Obesity and Hyperandrogenemia in Polycystic Ovary Syndrome: Clinical Implications.

Polycystic ovary syndrome (PCOS) is often accompanied with metabolic disturbances attributed to androgen excess and obesity, but the contribution of each has not been defined, and the occurrence of metabolic disturbances is usually not investigated. Ninety-nine women with PCOS and forty-one without PCOS were evaluated. The clinical biomarkers of alterations related to glucose (glucose, insulin, and clamp-derived glucose disposal - M), liver (aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase), and endothelium (arginine, asymmetric dymethylarginine, carotid intima-media thickness, and flow-mediated dilation) metabolism were measured; participants were categorized into four groups according to their obesity (OB) and hyperandrogenemia (HA) status as follows: Healthy (no-HA, lean), HA (HA, lean), OB (no-HA, OB), and HAOB (HA, OB). Metabolic disturbances were very frequent in women with PCOS (≈70%). BMI correlated with all biomarkers, whereas free testosterone (FT) correlated with only glucose- and liver-related indicators. Although insulin sensitivity and liver enzymes were associated with FT, women with obesity showed lower M (coef = 8.56 - 0.080(FT) - 3.71(Ob); p < 0.001) and higher aspartate aminotransferase (coef = 26.27 + 0.532 (FT) + 8.08 (Ob); p = 0.015) than lean women with the same level of FT. Women with obesity showed a higher risk of metabolic disorders than lean women, independent of hyperandrogenemia. Clinicians are compelled to look for metabolic alterations in women with PCOS. Obesity should be treated in all cases, but hyperandrogenemia should also be monitored in those with glucose-or liver-related disturbances.

Tratamiento quirúrgico conservador del embarazo intersticial, con antecedente de salpingectomía homolateral. Reporte de un caso / Conservative surgical management of interstitial pregnancy, with a history of ipsilateral salpingectomy. Report of a case

Resumen ANTECEDENTES: El procedimiento quirúrgico del embarazo intersticial puede complicarse con hemorragia difícil de controlar; por esto en los últimos años se recurre a las técnicas que permiten el control hemostático, con lo que disminuyen la morbilidad y mortalidad relacionadas con el procedimiento. OBJETIVO: Describir el proceso para establecer el diagnóstico y decidir el tratamiento quirúrgico conservador en una paciente con embarazo intersticial con antecedente de salpingectomía homolateral y deseo de preservación uterina. CASO CLINICO: Paciente de 27 años, con antecedentes de un parto, tres abortos y un embarazo ectópico previo, con salpingectomía izquierda. Acudió a consulta debido a un retraso menstrual de siete semanas y dolor pélvico agudo. Ante la sospecha de embarazo ectópico se integró el protocolo diagnóstico. La cuantificación de la fracción-β de hormona gonadotropina coriónica fue de 8962 mlU/mL, el ultrasonido transvaginal reportó una imagen compatible con saco gestacional hacia la región del cuerno izquierdo y probable hemoperitoneo. En la laparotomía exploradora se encontraron: hemoperitoneo y embarazo intersticial izquierdo. Con el propósito de preservar la fertilidad se hizo una doble ligadura de la arteria uterina izquierda, a nivel de istmo uterino y del ligamento útero-ovárico y resección del saco gestacional intersticial, con cornuostomía. CONCLUSION: El embarazo intersticial es una urgencia obstétrica con alto riesgo de ruptura y hemorragia, por fortuna poco frecuente. La ligadura de las arterias uterinas, previa a la ablación quirúrgica del saco gestacional, es una alternativa individualizada en pacientes con esta complicación.

Abstract BACKGROUND: The surgical procedure of interstitial pregnancy can be complicated by bleeding that is difficult to control; for this reason, in recent years, techniques that allow hemostatic control to have been used, thus reducing morbidity and mortality related to the procedure. OBJECTIVE: To describe the process to establish the diagnosis and decide the conservative surgical treatment in a patient with interstitial pregnancy with a history of homolateral salpingectomy and desire for uterine preservation. CLINICAL CASE: 27-year-old patient, with a history of one childbirth, three miscarriages and a previous ectopic pregnancy, with left salpingectomy. She came for consultation due to a seven-week menstrual delay and acute pelvic pain. In view of the suspicion of ectopic pregnancy, the diagnostic protocol was integrated. The quantification of the β-fraction of chorionic gonadotropin hormone was 8962 mlU/mL, the transvaginal ultrasound reported an image compatible with gestational sac towards the left horn region and probable hemoperitoneum. At exploratory laparotomy, hemoperitoneum and left interstitial pregnancy were found. To preserve fertility, a double ligation of the left uterine artery at the level of the uterine isthmus and the utero-ovarian ligament and resection of the interstitial gestational sac with cornuostomy was performed. CONCLUSION: Interstitial pregnancy is an obstetric emergency with a high risk of rupture and hemorrhage, fortunately rare. Ligation of the uterine arteries, prior to surgical ablation of the gestational sac, is an individualized alternative in patients with this complication.

