Eating behaviours related to psychological stress are associated with functional hypothalamic amenorrhoea in exercising women.

Functional hypothalamic amenorrhoea (FHA) can occur due to the independent or combined effects of psychogenic and energetic stressors. In exercising women, research has primarily focused on energy deficiency as the cause of FHA while psychological stressors have been ignored. To assess both psychological and metabolic factors associated with FHA in exercising women, we performed across-sectional comparison of 61 exercising women (≥2 hours/week, age 18-35 years, BMI 16-25kg/m2), who were eumenorrheic or amenorrhoeic confirmed by daily urine samples assayed for reproductive hormone metabolites. Psychological factors and eating behaviours were assessed by self-report questionnaires. Exercising women with FHA had lower resting metabolic rate (p=0.023), T3 (p<0.001), T4 (p=0.013), leptin (p=0.002), higher peptide YY (p<0.001), greater drive for thinness (p=0.017), greater dietary cognitive restraint (p<0.001), and displayed dysfunctional attitudes, i.e., need for social approval (p=0.047) compared to eumenorrheic women. Amenorrhoeic women displayed asignificant positive correlation between the need for social approval and drive for thinness with indicators of stress, depression, and mood, which was not apparent in eumenorrheic women. In exercising women with FHA, eating behaviours are positively related to indicators of psychological stress and depression.

Cortical excitability variability: Insights into biological and behavioral characteristics of healthy individuals.

Motor threshold (MT) measured by transcranial magnetic stimulation (TMS) has diagnostic utility in central nervous system disorders. Its diagnostic sensitivity may be enhanced by identification of non-pathological factors which may influence this measure. The aim of this study was to provide a description of MT variability across physiological and non-pathological behaviour characteristics in a large cohort, including hemispheric asymmetries. In a cross-sectional study, age, handedness, physical activity level, body mass index, gender/menstrual cycle phase, glycemic index and degree of stress were collected from 115 healthy participants. The resting MT of the first dorsal interosseous muscle to TMS was recorded in both hemispheres and served as an indicator of the cortical excitability level. Repeated measures ANOVAs revealed higher MT values in the non-dominant hemisphere, elderly people, stressed individuals and women with amenorrhea. Other biological and behavioral individual characteristics did not influence cortical excitability. Although the degree of interhemispheric difference varied (range: 0.2 to 4.3), depending on biological and behavioral characteristics, this variation was not significant (0.1 ≤ p ≤ 0.8). In conclusion, MT varied considerably between subjects. The difference between the hemisphere excitability that was less influenced by external factors, may be an alternative method of TMS measure to identify pathological changes of cortical excitability.

Early menopause: A hazard to a woman's health.

Early menopause or premature ovarian insufficiency (POI) is a common cause of infertility in women and affects about one per cent of young women. This disorder has significant psychological sequelae and major health implications. Its relevance has increased in recent years due to the fact that age of motherhood is being delayed in developed countries, with the risk of having either primary ovarian insufficiency or less possibilities of pregnancy. The main characteristics are absence of ovulation, amenorrhoea and high levels of serum gonadotropins (hypergonadotropic hypogonadism). Although the aetiology remains uncertain in most cases, several rare specific causes have been elucidated. Potential causes for POI are iatrogenic (ovarian surgery, radiotherapy or chemotherapy), environmental factors, viral infections, metabolic and autoimmune diseases, and genetic alterations. Because of the association with other autoimmune diseases, close follow up is recommended in patients with POI. The traditional indicators to evaluate ovarian ageing are age, serum hormonal levels, anti-Mullerian hormone, antral follicle count, and ultrasonography of ovaries. Hormone replacement therapy remains the mainstay of treatment, and the best chance of achieving a pregnancy is through oocyte donation. This article aims to present an overview of potential causes, clinical manifestations, and treatment options of POI.

Genetic mechanisms leading to primary amenorrhea in balanced X-autosome translocations.

