Clinical Value Of Serum Levels Of 11-Oxygenated Metabolites Of Testosterone In Women With Polycystic Ovary Syndrome

Abstract Context/Objective Recent data suggested that 11-oxygenated androgens may be the preponderant circulating androgens in women with PCOS. However, the pathophysiological significance of these hormones remains unclear. The aim of this study was to evaluate the relationships between serum 11-OH testosterone (11-OHT) and 11-Keto testosterone (11-KetoT) and clinical and biochemical hyperandrogenism, as well as the metabolic parameters, in women with PCOS. Subjects One hundred and twenty-three women with PCOS, diagnosed according to the Rotterdam criteria, and 38 healthy controls. Design The main classic and 11-oxygenated androgens were measured by LC-MS/MS and direct equilibrium dialysis. Insulin sensitivity was assessed by hyperinsulinemic euglycemic clamp. Results Serum 11-oxygenated androgens were higher in women with PCOS than in controls. Elevated levels of 11-OHT and 11-KetoT were found in 28.5% and 30.1% of PCOS women, respectively, whereas free testosterone (FT) was increased in 61.0% of them. Serum 11-oxygenated androgens showed a limited performance in recognizing women with classically-defined hyperandrogenism. Unlike FT, 11-oxygenated androgens did not show significant relationships with anthropometric and metabolic parameters, except for a direct association with insulin sensitivity. In multivariable analysis, 11-OHT and 11-KetoT, directly, and FT, inversely, remained significant independent predictors of insulin sensitivity. Conclusions Serum levels of 11-oxygenated androgens are higher in women with PCOS than in controls. However, these hormones show a poor performance in recognizing women with hyperandrogenism, as currently defined. The relationships of these androgens with insulin sensitivity strongly differ from that of FT, suggesting a different role of classic and 11-oxygenated androgens in the pathophysiology of PCOS.

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The Correlation between Hormonal Disturbance in PCOS Women and Serum Level of Kisspeptin

International Journal of Endocrinology ◽

10.1155/2020/6237141 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Razaw O. Ibrahim ◽

Shirwan H. Omer ◽

Chro N. Fattah

Keyword(s):

Menstrual Cycle ◽

Polycystic Ovary ◽

Essential Element ◽

Free Testosterone ◽

Serum Levels ◽

Normal Weight ◽

Normal Women ◽

And Control ◽

Lh Secretion ◽

Ovarian Syndrome

Background. Kisspeptin is a neuropeptide that upregulates gonadotropin-releasing hormone (GnRH) secretion. It is an essential element for the luteinizing hormone (LH) surge and ovulation. Women with polycystic ovary syndrome (PCOS) expose alteration in both GnRH and LH secretion levels. Objective. This paper aims to evaluate serum kisspeptin levels in healthy and polycystic ovarian syndrome women. Furthermore, it investigates the effect of obesity and age on circulating kisspeptin levels in both normal and PCOS women. Moreover, it points out the correlation between kisspeptin and other hormonal parameters. Methods and Patients. One hundred women (60 are with PCOS and 40 are normal) were enrolled in the study. Five milliliter samples of blood from all the patients and control women were obtained twice during the menstrual cycle. All the study samples were classified depending on the age factor for several subgroups. Results. Kisspeptin levels were higher in PCOS patients than those in the normal group. Kisspeptin correlated with serum free testosterone level (r=0.26). In healthy women, preovulatory kisspeptin levels were higher than follicular kisspeptin levels (P<0.05), while this difference was insignificant in PCOS patients. The variation in serum kisspeptin levels between overweight/obese and normal-weight women was insignificant. In normal women, serum kisspeptin levels were higher in women >35 years than those <24 years at (P=0.03). Conclusion. The serum kisspeptin level is higher in PCOS women. Its levels fluctuate during the menstrual cycle, but these fluctuations are disturbed in PCOS women. The effect of BMI on serum kisspeptin levels is insignificant, and kisspeptin serum levels increase with age.

