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San-Millan J.L.,University of Alcala | Escobar-Morreale H.F.,University of Alcala | Escobar-Morreale H.F.,Research Center Biomedica en Red Diabetes y Enfermedades Metabolicas Asociadas
Clinical Endocrinology | Year: 2010

Objective To study the association of polymorphisms in the genes encoding peroxisome proliferator-activated receptors (PPARs) with the polycystic ovary syndrome (PCOS). Design Case-control study and meta-analysis of published evidence. Patients One hundred and sixty-one polycystic ovary syndrome patients and 113 non-hyperandrogenic women. Measurements Genotyping for PPAR-γ coactivator-1 gene (PPARGC1A) Gly482Ser, PPAR-α Leu162Val, PPAR-δ rs2267668A/G, PPAR-δ -87T/C, PPAR-γ2 Pro12Ala and PPAR-γ2 -681C/G variants and systematic review of the literature using the Entrez-PubMed search engine, followed by meta-analysis whenever possible. Results Polycystic ovary syndrome patients carried the Gly482Ser variant in PPARGC1A more frequently than controls (72% vs. 58%, χ2=5·54 P = 0·019), whereas carriers of the PPAR-α Leu162Val, PPAR-δ rs2267668A/G, PPAR-δ -87T/C, PPAR-γ2 Pro12Ala and PPAR-γ2 -681C/G variants were distributed similarly among both groups. The interaction between the PPARGC1A Gly482Ser and PPAR-δ -87T/C variants was also associated with PCOS (OR = 1·24, 95% CI 1·05-1·50, P = 0·008). The systematic review identified 31 studies addressing associations between PPARs variants and PCOS; meta-analysis was possible for nine studies focusing on the PPAR-γ2 Pro12Ala variant. Although the individual studies did not reveal any statistically significant association, meta-analysis uncovered that carrying the PPAR-γ2 Pro12Ala variant was associated with a reduced probability of having PCOS (OR = 0·77, 95% CI 0·61-0·96, P = 0·025), and that this association may be mediated by an effect on insulin sensitivity. Conclusions Common polymorphisms in the PPARGC1A, PPAR-δ and PPAR-γ2 loci are associated with PCOS. © 2010 Blackwell Publishing Ltd.

Alpanes M.,University of Alcala | Alpanes M.,Research Center Biomedica en Red Diabetes y Enfermedades Metabolicas Asociadas | Sanchon R.,University of Alcala | Martinez-Garcia M.A.,University of Alcala | And 2 more authors.
Clinical Endocrinology | Year: 2013

Objective The prevalence of asymptomatic hyperprolactinaemia has been widely studied in certain populations such as antipsychotic drugs users, infertile women or patients with primary hypothyroidism, but data on the prevalence of hyperprolactinaemia and macroprolactinaemia in the healthy population are very scarce in the literature. We aimed to obtain an unbiased estimation of the prevalence in premenopausal women of: (i) hyperprolactinaemia and (ii) its aetiology, including macroprolactinaemia and stress-related hyperprolactinaemia, while considering simultaneously the use of hormonal contraceptives. Design Prevalence survey. Subjects Three-hundred and ninety-three consecutive premenopausal women reporting spontaneously for blood donation. Measurements We performed an exhaustive clinical history and physical examination, establishing the presence of hirsutism, acne, alopecia, menstrual dysfunction and reproductive history. We also measured serum prolactin (PRL) (ruling out macroprolactinaemia when indicated), thyrotrophin, total testosterone, androstendione, sex hormone binding globulin and dehydroepiandrosterone sulphate concentrations. Results Serum PRL concentrations were increased in 16 of 393 women (4·1% prevalence, 95% CI: 2·1-6·0). The prevalence of macroprolactinaemia was 0·6% (95% CI: 0-1) in the total female blood donor population and was 12·5% (95% CI: 6-31) among hyperprolactinaemic patients. The remaining hyperprolactinaemic women had stress-related hyperprolactinaemia as the more likely aetiology. Finally, the frequency of hyperprolactinaemia was similar in users and nonusers of hormonal contraceptives (4·5% and 3·9% respectively, P = 0·209). Conclusions The prevalence of hyperprolactinaemia in healthy female blood donors is low and is not influenced by the use of hormonal contraceptives. Pathological causes are very rare with stress-related hyperprolactinaemia and macroprolactinaemia being the most frequent causes of hyperprolactinaemia in these women. © 2013 John Wiley & Sons Ltd.