OBJECTIVE: To map the X-chromosome and autosome breakpoints in women with balanced X-autosome translocations and primary amenorrhea, searching candidate genomic loci for female infertility. DESIGN: Retrospective and case-control study. SETTING: University-based research laboratory. PATIENT(S): Three women with balanced X-autosome translocation and primary amenorrhea. INTERVENTION(S): Conventional cytogenetic methods, genomic array, array painting, fluorescence in situ hybridization, and quantitative reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURE(S): Karyotype, copy number variation, breakpoint mapping, and gene expression levels. RESULT(S): All patients presented with breakpoints in the Xq13q21 region. In two patients, the X-chromosome breakpoint disrupted coding sequences (KIAA2022 and ZDHHC15 genes). Although both gene disruptions caused absence of transcription in peripheral blood, there is no evidence that supports the involvement of these genes with ovarian function. The ZDHHC15 gene belongs to a conserved syntenic region that encompasses the FGF16 gene, which plays a role in female germ line development. The break in the FGF16 syntenic block may have disrupted the interaction between the FGF16 promoter and its cis-regulatory element. In the third patient, although both breakpoints are intergenic, a gene that plays a role in the DAX1 pathway (FHL2 gene) flanks distally the autosome breakpoint. The FHL2 gene may be subject to position effect due to the attachment of an autosome segment in Xq21 region. CONCLUSION(S): The etiology of primary amenorrhea in balanced X-autosome translocation patients may underlie more complex mechanisms than interruption of specific X-linked candidate genes, such as position effect. The fine mapping of the rearrangement breakpoints may be a tool for identifying genetic pathogenic mechanisms for primary amenorrhea.

Primary amenorrhea in two sisters: description of a Mexican family with 17α hydroxylase-17 lyase deficiency caused by arginine - stop mutation.

A rare cause of congental adrenal hyperplasia is 17α-hydroxylase deficiency. It results in sexual infantilism, primary amenorrhea in females, pseudohermaphroditism in males, hypertension, and hypokalemia. We studied two female siblings from a rural community in Mexico. The cause of consultation was primary amenorrhea. The proband had low levels of estrogen, progesterone and cortisol. Deoxycorticosterone and corticosterone levels were elevated. The proband was homozygous for a transversion of cytosine to thymine at exon 4 (CGA→TGA), causing a premature stop codon at position 239 (R239X). Analysis of family members showed the presence of this heterozygous mutation in the mother, father and one healthy sibling. In summary, we describe a Mexican family with 17α-hydroxylase deficiency due to R239X mutation.

Forearm bone mineral density changes during postpartum and the effects of breastfeeding, amenorrhea, body mass index and contraceptive use.

UNLABELLED: Prospective cohort study performed to evaluate bone mineral density (BMD) changes up to 12 months postpartum of healthy women and its association with breastfeeding, contraceptive methods, amenorrhea, and body mass index (BMI). There is a trend in bone loss during the first 6 months with posterior recovery, with evidence of a protective effect of hormonal contraception. INTRODUCTION: This study was conducted to evaluate bone mineral density (BMD) changes during postpartum period among healthy women and its association with breastfeeding, use of contraceptive methods, amenorrhea and body mass index (BMI). METHODS: A prospective cohort study including 100 healthy women. Distal BMD was measured 7-10 days, 3, 6, and 12 months postpartum at the nondominant forearm using dual-energy X-ray absorptiometry. Data about breastfeeding duration, amenorrhea, contraceptive use and BMI were collected. RESULTS: Seventy-eight women had a complete set of BMD measurements. The mean duration of exclusive breastfeeding was 125.9 (±66.6) days, with a median total lactation period of 263.5 days. The mean duration of amenorrhea was 164.2 (±119.2) days. BMD measurements showed a significant decrease in the distal radius, however with no significance in the ultradistal radius. When considering only the nonhormonal contraceptive users, the difference at 12 months was significant. Multivariate analysis of variance showed that both BMI and contraceptive use were significantly correlated with BMD. Multiple linear regression analysis showed significant correlation of distal radius with baseline BMD at the same site, pregestational BMI, age, years of schooling and difference in BMI. For ultradistal radius, there was a significant direct correlation with its baseline BMD and pregestational BMI. CONCLUSIONS: There was a trend in bone loss during the first 6 months postpartum with posterior recovery. Also, hormonal contraceptive methods provided protection of bone loss. However, the long duration of breastfeeding and the follow-up were not sufficient to draw definitive conclusions on postweaning BMD conditions.

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.

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.

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/m(2) (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.

Lactational amenorrhoea in well-nourished Toba women of Formosa, Argentina.

