Etiopatogenia de la amenorrea hipotalámica funcional: Interacción de las respuestas hormonales del sistema nervioso central y neuropéptidos periféricos / Ethiopatogeniae of functional hypothalamic amenorrhea: Interactions of central nervous system and peripherical neuropeptides responses

La amenorrea hipotalámica funcional (AHF) es una patología compleja provocada generalmente por el estrés psicológico, o por alteraciones psicógenas como la depresión en otras entidades como la amenorrea nerviosa y bulimia o en la excesiva actividad física (atletas competitivas, bailarinas clásicas) entre las causas más frecuentes. Habitualmente, estos factores se presentan asociados a dietas cuali y cuantitativamente inadecuadas, originando alteraciones en el balance energético (consumo /gasto calórico) y modificaciones en la composición corporal. En general, estas alteraciones se presentan combinadas e inducen reacciones hormonales tendientes a defender la homeostasis metabólica general. Los protagonistas de estos procesos adaptativos son un "circuito" constituido en el sistema nervioso central que se interrelaciona con otro "circuito periférico hormonal". Las manifestaciones del primero incluyen principalmente una atenuación funcional de los ejes hipotalamo-hipófiso-somatotrófico, prolactínico y tiroideo, amplificación de la secreción nocturna de la melatonina e hiperactividad adrenal. A su vez, las interrelaciones, a nivel hipotalámico, del eje CRH-ACTH-sistemas-opiodeo-dopaminérgico y la consiguiente inhibición de la secreción de Gn RH, constituye un mecanismo fisiopatológico crucial para el desarrollo de la disfunción gonadal. Por otro lado, el grado de alteración de la actividad pusátil del Gn RH está condicionado por la etiopatogenia, intensidad nosológica y el tiempo de evolución. La variabilidad y el tipo de irregularidades del ciclo menstrual, que frecuentemente son observados en las atletas competitivas, constituyen un reflejo representativo de ello. Por otro lado, el hipoestrogenismo e hipoandrogenismo de estas mujeres repercuten negativamente en el metabolismo general y osteocálcico, en particular. La osteopenia con su riesgo de fracturas, está omnipresente en este síndrome. No menos importante, el hipoestrogenismo es también uno de los factores de riesgo cardiovascular. No obstante, la administración de anticonceptivos que combinan estrógenos más progesterona, pueden aumentar significativamente los niveles de la proteína C reactiva, un reconocido y seguro marcador de riesgo cardiovascular. Ello induce a tomar precauciones en su utilización en estas amenorricas desnutridas. Asimismo, la administración de anticonceptivos no ha demostrado brindar un beneficio sustancial en el tratamiento de la osteosporosis de estas pacientes. El "circuito periférico", funcionalmente interrelacionado con el central, está principalmente compuesto por la leptina, adiponectina, ghrelin, insulina e IGF-1, péptidos provenientes del compartimiento graso ("adipocitokinas") tracto gastrointestinal superior, páncreas e hígado, respectivamente. Estos péptidos no sólo están involucrados en los mecanismos centrales del apetito y saciedad, sino que también participan en las respuestas de adaptación homeostática, tendientes a revertir los desvíos del metabolismo intermedio y fosfocálcico, que en grado variable afectan a estas pacientes. Conclusiones: la AHF relacionada en general con el estrés psicofísico prolongado y la mala nutrición, es un síndrome complejo, cuyas respuestas hormonales centrales y periféricas de adaptación, resultan primordiales en estas mujeres que padecen un cierto grado de compromiso nutritivometabólico general. Enfocando globalmente este abigarrado síndrome, estimamos que la AHF es, obviamente, un epifenómeno menos vital.