Calderon B.,Hospital Universitario Ramon y Cajal | Gomez-Martin J.M.,Hospital Universitario Ramon y Cajal | Vega-Pinero B.,Hospital Universitario Ramon y Cajal | Martin-Hidalgo A.,Hospital Universitario Ramon y Cajal | And 8 more authors.
Andrology | Year: 2016

To study the prevalence of male obesity-secondary hypogonadism (MOSH) in patients with moderate to severe obesity, we performed a prospective prevalence study including 100 male patients with moderate to severe obesity at a university tertiary hospital. Total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations among others were assayed in all patients. Serum-free testosterone (FT) concentration was calculated from TT and SHBG levels. Semen analysis was conducted in 31 patients. We found a prevalence of 45% (95% CI: 35-55%) when considering decreased TT and/or FT concentrations. Serum concentrations of TT were correlated negatively with glucose (r = -0.328, p < 0.001) and insulin resistance (r = -0.261, p = 0.011). The same occurred with FT and glucose (r = -0.340, p < 0.001) and insulin resistance (r = -0.246, p = 0.016). Sixty-two percent (95% CI: 39-85%) of the patients with seminogram also presented abnormal results in semen analysis. The frequencies of low TT or low FT values were similar in patients with abnormal or normal semen analysis (p = 0.646 and p = 0.346, respectively). Ejaculate volume inversely correlated with BMI (ρ = -0.400, p = 0.029) and with excess body weight (ρ = -0.464, p = 0.010). Our data show the prevalence of MOSH in patients with moderate to severe obesity is high. Low circulating testosterone is associated with insulin resistance and low ejaculate volume with higher BMI and excess body weight. Semen analysis must be performed in these patients when considering fertility whether or not presenting low circulating testosterone. © 2016 American Society of Andrology and European Academy of Andrology.

Insenser M.,University of Alcala | Insenser M.,Research Center Biomedica en Red Diabetes y Enfermedades Metabolicas Asociadas | Montes-Nieto R.,University of Alcala | Montes-Nieto R.,Research Center Biomedica en Red Diabetes y Enfermedades Metabolicas Asociadas | And 10 more authors.
Molecular and Cellular Endocrinology | Year: 2012

Subcutaneous (SAT) and visceral adipose tissue (VAT) differ in biochemical and metabolic properties, especially when obesity is present. We submitted paired SAT and VAT samples from six morbidly obese patients and six non-obese persons to two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight mass spectrometry. Compared with non-obese subjects, obese patients presented with increased carboxylesterase-1, zinc finger protein 324A, annexin A5, ubiquitin carboxyl-terminal hydrolase, α-crystallin B chain, osteoglycin, retinal dehydrogenase-1 and 14-3-3 protein γ, and decreased transferrin, complement C3, fibrinogen γ chain, albumin, α1-antitrypsin and peroxiredoxin-6, irrespective of the adipose tissue depot studied. SAT and VAT differed in protein species of fibrinogen and osteoglycin, whereas adipose tissue depot and obesity interacted on the protein abundance of actin, α-actinin 1, one protein species of carboxylesterase-1, retinal dehydrogenase-1 and 14-3-3 protein γ Our nontargeted proteomic approach identified novel protein species that may be involved in the development of obesity in humans. © 2012 Elsevier Ireland Ltd.

Alvarez-Blasco F.,University of Alcala | Alvarez-Blasco F.,Research Center Biomedica en Red Diabetes y Enfermedades Metabolicas Asociadas | Luque-Ramirez M.,University of Alcala | Luque-Ramirez M.,Research Center Biomedica en Red Diabetes y Enfermedades Metabolicas Asociadas | And 2 more authors.
Gynecological Endocrinology | Year: 2011

The polycystic ovary syndrome (PCOS) is a complex polygenic disorder in which environmental factors play an important modifying role. We aimed to find differences in diet and life-style that might contribute to the development of PCOS among overweight or obese premenopausal women. We compared diet composition and self-reported physical activity among 22 patients with PCOS and 59 women without androgen excess recruited from a total of 113 consecutive premenopausal women reporting for management of weight excess. After correcting for a difference in age between women with PCOS and controls, there were no overall statistical significant differences between them in the total caloric intake, in the intake of macro- and micro-nutrients, caffeine, fiber and alcohol, in the proportion of women exercising regularly, or in the number of hours of exercise per week. The proportion of fat in the diets of the overweight and obese women irrespective of PCOS was well-above current recommendations, yet this excessive fat intake occurred at the expense of monounsaturated fatty acids mostly. In conclusion, diet composition and physical activity were apparently not decisive for the development of PCOS among overweight and obese premenopausal women. © 2011 Informa UK, Ltd.

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