Analysis of polycystic ovary syndrome phenotypes and their impact on metabolic disturbancies

Sindrom policističnih jajnika (PCOS) je najčešća endokrinopatija kod žena u reproduktivnoj životnoj dobi. Zbog heterogenih kliničkih manifestacija sindroma, PCOS ima varijabilnu prevalencu, između 6% i 25% u različitim populacijama. Udružen je sa različitim reproduktivnim (hiperandrogenizam, menstrualna disfunkcija, infertilitet, spontani pobačaji u ranoj trudnoći, gestacioni dijabetes, hipertenzivni poremećaji u trudnoći, neonatalne komplikacije) i metaboličkim poremećajima (gojaznost, insulinska rezistencija-IR, oštećena tolerancija glukoze-IGT, dijabetes melitus tip 2-DMT2, hiperlipidemija, hipertenzija). Većina ovih metaboličkih poremećaja se obično manifestuje zajedno formirajući metabolički sindrom (MetS) koji predstavlja poznati faktor rizika za razvoj kardiovaskularnih bolesti (KVB). Po svemu sudeći IR je ključni faktor u etiologiji i metaboličkih ali i reproduktivnih komplikacija PCOS, ali i dalje nije jasno da li je IR intrinzična karakteristika PCOS ili samo posledica gojaznosti. Sa razvojem ESHRE/ASRM Roterdamskih kriterijuma za dijagnozu PCOS, pored ranije poznatih klasičnih fenotipova A (hiperandrogenizam-HA, anovulacija-ANOV i morfološki policistični jajnici prema ultrazvučnom nalazu-PCOM) i B (HA i ANOV), pojavila su se dva nova, ne-klasična fenotipa: C (HA i PCOM) i D (ANOV i PCOM). Iako postoji malo metodološki komplementarnih studija, često verifikovani diskretniji endokrinološki i metabolički poremećaji u ne-klasičnim fenotipovima su razlog kontinuirane debate stručne javnosti o tome da li ovi fenotipovi zaista mogu biti deo kompleksnog sindroma kao što je PCOS. Do sada postoje ograničena saznanja o relativnoj prevalenci kardiometaboličkih faktora rizika u različitim PCOS fenotipovima. Cilj ovog istraživanja je analiza endokrinoloških i metaboličkih karakteristika četiri različita PCOS fenotipa u našoj populaciji. Metodologija: Analizirali smo 365 žena sa PCOS (starosti: 25.48 ± 5.21 godina, indeksa telesne mase-BMI: 25.05 ± 6.24 kg/m2) i 125 zdravih žena (starosti: 30.35 ± 5.62 godina; BMI 24.50 ± 5.16 kg/m2). PCOS je dijagnostikovan pomoću ESHRE/ASRM kriterijumima, koji zahtevaju prisustvo najmanje dva od tri sledeća kriterijuma: ovulatorna disfunkcija, hiperandrogenizam i morfološki policistični jajnici prema nalazu na ultrazvuku...The polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. Because of heterogeneous clinical manifestations of the syndrome, it has variable prevalence that ranges from 6% to 25% in different populations. It is associated with a range of reproductive (hyperandrogenism, menstrual dysfunction, infertility, early pregnancy loss, gestational diabetes, pregnancy-induced hypertensive disorders and neonatal complications) and metabolic features (obesity, insulin resistance-IR, impaired glucose tolerance-IGT, diabetes mellitus type 2-DMT2, hyperlipidemia, hypertension). Majority of these metabolic disturbances are usually manifested together forming metabolic syndrome (MetS), a well known risk factor for cardiovascular diseases (CVD). It seems that IR is a key factor in etiology of both metabolic and reproductive complications of PCOS and there is ongoing debate as to whether this IR is intrinsic to PCOS, related to obesity alone or related to both factors. With introduction of ESHRE/ASRM Rotterdam criteria for diagnosis of PCOS, besides previously known classic phenotypes A (hyperandrogenism-HA, anovulation-ANOV and morphologically polycystic ovaries-PCOM) and B (HA and ANOV), two new, non-classic phenotypes: C (ovulatory phenotype: HA+PCOM) and D (non-hyperandrogenic phenotype: ANOV+PCOM) have emerged. Although there are few, methodologically complementary studies, more frequently observed less severe endocrine and metabolic features of non-classic PCOS phenotypes are the reason for ongoing debate weather these phenotypes could really be a part of complex syndrome like PCOS. To date, there is limited understanding of the relative prevalence of cardiometabolic risk factors across the different PCOS phenotypes. The aim of the study was to analyze endocrine and metabolic characteristics of four different PCOS phenotypes in our population Methodology: We analyzed 365 women with PCOS (age: 25.48 ± 5.21 years; body mass index-BMI 25.05 ± 6.24 kg/m2) and 125 healthy controls (age: 30.35 ± 5.62 years; BMI 24.50 ± 5.16 kg/m2). PCOS was diagnosed according to the ESHRE/ASRM criteria, requiring the presence of at least two out of the three following criteria: ovulatory dysfunction, androgen excess, and polycystic morphology of ovaries assessed by ultrasound..