Functional Hypothalamic Amenorrhea (FHA) is a complex pathology produced by psicological stress, as observed in amenorrhea nervosa and bulimia or in intensive physical activity (athletas, competitions, classic dancing). Frequently, these factors are associated to quali-quantitative inadequated diets and therefore they induce alterations in the energetic balance (caloric intake, caloric expend and modification in body composition). These factors are usually combinated and they induce hormonal reactions trend to sustain the general metabolic homeostasis. The protagonists of this adaptative process are a "central nervous system circuit" interrelated with "periferical hormonal circuit". The responses to the first, mainly includes functional atenuation of Hypothalamic- Hipophyseal Somatotropic, Prolactin and Thyroid axes, amplification of nocturnal melatonine secretion and hyper adrenal activity. The relationships, to hypothalamic level, of CRH-ACTH, opioid, and dopaminergic systems, and the subsequent inhibition of Gn-RH secretion, constitute a physiopathological mechanism for the development of gonadal disfunction. On the other hand, the degree of alteration in the Gn-RH pulsatility is conditioned by the ethipahogenic, nosologic intensity and time of evolution. Variability and type of irregularity of menstrual cycle observed in competitive athletes, is a demonstrative example. On the other hand, hypoestrogenism and hypoandrogenism in these women affect negatively the general metabolism and, particularly, the osteocalcic system. Osteopenia with its fracture risk is omnipresence in this syndrome. As important as that hypoestrogenism is also one of cardiovascular factor risk. However the administration of contraceptives which combines estrogens plus progesterone, may significantly increase the C-reactive protein level, a known and safety marker of cardiovascular risk. Therefore it induces to take precautions in its administration in these unnourished amenorrheic women. Also, the administration of contraceptives has not showed a substantial benefit in osteoporosis treatment of this patients. A "periferic circuit", functionally interrelated with the "central circuit", is mainly composed by leptin, adiponectine, ghrelin, insulin and IGF1 peptides, coming from fat compartiment (adipokines), gastro-intestinal tract, pancreas and liver, respectively. These peptides, are not only involved in the central mechanisms of appetite and saciety, but they also participate in homeostatic adaptative responses, with the aim of to balance the alteration of middle and phosphocalcic metabolism which affect these patients in a variable form. CONCLUSIONS: FHA, generally related with psychic/physic stress and malnutrition, is a complex syndrome in which the central and peripheral adaptative hormonal responses are mainly important in these women which are affected of a kind of nutritive and general metabolic compromise. Analazing this complex process we considerate that the hypothalamic amenorrhea is obviously a less vital phenomenon.

Pituitary gonadotropic hormones in women with oligo/amenorrhoea

Any abnormality of menstrual cycle makes women worried and requires proper evaluation. Oligomenorhea is one of the indicators of Polycystic Disease of the Ovary [PCO] which is associated not only with reproductive failure but it also has metabolic and cardiovascular complications. The recent study was conducted to find out the role of Pituitary Gonadotropins in the diagnosis. After diagnosing and finding out the cause for menstrual irregularities and chronic anovulation one can explain the prognosis and management of these disorders. Fifty patients were studied in the year 2005-06 in the outpatient department of Khyber Teaching Hospital Peshawar. A history Performa was duly completed in all subjects. Blood sample was collected for hormonal essay during first ten days of the cycle. Hormonal essay was performed by Microparticle enzyme immunoassay [MEIA] on AXSYM system of Abbott. Age ranged from 13-45 years, 82% of the women were infertile, 60% had infrequent periods and 22% of the women had amenorrhea, 30% patients were overweight while 48% were obese. Physical examination revealed hersuitism in 24%, acne in 8% and galactorrhea in 6% of the patients. Ultrasound examination showed classical picture of PCO in 28% patients while 32% women had multiple small follicles and 16% women were devoid of follicles. Elevated LH levels were found in 36% women. FSH level were found normal in 64% patients while in 16% women the levels were in menopausal range. LH/FSH ratio of more than two was observed in 52% women. Prolactin level was raised in 22% women. TSH level was below normal in 16% and higher in 22% women. Hormonal essays are mandatory in the evaluation of women presenting with Oligomenorhea/amenorrhea and chronic anovulatory infertility for finding out the cause and explaining the prognosis of the disease to the patient

