In the thicket of fears, doubts, and murky facts: some reflections on treatment modalities for endometriosis-associated pain.

Endometriosis-associated pain can be managed by either surgery or hormonal therapy. The final decision as to which treatment modality to take is based on efficacy and possible complications of different treatment modalities, risk of recurrence, and the patient's wishes and preferences. But in the thicket of fears, doubts, and murky facts, the choice may ultimately be the trade-off between irrational fears and ignorance versus scientific evidence. We elaborate some pros and cons of the two treatment modalities and highlight some notable downsides of hormonal therapy, in particular the possible yet unquantified risk of long-term hormonal therapy for malignant transformation, perhaps with the only exception of combined oral contraceptives. Thus, when discussing with patients, we advocate the approach of discussing the advantages and disadvantages of all treatment options in detail, accounting for the known pros and cons with a full understanding of the predictive irrationality of human beings. For endometriosis-associated pain, surgery is definitely not a failure of medicine but, rather, a viable option, especially given the recently surfaced undercurrent of wariness and dissatisfaction with the current hormonal drugs among patients with endometriosis. Above all, there is a pressing need to fill the knowledge gap of perioperative interventions intended to reduce the risk of recurrence and to fulfill the demand for the development of safe and efficacious non-hormonal therapeutics.

Is hormonal therapy effective in advanced endometrial cancer? A systematic review and meta-analysis.

BACKGROUND: Hormonal therapy (HT) is used commonly in the treatment of advanced endometrial cancer (EC). However, a 2010 Cochrane Review did not show a survival benefit for HT. Here, we quantify its effects and explore the influence of clinico-pathologic factors and hormone receptor (HR) status on overall response rates (ORR). METHODS: A systematic search of electronic databases identified publications of HT in advanced EC. Data from individual studies reporting ORR, median progression-free (PFS) or overall survival (OS) were weighted by individual study sample size and pooled in a meta-analysis. Outcomes of estrogen (ER) and progesterone receptor (PgR) subgroups were collected. Studies of first- and second-line HT were analyzed independently. Mixed studies were included if subgroup data based on previous HT exposure were provided. Meta-regression was performed to evaluate the influence of clinico-pathologic factors on outcomes. RESULTS: Thirty-nine studies were included, with seven providing subgroup data based on HR status. First-line HT was associated with a mean ORR of 21.6% and clinical benefit rate (CBR) of 36.7%. Median PFS and OS were 2.8 and 10.2months respectively. ORR was 20.4% in clinical trials and 25.3% in observational studies. Magnitude of ORR was lower in older age, adenosquamous histology and high grade. ORR was higher in ER+ (26.5%) and PgR+ (35.5%) disease, and lower in ER- (9.2%) or PgR- (12.1%) tumors. Second-line ORR was 18.5%. CBR was 35.8%, but was significantly associated with timing of stable disease assessments in first- and second-line. Meta-regression performed in mixed and second-line studies showed an association between previous HT and greater ORR (ß 0.561; p=0.024), suggesting potential confounding by indication (re-treatment of good responders to first-line HT). CONCLUSION: HT is associated with modest ORR in advanced EC, and is greatest in HR+ tumors. Response rates in second-line are likely dependent on response to previous HT.

Radiation-associated breast cancer and gonadal hormone exposure: a report from the Childhood Cancer Survivor Study.