The role of LCPUFA-ω3 on the obesity-associated hyperandrogenemia of pubertal girls: secondary analysis of a randomized clinical trial.

Introduction Hyperandrogenism (HA), either clinical or biochemical, is associated with obesity in adolescent girls. Long chain polyunsaturated fatty acids ω3 (LCPUFA-ω3) play protective roles in some obesity-associated morbidities, but their contribution to preventing HA is unclear. Our aim was to examine the potential positive relationships between erythrocyte LCPUFA-ω3, with or without supplementation, and hyperandrogenemia. Methods Secondary analysis of a clinical trial that was conducted previously to analyze the effect of LCPUFA-ω3 on insulin resistance and body weight. Here, we present a cross-sectional analysis of 180 girls with obesity, and a longitudinal analysis of 117 girls who completed a 3-month supplementation period (57 LCPUFA-ω3 [DO3] and 60 placebo [DP)]). Dehydroepiandrosterone sulfate (DHEAS), total testosterone (TT) and steroid hormone binding globulin (SHBG) were measured with chemiluminescence; free testosterone (FT) was calculated. Erythrocyte fatty acids were determined by gas chromatography. Non-parametric statistics was used for analysis. Results In cross-sectional analysis, age (odds ratio [OR] = 1.35; 95% confidence interval [CI] = 1.03, 1.78; p = 0.027), insulin (OR = 1.05; 95% CI: 1.00, 1.10; p = 0.018), and erythrocytes eicosapentaenoic acid (EPA) (OR = 0.04; 95% CI: 0.01, 0.65; p = 0.012) were predictors of hyperandrogenemia (FT >0.63 ng/mL). In longitudinal analysis, EPA, adiponectin and SHBG increased, while FT decreased, in the DO3 group (p < 0.05). The risk of hyperandrogenemia at the end of follow-up was predicted by basal hyperandrogenemia (OR = 18.16, 95% CI: 5.37, 61.4; p < 0.001) and by increases in EPA (OR = 0.40; 95% CI: 0.01, 0.65; p = 0.06 marginal significance). Conclusions Our results suggest a preventive role of EPA on the risk for hyperandrogenemia in girls with obesity, but further studies are needed to demonstrate a benefit.

Mioma intraligamentario de gran tamaño en una adolescente / Intra-ligamentary leiomyoma of giant elements in adolescent patient

Resumen ANTECEDENTES: Los leiomiomas uterinos son los tumores benignos ginecológicos más frecuentes en las mujeres en edad reproductiva; por tanto, son extremadamente raros en las adolescentes (menos de 1%) y solo se encuentran reportes de caso en la bibliografía. CASO CLÍNICO: Paciente de 16 años, con tumor suprapúbico de rápido crecimiento, acompañado de dolor abdominal generalizado, enviada a la unidad médica con diagnóstico de miomatosis uterina para descartar su malignidad. El ultrasonido pélvico reportó múltiples lesiones hipoecoicas diseminadas en el miometrio, similares a metástasis. La tomografía abdomino-pélvica informó hepatomegalia, a expensas del lóbulo izquierdo y leiomiomas intramurales de medianos y grandes elementos; los marcadores tumorales se encontraron en límites normales. En la laparotomía se encontró una tumoración interligamentaria izquierda de 25 cm; el estudio histopatológico reportó: leiomioma uterino de patrón histológico convencional. CONCLUSIONES: El cuadro clínico de los leiomiomas en adolescentes representa un reto clínico por la edad, signos, síntomas y necesidad de preservación de la función reproductiva, aspectos decisivos a la hora de decidir el tratamiento.

Abstract BACKGROUND: The uterine leiomyomas are the most common gynecological benign tumors in fertile females; however, they are very rare in adolescents (less than 1%) and there are only a few reports in the literature. CLINICAL CASE: A 16-year-old patient with a fast-growing suprapubic tumor, accompanied by generalized abdominal pain, sent to the hospital with diagnosis of pelvic tumor probable uterine miomatosis, to rule out malignant tumor. Pelvic ultrasound was performed with a report of multiple disseminated hypoechoic lesions in myometrium giving appearance of metastasis, without being the characteristic images of myomas, pelvic abdominal tomography reported hepatomegaly of the left lobe, intramural leiomyomas of medium and large elements, tumor markers within normal limits. The laparotomy was performed, left intraligamentary myoma of giant elements was located; and the histopathological study reported uterine leiomyoma of conventional histological pattern. CONCLUSIONS: The clinical of leiomyomas in adolescent patients represents a challenge for the gynecologist. The age, symptomatology, and preservation of reproductive function are important aspects to decide the therapeutic regimen.