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Serum Levels of Leptin and Homocysteine in Women with Polycystic Ovary Syndrome and Its Relationship to Endocrine, Clinical and Metabolic Parameters

Journal of International Medical Research ◽

10.1177/147323000803600113 ◽

2008 ◽

Vol 36 (1) ◽

pp. 96-105 ◽

Cited By ~ 18

Author(s):

A Atamer ◽

B Demir ◽

G Bayhan ◽

Y Atamer ◽

N Ilhan ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Serum Levels ◽

Metabolic Parameters ◽

Ovary Syndrome

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Circulating HMGB1 Levels Are Associated With Glucose Clamp-Derived Measures of Insulin Resistance in Women With PCOS

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1502 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A738-A739

Author(s):

Matteo Migazzi ◽

Marco Dauriz ◽

Francesca Cirillo ◽

Cecilia Catellani ◽

Michela Villani ◽

...

Keyword(s):

Insulin Resistance ◽

Potential Role ◽

Polycystic Ovary ◽

Equilibrium Dialysis ◽

Glucose Clamp ◽

Metabolic Parameters ◽

Blood Levels ◽

Healthy Controls ◽

Anthropometric Parameters

Abstract Context: High mobility group box 1 (HMGB1) is a nuclear constitutive and highly conserved mammalian protein which shows several important physiologic functions, playing a crucial role in local and systemic inflammation. It also seems to be implicated in the development of metabolic syndrome, whereas some in vitro and animal models and recent preliminary human studies suggested its potential role in polycystic ovary syndrome (PCOS) pathophysiology. In particular, some data suggested a potential role of HMGB1 in follicular maturation block. Moreover, increased blood and follicular fluid HMGB1 concentrations have been reported in PCOS women, showing a direct correlation with surrogate indexes of insulin-resistance (IR) (i.e. HOMA-IR). Objective: The purpose of the present study was to investigate the relationships between serum HMGB1 levels and clinical, endocrine and metabolic parameters of PCOS patients. Design and patients: Sixty women with PCOS, 30 with IR and 30 with normal insulin sensitivity (IS), and 30 healthy controls were included in the study. In these subjects, body fat was quantified by bioelectrical impedance; plasma HMGB1 levels were measured using a specific ELISA method (Tecan, Mannedorf, Switzerland); and serum androgens were measured by liquid chromatography/mass spectrometry and equilibrium dialysis. In PCOS women, IR was measured using the gold standard hyperinsulinemic-euglycemic clamp technique, combined with indirect calorimetry. Results: HMGB1 levels did not differ between PCOS women and healthy controls (4.11 ± 3.22 vs 3.77 ± 2.50 ng/mL, respectively; p=0.61). Moreover, HMGB1 levels did not differ between PCOS phenotype subgroups. However, PCOS IR women showed higher levels of this protein as compared with PCOS IS (5.00 ± 3.53 vs 3.16 ± 2.59 ng/mL, respectively; p=0.017). In women with PCOS, HMGB1 levels were associated with several metabolic parameters, including IR measured by glucose utilization during the clamp (rho -0.37, p=0.005). This correlation was preserved after adjusting for potential confounding parameters, such as age, fat mass and serum free testosterone. HMGB1 levels did not change during glucose-clamp induced acute hyperinsulinemia, either in the whole cohort of patients or in IR and IS subgroups analyzed separately. Both in the whole population under study and in PCOS women, HMGB1 levels did not correlate with anthropometric parameters, hormonal features and ovarian morphology. Conclusions: In women with PCOS, HMGB1 blood levels show an independent association with insulin resistance. However, no associations with other typical features of the syndrome were found. Further research is needed in order to establish whether this protein may play a role in the pathogenesis of PCOS.