BACKGROUND: The relationship between hormone exposure and breast cancer risk in women treated with chest radiotherapy for childhood cancer is uncertain. METHODS: Participants included 1108 females from the Childhood Cancer Survivor Study who were diagnosed with childhood cancer 1970-1986, treated with chest radiotherapy, and survived to ages ⩾20 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox models adjusted for chest radiation field, delivered dose, anthracycline exposure, and age at childhood cancer estimated risk. RESULTS: Among 195 women diagnosed with breast cancer, 102 tumours were oestrogen-receptor positive (ER+). Breast cancer risk increased with ⩾10 years of ovarian function after chest radiotherapy vs <10 years (HR=2.89, CI 1.56-5.53) and for radiotherapy given within 1 year of menarche vs >1 year from menarche (HR=1.80, CI 1.19-2.72). Risk decreased with decreasing age at menopause (Ptrend=0.014). Risk factors did not differ for ER+ breast cancer. Survivors with an age at menopause <20 years treated with hormone therapy had a lower breast cancer risk than premenopausal survivors (HR=0.47, CI 0.23-0.94). CONCLUSIONS: Endogenous hormones are key contributors to breast cancer observed among childhood cancer survivors. Hormone therapy given for premature ovarian insufficiency does not fully replace the function that endogenous hormones have in breast cancer development.

Effect of pubertal suppression and cross-sex hormone therapy on bone turnover markers and bone mineral apparent density (BMAD) in transgender adolescents.

Puberty is highly important for the accumulation of bone mass. Bone turnover and bone mineral density (BMD) can be affected in transgender adolescents when puberty is suppressed by gonadotropin-releasing hormone analogues (GnRHa), followed by treatment with cross-sex hormone therapy (CSHT). We aimed to investigate the effect of GnRHa and CSHT on bone turnover markers (BTMs) and bone mineral apparent density (BMAD) in transgender adolescents. Gender dysphoria was diagnosed based on diagnostic criteria according to the DSM-IV (TR). Thirty four female-to-male persons (transmen) and 22 male-to-female persons (transwomen)were included. Patients were allocated to a young (bone age of <15years in transwomen or <14 in transmen) or old group (bone age of ≥15years in transwomen or ≥14years in transmen). All were treated with GnRHa triptorelin and CSHT was added in incremental doses from the age of 16years. Transmen received testosterone esters (Sustanon, MSD) and transwomen received 17-ß estradiol. P1NP, osteocalcin, ICTP and BMD of lumbar spine (LS) and femoral neck (FN) were measured at three time points. In addition, BMAD and Z-scores were calculated. We found a decrease of P1NP and 1CTP during GnRHa treatment, indicating decreased bone turnover (young transmen 95% CI -74 to -50%, p=0.02, young transwomen 95% CI -73 to -43, p=0.008). The decrease in bone turnover upon GnRHa treatment was accompanied by an unchanged BMAD of FN and LS, whereas BMAD Z-scores of predominantly the LS decreased especially in the young transwomen. Twenty-four months after CSHT the BTMs P1NP and ICTP were even more decreased in all groups except for the old transmen. During CSHT BMAD increased and Z-scores returned towards normal, especially of the LS (young transwomen CI 95% 0.1 to 0.6, p=0.01, old transwomen 95% CI 0.3 to 0.8, p=0.04). To conclude, suppressing puberty by GnRHa leads to a decrease of BTMs in both transwomen and transmen transgender adolescents. The increase of BMAD and BMAD Z-scores predominantly in the LS as a result of treatment with CSHT is accompanied by decreasing BTM concentrations after 24months of CSHT. Therefore, the added value of evaluating BTMs seems to be limited and DXA-scans remain important in follow-up of bone health of transgender adolescents.

Effect of Gonadal Hormones on Neurotransmitters Implicated in the Pathophysiology of Obsessive-Compulsive Disorder: A Critical Review.