Subtle metabolic alterations in adolescents with obesity and polycystic ovarian syndrome. / Alteraciones metabólicas sutiles en adolescentes con obesidad y síndrome de ovario poliquístico.

Objective: To evaluate the frequency of some subtle metabolic alterations in a group of adolescents with obesity and polycystic ovary syndrome (PCOS). Materials and Methods: A cross-sectional, comparative study was conducted in a group of adolescents with obesity, and characterized as with or without PCOS according with the Rotterdam Consensus. Medical history, anthropometry, gynecologic pelvic ultrasound (to evaluate ovarian volumes, number of antral follicles and endometrial width), as well as serum glucose, insulin, lipoproteins, interleukin-6, tumor necrosis factor alpha, total testosterone, dehydroepiandrosterone, sexual hormones binding globulin, leptin, adiponectin and insulin-like growth factor 1, the free-androgen index, free and available testosterone, and homeostatic model assessment index were calculated. For statistics, mean and standard deviation, or median and ranges were used for description as appropriate. Likewise, Student t-test or Mann-Whitney test were used for comparisons. Results: From a sample of 180 adolescents, 47 attached to selection criteria. Mean age was 13.5 year and Z-score 2.5. Eighty percent of adolescents presented central distribution of body fat and 95% hyperinsulinemia. The more frequent dyslipidemias were hypertriglyceridemia in 57% and hypercholesterolemia in 12.8%; 25.5% of adolescents presented two out of three criteria for polycystic ovary syndrome (PCOS). Body mass index and insulin were correlated with free testosterone, but the multivariate analysis demonstrated that the magnitude of the association was significantly higher in SOP patients. Conclusions: The metabolic alterations detected in obese adolescents with SOP suggest that the clinical manifestations that accompany the syndrome characterize the PCOS as a metabolic disease, which carry important health risks at short, medium and long term. Therefore, they merit intervening actions to prevent, diagnose and provide timing treatment in order to limit the damage in the course of the natural history of PCOS.

Longitudinal Analysis of the Interaction Between Obesity and Pregnancy on Iron Homeostasis: Role of Hepcidin.

BACKGROUND AND AIMS: When pregnancy occurs in obese women, two opposite mechanisms for iron homeostasis concur: increased need for available iron to support erythropoiesis and decreased iron mobilization from diets and stores due to obesity-related inflammation linked to overexpressed hepcidin. Few studies have examined the role of hepcidin on maternal iron homeostasis in the context of obese pregnancy. The aim of the study was to evaluate the combined effect of maternal obesity and pregnancy on hepcidin and maternal iron status while accounting for inflammation and iron supplementation. METHODS: We conducted a secondary analysis of a cohort of pregnant women recruited from a referral obstetric hospital in Mexico City. Circulating biomarkers of iron status (hepcidin, ferritin [SF], transferrin receptor [sTfR], erythropoietin [EPO]), and inflammation (C-reactive protein [CRP], tumor necrosis factor-[TNF]α, and interleukin-[IL]6) were determined monthly throughout pregnancy. Repeated measures ANOVA and logistic regression models were used for statistics. RESULTS: Twenty-three obese (Ob) and 25 lean (Lc) women were studied. SF and hepcidin declined, and EPO and sTfR increased throughout pregnancy in both groups. sTfR increased more in Ob than in Lc (p = 0.024). The smallest hepcidin decline occurred in iron-supplemented Ob women compared to non-supplemented Lc women (p = 0.022). The risk for iron deficiency at the end of pregnancy was higher for Ob than for Lc (OR = 4.45, 95% CI = 2.07-9.58) after adjusting for iron supplementation and hepcidin concentration. CONCLUSION: Pre-gestational obesity increases the risk of maternal iron deficiency despite iron supplementation. Overexpressed hepcidin appears to be a potential mechanism.

[Contraception in women with chronic diseases]. / Anticoncepción en mujeres con enfermedades crónicas.

BACKGROUND: Almost 10% of women in reproductive age had a chronic disease, and contraception is frequently ignored by these patients. The lack of use of contraceptives methods has a higher repercussion in these patients; if pregnant, the risk is increased in morbidity and feto-maternal mortality. OBJECTIVES: to know the contraceptive coverage in women with chronic degenerative diseases, the kind of contraceptive methods and the unsatisfied demand. MATERIAL AND METHODS: A descriptive study was made with the application of a survey from the one elaborated by the IMSS. It explores contraception socio-demographic data, causes of non-protection and also explores Medical Doctor (MD) participation. Sample size was calculated in 385 women in reproductive age with a chronic disease. RESULTS: 428 women about 30-49 years old were interviewed, 53% of them were married, they had various diseases, the contraceptive coverage was 84%. The definitive methods were the most used with 47%, followed by the condom with 20%, intrauterine device with 13% and others in minor proportion. 38.5% of patients with sexual life have risk of pregnancy for lack of use of method or for using one of low effectiveness and continuity. Of 45 (16%) patients with sexual life that did not use methods, 29% because they wish pregnancy, 18% by collateral effects and the rest for other causes. From this same patients 21 wished getting pregnant and 24 did not, this is an unsatisfied demand of 53%. The MD's informed about risks in case of pregnancy of 83.4% of the patients. CONCLUSIONS: The contraceptive coverage is low and the unsatisfied demand is higher than in the general population. It requires the effective participation of health personal in this group of high reproductive risk.

