Tumor ovárico de células esteroideas sin otra especificación, durante el embarazo

Los tumores de células esteroides de ovario se clasifican en luteoma estromal, tumor de células de Leydig y tumor de células esteroideas sin otra especificación, según su origen embrionario. El tumor ovárico de células esteroideas sin otra especificación es un tumor benigno raro, pero con potencial maligno; representa menos del 0,1% de todos los tumores de ovario. Deben ser considerados como causa de virilización en mujeres adultas por la producción de testosterona. Solo un feto femenino corre riesgo de virilización. Al igual que otros tumores del estroma ovárico, los tumores deben ser tratados quirúrgicamente. La cirugía está indicada en casos de agrandamiento ovárico unilateral sólido, debido a un 50% de probabilidad de malignidad. En el embarazo, los tumores ováricos de células esteroideas sin otra especificación son excepcionalmente raros y deben ser diferenciados del luteoma del embarazo y otras neoplasias malignas del ovario. Con mayor frecuencia pueden complicarse con rotura y/o torsión. Se presenta un caso de tumor ovárico de células esteroideas sin otra especificación durante el embarazo.

Ovarian steroid cell tumors are classified into stromal luteoma, Leydig cell tumor and steroid cell tumor not otherwise specified, according to their embryonal origin. Ovarian steroid cell tumor not otherwise specified is a rare benign tumor, but with malignant potential; it accounts for less than 0.1% of all ovarian tumors. They should be considered as a cause of virilization in adult women due to testosterone production. Only a female fetus is at risk of virilization. Like other ovarian stromal tumors, the tumors must be treated surgically. Surgery is indicated in cases of solid unilateral ovarian enlargement, due to a 50% chance of malignancy. In pregnancy, ovarian steroid cell tumors not otherwise specified are exceptionally rare and should be differentiated from luteoma of pregnancy and other malignant ovarian neoplasms. More frequently they may be complicated by rupture and/or torsion. A case of nonspecific ovarian steroid cell tumor during pregnancy is presented.

Rendimiento cognitivo en mujeres con síndrome de ovario poliquístico: un estudio piloto / Cognitive Performance in Women with Polycystic Ovarian Syndrome: A Pilot Study

Resumen El Síndrome de ovario poliquístico (SOP) es la enfermedad endocrina-metabólica más frecuente en las mujeres en edad reproductiva. A pesar de su alta prevalencia, hay pocas investigaciones que analizan los efectos de los cambios hormonales sobre la cognición de pacientes con SOP. Objetivo: comparar el rendimiento en habilidades cognitivas y los niveles de hormonas sexuales de un grupo de pacientes con SOP y con las de un grupo control. Método: Participaron 20 mujeres mayores de 21 años, sin tratamiento hormonal, dividas en dos grupos, el primero compuesto por 10 pacientes diagnosticadas con SOP según los criterios de Rotterdam (GSOP) y el otro, de control, compuesto por 10 mujeres sin diagnóstico de SOP (GCT). Se aplicaron las pruebas WAIS III y fluidez verbal semántica y fonológica de la batería NEUROPSI Atención y memoria, y se realizaron análisis sanguíneos de hormonas sexuales. Resultados: Las pacientes del GSOP obtuvieron puntajes inferiores a las del GCT en el CI Verbal (p=0.009), CI Total (p=0.029), índice de comprensión verbal (p=0.005), índice de memoria de trabajo (p=0.023) y en la prueba de fluidez verbal semántica (p=0.029). No se encontraron diferencias significativas en los niveles hormonales. Conclusión: el GSOP presentó menor rendimiento que el GCT en pruebas de tipo verbal, aunque no se presentó déficit en su ejecución. Se sugiere estudiar la relación de la insulinorresistencia con la cognición en pacientes con SOP.

Abstract Polycystic ovarian syndrome (PCOS) is the most common endocrine-metabolic disease in women of reproductive age. Despite its high prevalence, little research analyzes the effects of hormonal changes on cognition in patients with PCOS. Objective: To compare the performance in cognitive abilities and sexual hormone levels of a group of patients with PCOS and those of a control group. Method: Twenty women older than 21 years, without hormone treatment, divided in two groups, the first consisting by 10 patients diagnosed with PCOS according to the Rotterdam criteria (GSOP), and the other composed of 10 women without diagnosis of PCOS (GCT). WAIS III and semantic and phonological verbal fluency tests of the NEUROPSI attention and memory test battery were applied, and blood analyzes of sexual hormones were analyzed. Results: The GSOP patients obtained lower scores than the GCT in Verbal IQ (p=0.009), full scale IQ (p=0.029), verbal comprehension index (p=0.005), working memory index (p=0.023) and semantic verbal fluency test (p=0.029). No significant differences were found in sexual hormone levels. Conclusion: the GSOP showed lower performance than the GCT in verbal tests, although there was not deficit in its execution. It is suggested to study the relationship of insulin resistance with cognition in patients with GSOP.