The effect of metformin on clinical features of women with polycystic ovary syndrome

Introduction: Insulin resistance (IR) is one of the main features of polycystic ovary syndrome (PCOS), and metformin is one of the most commonly prescribed insulin sensitizers in its treatment. Research carried out so far shows heterogeneous results on the effects of metformin on the hormonal and metabolic status of women with PCOS. The aim of the study was to investigate the effect of six-month treatment with metformin (2000 mg per day) on the hormonal and metabolic characteristics of women with PCOS, paired with healthy women by body mass index (BMI) and age. Material and Methods: A number of 20 women with PCOS [age: 23.5 ± 5.9 years, BMI: 24.8 ± 4.2kg / m2] and 20 healthy control group women were tested (age: 24.5 ± 5.3 years, BMI: 23.6 ± 3.0kg / m2). Polycystic ovary syndrome was diagnosed with ESHRE / ASRM criteria. Standard biochemical and hormonal parameters were determined, which were repeated in the PCOS group and after six months of metformin therapy. Insulin resistance was determined using a homeostatic model (HOMA-IR). Results: After six months of metformin therapy in the PCOS group, there was a significant increase in the frequency of menstrual cycle (65% versus 87%, p <0.001), reduction of the degree of hirzutism towards Ferrimann - Galway score (9.5 versus 8.5, p = 0.025), but after the therapy all parameters were still significantly different from the ZK group. After therapy, there was no difference in the concentration of triglycerides between PCOS and ZK (1.3 ± 0.7 versus 0.9 ± 0.4 mmol / L, p = 0.19), which were significantly higher in PCOS compared to ZK before therapy (1.4 ± 0.8 vs 0.9 ± 0.4 mmol / L, p = 0.03). There was no significant effect of BMI therapy, as well as on HOMA-IR and the concentration of androgens that were significantly higher in PCOS compared to ZK, while there was a favorable effect of metformin on the liver. Conclusion: Six-month treatment with metformin, at a dose of 2000 mg per day in women with PCOS, leads to a significant increase in the incidence of menstrual cycle, ovulation and reduction in the degree of hirsutism, as well as a beneficial effect on lipids and liver, and the independent effects of the drug on BMI and IR

Gojaznost i reproduktivna funkcija žene - mehanizmi nastanka i terapijske implikacije

Gojaznost se danas smatra uzrokom nastanka kardiovaskularne bolesti, tipa 2 dijabetesa, osteoartritisa, maligniteta, ali i faktorom koji doprinosi nastanku reproduktivnih poremećaja i problema plodnosti. Postoji povećan relativni rizik za nastanak anovulatornog infertiliteta u žena sa izraženom gojaznošću i produženo vreme do koncepcije. U žena u reproduktivnom periodu gojaznost je povezana sa povećanim rizikom za nastanak hiperandrogenizma i anovulacije, kao što je slučaj u sindromu policističnih jajnika (PCOS) kao najčešćem hiperandrogenom poremećaju. Postoji veliki broj dokaza u prilog postojanja bliskog odnosa adipokina, gojaznosti, metaboličkog sindroma i reproduktivnih posledica. Redukcija težine za 5-10% dovodi do poboljšanja u kliničkim, metaboličkim i reproduktivnim karakteristikama, kao što je slučaj u žena sa PCOS. Primena insulinskih senzitajzera vodi sniženju hiperinsulinemije, insulinske rezistencije, uspostavljanju normalne menstrualne cikličnosti i ovulacije kod značajnog broja žena sa PCOS. Gojaznost može uticati na stimulaciju ovulacije njenim produžavanjem, povećanjem doze gonadotropina, incidence folikularne asinhronije i prekida stimulacije. Hirurško lečenje gojaznosti predstavlja alternativni vid terapije u slučaju kada ni promena načina života ni farmakoterapijske mere ne daju povoljne rezultate. Za sada ne postoji dovoljno dokaza u prilog preporuke da se barijatrijska hirurgija koristi u lečenju gojaznih žena sa PCOS.Projekat ministarstva br. 175032 i br. 4100