[Interactions between markers of endothelial damage (homocysteine and asymmetric dimethylarginine) and antioxidants and B-vitamins in preeclamptic women]. / Interacción entre los marcadores de daño endotelial (homocisteóna y dimetilarginina asimétrica) con las vitaminas antioxidantes y del grupo B en pacientes con preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-related pathological condition triggered by an abnormal placentation which produces endothelial dysfunction (ED). ED, in turn, is associated with an increase in homocysteine (hcy) and asymmetric dimethylarginine (ADMA); these molecules are also increased when some of the B-vitamins are deficient. It is unclear whether increases in hcy and ADMA during preeclampsia are the result of ED, or the consequence of a B-vitamin deficiency. OBJECTIVE: To evaluate hcy, ADMA, folic acid (FA), vitamin B6 and B2 concentrations in patients with preeclampsia. METHODS: In a cross-sectional design 19 patients with severe preeclamp- sia (preeclampsia) and 57 with normal pregnancy (no-preeclampsia), paired by gestational age and body mass index, were studied. Plasma hcy, ADMA, FA and vitamins B6 and B12 were determined. Non-parametric statistics was used for between-groups comparisons and regression analyses to evaluate interactions among molecules. RESULTS: 72% of women were vitamin B deficient, 40% were deficient of B12 and 4% of FA. Preeclamptic patients presented hcy and ADMA concentrations higher than no-preeclamptic ones. Inferential analyses demonstrated that: hcy and ADMA are increased during preeclampsia independently from vitamins blood concentration; that the risk for pre- eclampsia is associated with high hcy but not with vitamins deficiency; and that the ratio L-arginine:ADMA decreases the preeclampsia risk. CONCLUSION: In patients with preeclampsia, increases of hcy and ADMA are associated with ED, but not with deficiency of the vitamins involved in their metabolism.

[Clinical practice guideline. Diagnosis and treatment of postmenopausal and perinemopausia]. / Guía de práctica clínica. Diagnóstico y tratamiento de la perimenopausia y la posmenopausia.

Post-menopause is the period of life where a deep decline occurs in circulating estrogen levels, inducing the appearance of psycho and somatic symptoms. The classification to understand the chronology of reproductive aging in women (known as STRAW) determines the clinical and endocrine changes contemplating menstrual cycles, symptoms, measurements of FSH, LH, inhibin B, anti-Mullerian hormone , and follicular account. The diagnosis of menopause is established by the absence of menstruation for 12 months or more. The most frequent clinical manifestations of the climacteric syndrome transition to menopause are menstrual disorders, vasomotor symptoms (flushes and/or sweats) and genitourinary manifestations. The assessment of women in the peri- or postmenopause aims to develop: cervicovaginal cytology , lipid profile , serum glucose, basal Mammography at least a year before, pelvic ultrasound, urinalysis, serum TSH, Densitometry in patients older than 60 years if there is no recourse can be applied and FRAX. Drug therapy for the treatment of disorders of the transition to menopause or menopause is divided into: hormone therapy (HT) based estrogens and progestin hormone not being the most recommended the serotonin reuptake inhibitors and norepinephrine, clonidine, gabapentin or veralipride.

La posmenopausia es el periodo de la vida en el que ocurre un profundo descenso en las concentraciones circulantes de estrógenos, lo cual induce la aparición de los síntomas psico y somáticos. La clasificación para entender la cronología del envejecimiento reproductivo en la mujer (reconocida como STRAW) determina los cambios clínicos y endocrinos a partir de examinar los ciclos menstruales, los síntomas, las mediciones de FSH, LH, inhibina B, hormona antimulleriana y la cuenta folicular. El diagnóstico de menopausia se establece por la ausencia de menstruación por 12 meses o más. Las manifestaciones clínicas más frecuentes del síndrome climatérico o transición a la menopausia son los trastornos menstruales, los síntomas vasomotores (bochornos o sudoraciones) y las manifestaciones genitourinarias. La evaluación de la mujer en la peri o la postmenopausia contempla la realización de citología cervicovaginal, perfil de lípidos, glucosa sérica, mastografía basal (por lo menos un año antes), ultrasonido pélvico, examen general de orina, TSH sérica, densitometría (ver la Guía de práctica clínica de osteoporosis) en pacientes mayores de 60 años (y si no se cuenta con el recurso se puede aplicar el FRAX). El tratamiento farmacológico para las alteraciones de la menopausia (o de la transición a esta) se divide en: tratamiento hormonal (TH) con base en estrógenos o progestágenos, y tratamiento no hormonal; los más recomendados son los inhibidores de recaptura de serotonina y norepinefrina, clonidina, gabapentina o veraliprida.