Consideraciones clínicas y endocrinológicas en mujeres con trastorno bipolar / Clinical and endocrine considerations in bipolar women

El trastorno bipolar es una de las enfermedades mentales más discapacitantes. Existen diferencias en cuanto al tipo de episodios más frecuentes, la polaridad predominante y la frecuencia de comorbilidad según el sexo. En la mujer es importante considerar la etapa de vida reproductiva en que se encuentra, pues se sabe que puede influir en el curso de la enfermedad. Se ha informado una elevada comorbilidad del trastorno bipolar con trastorno disfórico premenstrual y una exacerbación de los síntomas en el período premenstrual en el 44% al 65%, que puede conducir a un peor curso de la enfermedad. El embarazo no parece incrementar la presencia de episodios de la enfermedad; sin embargo, el tratamiento se complica de forma importante, mientras que la suspensión de la medicación puede llevar a recaídas, el mantenerlo puede llevar a resultados obstétricos negativos, malformaciones congénitas e incluso alteraciones del neurodesarrollo. De tal manera que la evaluación de riesgo-beneficio en estas pacientes tiene que ser muy cautelosa. En el posparto, claramente se relaciona con un incremento en el riesgo de presentar algún episodio afectivo. Al llegar a la transición a la menopausia parecieran incrementarse los episodios de tipo depresivo. La relación entre el ciclo reproductivo y la presencia de episodios de enfermedad, así como los estudios en otras entidades psiquiátricas, han llevado a considerar que una relación entre las hormonas gonadales y los neurotransmisores podrían subyacer a esta entidad. En el presente artículo describimos algunas de las observaciones relacionadas con estrógenos, progesterona y sus metabolitos, testosterona y deshidroepiandrosterona

Bipolar disorder is one of the most disabling psychiatric illnesses. Some characteristics of the disorder vary with sex, such as predominant polarity, frequency and type of comorbidity, and type of episodes presented. In the case of bipolar women, it is important to consider reproductive events, due to their influence in the course of the disorder. High comorbidity of bipolar disorder and premenstrual dysphoric disorder with an exacerbation of symptoms in the premenstrual period has been reported in 44% to 65% which may lead to a worse disease course. In general, women with premenstrual symptom exacerbation show more affective - particularly depressive - episodes, more frequent relapses, and more severe symptomatology. Pregnancy does not appear to increase presence of bipolar episodes, but significantly complicates treatment. On the one hand, stopping the treatment, particularly abruptly, increases the risk of relapse; while on the other, the use of mood stabilizers represents a risk for the newborn. Poor neonatal outcomes, congenital malformations and neurodevelopment alterations in children of mothers exposed to mood stabilizers during pregnancy have been reported. So, a meticulous benefit-risk assessment should be carried out in pregnant bipolar women. In the postpartum period, a clearer relation with increased risk of affective episode has been observed; while the perimenopause increases depressive episodes. The inter-relation between reproductive cycle and bipolar episodes suggests that gonadal hormones are involved in their physio-pathology. Here we discuss some of the observations related to testosterone, dehydroepiandrosterone, estrogens, and progesterone

Perimenopausia y trastornos afectivos: aspectos básicos y clínicos / Perimenopause and affective disorders: basic and clinical topics