Gojaznost i reproduktivna funkcija žene - mehanizmi nastanka i terapijske implikacije

Gojaznost se danas smatra uzrokom nastanka kardiovaskularne bolesti, tipa 2 dijabetesa, osteoartritisa, maligniteta, ali i faktorom koji doprinosi nastanku reproduktivnih poremećaja i problema plodnosti. Postoji povećan relativni rizik za nastanak anovulatornog infertiliteta u žena sa izraženom gojaznošću i produženo vreme do koncepcije. U žena u reproduktivnom periodu gojaznost je povezana sa povećanim rizikom za nastanak hiperandrogenizma i anovulacije, kao što je slučaj u sindromu policističnih jajnika (PCOS) kao najčešćem hiperandrogenom poremećaju. Postoji veliki broj dokaza u prilog postojanja bliskog odnosa adipokina, gojaznosti, metaboličkog sindroma i reproduktivnih posledica. Redukcija težine za 5-10% dovodi do poboljšanja u kliničkim, metaboličkim i reproduktivnim karakteristikama, kao što je slučaj u žena sa PCOS. Primena insulinskih senzitajzera vodi sniženju hiperinsulinemije, insulinske rezistencije, uspostavljanju normalne menstrualne cikličnosti i ovulacije kod značajnog broja žena sa PCOS. Gojaznost može uticati na stimulaciju ovulacije njenim produžavanjem, povećanjem doze gonadotropina, incidence folikularne asinhronije i prekida stimulacije. Hirurško lečenje gojaznosti predstavlja alternativni vid terapije u slučaju kada ni promena načina života ni farmakoterapijske mere ne daju povoljne rezultate. Za sada ne postoji dovoljno dokaza u prilog preporuke da se barijatrijska hirurgija koristi u lečenju gojaznih žena sa PCOS.Projekat ministarstva br. 175032 i br. 4100

Overweight and Obesity in Polycystic Ovary Syndrome: Association with Inflammation, Oxidative Stress and Dyslipidemia

Objective: Polycystic ovary syndrome (PCOS) is associated with altered lipid profile and increased small, dense LDL particles (sdLDL). Considering that paraoxonase 1 (PON1) is an anti-oxidative enzyme located on high-density lipoprotein (HDL) particles, the aim of this study was to investigate the connection between oxidative stress (OS) and PON1 activity with lipoprotein subclasses in PCOS depending on obesity. Methods: In 115 PCOS patients lipoprotein subclasses distributions were determined by gradient gel electrophoresis. OS status was assessed by total oxidative status (TOS), advanced oxidation protein products (AOPP), malondialdehyde (MDA), prooxidant-Antioxidant balance (PAB), total antioxidant status (TAS) and superoxide dismutase (SOD) and PON1 activity. Results: Overweight/obese PCOS patients (n=55) had increased OS compared to normal weight patients (n=60). In addition, overweight/obese group had lower HDL size and higher proportion of HDL 3a subclasses (P<0.05). PAB was in negative correlation with HDL 2a (P<0.001), whereas MDA and SOD correlated positively with HDL 3 subclasses (P<0.05). Serum PON1 activity was positively associated with proportions of PON1 activity on HDL 2b (P<0.05) and 2a (P<0.01), but negatively with the proportion on HDL 3 particles (P<0.01). LDL B phenotype patients had increased TAS, SOD and PON1 activity on HDL 2b, but decreased PON1 activity on HDL 3 subclasses. Conclusion: OS is associated with altered lipoprotein subclasses distribution in PCOS patients. Obesity in PCOS affects the profile of HDL subclasses, reflected through the reduced proportion of PON1 activity on HDL 3 subclasses in the presence of sdLDL particles.Peer-reviewed manuscript: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/3974