Obsessive-compulsive disorder (OCD) is a relatively common neuropsychiatric disorder affecting between 1.6 and 3.2% of the population. A number of studies have previously reported increased incidence of OCD, or exacerbation of preexisting symptoms in females during reproductive events. Since these periods are known to involve fluctuating levels of gonadal hormones, these steroids have been suggested to be involved in modulating the course of the disorder. However, to date, only a few studies have measured hormone levels and obsessive-compulsive (OC) symptoms concurrently; thus, direct evidence for this relationship is limited. In turn, investigations into neurotransmission in OC individuals have been more extensive, and have implicated the serotonergic, dopaminergic, and glutamatergic neurotransmitter systems in OCD pathology. There is evidence suggesting that reproductive hormones estrogens and progesterone can modulate neurotransmission in the aforementioned signaling pathways by regulating the expression of receptors and channels, as well as the synthesis and release of the neurotransmitter itself. Overall, estrogen and progesterone appear to enhance serotonin signaling, which has been associated with improved OC symptoms. The effect of the gonadal hormones in dopaminergic and glutamatergic signaling is much more variable, highlighting the need for further research in this field. The existing evidence shows that gonadal hormones can have profound impacts on neurotransmission in the brain, leading to the conclusion that the hormonal fluctuations during reproductive events are a plausible factor contributing to the change in OCD course during these times.

The Potential of Gonadal Hormone Signalling Pathways as Therapeutics for Dementia.

Dementia is an ever-expanding problem facing an ageing society. Currently, there is a sharp paucity of treatment strategies. It has long been known that sex hormones, namely 17ß-estradiol and testosterone, possess neuroprotective- and cognitive-enhancing qualities. However, certain lacunae in the knowledge underlying their molecular mechanisms have delayed their use as treatment strategies in dementia. With recent advancements in pharmacology and molecular biology, especially in the development of safer selective oestrogen receptor modulators and the recent discovery of the small-molecule brain-derived neurotrophic factor receptor agonist, 7,8-dihydroxyflavone, the exploitation of these signalling pathways for clinical use has become possible. This review aims to adumbrate the evidence and hurdles underscoring the use of sex hormones in the treatment of dementia as well as discussing some direction that is required to advance the translation of evidence into practise.

The Impact of Gonadal Hormones on the Expression of Human Neurological Disorders.

The effects of gonadal steroids on neurological well-being and disease constitute a rich and rapidly expanding area of basic and clinical neuroscience. Gonadal hormones exert potent effects on monoaminergic, cholinergic and peptidergic pathways as well as neurosteroidogenesis which, in turn, impact normal brain organization and function. A spectrum of human neurological conditions are influenced by hormonal fluctuations associated with the menstrual cycle, pregnancy, the menopause and use of oral contraceptives. An appreciation of these relationships may facilitate the development of specific hormonal and anti-hormonal therapies for neurological disorders as disparate as catamenial epilepsy and acute intermittent porphyria.

The impact of gonadal hormones on cannabinoid dependence.

Cannabis is the most widely used illicit substance in the United States. Women report greater positive subjective effects of cannabis, and greater cannabis withdrawal compared to men. Female rodents are more sensitive than males to some acute effects of Δ9-tetrahydrocannabinol (THC), and females also develop greater tolerance to THC in some assays. The purpose of this study was to determine whether gonadal hormones modulate THC dependence in rats. Adult rats were gonadectomized (GDX) or sham-GDX, and hormone was replaced in half of the GDX rats of each sex (testosterone in males; estradiol and/or progesterone in females). THC (30 mg/kg) or vehicle was administered twice daily for 6.5 days, followed on the seventh day by vehicle or rimonabant challenge and assessment for withdrawal-related behaviors. Sham-GDX females developed greater tolerance than males to THC-induced hypothermia, and GDX females given progesterone showed greater tolerance to THC-induced locomotor suppression. Rimonabant precipitated withdrawal, as evidenced by increased somatic signs (forepaw tremors, licking) and increased startle amplitude. Testosterone in GDX males decreased withdrawal-induced licking. Estradiol and progesterone in GDX females increased withdrawal-induced chewing, and progesterone increased withdrawal-induced sniffing. These results suggest that estradiol and progesterone may promote the development of dependence, whereas testosterone may protect against dependence. While the present study indicates that testosterone and estradiol produce opposite effects on THC-induced behavior, estradiol appears to play a broader role than testosterone in modulating THC's behavioral effects.

Sex hormones and oxytocin augmentation strategies in schizophrenia: A quantitative review.