Unruptured tubal pregnancy: different treatments for early and late diagnosis

CONTEXT AND OBJECTIVE: There is evidence that ectopic pregnancies present different behavioral patterns. These distinct evolutions of ectopic pregnancies represent two different natural histories. To evaluate these evolution patterns, we compared patients undergoing medical treatment and expectant management according to their gestational age and initial beta-hCG levels. DESIGN AND SETTING: Prospective study at the Department of Obstetrics of Universidade Federal de São Paulo, a tertiary center. METHODS: Among 119 cases of unruptured ectopic pregnancies diagnosed from April 1999 to February 2004, 57 received systemic treatment with methotrexate 50 mg/m² (body surface area) intramuscularly and 62 were managed expectantly. In this study we evaluated the beta-hCG levels at presentation and amenorrhea duration. RESULTS: There was a significant difference between the two groups regarding amenorrhea duration and initial beta-hCG levels (p < 0.001). The group with decreasing beta-hCG levels (managed expectantly) had longer amenorrhea (mean: 8.87 ± 1.71 weeks) and lower initial beta-hCG levels (mean: 648.8 ± 754.7 mIU/ml). On the other hand, the group treated with methotrexate had shorter amenorrhea (mean: 6.81 ± 1.88 weeks) and higher beta-hCG levels at presentation (2642.7 ± 2315.1 mIU/ml). CONCLUSIONS: The data suggest that ectopic pregnancies can be categorized into two groups: those with early diagnosis and shorter amenorrhea, increasing or maintained beta-hCG levels over 24 and 48-hour intervals and higher beta-hCG levels requiring medical treatment; and those with late diagnosis and longer amenorrhea, decreased beta-hCG levels over 24 and 48-hour intervals and lower beta-hCG levels requiring expectant management.

CONTEXTO E OBJETIVO: A gravidez ectópica apresenta comportamentos diferentes. Para avaliar as diferentes evoluções da gravidez ectópica, nós comparamos as pacientes submetidas ao tratamento medicamentoso e à conduta expectante de acordo com a idade gestacional e os valores iniciais de beta-hCG. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, realizado no Departamento de Obstetrícia da Universidade Federal de São Paulo, hospital terciário. MÉTODOS: Foram diagnosticados 119 casos de gravidez ectópica íntegra no período de abril de 1999 a fevereiro de 2004. O tratamento com metotrexato 50 mg/m² de superfície corpórea intramuscular foi realizado em 57 casos e a conduta expectante, em 62 casos. Neste estudo, nós avaliamos os valores iniciais de beta-hCG e o período de amenorréia. RESULTADOS: Houve diferença estatística significante entre os dois grupos com relação ao período de amenorréia e os valores iniciais de beta-hCG (p < 0,001). O grupo com títulos de beta-hCG em regressão (conduta expectante) apresentaram período de amenorréia mais longo (média:8,87 ± 1,71 semanas) e valores iniciais de beta-hCG mais baixos (648,8 + 754,7 mUI/ml). Por outro lado, o grupo tratado com metotrexato teve período menor de amenorréia (média 6,81 + 1,88 semanas) e valores de beta-hCG mais altos (2642,7 +2315,1 mUI/ml). CONCLUSÕES: Os resultados deste estudo sugerem que a gravidez ectópica pode ser categorizada em dois grupos: aquelas com diagnóstico precoce com período curto de amenorréia e valores elevados de beta-hCG que requerem tratamento com metotrexato, e aquelas com diagnóstico tardio com período longo de amenorréia e valores baixos de beta-hCG que requerem a conduta expectante.

Knowledge of, attitudes towards, and practices relating to child-spacing methods in northern Burkina Faso.