[Clinical practice guideline for the diagnosis and treatment of hyperprolactinemia]. / Guía de práctica clínica para el diagnóstico y tratamiento de la hiperprolactinemia.

BACKGROUND: Hyperprolactinemia is a common finding within clinical practice in both endocrinology and general practice fields, amongst other specialties. The general practitioner and other specialists must know the indications and serum prolactin determination parameters in order to, once detected, derive the patient for a correct assessment and begin treatment. OBJECTIVE: Formulate a clinical practice guideline evidence-based for the diagnosis and treatment of hyperprolactinemia. METHOD: It took the participation of eight gynecologists, two pathologists and a pharmacologist in the elaboration of this guideline due their experience and clinical judgement. These recommendations were based upon diagnostic criteria and levels of evidence from treatment guidelines previously established, controlled clinical trials and standardized guides for adolescent and adult population with hyperprolactinemia. RESULTS: During the conformation of this guideline each specialist reviewed and updated a specific topic and established the evidence existent over different topics according their field of best clinical expertise, being enriched by the opinion of other experts. At the end, all the evidence and decisions taken were unified in the document presented here. CONCLUSIONS: It is presented the recommendations established by the panel of experts for diagnosis and treatment of patients with high levels of prolactin; also the level of evidence for the diagnosis of hyperprolactinemia, handling drug-induced hyperprolactinemia and prolactinomas in pregnant and non-pregnant patients.

[Functionality and endometrial changes associated with induction ovulation with citrate of clomifene and recombinant FSH in infertile women]. / Funcionalidad y cambios endometriales asociados con la inducción de ovulación con citrato de clomifeno y FSH recombinante en mujeres con infertilidad.

It has been reported that infertility affects approximately 20% of couples in reproductive age around the world. Although many factors involved, ovulatory dysfunction and particularly the hypothalamus pituitary dysfunction are quite common. The first line treatment for these pathologies consists on the administration of inducing ovulation agents such as recombinant gonadotropins and clomiphene citrate which it was obtained high rates of ovulation but not of pregnancy. So determine the effect of these treatments on the endometrium at morphological and molecular level is very important to understand the female reproductive physiology and optimize clinical strategies to obtain better pregnancy rates after treatments. In this paper we detailed the studies that have reported changes at the molecular and morphological level in human endometrium.

[Insulin resistance frecuency in women's with polycystic ovary syndrome using hyperinsulinemic-euglycemic clamp]. / Frecuencia de resistencia a la insulina en pacientes con síndrome de ovario poliqulstico con el clamp hiperinsulinémico euglucémico.

OBJECTIVE: To assess IR in PCOS patients, using the HE-clamp as the IR gold standard. MATERIAL AND METHODS: A transversal design was done. All patients who accepted to participate provided written informed consent. PCOS was diagnosed according to the 2003 Rotterdam criteria. IR was assessed using the H-clamp, and other IR surrogates such as; fasting plasma insulin (FPI), homeostasis model assessment (HOMA) index and insulin/ glucose rate (I/G rate). Statistical analysis was performed using measures of location and spread was used according to data distribution. RESULTS: 21 patients were included. The mean age of the total group studied was 29.5 +/- 4.8 years, and the body mass index (BMI) was 27.2 +/- 3.08 kg/m2. The 85.7% of the patients met the three Rotterdam criteria for the diagnosis of PCOS. According to the HE clamp 95.2% were IR (M/I value < 6 mg/Kg/min), in contrast the prevalence of IR using sur- rogates was 47.6%, 33.3%, and 66.6% for FPI, G/I rate, and HOMA index respectively. CONCLUSIONS: Our findings show that IR is highly prevalent in patients with PCOS, and that this prevalence is even higher when insulin sensitivity is assessed using the glucose clamp technique. This evidence suggests that IR could be considered diagnostic criteria for PCOS.

PPARγ2 Pro12Ala polymorphism is associated with improved lipoprotein lipase functioning in adipose tissue of insulin resistant obese women.