Depression is an affective disorder that is more frequent in women than men. The etiology of depression disorders is multi-factorial, since social and biological influences have been determined. Coincidence between periods with hormonal fluctuations and affective alterations has lead to a hypothesis that considers fluctuations in gonadal hormones as a possible cause of depression in women. In this respect, pre-clinical studies by using laboratory animals (rodents) point toward a stronger relationship between hormonal oscillations and depressive behavior in different models designed to evaluate the antidepressant effect of drugs. This evidence could be interesting since in pre-clinical studies social factors are not included. Specifically, several authors have reported that depressive behavior is more prevalent in stages of rats' life characterized by low concentrations of gonadal hormones, such as postpartum, diestrous phase, lactancy and after ovariectomy. In contrast, a major presence of depressive behavior is observed in phases with higher concentration of hormones, like proestrus (a phase coincident with ovulation), pregnancy and after hormonal restitution with estrogens and progestins. Interestingly, the development of depressive behavior after ovari-ectomy has been established in female mice, with a critical period 12 weeks after ovaries extirpation. The participation of specific hormones in female depression could be studied in lab animals, since rodent female progress from a reproductive to a non-reproductive phase with vaginal and endocrine changes. Young females have a 4-5 days cycle named estrous cycle, in which each vaginal phase is associated with different concentrations of gonadal hormones. Although rodents do not exhibit menses, a state similar to peri- and post-menopause could be identified. Aging females exhibit irregular cycles before progressing to an estrous constant phase with elevated levels of estrogens. Decline of estrogen levels produces a persistent diestrous phase considered as a post-menopausal state. Aging rats in persistent diestrous, as well as ovari-ectomized females (the most economic model of post-menopause in lab animals) show physiological and behavioral changes associated to hormonal deprivation. Thus, they are considered a good model to evaluate affective and cognitive alterations as well as potential hormonal substitutive treatments. Clinical and epidemiologic studies report that perimenopause is linked to an increased risk of developing depression in women, or with the presence of more intense symptoms of depression. In agreement with Stages of Reproductive Aging Workshop (STRAW), perimenopause includes the period named transition to menopause plus one year after the last menses. This period is characterized by irregular menstrual cycles and fluctuations in levels of estrogens. In this stage, the levels of follicle-stimulating hormone (FSH) are elevated in order to further stimulate the production of estrogens from ovaries. Finally, concentrations of estrogens are significantly reduced in late perimenopause, although the levels of FSH continue to be increased. Fluctuations of estrogens and FSH have been related to symptoms such as affective alterations, hot flushes and insomnia, while hormonal deprivation in post-menopause is linked to changes in body fat, fatigue, cognitive disorders and reduction in bone density. Variations in estrogens and FSH level have been consistently related to depression symptoms in perimenopausal women, while changes in progestins and testosterone are associated with dysphoric mood and aggression, respectively. Thus, in agreement with the main hormonal hypothesis, a substitutive therapy with estrogens as an antidepressant therapy in peri- and post-menopausal women has been implemented. The results of different clinical studies are contradictory possibly due to methodological differences as the type of hormone used as an antidepressant therapy, dosage, time of administration of treatments and the period of hormonal deprivation in women. In a consistent manner, basic studies support the idea that steroi-dal gonadal hormones have antidepressant properties, but these seem to depend on both specific features of hormonal treatments and endocrine conditions in females. It has been reported that 17β-estradiol (E2), ethinyl-estradiol (EE2) and estradiol benzoate produce antidepres-sant-like actions in ovariectomized young females. Pharmacological studies have demonstrated that the serotonergic system has a major participation in the antidepressant-like effect of E2, revealing its potential as a treatment for depressed women. In the same sense, estrogens that bind to estrogen receptors β (ERβ) are more effective to produce antidepressant- and anxiolytic-like effects than estrogens with higher affinity at ERa This evidence leads to consider ERβ as an important pharmacological target in depression. Studies evaluating estrogens in depression have determined that dosage is an important issue in the production of antidepressant-like effects. Dosage of estrogens that attain a physiological range have been reported to have more antidepressant efficacy in respect to lower or higher dose provoking infra- or supra-physiological levels of estradiol. In fact, a U-shape in the antidepressant effect of E2 has been detected. Finally, timing of hormonal therapy seems to be a more relevant factor at moment to attain an antidepressant effect with estrogen treatment. Old rats (14 months) that received a prolonged estrogen treatment immediately after ovariectomy showed an antidepressant-like response which was not observed when treatment was began five months after ovaries extirpation. ERs are dependent on endogenous estrogens levels which suggest that a reduction in the target site of E2 may be linked to its reduced antidepressant-like effect in females with a long-term hormonal deprivation. An apparently successful strategy to reduce depression in women has been to adjunct a hormonal treatment with antidepressant drugs in order to enhance antidepressant efficacy. Studies with a reduced number of patients have determined that combined therapy is able to reduce the scores in the Hamilton Depression Scale, and to allow the effect of antidepressant drugs in women with refractory depression. At this respect, basic studies have established that estrogens facilitate the antidepressant effects of several antidepressant drugs. It was reported that the anxiolytic effect of desipramine was more evident in the proestrus, a phase characterized by high levels of estrogens and progesterone in young females. Both estrogens and progesterone participate in the anxiolytic effect of desipramine, although the synergism with estradiol was more significant. By using specific animal models of antidepressant effects, it was found that E2 facilitated the antidepressant effect of fluoxetine, desipramine, venlafaxine and bupropion in young, ovariectomized female rodents. In contrast, a chronic study using old, ovariectomized female rats showed that estradiol valerate was unable to improve the antidepressant effect of citalopram, even though the antidepressant efficacy of both estrogen and citalopram was established previously. Differences in results could be due to variations in methodological aspects such as age of rats (young, three months, versus old, 15 month), type of estrogen used in each study (E2 versus estradiol valerate), animal model of depression (forced swimming test, acute model, versus chronic mild stress model), type of antidepressant used (citalopram in the last case), and dosage for both estrogens and antidepressant drugs. Interestingly, the strategy of a combined treatment could be a therapeutic advantage for those women that suffer depression associated to endocrine changes. Evidence from clinical and basic studies should be taken into account at moment to select the most advantageous therapy to treat depression in mature women.