INTRODUCTION: Sex differences in incidence, onset and course of schizophrenia suggest sex hormones play a protective role in the pathophysiology. Such a role is also proposed for oxytocin, another important regulator of reproduction function. Evidence on the efficacy of sex hormones and oxytocin in the treatment of schizophrenia is summarized. METHODS: Double-blind, placebo-controlled, randomized studies were included, examining augmentation with estrogens, selective estrogen receptor modulators (SERMs), testosterone, dehydroepiandrosterone (DHEA), pregnenolone, and oxytocin. Outcome measures were total symptom severity, positive and negative symptom subscores, and cognition. In meta-analyses, combined weighted effect sizes (Hedges' g) per hormone were calculated. RESULTS: Twenty-four studies were included, examining 1149 patients. Significant effects were found for estrogen action (k=10), regarding total symptoms (Hedges' g=0.63, p=0.001), positive (Hedges' g=0.42, p<0.001), and negative symptoms (Hedges' g=0.35, p=0.001). Subgroup analyses yielded significant results for estrogens in premenopausal women (k=6) for total, positive, and negative symptoms, and for the SERM raloxifene in postmenopausal women (k=3) for total and negative, but not positive symptoms. Testosterone augmentation in males (k=1) was beneficial only for negative symptoms (Hedges' g=0.82, p=0.027). No overall effects were found for DHEA (k=4), pregnenolone (k=4), and oxytocin (k=6). Results for cognition (k=12) were too diverse for meta-analyses, and inspection of these data showed no consistent benefit. CONCLUSIONS: Estrogens and SERMs could be effective augmentation strategies in the treatment of women with schizophrenia, although potential side effects, partially associated with longer duration use, should be taken into account. Future trials are needed to study long-term effects and effects on cognition.

New perspectives in the hormonal treatment of gender dysphoria in adolescence.

Hormonal treatments have been used in adolescents with gender dysphoria in the last decade. The professionals working in gender dysphoria treatment units cannot ignore this new demand. The evolution of care for such adolescents according to the last three versions of the Standards of Care (SC) of the World Professional Association for Transgender Health is described. Starting with the fifth version of the SC, hormonal treatment of adolescents has been contemplated. Recent protocols for hormonal intervention carried out by specialized clinics are analyzed. Finally, the pros and cons of hormonal treatment are debated. These hormonal interventions have major impact on the physical, social, and psychosexual development of patients and have ethical and moral implications for professionals.

Nuevas perspectivas en el tratamiento hormonal de la disforia de género en la adolescencia / New perspectives in the hormonal treatment of gender dysphoria in adolescence

En la última década se están aplicando tratamientos hormonales a adolescentes con disforia de género. Los profesionales de las unidades de tratamiento de la disforia de género no pueden hacer oídos sordos a esta nueva demanda. En este trabajo se expone cómo ha evolucionado la atención a estos adolescentes en las tres últimas versiones de los Estándares Asistenciales (EA) de la Asociación Mundial de Profesionales para la Salud Transgénero, en las que, a partir de la quinta versión de los EA, se empieza a contemplar que los adolescentes pueden ser subsidiarios de recibir tratamientos hormonales. También se analizan los recientes protocolos de intervención hormonal llevados a cabo por clínicas especializadas. Por último, se debate sobre los argumentos a favor y en contra de estos tratamientos hormonales. Estas intervenciones hormonales tienen importantes repercusiones en el desarrollo físico, social y psicosexual de los usuarios y conllevan implicaciones éticas y morales para los profesionales

Hormonal treatments have been used in adolescents with gender dysphoria in the last decade. The professionals working in gender dysphoria treatment units cannot ignore this new demand. The evolution of care for such adolescents according to the last three versions of the Standards of Care (SC) of the World Professional Association for Transgender Health is described. Starting with the fifth version of the SC, hormonal treatment of adolescents has been contemplated. Recent protocols for hormonal intervention carried out by specialized clinics are analyzed. Finally, the pros and cons of hormonal treatment are debated. These hormonal interventions have major impact on the physical, social, and psychosexual development of patients and have ethical and moral implications for professionals

Ovarian hormones and chronic pain: A comprehensive review.