Lipoprotein lipase (LPL) plays a pivotal role in lipid metabolism, contributes to metabolic disorders related to insulin action and body weight regulation, and is influenced by inflammation. The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR)γ2 gene seems to influence LPL functioning, but its role in obesity and insulin resistance status, which usually coexist in the clinical setting, has not been explored. Our aim was to analyze the association of obesity and insulin resistance with adipose LPL activity and expression, and the influence of the PPARγ2 Pro12Ala polymorphism. A cross-sectional study was conducted in 58 reproductive-age women who underwent elective abdominal surgery. Free-fatty acids, glucose, insulin, and selected adipokines were measured in fasting blood samples. DNA was isolated and the polymorphism genotyped. Biopsies of abdominal subcutaneous adipose tissue obtained during surgery were used to determine enzymatic LPL activity and expression; and expression of selected cytokines. Overweight/obese women presented lower LPL activity (P=0.022) and higher circulating TNF-α (P=0.020) than controls. Insulin resistant women also showed borderline lower LPL activity than non-resistant (P=0.052), but adiposity and inflammatory molecules were comparable. Nevertheless, LPL activity was higher in Pro12Ala carriers than in non-carriers after adjusting for obesity, insulin resistance and inflammation. Likewise, adipose LPL expression was increased in carriers while expression of cytokines was decreased. Our data suggest that insulin resistance is associated with low adipose LPL activity independently of obesity, but the PPARγ2 Pro12Ala polymorphism seems to protect the LPL functioning of obese insulin resistant women, likely through regulating inflammation in adipose tissue.

[Insulin sensitivity in patients not responding to ovulation induction using clomiphene citrate]. / Sensibilidad a la insulina en pacientes con falta de respuesta a la inducción de ovulación con citrato de clomifeno.

BACKGROUND: The role of insulin resistance (IR) of infertile patients with chronic anovulation in their therapeutic failure to clomiphene citrate (CC) is not quite clear. OBJECTIVE: Determine the sensitivity to insulin in patients with chronic anovulation and failure to the treatment with clomiphene citrate. MATERIAL AND METHODS: A cross-sectional clinical study in infertile patients with clomiphene citrate resistance and in patients with adequate response to clomiphene citrate was carried out. In all patients insulin resistance was determined by the rate of glucose/insulin, HOMA (Homestatic Model Assessment) and the insulin sensitivity test. For the inferential statistical analysis, a Student's t test for independent samples was used. RESULTS: The average total basal insulin was 19.6 +/- 8.1 microU/mL. We observed higher concentrations in the clomiphene citrate resistance group (22.1 +/- 8.9 vs. 15.8 +/- 5.1 mU/mL p = 0.07). The glucose/insulin rate was statistically minor in patients with resistance to clomiphene citrate (4.2 +/- 1.9 versus 6.9 +/- 2.1 p = 0.02), but HOMA was not significantly different in both groups (4.3 +/- 1.4 vs. 3.9 +/- 1.3 p = 0.6). The total rate of glucose disappearance (KIIT) was 4.1 +/- 1.2. However, the statistical analysis did not show significant statistical differences between the two groups. CONCLUSIONS: Our preliminary results suggest that insulin resistance can be a mechanism involved in the pharmacologic response to ovulation induction in infertile patients, but coexisting pathophysiological mechanisms such as hyperandrogenism might also account for the lack of response to clomiphene citrate.

[Homocysteine after a methionine load in healthy subjects with adequate B-vitamin status]. / Homocisteína plasmática posterior a carga oral de metionina en sujetos sanos con nivel adecuado de vitaminas B.

BACKGROUND: Plasma homocysteine (Hcy) determination at 6-8 h after an oral methionine load (OML) allows for identification of some, but not all, individuals at risk to develop cardiovascular disease. It is probable that in some cases the Hcy increases occur later, or it elevates between normal ranges but in a sustained manner. However, the entire Hcy response curve has not been described. We undertook this study to determine Hcy concentrations from baseline to 24- and 48-h after an OML in non-B-vitamin deficient adult subjects with other risk factors for high levels of Hcy such as smoking and overweight. METHODS: In a cross-over, clinical design, Hcy concentrations were determined at 2-h intervals throughout 12 h and at 24 h and 48 h after an OML (0.1 g/kg). Hcy and vitamin B6 (VB6) concentrations were measured by high-performance liquid chromatography (HPLC). Folic acid (FA) and vitamin B12 (VB12) were measured by radioimmunoassay (RIA). Statistical analysis included delta values and areas under the curve. Student t-test and repeated measurement analyses were conducted to control for confounders. RESULTS: Twenty-nine subjects with adequate Hcy, FA, VB6 and VB12 status were included. The maximum Hcy concentration occurred 8 h after the load and returned to baseline concentrations after 24 h. All subjects presented Hcy after the load within normal ranges, but smoking and overweight synergistically influenced the response to the challenge, producing a sustained elevation after the dose. CONCLUSIONS: Hcy concentrations after an OML remained above baseline for at least 24 h. Smoking and overweight affected the response to the methionine challenge.

