Genetic polymorphisms of matrix metalloproteinases 1-3 and their inhibitor are not associated with premature labor.

AIM: Extracellular matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) are involved in the breakdown of fetal membranes before delivery. Our aim was to investigate the occurrence of any polymorphism on genes coding for MMPs 1-3 and TIMP 2 in preterm laboring patients as a potential source of this phenomenon. This question has not been studied before. METHODOLOGY & RESULTS: A prospective population study was performed in a Greek university hospital. Group A (control) included 66 women with no symptoms of premature labor. Group B (research) comprised 66 women, exhibiting signs of threatened preterm labor. No statistically significant difference in polymorphism, both in the distribution of genotype as well as allele frequencies, was detected between the two groups. This also applied to gestational age less or greater than 32 weeks. CONCLUSION: Gene polymorphisms of MMP 1-3 and TIMP 2 are not associated with premature rupture of membranes/contractions, as well as gestational age at preterm labor.

Is there any association between leptin levels and bone mineral density in haemophiliac men?

INTRODUCTION: Conflicting data exist regarding the role of leptin in bone metabolism. The purpose of the present study was to investigate serum leptin concentrations in male patients with haemophilia A and B, a disease known to be associated with low bone mass. MATERIAL AND METHODS: Eighty-one male patients, aged 45.4 ±15 years, were screened. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) in lumbar spine (LS), femoral neck (FN) and total hip (TH). RESULTS: Low bone mass was diagnosed in 20 patients (24.7%). Serum leptin concentrations were strongly associated with body weight (r s = 0.457, p = 0.0001) and body mass index (BMI) (r s = 0.491, p = 0.0001). In unadjusted analysis leptin was inversely associated with BMD in LS (r s = -0.255, p = 0.023), but not in FN and TH (r s = -0.205, p = 0.068 and r s = -0.191, p = 0.090, respectively). However, after adjusting for BMI and body weight, leptin was inversely associated with BMD in FN (F 1,76 = 7.727, p = 0.007, ß = -0.371, ΔR (2) = 0.089) and TH (F 1,76 = 4.533, p = 0.036, ß = -0.290, ΔR (2) = 0.054), but not in LS (F 1,75 = 2.076, p = 0.154, ß = -0.202, ΔR (2) = 0.026). No association was found between age, presence of HBV, HCV or HIV infection or alkaline phosphatase and leptin levels. CONCLUSIONS: Our study showed a negative association between circulating leptin levels and bone mass in males, independently of body weight and BMI.

Decreased active, total and altered active to total ghrelin ratio in normal weight women with the more severe form of polycystic ovary syndrome.

OBJECTIVE: To assess total, active and active to total serum ghrelin ratio in normal weight women with polycystic ovary syndrome (PCOS) and in healthy ovulatory control women. STUDY DESIGN: The study included 50 normal weight women with PCOS with a mean age of 23.70+/-4.99 years and 10 control women with a mean age of 30+/-5.80 years. The diagnosis of PCOS was based on the presence of biochemical hyperandrogenemia, chronic anovulation and polycystic ovarian morphology according to the Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Serum total and active ghrelin were measured by RIA, using commercially available kits. RESULTS: A significantly lower serum active/total ghrelin ratio was noted in the more severe form of PCOS with hyperandrogenemia, chronic anovulation and polycystic ovarian morphology. Both total and active serum ghrelin levels were negatively correlated to hirsutism score, to plasma glucose levels and to QUICKI and HOMA-IR indices of Insulin Resistance. A statistically significant difference was detected between the more severe and the milder forms of PCOS, concerning serum levels of total ghrelin (p=0.017), active ghrelin (p=0.007) and the active/total ghrelin ratio (p=0.026). CONCLUSIONS: The results of the present study demonstrate an altered active to total ghrelin ratio, as well as a tendency towards lower both total and active fasting serum ghrelin levels in normal weight PCOS, more pronounced in the more severe forms of the syndrome.

The administration of estrogens, combined with anti-androgens, has beneficial effects on the hormonal features and asymmetric dimethyl-arginine levels, in women with the polycystic ovary syndrome.

The present study was designed in order to: (a) compare ET-1 and ADMA levels, between women with PCOS (n=106) and healthy controls (n=30); (b) determine the effects of treatment with estrogens and anti-androgens on the hormonal features of PCOS, insulin resistance, ET-1 and ADMA levels. Women with PCOS were randomized in five therapeutic protocols: (I) 17beta-estradiol+cyproterone acetate 50mg; (II) conjugated estrogen+CA 50 mg; (III) ethinyl estradiole+CA 2mg; (IV) EE+CA 52 mg; (V) EE+desogestrel. In all women, gonadotropin, PRL, androgen, SHBG, insulin, glucose, ET-1 and ADMA levels were determined; in women with PCOS, testosterone, SHBG, ET-1 and ADMA levels were measured again after 3, 6, 12 months of treatment and insulin and glucose levels after 12 months. ET-1 and ADMA concentrations were higher in women with PCOS, and they were positively correlated with each other. ADMA levels were decreased and IR was increased with treatment. Treatment with synthetic estrogens (EE) resulted in a more pronounced increase in SHBG and a more pronounced decrease in FAI, compared to natural estrogens. Conclusively, PCOS is associated with endothelial dysfunction, which is ameliorated by the administration of estrogens and anti-androgens, independent of IR.