Most chronic noncancer pain (CNCP) conditions are more common in women and have been reported to worsen, particularly during the peak reproductive years. This phenomenon suggests that ovarian hormones might play a role in modulating CNCP pain. To this end, we reviewed human literature aiming to assess the potential role of ovarian hormones in modulating the following CNCP conditions: musculoskeletal pain, migraine headache, temporal mandibular disorder, and pelvic pain. We found 50 relevant clinical studies, the majority of which demonstrated a correlation between hormone changes or treatments and pain intensity, threshold, or symptoms. Taken together, the findings suggest that changes in hormonal levels may well play a role in modulating the severity of CNCP conditions. However, the lack of consistency in study design, methodology, and interpretation of menstrual cycle phases impedes comparison between the studies. Thus, while the literature is highly suggestive of the role of ovarian hormones in modulating CNCP conditions, serious confounds impede a definitive understanding for most conditions except menstrual migraine and endometriosis. It may be that these inconsistencies and the resulting lack of clarity have contributed to the failure of hormonal effects being translated into medical practice for treatment of CNCP conditions.

Factores que predicen el desarrollo de metástasis óseas por cáncer de próstata: recomendaciones de seguimiento y opciones terapéuticas / Factors that predict the development of bone metastases due to prostate cancer: Recommendations for follow-up and therapeutic options

Contexto: El cáncer de próstata representa un problema de salud pública en España y en el mundo occidental. En las fases avanzadas de la enfermedad la afectación ósea es prácticamente constante, asociada a una notable morbilidad. El objetivo de este trabajo es realizar una revisión de los factores pronósticos utilizados en la práctica clínica habitual que predicen el desarrollo de metástasis óseas y analizar las opciones de seguimiento y tratamiento en estos perfiles de pacientes. Adquisición de evidencia: Realizamos una revisión de la literatura sobre los factores útiles en el contexto de terapia de intención curativa; incluimos los valores clínicos clásicos al diagnóstico (PSA, estadio clínico, Gleason de la biopsia) factores patológicos (estadio pT, márgenes, invasión de vesículas, volumen tumoral, afectación ganglionar) y la cinética de PSA en sus diferentes contextos, así como parámetros histológicos y moleculares. Síntesis de evidencia: El grado de diferenciación tumoral «Gleason» y el PSA son los factores predictivos más importantes en la predicción de metástasis óseas en pacientes con intención curativa. Factores cinéticos como TDPSA < 8 meses o PSA > 10 ng/ml en la situación de CPRC son factores predictivos de desarrollo de metástasis. El ácido zoledrónico y el denosumab han demostrado su efectividad para el tratamiento de la enfermedad ósea en estudios aleatorizados. Conclusiones: Existen factores predictivos dentro de la práctica clínica habitual que permiten reconocer el «paciente riesgo» para el desarrollo de enfermedad metastásica ósea. Los tratamientos actualmente disponibles, ácido zoledrónico o denosumab, pueden ayudarnos en el manejo de paciente con riesgo de desarrollo de metástasis o metastásico, aumentando la calidad de vida y disminuyendo los eventos esqueléticos