This study was carried out to document current trends in knowledge of, attitudes towards, and practices relating to traditional and modern child-spacing methods in a remote area in northern Burkina Faso. Information on sexual abstention, weaning, and contraception was elicited from 296 women of reproductive age, involving 413 postpartum intervals. A number of older women and key informants were also interviewed. The findings depicted significant diversity in that durations of individual postpartum sexual abstinence varied between 40 days and 3 years, with shorter durations associated with stricter adherence to Islamic beliefs and, possibly, a trend towards a less collective and, for the family unit, more labour intensive, agro-pastoral subsistence economy. Although durations of amenorrhoea were relatively short at between (median) 9 and 11 months, they determined the length of non-susceptible periods in almost 90% of cases. The median timing of weaning was stable at 24 months across all three main ethnic groups. However, changes in the frequency and type of complementary feeds may have impacted on the duration of amenorrhoea. Both demand for modem contraception and contraceptive prevalence (< 1%) were very low. The creation of new child-spacing norms and the promotion of modern contraceptive methods are likely to be successful in areas like this one only, if the population can be sensitized to the idea that Islam does not necessarily discourage contraception.

Impact of lactational performance on bone mineral density in marginally-nourished Bangladeshi women.

This cross-sectional study, carried out during July 1997-June 1998, evaluated the effects of prolonged breast-feeding and lactational amenorrhoea on bone mineral density (BMD) in 400 marginally-nourished Bangladeshi women aged 20-81 years. A bone densitometer was used for measuring BMD in the distal and ultra-distal end of radius and ulna. The results showed that the women who breastfed for 60 months or less had a higher mean BMD compared to those who breastfed for 61-120 months and for over 120 months. There was a significantly higher BMD in the women who had a shorter duration of lactational amenorrhoea compared to those having a longer duration of lactational amenorrhoea. BMD was significantly and negatively correlated with total duration of lactational amenorrhoea (slope -0.024, p<0.05) after controlling for parity, physical workload, and total duration of breast-feeding. The study concluded that there was a negative correlation between longer duration of breast-feeding and BMD, but it was not found when other factors were controlled in multivariate analysis. The duration of lactational amenorrhoea, which is a proxy indicator of breast-feeding, showed a negative correlation with BMD. It is recommended that all lactating women be given diet with adequate calcium to support breast-feeding for maintaining good nutrition of their bones.

Estudo citogenético em 80 casos de amenorréia secundária / Cytogenetic study in 80 cases of secondary amenorrhea

OBJETIVO: investigar as alteraçöes citogenéticas, em sangue periférico, em um grupo de mulheres com queixa de amenorréia secundária. AMOSTRA: 80 mulheres atendidas no setor de ginecologia do CAISM, no período de abril de 1990 a março de 1997. DESENHO: idade inferior a 40 anos e queixa principal de amenorréia por período mínimo de 3 ciclos. Os parâmetros estudados compreenderam as dosagens de FSH e LH, realizadas através da técnica de radioimunoensaio, o estudo cromossômico em sangue periférico, realizado em bandas GTG e as quantificaçöes da cromatina X em sedimento urinário. RESULTADOS: a análise citogenética revelou 73 casos com cariótipo normal 46,XX e valores de cromatina X compatíveis com a normalidade, inclusive em 6 casos com estigmas turnerianois. As alteraçöes observadas compreenderam 4 casos de aneuploidias puras, (47,XXX e 45,X), 2 casos de mosaicismo (45,X/46,XX e 45,X/46,X,isoXq) e um caso de deleçäo em braço longo (46,X,delXq(p22q22.1), todos com valores de cromatina X compatíveis com os resultados de cariótipo. As dosagens de LH e FSH permitiram a divisäo da amostra nos subgrupos normo e hipergonadotróficos, com maior incidência deste último e distribuiçäo aproximadamente eqüitativa de alteraçöes citogenéticas nos mesmos. CONCLUSÄO: no grupo estudado, 9 por cento das mulheres apresentaram amenorréia secundária de origem citogenética. Nestes casos, a instalaçäo do quadro clínico ocorreu com idade inferior a 30 anos, em mulheres com sinais clínicos específicos, como baixa ou alta estatura e graus variados de hipodesenvolvimento dos caracteres sexuais secundários. Os valores de cromatina sexual, embora compatíveis com os resultados de cariótipo, mostratam-se ineficazes na detecçäo de mosaicismo e/ou alteraçöes estruturais do cromossomo X. Os autores salientam a necessidade de investigaçäo citogenética de sangue periférico nas mulheres com manifestaçäo de amenorréia secundária com idade inferior a 30 anos e, nos casos de infertilidade por falência ovariana de origem desconhecida e cariótipo 46,XX, a investigaçäo de mosaicismo gonadal.

