Anastasia K. Armeni

Measurement of salivary resistin, visfatin and adiponectin levels

Hormonal determination in saliva offers several advantages. Peptides enter the salivary glands either by active transport mechanisms or are expressed and secreted by the salivary glands themselves. The collection of saliva is a noninvasive, easily repeatable and less stressful technique than blood withdrawal. The purpose of the present study was to introduce a method for measuring salivary resistin, visfatin and adiponectin levels and to evaluate their associations with serum levels. Resistin, visfatin and adiponectin levels were measured in serum and saliva of 50 healthy adult volunteers (17 male and 33 female) using commercial enzyme immunoassay kits for serum with minor modifications. The present study documented the determination of resistin and adiponectin levels in saliva and the significant correlation of salivary levels with serum levels (r=0.441, p<0.01 and r=0.347, p<0.05, respectively). Moreover, the identification of visfatin in saliva was achieved, but no significant correlation with serum visfatin levels was observed. To our knowledge, this is the first study to report the determination of resistin and visfatin in saliva and the significant correlation of salivary resistin with serum levels, while it confirmed the significant association between salivary and serum adiponectin. The introduction of salivary determinations of adipokines could contribute to the elucidation of the physiology and the role of the specific adipokines in various clinical conditions (obesity, insulin resistance, inflammation, reproduction, energy imbalance and stress response).

Serum Anti-Müllerian hormone (AMH) levels are differentially modulated by both serum gonadotropins and not only by serum Follicle Stimulating Hormone (FSH) levels

It is generally accepted that serum AMH levels are thought to reflect the size of the ovarian follicle pool. Therefore, an inverse correlation between serum AMH and Follicle Stimulating Hormone (FSH) levels has been noted in older women with abnormal or exhausted follicular development, such as menopause, leading to the use of serum AMH as a marker of ovarian reserve. In clinical practice the use of serum AMH for the assessment of ovarian reserve has been expanding to women irrespective of age, such as women in early menopause or women undergoing ovarian stimulation for in vitro fertilization (IVF). To our knowledge, this opinion article aims to show that serum AMH levels are differentially modulated by both serum gonadotropins, depending on the degree of ovarian reserve. For instance, in conditions of increased LH and normal to low FSH such as young PCOS women with hyperandrogenemia, serum AMH levels are increased and tend to be associated to serum LH, while in conditions of increased FSH such as premature ovarian failure, serum AMH levels are decreased and tend to be associated to serum FSH. The evidence that supports the theory of a link between AMH and LH in PCOS comes from both in vitro and in vivo experiments. Serum AMH levels have been directly linked to serum LH levels in the most severe forms of PCOS. LH has also been shown in vitro to directly increase serum AMH levels in PCOS derived granulosa cells. Finally, hyperandrogenism, obesity, insulin resistance and OCs administration, indirectly affect serum AMH levels, by modulating serum LH. Concerning PCOS, the correlation between AMH and LH can be used in the future for the assessment of the severity of PCOS, of the amelioration of PCOS under OCs treatment, as well as of the efficacy of infertility treatment in clomiphene resistant PCOS women. Apart from PCOS, the clinical implications of this theoretical approach might become important in a variety of medical conditions. For instance, serum AMH levels might be used in the future as a marker of cysts formation in the ovaries as well as of ovarian endometriosis, or as a marker of ovarian response to treatment of ovarian cysts or ovarian endometriosis by oral contraceptives, etc. Additionally, in infertile women with hypothalamic amenorrhea, serum AMH levels might be used for the assessment of ovarian recovery under treatment.

The effect of prolonged aerobic exercise on serum adipokine levels during an ultra-marathon endurance race.

OBJECTIVE: To evaluate the effect of prolonged intensive aerobic exercise and acute energy deficit (180 km ultra-marathon race) on serum leptin, adiponectin, resistin and visfatin levels and their association and interaction with serum cortisol and insulin levels in highly trained ultra-endurance runners. DESIGN: The study included 17 highly trained ultra-endurance male athletes (mean age 51.29±6.84 years and body mass index (BMI) 23.51±1.90) participating in the 5th Olympian Race held in Greece on May 2010. Anthropometric values were assessed; serum cortisol, insulin, leptin, adiponectin, resistin and visfatin levels were measured at baseline, post-exercise and ∼20 hours after the end of the race. RESULTS: All hormonal values of the post-exercise and recovery status were corrected for plasma volume changes. The estimated energy deficit during the ultra-endurance event was about 5000 Kcal. At the end of the race serum resistin levels were elevated (p<0.001) and serum leptin levels were reduced (p<0.001) and failed to reach pre-exercise levels, although showing a tendency towards restoration. No significant changes were noted in serum adiponectin and visfatin levels. CONCLUSIONS: Ultra-endurance aerobic exercise and acute negative energy balance lead to an up-regulation of serum resistin levels and a down-regulation of serum leptin levels.