La depresión es un trastorno afectivo de origen multifactorial que se presenta con mayor frecuencia en la mujer que en el hombre. Las causas de esta diferencia se atribuyen tanto a factores sociales como biológicos. La coincidencia entre los periodos de fluctuaciones hormonales y la presencia de síntomas afectivos ha dado fuerza a la teoría de que los factores hormonales pueden ser una causa de la mayor prevalencia de depresión en la mujer. Los estudios básicos en los cuales no se presentan factores sociales sugieren que la depresión en la mujer podría tener un origen biológico. Uno de los periodos de mayor riesgo en la mujer es la perimenopausia. De acuerdo con el Grupo de Trabajo de los Estadios de la Edad Reproductiva (STRAW), la perimenopausia comprende el periodo denominado transición a la menopausia más un año después de la última menstruación. Este periodo se caracteriza por ciclos menstruales de duración variable y fluctuaciones en la concentración de estrógenos y progesterona. Conforme los ciclos se hacen impredecibles, ocurre una disminución de estrógenos, que genera alteraciones fisiológicas y afectivas. Diversos estudios epidemiológicos han logrado relacionar la perimenopausia con cambios en el estado afectivo de la mujer. Tomando en cuenta la hipótesis de que la privación de estrógenos se relaciona con los síntomas depresivos en la mujer, los tratamientos con estrógenos han sido considerados como una de las opciones terapéuticas. Los hallazgos clínicos son controvertidos, y la posible explicación son las diferencias en la metodología empleada en cada estudio, así como la falta de consistencia en la definición de perimenopausia y en los instrumentos de medición hormonal y del estado emocional de la mujer. De manera interesante, los estudios básicos apoyan la idea de que los estrógenos producen efectos antidepresivos importantes. Sin embargo, existen diferencias en la respuesta antidepresiva que dependen tanto del tipo de estrógeno como del estado hormonal de la hembra. Hasta el momento, los hallazgos más consistentes refieren al 17β-estradiol como la hormona más relevante para producir acciones antidepresivas en la hembra. El mismo estrógeno es efectivo en ratas viejas, con un periodo de privación hormonal moderado; sin embargo, deja de ser efectivo en la depresión experimental cuando ese periodo se extiende por varios meses. Otra alternativa terapéutica para tratar la depresión en la perimenopausia y posmenopausia es la terapia combinada de agentes hormonales y fármacos antidepresivos. En dos estudios con un reducido número de pacientes se determinó que la adición de estrógenos favorece el efecto de los fármacos antidepresivos en mujeres con depresión refractaria a dichos tratamientos. La investigación básica aporta resultados consistentes al respecto, ya que, por un lado, se ha determinado que diferentes estrógenos inducen un efecto tipo antidepresivo en ratas ovariectomizadas, y por otro, que la administración de dosis subefectivas de dichos estrógenos facilita el efecto antidepresivo, o incluso acorta la latencia de aparición del efecto antidepresivo de fármacos como la fluoxetina, la desipramina y la venlafaxina. Los resultados sugieren que los estrógenos pueden interactuar con diferentes sistemas de neurotransmisión para mejorar las acciones de los fármacos antidepresivos. Más aún, ha sido demostrado que el sistema serotonérgico participa en buena medida en las acciones antidepresivas de algunos estrógenos, lo cual aporta más evidencia sobre las fallas en la neurotransmisión serotonérgica en etapas de privación hormonal. La evidencia de los estudios básicos y clínicos apoya la idea de que la mujer tiene periodos de vulnerabilidad afectiva que se relacionan con cambios endocrinos importantes. Los tratamientos para la depresión en la mujer deben ser elegidos con base en las condiciones endocrinas de la paciente, así como en las características propias de los tratamientos.