Regression analysis of the effect of full and partial lactation on post-partum amenorrhoea in lower middle class Indian females.

This study presents a simple regression analysis of the impact of full and partial breast feeding on post-partum amenorrhoea (PPA) in lower middle class Indian women. The study has been done on a sample of hospital based data collected in 1992. The analysis shows a highly significant correlation. Further, the impact of lactation on PPA was notably less in case with partial breast feeding as compared to those with full breast feeding.

Consenso acerca de la recuperación del ciclo mentrual y fertilidad posterior al uso de anticonceptivos hormonales / A consensus upon menstrual cyclo and fertility restoration after hormonal contraception

Se revisa la frecuencia de amenorrea y esterilidad a la suspención de anticonceptivos hormonales, concluyéndose que ésta es baja. Destaca que la población más susceptible de presentar alteraciones en este sentido es aquella con anteceentes de disfunción hipotálamo-hipofisaria

Himen imperforado como causa de hematometrocolpos e hidronefrosis / Imperforate Hymen causing hematocolpometra and hydronephrosis

El himen imperforado es una malformación congénita poco frecuente, que generalmente se descubre al iniciarse la menarca, las menstruaciones sucesivas ocasionan hematometrocolpos, dando diversas manifestaciones clínicas. Informamos el caso clínico de una adolescente que presentó himen imperforado con salpingohematometrocolpos manifestándose con dolor abdominal crónico, estreñimiento, vómito, disuria, tenesmo vesical, retención aguda de orina, hidronefrosis y tumor pélvico-abdominal. Un diagnóstico temprano con evacuación de la sangre acumulada evitará la hematometra y el hematosalpinx reduciéndose el riesgo de endometriosis pélvica y el futuro de la fertilidad

Prolactina sérica durante metoclopramida oral en mujeres nuligestas normales / Serum prolactin during oral metoclopramide in normal nulliparous women

Como la primera fase de un extenso proyecto encaminado a determinar los valores de prolactina (PRL) sérica en respuesta a la metoclopramida oral en mujeres con diferentes antecedentes ginecoontétricos, se decidío estudiar a 51 mujeres nulíparas, clínicamente sanas entre 15.8 y 48.8 años, con antecedentes de ciclos menstruales regulares cuando menos un año antes del estudio (salvo tres mujeres menopáusicas), sin ingestión regular de medicamentos los seis meses previos a la prueba. Se estudiaron en condiciones basales, en días 18 a 22 del ciclo menstrual, después de un descanso mínimo de 30 minutos (3 muestras) y 60, 90 y 120 minutosdespués de una dosis única de 10 mg. de metoclopramida por vía oral. En todas las muestras se determinó la PRL y progesterona (P) sólo en una alícuota de las tres muestras basales, en duplicado y mediante radioinmunoanálisis. Todas las mujeres tuvieron niveles séricos de P * 4.0 ng/ml. Se observó una correlación lineal positiva (r=0.6795,p<0.001) entre la edad cronológica (EC) y los niveles séricos de PRL, independientemente de la forma de expresión. considerando las respuestas individuales se decidió dividir al grupo de acuerdo con la EC y se observó que los niveles del PRL **expresados en cualquier forma**eran siempre significativamente mayores en las mujeres> 25 años (Grupo 2) en comparación con las * 25 años (Grupo 1). Dado que las diferencias eran evidentes, se calcularon las percentilas 3.50 y 97 de los niveles séricos de PRL durante cada tiempo de la prueba 3een cada grupo. En conclusión, se presentan los resultados de una prueba con un agente antiopaminérgico (metoclopramida por vía oral) en mujeres nulíparas, Clinicamente sanas en forma de curvas percentilares para mujeres * y > de 25 años de edad.Se sugiere que esta prueba sencilla y segura puede ser de utilidad en la evaluación clínica de mujeres nulíparas con problemas asociados con variaciones en los niveles séricos de PRL, principalmente en el caso de mujeres con alteraciones menstruales y en especial en aquellas con normoprolactinemia basal.

