evaluation of the bleeding includes self-report and more objective methods. Work out should focus on diagnosing anemia and researching for causal factors. It is important to differentiate AUB caused by anatomical changes and functional causes, and the PALM-COIEN classification has been developed on that dichotomy. Investigations may include blood test, ultrasound, hysteroscopy and endometrial sampling is required in a certain number of situations. Treatment for AUB can be medical and/or surgical depending on the cause. Medical treatment is based on iron supplementation, hormonal and non-hormonal therapies. Surgical treatments include removal of a focal lesion, endometrial resection or destruction and hysterectomy. Age, desire for future pregnancy and etiology for AUB are key factors to consider before initiating a treatment. Treatment efficiency can be assessed using the same tools as pretherapeutic evaluation, and improvement of quality of life has now become the main goal for most international guidelines addressing the subject.

Vasomotor symptoms resulting from natural menopause: a systematic review and network meta-analysis of treatment effects from the National Institute for Health and Care Excellence guideline on menopause.

BACKGROUND: Vasomotor symptoms (VMSs) are the hallmarks of menopause, occurring in approximately 75% of postmenopausal women in the UK, and are severe in 25%. OBJECTIVES: To identify which treatments are most clinically effective for the relief of VMSs for women in natural menopause without hysterectomy. SEARCH STRATEGY: English publications in MEDLINE, Embase, and The Cochrane Library up to 13 January 2015 were searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) of treatments for women with a uterus for the outcomes of frequency of VMSs (up to 26 weeks), vaginal bleeding, and discontinuation. DATA COLLECTION AND ANALYSIS: Bayesian network meta-analysis (NMA) using mean ratios (MRs) and odd ratios (ORs). MAIN RESULTS: Across the three networks, 47 RCTs of 16 treatment classes (n = 8326 women) were included. When compared with placebo, transdermal estradiol and progestogen (O+P) had the highest probability of being the most effective treatment for VMS relief (69.8%; MR 0.23; 95% credible interval, 95% CrI 0.09-0.57), whereas oral O+P was ranked lower than transdermal O+P, although oral and transdermal O+P were no different for this outcome (MR 2.23; 95% CrI 0.7-7.1). Isoflavones and black cohosh were more effective than placebo, although not significantly better than O+P. Not only were selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) found to be ineffective in relieving VMSs, but they also had significantly higher odds of discontinuation than placebo. Limited data were available for bleeding, therefore no conclusions could be made. CONCLUSION: For women who have not undergone hysterectomy, transdermal O+P was the most effective treatment for VMS relief. TWEETABLE ABSTRACT: Which treatment best relieves menopause flushes? Results from the #NICE guideline network meta-analysis.