Elevated serum androstenedione is associated with a more severe phenotype in women with polycystic ovary syndrome (PCOS)

OBJECTIVETo evaluate the impact of elevated serum Δ4A levels on the hormonal and metabolic features of the different phenotypes of PCOS.DESIGN1276 women with PCOS according to the Rotterdam criteria were included, in whom serum hormonal levels were determined.RESULTSIn PCOS women as a whole, as well as in patients presenting clinical and/or biochemical hyperandrogenemia (phenotypes I and II), Δ4A levels >3.8 ng/ml were positively related to LH, LH/FSH ratio, T, DHEAS, 17 OH progesterone and FAI and negatively related to T/Δ4A ratio. In the milder phenotype III, a positive correlation between Δ4A levels >3.8 ng/ml and T, DHEAS, 17 OH progesterone and FAI and a negative one between increased Δ4A and T/Δ4A ratio were reported. In the whole PCOS group with androstenedione >3.8 ng/ml, an increased ovarian volume was observed, while a greater mean follicular number was found only in phenotypes I and II.CONCLUSIONSIncreased serum Δ4A levels, which are associated with more severe PCOS phenotypes, possibly contribute to the worsening of PCOS features and therefore could be a valuable marker of biochemical hyperandrogenemia.

Growth velocity and final height in elite female rhythmic and artistic gymnasts

PURPOSEThe aim of this study was to determine the impact of intensive training on adult final height in elite female rhythmic and artistic gymnasts.METHODSThe study included 215 rhythmic gymnasts (RG) and 113 artistic gymnasts (AG).RESULTSAG were below the 50th percentile, while RG were taller than average. Final adult height was lower than target height in AG, while in RG, it exceeded target height. AG started training earlier than RG (p<0.001) and reported lower intensity of training (p<0.001). RG were taller than AG, with higher target height, greater final height-target height and lower body fat and BMI (p<0.001). Using multiple regression analysis, the main factors influencing final height were weight SDS (p<0.001), target height SDS (p<0.001) and age of menarche (p<0.001) for RG, and weight SDS (p<0.001) and target height SDS (p<0.001) for AG.CONCLUSIONIn both elite female RG and AG, genetic predisposition to final height was not disrupted and remained the main force of growth. Although in elite RG genetic predisposition for growth was fully preserved, in elite female AG final adult height falls shorter than genetically determined target height, though within the standard error of prediction.

Increased frequency of the DI genotype of the angiotensin-I converting enzyme and association of the II genotype with insulin resistance in polycystic ovary syndrome

OBJECTIVE The polycystic ovary syndrome (PCOS) is a common and complex disease with unclear pattern of inheritance, characterized by an androgen excess, while hyperinsulinemia and insulin resistance (IR) are common features of the syndrome. The angiotensin I converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism was proved to be involved in many pathophysiological conditions, including hypertension and IR. DESIGN The purpose of this study was to evaluate the involvement of the ACE gene polymorphism in the pathogenesis of PCOS. METHODS In a case-control association study involving 801 PCOS women and 266 healthy controls, hormonal determinations and ACE polymorphism genotyping were performed. The PCOS women were classified into three groups: Group A presented biochemical hyperandrogenism, combined with anovulation and polycystic ovarian morphology; Group B, clinical hyperandrogenism combined with anovulation and polycystic ovarian morphology; and Group C, chronic anovulation and polycystic ovarian morphology. RESULTS A significant increase in the frequency of the DI genotype of the ACE polymorphism was detected in PCOS women as a whole (P=0.035), in PCOS Group A (P=0.039) and Group B (P=0.010), while there was no difference in Group C (P=0.939). Significant difference was also observed in hyperandrogenic PCOS women as a whole (Group A+B) (P=0.017). The II genotype was positively correlated with HOMA-IR and QUICKI and with fasting insulin and glucose/insulin ratio in these groups. CONCLUSIONS The association study of the ACE I/D polymorphism in PCOS women demonstrates an increase in the DI genotype incidence and an association of the II genotype with IR.