[TNF-alpha, C-reactive protein and serum adiponectin modified in infertile patients with insulin resistance]. / Alteración del factor de necrosis tumoral-alpha, proteína C reactiva y adiponectina séricas en pacientes infértiles con resistencia a la insulina.

BACKGROUND: Women's reproductive potential is closely related to nutritional status. Some of the molecules that participate in ovarian regulation are produced in the adipose tissue, and therefore their production is associated with adiposity. OBJECTIVE: To determine serum leptin, adiponectin, C-reactive protein, interleukin-6, and tumor necrosis factor alpha in infertile women with or without insulin resistance; and to associate these molecules with adiposity. METHODS: Thirty-one infertile women were included. Nutritional status was evaluated through clinical and biochemical parameters. Patients were stratified according with their body mass index and the presence of insulin resistance. For statistics, parametric analyses were conducted. RESULTS: The prevalence of overweight was 67.5%; high adiposity was present in 92.3% and central distribution of fat in 96.2% of studied women. Hypercholesterolemia was found in 32.3% of patients, hypertriglyceridemia in 25.8%, and 61.3% presented hyperinsulinemia. Overweight women presented lower adiponectin, and higher TNF-alpha and C-reactive protein concentrations, than those with normal body mass index (p < 0.05). Overweight women had also a higher probability for insulin resistance (p = 0.04). These women with insulin resistance presented lower adiponectin and higher C-reactive protein concentrations than non insulin resistance women. Body mass index correlated with leptin (r= 0.41), TNF-alpha (r= 0.41), and C-reactive protein (r= 0.33) concentrations. CONCLUSION: The prevalence of overweight, high adiposity, dislipidemias, and IR was high in our population studied. We conclude that adiposity is closely associated with some of the molecules that participate in the reproductive process and that also regulate inflammatory responses.

[Serum levels of IL-1beta, IL-6 and TNF-alpha in infertile patients with ovarian dysfunction]. / Concentraciones séricas de IL-1beta, IL-6 y TNF-alpha en pacientes infértiles con disfunción ovárica.

BACKGROUND: Some cytokines that take part in the ovarian cycle regulation, such as IL-1beta, IL-6 and TNF-alpha play an important role during growth and development of ovarian follicle. Quantification of some cytokines is promissory in the work-up of ovarian reproductive pathology. OBJECTIVE: To determine serum levels of IL-1beta, IL-6 and TNF-alpha in infertile patients with ovarian dysfunction and to compare them with those found in ovulatory patients. PATIENTS AND METHODS: We conducted a cross-sectional study in infertile patients with premature ovarian failure, diminished ovarian reserve, chronic anovulation and ovulatory patients that were well-characterized by clinical and hormonal parameters. We determined serum concentrations of IL-1beta, IL-6 and TNF-alpha by an ELISA method. Statistics was conducted by using one way ANOVA, Kruskall-Wallis and Pearson correlation analyses. RESULTS: We studied a total of forty patients. The mean age was 30 years; we did not find significant differences among groups. Overall mean of cytokines concentration was: 13.2 pg/mL for IL-1beta; 8.4 pg/mL for IL-6; and 1.5 pg/mL for TNF-alpha. We observed a significant difference in the concentration of TNF-alpha in the premature ovarian failure group when it was compared to the control group. Pearson correlation coefficients were no significant. CONCLUSION: A wide range of dispersion of serum cytokines concentration was observed. Serum concentrations of TNF-alpha in woman with premature ovarian failure were significantly lower than those in the control group. Our findings represent a precedent in the powerful utility of the quantification of these cytokines in reproductive medicine.

[Serum levels of antioxidants and vitamins related to the homocystein's metabolism during postmenopause]. / Concentraciones séricas de vitaminas antioxidantes y vitaminas relacionadas con el metabolismo de la homocisteína durante la posmenopausia.

OBJECTIVE: To describe nutritional status, B6, B12, and antioxidant vitamins, as well as homocysteine concentrations in postmenopausal women. PATIENTS AND METHODS: A cross-sectional study was conducted in Mexico City. One hundred twenty-five women were selected if they were healthy and were in their first five years after menopause onset. Women were spontaneously divided in two groups: women who did not receive any hormonal treatment for at least six months before the study (n = 66), and those who received hormonal treatment at the moment of the study (n = 59). Anthropometry was measured and a fasting blood sample from a peripheral vein was obtained to determine homocysteine, vitamins A, C, E, B6, B12, and folic acid. Results were compared with Student t-test, and a logistic regression model was used to calculate the risk of hyperhomocystinemia after adjusting by some potential confounders. RESULTS: Women who did not receive hormone replacement therapy presented higher body mass index and waist-hip ratio than those who received such treatment. In contrast, this group presented higher prevalence of folic acid deficiency and hyperhomocystinemia, despite they consumed higher amounts of folic acid in the diet. This high risk of hyperhomocystinemia was independent of vitamin serum concentrations and the level of physical activity (OR = 15.1, IC95 = 1.60,141.9). CONCLUSIONS: These results suggest that hormone replacement therapy may protect against overweight and central fat distribution that occur after menopause, but increases the risk of hyperhomocystinemia.

