Efectos del tratamiento con andrógenos sobre la neurocognición en adolescentes transgénero de mujer a hombre / Androgen treatment effects on neurocognition in female-to-male transgender adolescents

Introducción Se ha planteado la hipótesis de que la neurocognición en personas transgénero durante el tratamiento hormonal cruzado podría aproximarse a la del género subjetivo. Sin embargo, la investigación sobre este tema ha producido resultados inconsistentes y, hasta donde sabemos, ningún estudio ha investigado los cambios neurocognitivos en adolescentes transgénero de mujer a hombre (FM) tratados con andrógenos. Sujetos y métodos Quince adolescentes transgénero FM (14-17 años) se sometieron a pruebas neuropsicológicas para examinar los efectos de los andrógenos en sus habilidades visuoespaciales, memoria verbal, velocidad de procesamiento y funciones ejecutivas. Utilizamos un diseño longitudinal en el que se evaluó a 10 participantes dos veces, antes y después de recibir, durante 12 meses, tratamiento con testosterona. Este grupo también se comparó con cinco adolescentes transgénero FM sin tratamiento con andrógenos. Resultados Los participantes evaluados antes y después de 12 meses de tratamiento con andrógenos mejoraron significativamente en velocidad de procesamiento en una tarea visuoespacial (prueba de la figura compleja de Rey-Osterrieth) y en una tarea visual (Stroop), en una tarea de memoria verbal (test de aprendizaje verbal España-Complutense) y en interferencia (Stroop), y exhibieron un menor control de la impulsividad (test de percepción de diferencias revisado). Los adolescentes que recibieron tratamiento con andrógenos mostraron un peor control de la impulsividad cognitiva que los adolescentes que no recibieron tratamiento con andrógenos. Conclusiones Los resultados indican que los andrógenos influyen en la memoria verbal, la interferencia cognitiva, el control de la impulsividad y la velocidad de procesamiento. (AU)

INTRODUCTION It has been hypothesized that cognitive and memory-related brain function in transgender during cross-sex hormonal treatment might be activated towards that of the subjective gender. However, research on this topic has produced inconsistent results, and to the best of our knowledge no studies have investigated neurocognitive changes in androgen-treated female-to-male (FM) transgender adolescents. SUBJECTS AND METHODS A total of 15 FM transgender adolescents (14-17 years) underwent neuropsychological testing in order to examine the effects of androgen on visuo-spacial abilities, verbal memory language, processing speed and executive functions. We used a longitudinal design in which 10 participants were tested twice, before and after receiving 12 months of testosterone treatment. This group was also compared with 5 FM transgender adolescents off-androgen treatment. RESULTS Participants tested before and after 12 months of androgen treatment improved significantly on processing speed in a visuo-spatial (Rey-Osterrieth complex figure test) and in a visuo-oral task (Stroop), their performance on a verbal memory task (TAVEC) and on interference (Stroop) and they exhibited lower impulsivity control (CARAS-R). On-androgen treatment adolescents exhibited worse cognitive impulsivity control than off-androgen treatment adolescents. CONCLUSIONS The results indicate that androgen has an influence on immediate verbal memory, cognitive interference, impulsivity control and processing speed. (AU)

Ovarian, breast, and metabolic changes induced by androgen treatment in transgender men.

Gender-affirming hormone therapy (GAHT) is often provided to transgender people. In this review of the literature, the current knowledge of ovarian, breast, and metabolic changes (body composition, insulin resistance, bone density, cardiovascular risk factors such as lipids, blood pressure, and hematocrit) observed following GAHT in adult transgender men is discussed. A body of literature concurs to describe that long-term androgen therapy in transgender men exerts atrophic effects on the breast. There is currently no evidence of an increased risk of breast cancer. Long-term testosterone treatment induces ovarian effects that become visible after 6 months of therapy. These changes consist of both macroscopic and microscopic alterations of ovarian morphology that mimic the typical ovarian aspect encountered in women with polycystic ovary syndrome but without an effect on antral follicle count. Metabolic effects of long-term androgen treatment in transgender men put them at par with cisgender men in terms of lipid profile, insulin resistance, and overall mortality. Body composition changes as desired after testosterone administration in most transgender men, and insulin resistance decreases with virilization. There are no detrimental effects on bone mineral density. Cardiometabolic risk and morbidity data are currently reassuring, even if certain studies show conflicting results. An increase in blood pressure and a decrease in high-density lipoprotein cholesterol have been reported as risk factors, whereas polycythemia is rare and treatable. Most available data are observational and based on biochemical markers instead of the more direct measures of cardiovascular damage. An explanation for these observed changes is mostly lacking. Psychological stress and lifestyle factors are often forgotten in a much needed integrated approach.

A Selective Androgen Receptor Modulator (OPK-88004) in Prostate Cancer Survivors: A Randomized Trial.