Context: Prostate cancer is a public health problem in Spain and in the Western world. Bone involvement, associated to significant morbidity, is practically constant in the advanced stages of the disease. This work aims to review the prognostic factors used in the usual clinical practice that predict the development of bone metastases and to analyze the follow-up and treatment option in these patient profiles. Acquiring of evidence: We performed a review of the literature on the useful factors in the context of therapy with intention to cure. We included the classical clinical values in the diagnosis (PSA, clinical stage, Gleason score on the biopsy) pathological factors (pT stage, margins, bladder invasion, tumor volume, lymph node involvement) and PSA kinetics in their different contexts and the histological and molecular parameters. Synthesis of evidence: The tumor differentiation «Gleason» score and PSA are the most important predictive factors in the prediction of bone metastases in patients with intention to cure. Kinetic factors such as PSA doubling time (TDPSA) < 8 months or PSA > 10 ng/ml in the case of castration-resistant prostate cancer (CPRC), are predictive factors for the development of metastasis. Zoledronic acid and denosumab have demonstrated their effectiveness for the treatment of bone disease in randomized studies. Conclusions: There are predictive factors within the usual clinical practice that make it possible to recognize the «patient at risk» to develop bone metastatic disease. The currently available treatments, zoledronic acid or denosumab, can help us in the management of the patient at risk of developing metastasis or metastatic patient, increasing the quality of life and decreasing skeletal events

Rare cases of disorders of sex development (DSD) in adolescents with female phenotype.

BACKGROUND: Disorders of sex development (DSD) belong to uncommon pathologies; in addition, there are especially rare forms, such are ovotesticular disorders (OT), Turner syndrome and early malignisation of intraabdominal located gonads in the cases of androgen insensitivity syndrome. OBJECTIVE: In this article we present four rare cases of DSD in female phenotype adolescents: two cases of ovotesticular DSD with 46,XX and 46,XY karyotypes; one familial case of androgen insensitivity syndrome (AIS) with early malignancy (19-year-old) of intra-abdominally-located testicle in older siblings, and a case of spontaneous menstruation in a patient with Turner syndrome and mosaic karyotype 45,X/47,XXX. Rare cases of DSD are connected with diagnostic and management difficulties and so description of each such case and collection of data in this field is very important from a scientific, as well as a practical, point of view. Determination of prognosis and adequate management of each individual patient are also essential. Study of this issue is especially sensitive in the case of adolescent patients in order to avoid physiological stress, to reduce health risks and to improve quality of life.

Guías de práctica clínica para la valoración y tratamiento de la transexualidad. Grupo de Identidad y Diferenciación Sexual de la SEEN (GIDSEEN)*(anexo 1) / Clinical Practice Guidelines for Assessment and Treatment of Transsexualism. SEEN Identity and Sexual Differentiation Groupd (GIDSEEN)

El abordaje diagnóstico-terapéutico de los pacientes transexuales solo puede desarrollarse en unidades funcionales de Identidad de Género, con la provisión de servicios de alta calidad asistencial, desarrollo de guías de práctica clínica y grupos de trabajo interdisciplinarios. El proceso terapéutico consta de 3 pilares fundamentales: evaluación diagnóstica psicológica inicial y psicoterapia, evaluación endocrinológica y terapia hormonal y cirugías de reasignación sexual. El tratamiento hormonal cruzado es un elemento importante en el proceso de transición anatómica y psicológica de los pacientes apropiadamente seleccionados. Las hormonas contribuyen a optimizar el proceso de vida real en el sexo identitario, mejoran la calidad de vida y limitan las comorbilidades psiquiátricas que muchas veces se asocian a la falta de este tratamiento. La elaboración de esta guía de práctica clínica responde a la necesidad de implantación de un protocolo de actuación coordinado para la atención sanitaria integral a las personas transexuales en el Sistema Nacional de Salud (AU)

Transsexual patients can only be diagnosed and treated at functional gender identity Units with provision of high quality care, development of clinical practice guidelines, and interdisciplinary working groups. The therapeutic process has three mainstays: initial psychological diagnostic evaluation and psychotherapy, endocrinological evaluation and hormone therapy, and sex reassignment surgery. Cross-sex hormone therapy is essential for the anatomical and psychological transition process in duly selected patients. Hormones help optimize real-life sex identity, improve quality of life, and limit psychiatric co-morbidities often associated to lack of treatment. Development of this clinical practice guideline addresses the need for implementing a coordinated action protocol for comprehensive health care for transgender people in the National Health System (AU)

