scholarly journals Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS

Reproduction ◽  
2016 ◽  
Vol 151 (4) ◽  
pp. 305-311 ◽  
Author(s):  
Javad Ranjbaran ◽  
Marzieh Farimani ◽  
Heidar Tavilani ◽  
Marzieh Ghorbani ◽  
Jamshid Karimi ◽  
...  

It is believed that matrix metalloproteinases (MMPs) play important roles in follicular development and pathogenesis of polycystic ovary syndrome (PCOS). However, conflicting results are available about the alteration of MMP2 and MMP9 concentrations or activities in PCOS. In fact, there is no study entirely investigating both concentration and activity of these MMPs and serum levels of their tissue inhibitors TIMP2 and TIMP1, as well as lipocalin-bound form of MMP9 (MMP9/NGAL). Therefore, the thoroughness of previous studies is questionable. This study was conducted to determine circulatory concentration of MMP2, MMP9, MMP9/NGAL complex, TIMP1 and TIMP2 as well as gelatinase activities of MMP2, MMP9 and MMP9/NGAL complex in women with PCOS and controls. Mean age and BMI as well as serum levels of total cholesterol, triacylglycerol, HDL-C, LDL-C, fasting blood sugar (FBS), insulin, estradiol and sex hormone-binding globulin did not differ between groups, whereas a marked decrease in FSH and significant increases in LH, LH/FSH ratio, testosterone and free androgen index were observed. Women with PCOS and controls showed closed concentrations of MMP2, MMP9, MMP9/NGAL, TIMP1 and TIMP2. Gelatinase activity of MMP9 was found significantly higher in PCOS than in controls (64.53±15.32 vs 44.61±18.95 respectively) while patients and healthy subjects showed similar activities of MMP2 and MMP9/NGAL complex. Additionally, PCOS patients showed a higher MMP9/TIMP1 ratio compared with control women. Direct correlations were also observed between circulatory MMP9 level and the concentration and activity of MMP9/NGAL complex. In conclusion, based on the results of present study, we believe that MMP9 may be involved in the pathogenesis of PCOS.

Reproduction ◽  
2017 ◽  
Vol 153 (5) ◽  
pp. 555-563 ◽  
Author(s):  
Patricia G Oppelt ◽  
Andreas Müller ◽  
Liana Stephan ◽  
Ralf Dittrich ◽  
Johannes Lermann ◽  
...  

Patients with the Mayer–Rokitansky–Küster–Hauser syndrome (MRKH) have a congenital utero–vaginal cervical aplasia, but normal or hypoplastic adnexa and develop with normal female phenotype. Some reports mostly demonstrated regular steroid hormone levels in small MRKH cohorts including single MRKH patients with hyperandrogenemia and a clinical presentationof hirsutism and acne has also been shown. Genetically a correlation of WNT4 mutations with singular MRKH patients and hyperandrogenemia was noted. This study analyzed the hormone status of 215 MRKH patients by determining the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, 17-OH progesterone, testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone–binding globulin (SHBG) and prolactin to determine the incidence of hyperandrogenemia and hyperprolactinemia in MRKH patients. Additional calculations and a ratio of free androgen index and biologically active testosterone revealed a hyperandrogenemia rate of 48.3%, hyperprolactinemia of 9.8% and combined hyperandrogenemia and hyperprolactinemia of 4.2% in MRKH patients. The rates of hirsutism, acne and especially polycystic ovary syndrome (PCOS) were in the normal range of the population and showed no correlation with hyperandrogenemia. A weekly hormone assessment over 30 days comparing 5 controls and 7 MRKH patients revealed high androgen and prolactin, but lower LH/FSH and SHBG levels with MRKH patients. The sequencing of WNT4, WNT5A, WNT7A and WNT9B demonstrated no significant mutations correlating with hyperandrogenemia. Taken together, this study shows that over 52% of MRKH patients have hyperandrogenemia without clinical presentation and 14% hyperprolactinemia, which appeals for general hormone assessment and adjustments of MRKH patients.