Prostacyclin/thromboxane early changes in pregnancies that are complicated by preeclampsia.

OBJECTIVE: The purpose of this study was to examine 6-keto-prostaglandin F(1)(alpha) and thromboxane B(2) plasma levels throughout normotensive and preeclamptic pregnancies and to analyze the predictive values of these quantifications for the detection of preeclampsia during the second trimester of pregnancy. STUDY DESIGN: Blood samples were collected from 30 healthy, nonpregnant women and at 4-week intervals from a cohort of nulliparous women who were recruited before 16 weeks of gestation. Preeclampsia developed in 26 patients; 52 normotensive control subjects were matched from the same cohort. The 6-keto-prostaglandin F(1)(alpha) and thromboxane B(2) were assayed by radioimmunoassay. Trends were compared between pregnancy groups and with the nonpregnant women. Predictive values were determined with the second-trimester assessments. RESULTS: The 6-keto-prostaglandin F(1)(alpha)/thromboxane B(2) ratio decreased throughout pregnancy in women with preeclampsia; there were no significant changes in normotensive women. We found higher thromboxane B(2) levels within the group with preeclampsia during the first gestational trimester (preeclampsia, 188 +/- 17 pg/mL; control, 119 +/- 4.8 pg/mL [mean +/- SEM]; P =.001). During the third trimester, patients with preeclampsia had lower 6-keto-prostaglandin F(1)(alpha) levels than did control subjects (preeclampsia, 191 +/- 9.8 pg/mL; control, 288 +/- 10 pg/mL; P =.001). The 6-keto-prostaglandin F(1)(alpha)/thromboxane B(2) ratio was suitable to calculate predictive values; the best cutoff point and time interval were 3.0 and 22 to 26 weeks of gestation, respectively. Sensitivity, specificity, and positive and negative predictive values were 88%, 97%, 69%, and 99%, respectively; the odds ratio was 14.6 (95% CI, 6.9-30.4). CONCLUSION: The prostacyclin/thromboxane ratio favored vasoconstriction early in gestation in women in whom preeclampsia developed. A 6-keto-prostaglandin F(1)(alpha)/thromboxane B(2) ratio of

Apoptosis ovárica / Ovarian apoptosis

La apoptosis o muerte celular programada es uno de los principales mecanismos de pérdida tisular. Es un proceso activo de pérdida celular, que participa de manera directa en la homeostasis tisular a lo largo de la vida. Además, el proceso apoptósico es un evento clave dentro de la patología del desarrollo tumoral. El proceso apoptósico es de naturaleza génica y es desencadenado por factores externos. Los ejecutores de la apoptosis son las caspasas y el resultado final es la muerte celular específica. El equilibrio proliferación/muerte celular, está determinado por factores de sobrevida y por promotores de la pérdida celular entre los cuales se encuentran: reguladores génicos, hormonas, citocinas, y factores de crecimiento. En el ovario, la apoptosis regula la proliferación y diferenciación folicular. Durante la embriogénesis, la población de ovogonias parece estar mediada por apoptosis y durante el ciclo ovárico la apoptosis participa de manera conjunta en el proceso de atresia folicular. Probablemente la apoptosis sea uno de los eventos que participan de manera directa en la atresia folicular acelerada, que se ha hipotetizado sea uno de los mecanismos fisiopatológicos involucrados en la falla ovárica prematura. Aún hace falta aclarar el papel que juega la apoptosis en algunos eventos patológicos reproductivos como son: anovulación crónica, baja reserva ovárica y disfunción ovárica temprana. El conocimiento del papel que guarda la apoptosis en estas patologías, contribuirá a comprender mejor la fisiología ovárica y probablemente en un futuro próximo nos permitirá intervenir tempranamente en la historia natural de la enfermedad.La apoptosis o "muerte celular programada" forma parte de los mecanismos de equilibrio celular. El término fue utilizado primeramente para describir los cambios morfológicos que ocurren durante la muerte celular en diferentes tejidos. La apoptosis es un fenómeno universal presente en todos los seres vivos y que ocurre a lo largo de la vida. Conjuntamente con la mitosis, mantiene la homeostasis tisular. Además, la apoptosis juega un papel crucial en algunos eventos patológicos como lo es el desarrollo tumoral. En el presente trabajo se revisan algunos de los mecanismos básicos del proceso apoptósico y su vinculación con el crecimiento y desarrollo ovárico a lo largo de la vida en la mujer.