Changes of plasma beta-endorphin levels in case of amenorrhea

Fifty six amenorrheic women and 10 normal menstruating fertile controls were included in this study. Amenorrheic women were classified into 5 groups. The first group consisted of 16 hyperprolactinemic women. The second group comprised 12 women with primary ovarian failure. The third group comprised 12 polycystic ovarian diseased patients. The fourth group comprised 12 patients with hypogonadotrophic hypopituitarism. The last group was four cases with hypothalamic dysfunction. Plasma B-endorphin levels were lower in the 5 amenorrheic groups than controls. The lowest levels were found in the hypothalamic dysfunction group [P < 0.001], then the hyperprolactinemic and primary ovarian failure groups [P < 0.001 for both]. Levels of B-endorphin in PCO and hypogonadotrophic hypopituitarism were mildly lower than controls [P< 0.05 for both]

Hiperprolactinemia: efecto sobre la función reproductiva / Hyperprolactinemia: effect over reproductive function

Se estudiaron 37 mujeres con hiperprolactinemia (HPRL) para establecer los niveles de prolactina (PRL) plasmática en relación con su etiología. Además a través de la medición de Estrógenos totales se determina el efecto de la HPRL sobre la función ovárica. Las mujeres que presentaron microadenomas se asocian a niveles de PRL mayores de 80 ng,ml y para macroadenomas de 200 ng,ml o más. En 22 mujeres con medición de estrógenos totales se encontró una medida de 40 pq,ml y se estableció una relación inversa con los niveles de PRL lo que demostraría el efecto de la HPRL sobre la inhibición de la esteroidogénesis ováric

Falla ovárica prematura / Premature ovarian failure

Se revisaron los expedientes clínicos de 13 pacientes con el diagnóstico de falla gonadal prematura, se analizó su forma de presentación, niveles de gonadotropinas hipofisiarias y biopsia de endometrio. Niveles de hormonas tiroideas, estradio, prolactina, edad y paridad. Dichas pacientes fueron captadas en la consulta externa del Instituto Nacional de Perinatología, por presentar esterilidad primaria en 6 casos (6.15%) y esterilidad secundaria en 7 casos (53.85%). La edad de instalación de la falla ovárica tuvo un rango de 1 a 33 años, con un x = 23.5 + - SD 5.65 años. Todas las pacientes presentaron hipoestrogenismo asociado a hipergonadotropismo, con niveles de estradiol sérico menos de 37 pg/ml y un promedio para FSH de 54.77 mU/ml y para LH de 54.73 mU/ml. En 11 casos (84.6%), se realizó estudio histológico del ovario, en los que se demostró en todos ellos el diagnóstico de falle ovárica prematura.

B-endorphin pattern in infertile woman

The pattern of B-endorphin in the plasma of 50 infertile women was studied besides its the level in 10 normal fertile women taken as control. The results showed that among the normal groups there is a cyclicity of B-endorphin levels pre-ovulatory and post-ovulatory which is parallel to the cyclicity of prolactin. In the infertile women, the cyclicity is lost with persistent elevation of the B-endorphin levels. This in part inhibits the cyclic gonadotrophins and on the other hand stimulates prolactin secretion, where both are sharing in the aetiology of anovulation and amenorrhea