BACKGROUND: Androgen deficiency is common among prostate cancer survivors, but many guidelines consider history of prostate cancer a contraindication for testosterone replacement. We determined the safety and efficacy of a selective androgen receptor modulator (OPK-88004) in symptomatic, testosterone-deficient men who had undergone radical prostatectomy for low-grade, organ-confined prostate cancer. METHODS: In this placebo-controlled, randomized, double-blind trial, 114 men, ≥19 years of age, who had undergone radical prostatectomy for low-grade, organ-localized prostate cancer, undetectable PSA (<0.1 ng/mL) for ≥2 years after radical prostatectomy and testosterone deficiency were randomized in stages to placebo or 1, 5, or 15 mg OPK-88004 daily for 12 weeks. Outcomes included PSA recurrence, sexual activity, sexual desire, erectile function, body composition, muscle strength and physical function measures, mood, fatigue, and bone markers. RESULTS: Participants were on average 67.5 years of age and had severe sexual dysfunction (mean erectile function and sexual desire domain scores 7.3 and 14.6, respectively). No participant experienced PSA recurrence or erythrocytosis. OPK-88004 was associated with a dose-related increase in whole-body (P < 0.001) and appendicular (P < 0.001) lean mass and a significantly greater decrease in percent body fat (P < 0.001) and serum alkaline phosphatase (P < 0.001) than placebo. Changes in sexual activity, sexual desire, erectile function, mood, fatigue, physical performance, and bone markers did not differ among groups (P = 0.73). CONCLUSIONS: Administration of OPK-88004 was safe and not associated with PSA recurrence in androgen-deficient men who had undergone radical prostatectomy for organ-confined prostate cancer. OPK-88004 increased lean body mass and decreased fat mass but did not improve sexual symptoms or physical performance.

STAMP2 Expression Mediated by Cytokines Attenuates Their Growth-Limiting Effects in Prostate Cancer Cells.

Inflammatory events and dysregulated cytokine expression are implicated in prostate cancer (PCa), but the underlying molecular mechanisms are poorly understood at present. We have previously identified six transmembrane protein of the prostate 2 (STAMP2, also known as STEAP4) as an androgen-regulated gene, as well as a key regulator of PCa growth and survival. STAMP2 is also regulated by, and participates in, inflammatory signaling in other tissues and pathologies. Here, we show that the proinflammatory cytokines interleukin 6 (IL-6) and Interleukin 1 beta (IL-1ß) significantly increase and strongly synergize in promoting STAMP2 expression in PCa cells. The two cytokines increase androgen-induced STAMP2 expression, but not expression of other known androgen target genes, suggesting a unique interplay of androgens and cytokines in regulating STAMP2 expression. Interestingly, STAMP2 knockdown significantly increased the ability of IL-6 and IL-1ß to inhibit PCa cell growth in vitro. These results suggest that STAMP2 may represent a unique node through which inflammatory events mediate their effects on PCa growth and survival.

A pharmacogenetic approach to improve low ovarian response: The role of CAG repeats length in the androgen receptor gene.

The AR (androgen receptor) polymorphism is associated with POR risk. Furthermore, the use of androgens in POR remains controversial. Our data could clarify the effectiveness of androgen pretreatment. AR genotyping could help us to identify patients at risk for POR and POR patients that will be benefited of androgen pretreatment. OBJECTIVE: The aim of this project was to investigate if the AR (androgen receptor) polymorphism could be used to identify patients at risk for POR and that will benefit from androgens pretreatment. STUDY DESIGN: To evaluate the POR risk we performed a cohort study including 231 patients (54 POR and 177 control). Moreover, we included 88 IVF-cycles performed by 44 POR-patients to assess the effect on ovarian response. All patients performed two cycles: a standard ovarian stimulation and a second one with androgen preparation. We compare the results in pair from each. RESULTS: POR showed the highest frequency of CAG repeats at 24 vs 22 in controls. Only 33% of POR have alleles with a repeat number below 23, compared with 50% of controls (p < 0.05). According to AR polymorphism ovarian response differences were shown. Patients that carried CAG repeats in AR gene between 22 and 24 showed an increased in the number of oocytes (2.61 in cycles without androgens vs 5.11 when they were pretreated with androgens; p < 0.05). For the patients that carried repeats lower than 22 and higher than 24, no differences were reported in the number of oocytes obtained in the cycle with or without androgens (2.94 vs 2.56; p = 0.88). Similar results were obtained for mature oocytes in patients that carry a number of CAG repeats between 22 and 24 (1.86 MII in cycles without androgens vs 4.04 MII when they were pretreated with androgens; p < 0.05). No differences in the number of MII oocytes were found in patients that get out of 22 and 24 repeats between the two cycles (2.31 vs 2.13; p = 0.88). CONCLUSION: The AR polymorphism is associated with POR risk, patients with repeats greater than 22 show a higher risk. Our data suggest that AR genotype could play a role in natural ovarian aging. Furthermore, the use of androgens in POR remains controversial. Our data suggest that the AR genotype could clarify the effectiveness of the androgen pretreatment. AR genotyping could help us to identify patients at risk of POR and POR patients that could benefit from transdermal testosterone pretreatment.

Hormone dependent metastatic salivary gland carcinoma: a case report.

Adenocarcinoma of the salivary gland is a histology subtype of salivary gland carcinoma (SGC). Salivary gland carcinomas are rare tumors accounting for less than 5% of all cancers of the head and neck. Consequently, clinical data for systemic treatment including targeted treatment in metastatic SGC is limited and supported mainly by sporadic cases, retrospective reports, and early phase trials with a limited number of patients. We present a case of a patient who suffered from metastatic SGC, in whom novel molecular testing that uses immunohistochemical analysis and DNA microarray implied that the tumor would respond to anti-androgen treatment. The patient was given bicalutamide and achieved complete objective response.