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Heterogeneity of Endocrinologic and Metabolic Parameters in Reproductive Age Polycystic Ovary Syndrome (PCOS) Women Concerning the Severity of Hyperandrogenemia—A New Insight on Syndrome Pathogenesis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17249291 ◽

2020 ◽

Vol 17 (24) ◽

pp. 9291

Author(s):

Katarzyna Ozegowska ◽

Marcin Korman ◽

Agnieszka Szmyt ◽

Leszek Pawelczyk

Keyword(s):

Insulin Sensitivity ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Dehydroepiandrosterone Sulfate ◽

Reproductive Age ◽

Metabolic Parameters ◽

Ovary Syndrome ◽

Group 3

Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, infertility, obesity, and insulin resistance, which results in increased concentrations of testosterone (T), which disturbs follicular growth and ovulation. This study aimed to assess PCOS women’s clinical, endocrinological, and metabolic parameters concerning hyperandrogenism severity. Results: 314 women (mean age 27.3 ± 4.6; mean body mass index (BMI) 25.7 ± 5.6) with PCOS, were divided into terciles according to T concentrations: <0.64 ng/mL (group 1), 0.64 to 0.84 ng/mL (Group 2) and >0.84 ng/mL (group 3). The mean concentration of T in all women was 0.59 ng/mL and correlated negatively with the number of menstrual cycles per year (MPY) (r = −0.36; p < 0.0001) and positively with Ferriman-Gallway score (FG) (r = 0.33; p < 0.0001), luteinizing hormone (LH) (r = 0.19; p < 0.0001) and dehydroepiandrosterone sulfate (DHEAS) (r = 0.52; p < 0.0001). Positive correlation between BMI and hirsutism (r = 0.16; p < 0.0001), total cholesterol (TC) (r = 0.18; p < 0.0001), low-density lipoprotein (LDL) (r = 0.29; p < 0.0001), and triglycerides (TG) (r = 0.40; p < 0.0001) was demonstrated. The division into subgroups confirmed the lowest MPY, highest LH, and hirsutism in group 3. BMI, insulin sensitivity indices, and lipid profile parameters were not different between the three T subgroups. Conclusions: We found no correlation between testosterone levels and insulin sensitivity or dyslipidemia in women with PCOS. Metabolic abnormalities may contribute more significantly than hyperandrogenemia to PCOS development.

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Ambient Circulating LH, but Not Insulin, Predicts Rise in Testosterone Levels After Recombinant hCG in Girls With Obesity

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1499 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A737-A737

Author(s):

Christine Michele Burt Solorzano ◽

Eleanor G Hutchens ◽

Amy D Anderson ◽

Jessicah S P Collins ◽

Su Hee Kim ◽

...

Keyword(s):