Analysis of polycystic ovary syndrome phenotypes and their impact on metabolic disturbancies

Sindrom policističnih jajnika (PCOS) je najčešća endokrinopatija kod žena u reproduktivnoj životnoj dobi. Zbog heterogenih kliničkih manifestacija sindroma, PCOS ima varijabilnu prevalencu, između 6% i 25% u različitim populacijama. Udružen je sa različitim reproduktivnim (hiperandrogenizam, menstrualna disfunkcija, infertilitet, spontani pobačaji u ranoj trudnoći, gestacioni dijabetes, hipertenzivni poremećaji u trudnoći, neonatalne komplikacije) i metaboličkim poremećajima (gojaznost, insulinska rezistencija-IR, oštećena tolerancija glukoze-IGT, dijabetes melitus tip 2-DMT2, hiperlipidemija, hipertenzija). Većina ovih metaboličkih poremećaja se obično manifestuje zajedno formirajući metabolički sindrom (MetS) koji predstavlja poznati faktor rizika za razvoj kardiovaskularnih bolesti (KVB). Po svemu sudeći IR je ključni faktor u etiologiji i metaboličkih ali i reproduktivnih komplikacija PCOS, ali i dalje nije jasno da li je IR intrinzična karakteristika PCOS ili samo posledica gojaznosti. Sa razvojem ESHRE/ASRM Roterdamskih kriterijuma za dijagnozu PCOS, pored ranije poznatih klasičnih fenotipova A (hiperandrogenizam-HA, anovulacija-ANOV i morfološki policistični jajnici prema ultrazvučnom nalazu-PCOM) i B (HA i ANOV), pojavila su se dva nova, ne-klasična fenotipa: C (HA i PCOM) i D (ANOV i PCOM). Iako postoji malo metodološki komplementarnih studija, često verifikovani diskretniji endokrinološki i metabolički poremećaji u ne-klasičnim fenotipovima su razlog kontinuirane debate stručne javnosti o tome da li ovi fenotipovi zaista mogu biti deo kompleksnog sindroma kao što je PCOS. Do sada postoje ograničena saznanja o relativnoj prevalenci kardiometaboličkih faktora rizika u različitim PCOS fenotipovima. Cilj ovog istraživanja je analiza endokrinoloških i metaboličkih karakteristika četiri različita PCOS fenotipa u našoj populaciji. Metodologija: Analizirali smo 365 žena sa PCOS (starosti: 25.48 ± 5.21 godina, indeksa telesne mase-BMI: 25.05 ± 6.24 kg/m2) i 125 zdravih žena (starosti: 30.35 ± 5.62 godina; BMI 24.50 ± 5.16 kg/m2). PCOS je dijagnostikovan pomoću ESHRE/ASRM kriterijumima, koji zahtevaju prisustvo najmanje dva od tri sledeća kriterijuma: ovulatorna disfunkcija, hiperandrogenizam i morfološki policistični jajnici prema nalazu na ultrazvuku...The polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. Because of heterogeneous clinical manifestations of the syndrome, it has variable prevalence that ranges from 6% to 25% in different populations. It is associated with a range of reproductive (hyperandrogenism, menstrual dysfunction, infertility, early pregnancy loss, gestational diabetes, pregnancy-induced hypertensive disorders and neonatal complications) and metabolic features (obesity, insulin resistance-IR, impaired glucose tolerance-IGT, diabetes mellitus type 2-DMT2, hyperlipidemia, hypertension). Majority of these metabolic disturbances are usually manifested together forming metabolic syndrome (MetS), a well known risk factor for cardiovascular diseases (CVD). It seems that IR is a key factor in etiology of both metabolic and reproductive complications of PCOS and there is ongoing debate as to whether this IR is intrinsic to PCOS, related to obesity alone or related to both factors. With introduction of ESHRE/ASRM Rotterdam criteria for diagnosis of PCOS, besides previously known classic phenotypes A (hyperandrogenism-HA, anovulation-ANOV and morphologically polycystic ovaries-PCOM) and B (HA and ANOV), two new, non-classic phenotypes: C (ovulatory phenotype: HA+PCOM) and D (non-hyperandrogenic phenotype: ANOV+PCOM) have emerged. Although there are few, methodologically complementary studies, more frequently observed less severe endocrine and metabolic features of non-classic PCOS phenotypes are the reason for ongoing debate weather these phenotypes could really be a part of complex syndrome like PCOS. To date, there is limited understanding of the relative prevalence of cardiometabolic risk factors across the different PCOS phenotypes. The aim of the study was to analyze endocrine and metabolic characteristics of four different PCOS phenotypes in our population Methodology: We analyzed 365 women with PCOS (age: 25.48 ± 5.21 years; body mass index-BMI 25.05 ± 6.24 kg/m2) and 125 healthy controls (age: 30.35 ± 5.62 years; BMI 24.50 ± 5.16 kg/m2). PCOS was diagnosed according to the ESHRE/ASRM criteria, requiring the presence of at least two out of the three following criteria: ovulatory dysfunction, androgen excess, and polycystic morphology of ovaries assessed by ultrasound..