Increased Frequency of the Anti-Müllerian-Inhibiting Hormone Receptor 2 (AMHR2) 482 A>G Polymorphism in Women With Polycystic Ovary Syndrome: Relationship to Luteinizing Hormone Levels

CONTEXT The polycystic ovary syndrome (PCOS) is a common and complex disease without a clear pattern of inheritance. Anti-Müllerian hormone (AMH) has an inhibitory effect on FSH-stimulated follicle growth. Serum AMH levels are higher in women with PCOS than in normo-ovulatory women. The elevated AMH levels may reflect abnormalities in AMH signaling. OBJECTIVE The purpose of this study was to evaluate the association of the anti-Müllerian hormone receptor 2 (AMHR2) -482 A>G polymorphism (rs2002555) with the pathophysiology of PCOS. DESIGN AMHR2 -482 A>G polymorphism genotyping were performed in a large cohort of women with PCOS and in a healthy control group. SETTING/SUBJECTS A total of 858 Caucasian Greek women with PCOS and 309 healthy control women were studied. INTERVENTIONS Genotyping and hormonal measurements were preformed. MAIN OUTCOME MEASURES Hormone levels in women with PCOS were analyzed. RESULTS The AMHR2 polymorphism was more common in women with PCOS than in control women (P = .026). Homozygous AMHR2 -482 A>G gene polymorphisms (GG) were associated with decreased levels of LH (P = .003) and lower LH to FSH ratios (P = .01) in women with PCOS, as well as with lower prolactin levels (P = .004). No other associations related to AMHR2 -482 A>G polymorphisms were observed in women with PCOS or control women. CONCLUSION In this study, the role of the AMHR2 -482 A>G gene polymorphism in the pathogenesis of PCOS was suggested by the association of the variant with PCOS risk. Thus, further research is needed to elucidate a possible association of the AMHR2 -482 A>G gene polymorphism with AMH signaling and impaired ovarian function and its clinical significance in women with PCOS.

Association of estrogen receptor alpha (ERα) gene polymorphisms with endometrial thickness and lipid profile in women with breast cancer treated with aromatase inhibitors.

Aromatase inhibitors (AIs) provide an alternative to tamoxifen as an adjuvant therapy for post-menopausal, hormone-receptor positive breast cancer patients. The aim of the present study was to evaluate the effect of PvuII and XbaI polymorphisms of the ERα gene at ΑΙs treatment’s adverse effects in post-menopausal women with breast cancer. The study included 87 post-menopausal women with ER-positive breast cancer treated with AIs and 80 healthy controls. The overall presence of ERα polymorphisms in all women with breast cancer was not different from the healthy controls. Endometrial thickness under AIs treatment was reduced from (mean value ± SD) 6,404 ± 2,901 mm to 3,666 ± 1,4656 mm. Moreover, the AA XbaI genotype was associated with greater reduction in endometrial thickness during therapy with AIs (p = 0.005). The presence of the CC PvuII and the AA XbaI genotypes were associated with elevated LDL levels and elevated triglycerides. In conclusion, the results of the present study showed that the genotype of women with breast cancer under AIs treatment might influence treatment’s adverse effects, as, the presence of the CC PvuII and the AA XbaI genotypes of the ERα were associated with elevated LDL and triglycerides serum levels, while the AA XbaI genotype was associated with a greater reduction in endometrial thickness.

No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia

PurposeThe aim of the present study was to determine the prevalence and association of the G972S polymorphism of the insulin receptor substrate-1 gene (IRS-1 G972S SNP) with polycystic ovary syndrome (PCOS) and insulin resistance-related traits in a distinct phenotypic group of lean PCOS women with biochemical hyperandrogenemia, excluding obesity, which is considered to be an aggravating parameter of insulin resistance.MethodsThe study included 162 women with PCOS and 122 regularly menstruating, ovulatory women as controls. Physical measurements included weight, height, fat-free mass, fat mass, systolic and diastolic blood pressure and resting heart rate. Biochemical parameters included the serum testosterone, free testosterone, androstenedione, total cholesterol, triglycerides, HDL and LDL cholesterol and glucose levels. Insulin resistance was assessed by determining fasting insulin levels, fasting glucose levels, the fasting glucose/insulin ratio, as well as the HOMA and QUICKI indexes. All DNA samples were genotyped by a PCR–restriction fragment length polymorphism (RLFP) assay.ResultsNo association of the genotype frequencies of the G972S polymorphism in insulin receptor substrate-1 gene (IRS-1 G972S SNP) with PCOS phenotype and insulin resistance was detected.ConclusionThe G972S polymorphism of the IRS-1 gene should not be viewed as major contributor to the development of PCOS or as a causative variant for insulin resistance.

The influence of obesity on Androstenedione to Testosterone ratio in women with polycystic ovary syndrome (PCOS) and hyperandrogenemia

The aim of the present study was to evaluate the impact of obesity and insulin resistance on testosterone formation from androstenedione and its contribution to biochemical hyperandrogenemia in all different phenotypic subgroups of PCOS patients. The case-control study included 1087 PCOS women and 206 regularly menstruating, ovulatory controls. The main clinical measurements included anthropometric and basal hormonal characteristics and evaluation of hyperandrogenic and insulin resistance-related features. The results were the following: In PCOS women with biochemical hyperandrogenemia, obesity significantly lowers serum A levels and increases T to A ratio. These findings were not present in PCOS women with clinical hypeandrogenemia and in normal ovulatory controls.