Serum parathyroid hormone concentrations are increased in women with polycystic ovary syndrome.

BACKGROUND: The present study was designed to investigate the effects of polycystic ovary syndrome (PCOS) and of obesity on serum parathyroid hormone (RhoTauEta), 25-hydroxyvitamin D (25-OH-vitamin D), and 1,25-dihydroxyvitamin D [1,25-(OH)2-vitamin D] concentrations and the possible associations of the above calciotropic hormones with the hormonal and metabolic characteristics of the syndrome. METHODS: We studied 58 obese [body mass index (BMI)>30 kg/m2] women with PCOS, 64 overweight (BMI, 25-30 kg/m2) women with the syndrome, 169 normal-weight (BMI<25 kg/m2) women with PCOS, 29 obese controls (ovulatory women without clinical or biochemical hyperandrogenemia), 14 overweight controls, and 70 normal-weight controls. Blood samples were collected (at 0900 after an overnight fast) between the 3rd and 6th days of a menstrual cycle in the control groups and during a spontaneous bleeding episode in the PCOS groups. Circulating concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), testosterone, Delta4-androstenedione, 17alpha-hydroxyprogesterone, sex-hormone-binding globulin (SHBG), insulin, glucose, PTH, 25-OH-vitamin D, and 1,25-(OH)2-vitamin D were measured. RESULTS: Both PCOS and increased body weight had a significant positive effect on serum PTH values. PTH concentrations were significantly correlated with age, BMI, glucose, PRL, SHBG, and testosterone. Only the correlations with testosterone and PRL were BMI-independent. The effect of PCOS on PTH concentrations remained significant after adjustment for BMI, but not after adjustment for testosterone concentration. Increased body weight also had a significant negative effect on 25-OH- and 1,25-(OH)2-vitamin D concentrations, but no association with the syndrome was observed. CONCLUSIONS: The results of the present study are in agreement with previous data supporting an association of increased PTH and decreased vitamin D metabolite concentrations with obesity. Moreover, the present findings indicate, for the first time, that PTH probably is also linked to PCOS-associated hyperandrogenism.

Differential effects of unopposed versus opposed hormone therapy, tibolone, and raloxifene on substance p levels.

OBJECTIVE: To evaluate the effects of unopposed therapy (conjugated equine estrogens [CEE]) vs. opposed therapy (CEE and medroxyprogesterone acetate), tibolone, and raloxifene on serum substance p levels. DESIGN: Clinical study. SETTING: University hospital. PATIENT(S): One hundred eight postmenopausal women were assigned to four treatment groups: unopposed hormone therapy (HT) (n = 30), opposed HT (n = 48), tibolone (n = 18), and raloxifene (n = 12). INTERVENTION(S): Conjugated equine estrogens, CEE and medroxyprogesterone acetate, tibolone, and raloxifene were administered orally; blood samples were collected before therapy and 3 months after. MAIN OUTCOME MEASURE(S): Serum substance p levels were measured before and at the end of the third month of the treatment.The serum substance p levels were increased in the unopposed HT group after treatment. On the contrary, substance p levels were decreased in the opposed HT group, in the tibolone group, and in the raloxifene group. CONCLUSION(S): Addition of progesterone (P) to estrogen (E) treatment significantly decreases serum substance p levels. Tibolone and raloxifene exert the same effect.

beta-thalassemia and gonadal axis: a cross-sectional, clinical study in a Greek population.

beta-thalassemia (beta-thal) is characterized by disturbances of the reproductive system. The aim of the present study was: 1) to assess the hypothalamic- pituitary-gonadal axis in patients with beta-thal in relation to their phenotype and 2) to determine prognostic features of current gonadal status. We studied 135 patients (67 males and 68 females) with beta-thal through history, physical examination, spermiograms and GnRH test. These patients were divided into beta-thal major (51 males and 62 females) and beta-thal intermedia phenotypes (16 males and 6 females). Male patients with beta-thal major were subdivided into three groups a) eugonadal (35%, Tanner's stage V, normal testicular volume, normal spermiograms, normal basal and stimulated hormone values), b) patients with hypogonadotrophic hypogonadism (HH) of late onset (24%, Tanner's stage II-V, low-normal testicular volume, abnormal spermiograms, normal basal gonadotrophin values and abnormal response to GnRH test) and c) patients with HH of early onset (41%, Tanner's stage I, small testicular volume, abnormal spermiograms, abnormal basal and stimulated hormone values). Female patients with beta-thal major were subdivided into: a) eugonadal (32%, Tanner's stage V, regular menstruation, normal basal and stimulated hormone values), b) patients with hypogonadotrophic hypogonadism (HH) of late onset (34%, Tanner's stage II-V, secondary amenorrhea, subnormal basal and stimulated gonadotrophin values) and c) patients with HH of early onset (34%, Tanner's stage I, primary amenorrhea, subnormal basal and stimulated hormone values). Patients with beta-thal intermedia were subdivided into eugonadal (75% of males, 33% of females) and hypogonadal (25% of males, 67% of females). Current gonadal status could not be predicted by means of transfusion or chelation parameters. In conclusion, beta-thal patients could be eugonadal or develop early or late onset HH. trade mark-thal intermedia patients have a more favorable profile than beta-thal major individuals. Current gonadal status of beta-thal patients cannot be predicted by means of history, clinical or laboratory parameters.