Health-related quality of life questionnaire for polycystic ovary syndrome (PCOSQ-50): a psychometric study with the Serbian version.

This study aimed to analyze the measurement properties of the Health-related quality of life questionnaire for polycystic ovary syndrome (PCOSQ-50) in a sample of Serbian women with polycystic ovary syndrome (PCOS). Seventy-six women with PCOS from an endocrinology clinic and 28 healthy women participated between October 2016 and March 2017. The measure was rigorously translated and culturally adapted into Serbian. Psychometric evaluation included descriptive analysis, internal consistency (Cronbach's alpha coefficient), test-retest reliability (intraclass-correlation coefficient - ICC) and construct validity testing. Cronbach's alpha coefficient ranged from 0.67 to 0.96 for domain scales of PCOSQ-50 scores, while the ICCs for test-retest reliability for these domains ranged from 0.66 to 0.89. Women with PCOS had significantly lower scores than healthy women for hirsutism, obesity and menstrual disorders and the total PCOSQ-50 scale score (p ≤ 0.03), but not for the psychosocial and emotional, fertility, sexual function, and coping scales. These results show that the Serbian PCOSQ-50 measure is acceptable and could produce reliable and valid assessments of PCOS-related quality of life for at least four out of seven domains. Considering that validity testing is an iterative process, additional work is needed before the whole measure is used in routine clinical practice

Development of a “Green” Emulsion with a Milk Protein Hydrolysate: An Evaluation of Rheology, Texture, In Vitro Bioactivity, and Safety

Bioactive peptides are promising cosmetic active ingredients that can improve skin health and appearance. They exhibit a broad spectrum of activity, including anti-aging, antioxidant, an- timicrobial, and anti-inflammatory effects. The aim of this study was to develop a safe, stable, and efficacious environmentally friendly (“green”) emulsion using a milk protein hydrolysate as a model active ingredient. Potential emulsions were formulated with biodegradable emollients, stabilized with naturally derived mixed emulsifier, and prepared by cold process. They were evaluated for rheological behavior (continuous rotation and oscillation tests), physical stability (dynamic me- chanical thermal analysis—DMTA test), and texture profiles, as well as cytotoxic, antioxidant, and antimicrobial effects. Rheological characterization revealed shear-thinning flow behavior with yield point from continuous rotation tests and predominantly elastic character from oscillation (amplitude and frequency sweep) tests, with small structural change detected in the DMTA test. These results implied satisfactory rheological properties and good stability. Texture analysis revealed acceptable spreadability and substantivity of the emulsions. The protein hydrolysate showed antioxidant activity. The developed emulsions showed low antibacterial activity against selected microorganisms, but this was due to the action of preservatives, not peptides. All potential emulsions showed a desirable safety profile. The results obtained provide the basis for the next stage of formulation development, i.e., in vivo efficacy tests