The proximate causes of the contraceptive effect of lactation are still a matter of productive debate. This study sought to disentangle the relative impact that intense breast-feeding practices and maternal nutrition have on the regulation of ovarian function in nursing women. A mixed-longitudinal, direct-observational, prospective study was conducted of the return to postpartum fecundity in 113 breast-feeding, well-nourished Toba women. A sub-sample of 70 women provided data on nursing behaviour, daily activities, diet quality and urinary levels of oestrone and progesterone metabolites. Well-nourished, intensively breast-feeding Toba women experienced a relatively short period of lactational amenorrhoea (10.2 +/- 4.3 months) and a high lifetime fertility (TFR=6.7 live births/woman). Duration of lactational amenorrhoea was not correlated with any of the nursing parameters under study or with static measures of maternal nutritional status. The results indicated that the pattern of resumption of postpartum fertility could be explained, at least partly, by differences in individual metabolic budgets. Toba women resumed postpartum ovulation after a period of sustained positive energy balance. As the relative metabolic load hypothesis suggests, the variable effect of lactation on postpartum fertility may not depend on the intensity of nursing per se but rather on the energetic stress that lactation represents for the individual mother.

Resumption of ovarian function during lactational amenorrhoea in breastfeeding women with polycystic ovarian syndrome: metabolic aspects.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common endocrine-metabolic disorder in women, a high percentage of whom exhibit peripheral insulin resistance. After delivery, in normal women, lactation imposes a metabolic adaptation, the impact of which on the insulin resistance of PCOS patients is not known. The aim of this study was to evaluate the effect of lactation on insulin resistance, glucose and insulin metabolism, and sex hormone-binding globulin (SHBG) and insulin-like growth factor binding protein-1 (IGFBP)-1 concentrations in fully breast-feeding normal and PCOS women during the postpartum period (lactational amenorrhoea) and also after weaning. METHODS: Twelve lactating PCOS (LPCOS) women and six normal lactating (NL) women of similar age and body mass index (BMI) were selected for the study. At the 4th and the 8th week postpartum (pp), and 8 weeks after weaning, a 2 h, 75 g oral glucose tolerance test (oGGT) was performed, followed by an insulin tolerance test 2 days later. For the oGGT, glucose and insulin were measured in each sample and SHBG and IGFBP-1 were determined in the fasting sample. RESULTS: During lactation, fasting insulin levels were similar in both groups. In LPCOS women 2 h insulin concentrations were significantly higher, and SHBG and IGFBP-1 concentrations were significantly lower, than those observed in NL women. In both groups, insulin sensitivity evaluated by the insulin tolerance test was not modified. After weaning, in LPCOS women, SHBG and IGFBP-1 concentrations remained lower and insulin concentrations remained higher than those observed in NL women ( P < 0.05 ). CONCLUSIONS: In PCOS women, insulin resistance is not modified during lactation. Lactation has a transitory beneficial effect on insulin levels and biological markers of insulin resistance.

Resumption of ovarian function during lactational amenorrhoea in breastfeeding women with polycystic ovarian syndrome: endocrine aspects.

BACKGROUND: The aim of this study was to evaluate the changes in gonadotrophin concentrations and the dynamics of the episodic fluctuations of circulating LH during night-time, in fully breastfeeding normal women and in those with polycystic ovarian syndrome (PCOS) during lactational amenorrhoea and after weaning, in order to provide insights into the onset of this syndrome. Additionally, ovarian activity was evaluated by ultrasound examination and steroid concentrations. METHODS: Twelve lactating PCOS (LPCOS) women and six normal lactating (NL) women of similar age were selected. On the 4th and 8th week postpartum (PP) and eight weeks after weaning, blood samples were collected every 10 min (10.00--20.00h). Gonadotrophin concentrations were determined in all samples. Steroid hormones were measured in one fasting sample and ovarian morphology was assessed by ultrasound. RESULTS: On the 8th week PP, LH pulse frequency was higher and FSH concentrations were lower in LPCOS women compared with NL women, and steroid hormone concentrations remained low, except for androstenedione which was higher in LPCOS patients. After weaning, similar differences were observed between both groups. PCOS patients also showed enlarged ovaries with a PCOS pattern in the three study periods. CONCLUSIONS: The enlarged ovaries associated with higher androstenedione concentrations suggest that PCOS is a primary ovarian defect, making it difficult to establish if the abnormal LH pattern observed in these women is primary or secondary to the ovarian dysfunction.

Secretory pattern of leptin and LH during lactational amenorrhoea in breastfeeding normal and polycystic ovarian syndrome women.