2018 ◽  
Vol 10 (1) ◽  
pp. 46
Author(s):  
Hartanto Bayuaji ◽  
Heda Melinda Nazaruddin Nataprawira ◽  
Herri Suhari Sastramihardja

BACKGROUND: Polycystic ovary syndrome (PCOS), a common reproductive endocrinologic disorder in woman, was considered to be related to sleep disturbance. This study is aimed to analyze the correlation between excess androgen markers and Athens Insomnia Scale (AIS) in PCOS.METHODS: This observational, cross-sectional study of PCOS was conducted to 31 subjects to evaluate the correlation between serum total testosterone, sex hormone binding globulin (SHBG) and free androgen index with the incidence of sleep disturbance using AIS. Sleep disturbance was present if the score ≥6. The correlation between excess androgen markers and sleep disturbance was analyzed using Pearson’s coefficient of correlation or Spearman’s rho test. Correlation coefficient more than 0.5 with p<0.05 was considered significant.RESULTS: Out of 31 PCOS subjects aged 20-40 years, 39% subjects had AIS score ≥6. Mean serum testosterone in AIS score >6 group was higher than AIS score <6 group but not statistically significant (46.68 vs. 28.49 ng/mL, p>0.05). No significant correlation was found between serum total testosterone, SHBG and free androgen index with AIS score. After adjusting for AIS score, there was the moderate positive correlation between serum total testosterone level although not statistically significant (r=0.54, p=0.07).CONCLUSION: The serum total testosterone level might influence the occurrence of sleep disturbance in PCOS.KEYWORDS: PCOS, androgen excess, testosterone, sleep disturbance, Athens Insomnia Scale


Author(s):  
P. Falcetta ◽  
E. Benelli ◽  
A. Molinaro ◽  
C. Di Cosmo ◽  
B. Bagattini ◽  
...  

Abstract Purpose To assess the distribution of clinical features and metabolic abnormalities of polycystic ovary syndrome (PCOS) women according to their age. Methods Retrospective study on 602 women (mean age 23.9 ± 6.2 years), diagnosed according to International PCOS Network Guidelines criteria as having PCOS in a University-based Hospital. Anthropometric features, hormonal and metabolic parameters were measured and compared between the different age groups (group A ≤ 20 years; group B 21–30 years; group C > 30 years). Results Patients in group A were more often hyperandrogenic, while in group C hypertension, dyslipidemia, obesity, impaired fasting glucose, and insulin resistance (IR) were more prevalent. After adjusting for BMI, age correlated positively with sex hormone-binding globulin (SHBG), IR, total- and LDL-cholesterol, and negatively with DHEAS, insulin, and free androgen index (FAI). SHBG was significantly associated with IR and atherogenic dyslipidemia, while FAI levels were linked to hypertension, independently of other factors considered. Furthermore, the regression analysis showed a stronger relationship between BMI and metabolic outcomes, regardless of age. Conclusion Polycystic ovarian syndrome (PCOS) phenotype changes with age. Clinical and biochemical hyperandrogenism are a major concern in young PCOS women, while metabolic burden tends to increase with aging. Some of the cardiovascular risk factors are dependent on FAI and SHBG levels, whereas BMI confirms its key role in the genesis of most of the metabolic sequelae in PCOS, independently of age.


Author(s):  
Maria Forslund ◽  
Johanna Schmidt ◽  
Mats Brännström ◽  
Kerstin Landin-Wilhelmsen ◽  
Eva Dahlgren