Efecto de las hormonas sexuales sobre las concentraciones de homocisteína en preeclámpticas y embarazadas normales / Effect of sexual hormones on homocysteine concentrations in preeclamptic and normotensive pregnant women

Objetivo. Establecer los efectos de las hormonas sexuales sobre las concentraciones plasmáticas de homocisteína en preeclámpticas y embarazadas normales. Métodos. Los grupos consistieron en 35 preeclámpticas (grupo A) y 35 embarazadas normotensas (grupo B), consideradas como controles. Las muestras de sangre se recolectaron en todas las pacientes antes del parto y en el grupo de estudio (grupo A) inmediatamente después del diagnóstico. Se midieron las concentraciones de testosterona, testosterona libre, sulfato de dehidroepiandrosterona, androstenodiona, estradiol y homocisteína. Resultados. Se observaron diferencias estadísticamente significativas en la edad gestacional, presencia de proteinuria, peso de los recién nacidos y de la presión arterial sistólica y diastólica (p<0,05). Las concentraciones de testosterona, testosterona libre, sulfato de dehidroepiandrosterona y homocisteína fueron significativamente superiores en el grupo A comparado con los controles (p<0,05). Las concentraciones de estradiol se encontraron disminuidas en el grupo A comparado con los controles (p<0,05). Se encontraron correlaciones positivas fuertes de testosterona, sulfato de dehidroepiandrosterona y testosterona libre y una correlación moderada negativa con las concentraciones de estradiol con las concentraciones plasmáticas de homocisteína (p<0,05). Conclusiones. Las concentraciones plasmáticas de homocisteína son afectadas en forma positiva por testosterona, sulfato de dehidroepiandrosterona y testosterona libre y negativa por el estradiol en pacientes preeclámpticas y embarazadas normotensas (AU)

Objective. To establish the effects of sexual hormones on plasma homocysteine concentrations in preeclamptic and normotensive pregnant women. Methods. There were two groups: group A consisted of 35 preeclamptic patients and group B of 35 normotensive pregnant women used as controls. Blood samples were collected before labor in both grops and immediately after diagnosis in group A. Concentrations of testosterone, free testosterone, dehidroepiandrosterone sulphate, androstenodione, estradiol and homocysteine were measured. Results. There were statistically significant differences in gestational age, the presence of proteinuria, birthweight and systolic and diastolic blood pressure (p<0.05). Testosterone, free testosterone and dehidroepiandrosterone sulphate were significantly higher in group A than in group B (P<.05). Estradiol concentrations were significant lower in the group A than in group B (P<.05). Strong positive and significant correlations were found between testosterone, dehidroepiandrosterone sulphate and free testosterone and a moderate negative correlation was found between estradiol and plasma homocysteine concentrations (P<.05). Conclusions. In preeclamptic and normotensive pregnant women, plasma homocysteine concentrations are positively affected by testosterone, dehidroepiandrosterone sulphate and free testosterone and are negatively affected by estradiol (AU)

Effects of progesterone and testosterone on ICH-induced brain injury in rats.

Studies have shown that progesterone reduces brain injury, whereas testosterone increases lesion size after ischemic stroke. This study examined the effects of progesterone and testosterone on intracerebral hemorrhage (ICH)-induced brain injury. Male Sprague-Dawley rats received an injection of 100 µL autologous whole blood into the right basal ganglia. Progesterone (16 mg/kg), testosterone (15 mg/kg) or vehicle was given intraperitoneally 2 h after ICH. Behavioral tests were performed, and the rats were killed after 24 h for brain edema measurement. Perihematomal brain edema was reduced in progesterone-treated rats compared to vehicle-treated rats (p<0.05). Progesterone also improved functional outcome following ICH (p<0.05). Testosterone treatment did not affect perihematomal edema formation, but resulted in lower forelimb placing score (p<0.05). In conclusion, progesterone can reduce brain edema and improve functional outcome, whereas testosterone may have a deleterious effect after ICH in male rats.