Several studies have suggested that leptin modulates hypothalamic-pituitary-gonadal axis function. A synchronicity of LH and leptin pulses has been described in healthy women and in patients with polycystic ovarian syndrome (PCOS), suggesting that leptin may modulate the episodic secretion of LH. The aim of the present investigation was to assess the episodic fluctuations of circulating LH and leptin during lactational amenorrhoea in fully breastfeeding normal and PCOS women at 4 and 8 weeks postpartum, in order to establish LH-leptin interactions in the reactivation of the gonadal axis during this period. Six lactating PCOS patients and six normal lactating women of similar age and body mass index were studied. During a 12 h period on the 4th and 8th weeks postpartum, blood samples were collected at 10 min intervals for 12 h (22:00-10:00). Serum LH and leptin concentrations were measured in all samples. For pulse analysis, the cluster algorithm was used. To detect an interaction between LH and leptin pulses, an analysis of co-pulsatility was employed. LH concentrations tended to increase in both groups between the 4th and 8th weeks postpartum; however, serum leptin concentrations were not modified. Leptin pulse frequencies were similar at the 4th and 8th weeks postpartum, and did not differ between groups. Moreover, leptin pulse frequency was higher than LH pulse frequency in both groups, and in the two study periods. There was no synchronicity between LH and leptin pulses, and there were no increments in leptin concentration during the night. The fact that leptin concentrations were not modified and no synchronicity between LH and leptin pulses was observed suggests that, during lactational amenorrhoea, circulating leptin is probably not involved as a primary signal in promoting the reactivation of pulsatile LH secretion.

Contraceptive efficacy and clinical performance of Nestorone implants in postpartum women.

The objective of this study was to evaluate the contraceptive efficacy and clinical performance of a Nestorone subdermal implant (NES) in the postpartum period. NES (n = 100) and Copper T intrauterine device (T-Cu; n = 100) acceptors initiated contraception at 8 weeks postpartum and were followed at monthly intervals during the first year and at 3-month intervals thereafter. Pregnancy rates, breastfeeding performance, infant growth, bleeding pattern, and side effects were assessed. Blood and milk NES concentration were measured. No pregnancy occurred in 2195 and 2145 woman-months of NES implant and T-Cu use, respectively. No effect of NES on lactation and infant growth and no serious adverse events were observed. Lactational amenorrhea was significantly longer in NES users (353 +/- 20 days) than in T-Cu users (201 +/- 11 days). More NES users (55.8%) experienced prolonged bleedings than did T-Cu users (36.2%). Concentrations of NES in breast milk ranged between 54-135 pmol/liter. The Nestorone implant is a highly effective contraceptive, safe for breastfed infants because the steroid is inactive by the oral route.

Rokitansky syndrome and MURCS association--clinical features and basis for diagnosis.

OBJECTIVE: To describe 19 cases with Rokitansky syndrome, as well as their endocrine features, and other associated malformations. METHODS: Nineteen cases of utero-vaginal atresia are reported. Serum levels of luteinizing hormone, follicle stimulating hormone, prolactin, estradiol, and progesterone were measured. Genetic study was done by karyotype and X chromatin. Pelvic ultrasound was performed, and searches for associated urinary and bone malformations were done by intravenous pyelogram and spinal column X-rays, respectively. RESULTS: In all patients, mammary growth began between 9 and 12 years, and pubic hair growth between 11 and 14 years. Nine of them sought advice for primary amenorrhea, and 10 for difficulty in sexual intercourse. Thirteen patients had begun sexual activity, between 18 and 30 years of age; six of them had dyspareunia, and in four it was impossible to have sexual intercourse, but three reported satisfactory sexual relations. External genitalia were normal in all, vaginal length was between 0.5 and 7 cm, and in all ended in a blind pouch. On pelvic ultrasound, normal ovaries and absent uterus were delineated; only one had polycystic ovaries. All had a 46XX karyotype and positive X chromatin. Hormone levels were normal in 16, 3 had hyerprolactinemia. In 7 out of 11 in whom progesterone was measured, it was ovulatory. In 8 out of 11, the pyelogram was abnormal, and in the same number, skeletal anomalies were found. CONCLUSIONS: In three patients, MURCS association was documented. It is proposed as an easy and minimally invasive study protocol for diagnosis.

Induction of ovulation with clomiphene citrate in combination with metoclopramide in patients with amenorrhea of hypothalamic origin.