Abstract Context There is a lack of knowledge about hormonal and anthropometric changes in women with polycystic ovary syndrome (PCOS) after the menopause. Objective This work aimed to study reproductive hormones and anthropometry in women with PCOS older than 80 years. Design and Setting This prospective cohort study was conducted at a university hospital. Patients A well-defined cohort of women with PCOS, previously examined in 1987 and 2008 (21 years) was reexamined in 2019 (11 years). Of the original cohort (n = 37), 22 women were still alive and 21 (age range, 72-91 years) participated. Comparisons were made with age-matched controls (n = 55) from the original control cohort (body mass index [BMI] similar to PCOS women). The results were compared with results from 1987 and 2008. Interventions Hormonal measurements and a physical examination were performed. Main Outcome Measures Follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, sex hormone–binding globulin (SHBG), free androgen index (FAI), hirsutism score, BMI, and waist to hip ratio (WHR) were measured. Results At mean age 81 years, FSH levels were lower in women with PCOS (50 vs 70 IU/L) who were still more hirsute than controls (33% vs 4%). No differences were found in FAI, testosterone, SHBG or LH levels, BMI, or WHR. From perimenopausal age until the present age, levels of testosterone and FAI continued to decline in women with PCOS. SHBG levels continued to increase with age. FSH had not changed over time during the last 11 years. Conclusions Women with PCOS at age 72 to 91 had lower FSH levels, remained clinically hyperandrogenic, and had similar FAI and body composition as controls.


2021 ◽  
Author(s):  
Marika Paalanne ◽  
Marja Vääräsmäki ◽  
Sanna Mustaniemi ◽  
Marjaana Tikanmäki ◽  
Karoliina Wehkalampi ◽  
...  

Objective: It has been suggested that adverse early life exposures increase the risk of developing polycystic ovary syndrome (PCOS) in later life. We hypothesized that women born preterm would have more biochemical and clinical signs of PCOS than women born at term. Design: The ESTER Preterm Birth Study participants were born in Northern Finland, and identified from the Northern Finland Birth Cohort and the Finnish Medical Birth Register. Altogether, 74 women born very or moderately preterm (<34 gestational weeks, VMPT), 127 born late preterm (at 34–36 weeks, LPT), and 184 born full term (≥37 weeks, controls) were included in the analysis (mean age 23.2y). Methods: We measured serum total testosterone and sex hormone binding globulin (SHBG) and calculated free androgen index (FAI). PCOS according to the clinical and biochemical signs was defined either as hirsutism and oligoamenorrhea (via questionnaire), or as oligoamenorrhea and elevated testosterone levels (>2.4 nmol/l). Results: Women born VMPT/LPT exhibited 33.0% (8.7, 62.8)/16.4% (-2.0, 38.1) higher testosterone, 28.5% (5.3, 45.9)/24.1% (5.6, 38.9) lower SHBG levels, and 64.6% (19.4, 127.1)/ 42.5% (11.1, 82.9) higher FAI than controls after adjusting for age and recruitment cohort, maternal BMI, smoking, and pregnancy disorders, parental education, history of hypertension, diabetes, myocardial infarction or stroke, and subject’s birth weight SD. Odds ratios for having PCOS were 1.67 (0.44, 6.23)/3.11 (1.26, 7.70). Conclusions: Women born preterm have a more hyperandrogenic hormonal profile, and those born LPT are approximately three times more likely at risk to have PCOS compared to women born at term.


2003 ◽  
Vol 88 (12) ◽  
pp. 5976-5980 ◽  
Author(s):  
Nectaria Xita ◽  
Agathocles Tsatsoulis ◽  
Anthi Chatzikyriakidou ◽  
Ioannis Georgiou

Abstract SHBG levels are frequently low in women with polycystic ovary syndrome (PCOS) and may contribute to increased tissue exposure to free androgens. A (TAAAA)n repeat polymorphism in the promoter of the SHBG gene has been described recently, and its transcriptional activity has been shown to be related to the number of tandem repeats. Recent evidence also suggests that prenatal exposure to androgen excess may program for the development of the PCOS phenotype during adulthood. Our aim was to investigate the possible association of the functional (TAAAA)n polymorphism in the promoter of the SHBG gene with PCOS and its relation to SHBG levels. We studied 185 women with PCOS and 324 normal controls. Genotype analysis revealed six (TAAAA)n alleles containing 6–11 repeats. The distribution of these alleles was different in the two groups. Women with PCOS had a significantly greater frequency of longer (TAAAA)n alleles (more than eight repeats) than normal women who had shorter alleles (less than eight repeats) in higher frequency (P = 0.001). Furthermore, in the PCOS group, carriers of the longer allele genotypes had lower SHBG levels [1.17 ± 0.68 μg/dl (35.1 ± 20.5 nmol/liter)] than those with shorter alleles [1.51 ± 0.93 μg/dl (45.3 ± 28 nmol/liter P = 0.02). A novel (TAAAA)n allele, which has not been previously reported, was found in low frequency, mainly in the control population. From these results, there is evidence that there may be a genetic contribution to decreased SHBG levels frequently seen in women with PCOS. The SHBG gene may act as a susceptibility gene for PCOS and may provide the genetic link for the developmental origin hypothesis for PCOS that was recently proposed on the basis of experimental observation in prenatally androgenized sheep and primates.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Wang ◽  
Jiahua Zheng ◽  
Na Cui ◽  
Lei Jiang ◽  
Han Zhou ◽  
...  