Tratamiento combinado con radioterapia externa y hormonoterapia en los pacientes con cáncer de próstata localmente avanzado: factores predictivos de toxicidad genitourinaria / Combined External Radiotherapy and Hormone Therapy in Patients with Locally Advanced Prostate Cancer: Predictive Factors of Genitourinary Toxicity

Introducción: una opción de tratamiento del cáncer de próstata localmente avanzado es la radioterapia combinada con la ablación androgénica. Revisamos los resultados de eficacia y toxicidad del tratamiento combinado en un grupo de pacientes tratados con esta terapia combinada en nuestra institución. Material y método: estudio retrospectivo de 80 pacientes con cáncer prostático localmente avanzado tratados con radioterapia externa y hormonoterapia neoadyuvante (dos meses) y adyuvante (24 meses). Se realiza un estudio descriptivo de las variables clínico-patológicas y de los efectos secundarios. Evaluamos la respuesta al tratamiento mediante el PSA nadir y recidiva bioquímica. Analizamos la toxicidad aguda y crónica genitourinaria, intentando establecer qué factores influyen en su aparición mediante análisis uni y multivariante (regresión logística múltiple). Resultados: la media de edad fue 68 ± 5,81 años, el PSA inicial 20,05 ±1 6,27 ng/ ml y el volumen prostático medio 43,7 ± 27,57 cc. El 33% fueron estadio T3a y el 66% T3b. El Gleason fue < 7 en el 39%, 7 en el 46% y ≥ 8 en el 15%. Tras un seguimiento medio de 44,4 meses se detectó recidiva bioquímica en tres casos. La toxicidad aguda postirradiación genitourinaria apareció en el 90% (35% tardía) y gastrointestinal en el 75% (32% tardía). El análisis univariante muestra relación entre el volumen prostático y los síntomas urinarios previos con la toxicidad genitourinaria aguda y crónica. Estos se confirman como factores predictivos independientes de toxicidad geniturinaria en el análisis de regresión logística. Conclusiones: la hormono-radioterapia es una opción válida para el tratamiento del cáncer localmente avanzado con resultados óptimos a corto plazo, aunque no está exenta de efectos secundarios. La sintomatología urinaria previa y el volumen prostático pueden predecir la toxicidad genitourinaria (AU)

Introduction: Radiotherapy and androgen deprivation are an established treatment option for locally advanced prostate cancer. We evaluate outcomes in efficacy and toxicity for patients treated with this combined therapy at our institution. Methods: A retrospective study of 80 patients with locally advanced prostate cancer treated with radiotherapy combined with neo-adjuvant (2 months) and adjuvant (24 months) androgen deprivation. We studied the clinical variables and side effects. We evaluated treatment outcomes using PSA nadir and biochemical failure, and recorded acute and late gastrointestinal and urinary toxicity. We assessed the correlation between clinical variables and urinary toxicity by means of univariate and multivariate analyses (multiple logistic regression). Results: The mean patient age was 68 ± 5.81 years; the initial PSA was 20.05 ± 16.27 ng/ ml and the mean prostate volume 43.7 ± 27.57 cc. The clinical stage was T3a in 33% and T3b in 66%. The Gleason score was <7 in 39%, 7 in 46% and ≥8 in 15%. The mean follow-up was 44.4 months and biochemical failure was observed in 3 cases. Acute urinary toxicity was recorded in 90% of the patients (chronic in 35%) and acute gastrointestinal toxicity in 75% (late in 32%). In a univariate analysis, prostate volume and urinary symptoms were statistically correlated to acute and late urinary toxicity. Both prostate volume and urinary symptoms were independently associated with an increase in urinary toxicity in the logistic regression analysis. Conclusions: Hormone-radiotherapy is a valid option to locally treat advanced prostate cancer with optimal short-term outcomes, although it is not devoid of side effects. Prostate volume and urinary symptoms before treatment can predict genitourinary toxicity (AU)