Literature data have demonstrated that the chronic use of metoclopramide (MCP), a dopamine antagonist, causes increased gonadotropin secretion in patients with hypothalamic amenorrhea but without triggering ovulation. It has also been observed that women with hypothalamic amenorrhea respond poorly to ovulation induction with clomiphene citrate (CC). On this basis, the objective of the present study was to determine the effect of MCP on the response to CC in patients with hypothalamic amenorrhea in order to evaluate the validity of the simultaneous use of these drugs as ovulation inducers in this type of chronic anovulation. Twenty-two patients with amenorrhea of hypothalamic origin were submitted to a randomized double blind study in which one tablet of 5 mg MCP or placebo was administered every 8 hours for 2 months. After the 30th day of medication (MCP or placebo), CC, 100 mg orally, was additionally administered to both groups for 5 days. Blood samples were collected on days 1, 15 and 30 during the first month of the study and on days 7, 14 and 21 after the last CC tablet during the second month, for later measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol and progesterone by radioimmunoassay. The group that received MCP showed a significant increase in LH and FSH during the first month of the study, as well as a slighter increase in estradiol. Prolactin increased only during the second stage of treatment. No significant increases in gonadotropins, prolactin or estradiol occurred in the placebo group. In the group treated with MCP, 40% of the patients ovulated after CC, with menstruation occurring in 60% of them. In the placebo group, 33.3% of the women ovulated after CC and 44.4% menstruated at the end of the study. We conclude that MCP increases the circulating levels of LH, FSH, estradiol and prolactin in patients with hypothalamic amenorrhea and low estrogen levels, supporting the hypothesis that an increase in hypothalamic dopaminergic tonus occurs in these patients. On the other hand, the combination of MCP and CC does not improve the rate of ovulation compared to placebo.

[Has oligomenorrhea a pathological meaning? The importance of this symptom in internal medicine]. / Tiene la oligomenorrea un significado patológico? Importancia de este síntoma en medicina interna.

BACKGROUND: Oligomenorrhea, defined as a menstrual cycle lasting 36 to 90 days, can be a normal condition in the first years after the menarche. When it persists or appears after a period of normal menstrual cycles, an underlying illness must be sought. AIM: To assess ovulation and causes of anovulatory cycles in women with oligomenorrhea, compared with causes of secondary amenorrhea. PATIENTS AND METHODS: One hundred one women of less the 35 years old, presenting with oligomenorrhea persisting 5 years after menarche or lasting more than two years after a period of normal menstrual cycles, were studied. Ovulation was studied measuring serial plasma progesterone during normal or induced (with intramuscular progesterone) menstrual cycles. RESULTS: Eighty nine percent of women had anovulatory oligomenorrhea. The main causes were polycystic ovarian disease in 51% and hypothalamic dysfunction in 31%. Thirty percent of women with secondary amenorrhea had polycystic ovarian disease and 14% had hyperprolactinemia. Women older than 20 years old or with more than 10 years of gynecological age had a higher frequency of polycystic ovarian disease and a lower prevalence of hypothalamic dysfunction. CONCLUSIONS: There is a high frequency of anovulatory oligomenorrheas. Therefore, this symptom deserves a thorough endocrinological assessment to uncover underlying diseases. Special attention must be paid to polycystic ovary syndrome, due to its importance in internal medicine as a risk factor for myocardial infarction, high blood pressure, and type 2 diabetes mellitus.

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.

Contraceptive use and pregnancy before and after introducing lactational amenorrhea (LAM) in a postpartum program.

There is good evidence that lactational amenorrhea (LAM) is an effective method of fertility regulation during the first 6 months postpartum, provided no other food is given to the baby and the mother remains amenorrheic. However, although breast-feeding is strongly promoted in many maternity hospitals that also run postpartum family planning programs, LAM is rarely included among the contraceptive options being offered. This paper presents the results of an operational study which compared the prevalence of contraceptive use and the cumulative pregnancy rate at 12-months postpartum among 350 women observed before and 348 women studied after introducing LAM as an alternative contraceptive option offered to women following delivery at the Instituto Materno Infantil de Pernambuco (IMIP), in Recife, Brazil. The percentage of women not using any contraceptive method was significantly lower (p<0.0001) after the intervention (7.4%) than before (17.7%). This difference remained statistically significant after controlling for age, number of living children, marital status and years of schooling. The proportion pregnant one year postpartum was also significantly lower (p<0.0001) after the introduction of LAM (7.4%) than before (14.3%), but the difference was no longer significant after controlling for the same variables. It is concluded that LAM is a useful addition to family planning postpartum programs.