Abstract Polycystic ovary syndrome (PCOS) is a complex endocrine disorder and regarded as the leading cause of anovulatory infertility. PCOS is characterized by reproductive dysfunction and metabolic disorders. Baicalin (BAL) is one of the most potent bioactive flavonoids isolated from the radix of Scutellaria baicalensis. In the present study, we investigated the potential effects of BAL on PCOS in dehydroepiandrosterone-treated rats. We found that BAL notably reduced the serum levels of free testosterone, total testosterone, follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol in PCOS rats. The increase of serum insulin level and HOMA-IR was markedly inhibited by BAL. Moreover, BAL decreased body weights, increased the number of rats with the regular estrous cycle, and ameliorated ovarian histological changes and follicular development in the DHEA-treated PCOS rats. The increase of pro-inflammatory cytokines (TNFα, IL-1β, and IL-18) and decrease of anti-inflammatory cytokine (IL-10) in PCOS rats were suppressed by BAL. BAL induced a significant decrease in the mRNA expression of steroidogenic enzymes, including 3β-HSD, CYP11A1, CYP19A1, StAR, in ovarian tissues in PCOS rats. Furthermore, BAL inhibited the decrease of AMPK protein level and phosphorylation, the decrease of Akt phosphorylation and the increase of 5α-reductase enzyme 1 expression in ovarian tissues in PCOS rats. The effects of BAL were inhibited by an inhibitor of AMPK, dorsomorphin. The upregulation of AMPK contributed to the beneficial effects of BAL. The results highlight the potential role of BAL for the intervention of PCOS.


Author(s):  
Gislaine Satyko Kogure ◽  
Victor Barbosa Ribeiro ◽  
Flávia Ganoa de Oliveira Gennaro ◽  
Rui Alberto Ferriani ◽  
Cristiana Libardi Miranda-Furtado ◽  
...  

Abstract Objective The present study aimed to investigate the physical performance of handgrip strength (HGS) in women with polycystic ovary syndrome (PCOS). Methods A case-control study that included 70 women with PCOS and 93 age-matched healthy women aged between 18 and 47 years with body mass index (BMI) between 18 Kg/m2–39.9 Kg/m2. The serum levels of total testosterone, androstenedione, insulin, estradiol, thyroid-stimulating hormone (TSH), prolactin, sex hormone-binding globulin (SHBG), and 17-hydroxyprogesterone (17-OHP) were measured. The free androgen index (FAI) and the homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. The body composition regions of interest (ROIs) were assessed by dual-energy X-ray absorptiometry (DXA), and the handgrip strength (HGS) was evaluated for both the dominant and the non-dominant hands with a manual Sammons Preston (Bolingbrook, IL, US) bulb dynamometer. Results Women with PCOS had high serum levels of total testosterone (p < 0.01), androstenedione (p = 0.03), and insulin (p < 0.01), as well as high FAI (p < 0.01) and HOMA-IR (p = 0.01) scores. Compared with the non-PCOS group, the PCOS group had greater total lean mass in the dominant hand (p < 0.03) and greater HGS in both the dominant and the non-dominant hands (p < 0.01). The HGS was correlated with lean mass (p < 0.01). Conclusion Women with PCOS have greater HGS. This may be associated with age and BMI, and it may be related to lean mass. In addition, the dominance effect on muscle mass may influence the physical performance regarding HGS in women with PCOS.


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