Partial Correlation ◽

Polycystic Ovary ◽

Free Testosterone ◽

Mean Value ◽

Stimulation Protocol ◽

Adrenal Androgen ◽

Mixed Meal ◽

Relative Contribution ◽

Significant Relationships ◽

The Mean

Abstract Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance. Adolescent hyperandrogenemia (HA) may precede adult PCOS. Androgen production in females occurs in both the adrenals and the ovaries, but the relative contribution of each to adolescent HA is unknown. Both luteinizing hormone (LH) and insulin contribute to HA in adult PCOS, and both correlate with HA in obese girls, but detailed assessments of LH and insulin in combination with ovarian and adrenal androgen responses to stimulation (in the same individual) have not been described. To assess the relative roles of stimulatory factors (LH and insulin) and end organ (adrenal, ovarian) responsiveness to stimulation, we have studied 16 girls with obesity: age 13.4 (10.5–15.9) y (median [range]); Tanner 5 (2 girls 2-3; 14 girls 4-5); BMI Z 2.2 (1.7–2.7); free testosterone (T) 17.7 (6.6–88.3) pmol/L. Subjects underwent a detailed study including (a) frequent blood sampling for LH (6p–9a), to estimate mean 24-h LH; (b) sampling for insulin from 1 h before to 2 h after a standardized mixed meal (7p) and while fasting (7a–9a), to estimate mean 24-h insulin; (c) an adrenal stimulation protocol (dexamethasone [DEX] given at 10p, with 17-OHProgesterone [17OHP], T, and androstenedione (∆4A) drawn before plus 30 and 60 min after synthetic ACTH [250 mcg iv] given at 7a); and (d) an ovarian stimulation protocol (after the 8a sample above, recombinant hCG [r-hCG, 25 mcg iv] given, DEX given at 10p, with 17OHP, T, and ∆4A drawn the next morning at 8a). Responses to ACTH and r-hCG stimulation were defined as the mean value 30 and 60 min post-ACTH and the value 24 h post-hCG, respectively, minus the post-DEX morning value. Relationships between such responses and estimated mean 24-h LH and 24-h insulin were assessed using Spearman partial correlation (correcting for differences in 24-h insulin and 24-h LH, respectively). Estimated 24-h LH was 3.7 (1.8–21.5) mIU/mL in the group, while estimated 24-h insulin was 61.4 (23.2–175) uIU/mL. After correcting for differences in 24-h insulin, estimated 24-h LH predicted hCG-stimulated changes in T (r = 0.61, p = 0.02), but did not predict ACTH-stimulated changes in T. When corrected for 24-h LH, there were no significant relationships between estimated 24-h insulin and T responses to either r-hCG or ACTH. Estimated 24-h LH and 24-h insulin were not correlated with ACTH- or hCG-stimulated changes in either 17OHP or ∆4A. These data suggest that, in pubertal girls with obesity, either that ovarian T responses to stimulation are influenced by ambient LH concentrations, but not by insulin, or that ovarian hyperresponsiveness leads to increased LH. Similar relationships with 17OHP or ∆4A were not evident, for either ambient LH or insulin. Simultaneous detailed assessments of LH, insulin, and end organ (adrenal, ovarian) responsiveness to stimulation may help discriminate the determinants of HA in girls with obesity.

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Are There Any Sensitive and Specific Sex Steroid Markers for Polycystic Ovary Syndrome?

Endocrine Reviews ◽

10.1210/edrv.31.1.9990 ◽

2010 ◽

Vol 31 (1) ◽

pp. 134-134

Author(s):

Elisabet Stener-Victorin ◽

Göran Holm ◽

Fernand Labrie ◽

Lars Nilsson ◽

Per Olof Janson ◽

...

Keyword(s):

Mass Spectrometry ◽

Polycystic Ovary Syndrome ◽

Sensitivity And Specificity ◽

Polycystic Ovary ◽

High Sensitivity ◽

Free Testosterone ◽

Serum Levels ◽

Sex Steroid ◽

Ovary Syndrome ◽

Cross Sectional

ABSTRACT Context Despite the high prevalence of hyperandrogenemia, the principal biochemical abnormality in women with polycystic ovary syndrome (PCOS), a definitive endocrine marker for PCOS has so far not been identified. Objective To identify a tentative diagnostic marker for PCOS, we compared serum levels of sex steroids, their precursors, and main metabolites in women with PCOS and controls. Design and Methods In this cross-sectional study of 74 women with PCOS and 31 controls, we used gas and liquid chromatography/mass spectrometry to analyze serum sex steroid precursors, estrogens, androgens, and glucuronidated androgen metabolites; performed immunoassays of SHBG, LH, and FSH; and calculated the LH/FSH ratio. Results Androgens and estrogens, sex steroid precursors, and glucuronidated androgen metabolites were higher in women with PCOS than in controls. In multivariate logistic regression analyses, estrone and free testosterone were independently associated with PCOS. The odds ratios per sd increase were 24.2 for estrone [95% confidence interval (CI), 4.0-144.7] and 12.8 for free testosterone (95% CI, 3.1-53.4). In receiver operating characteristic analyses, the area under curve was 0.93 for estrone (95% CI, 0.88-0.98) and 0.91 for free testosterone (95% CI, 0.86-0.97), indicating high sensitivity and specificity. Conclusion Women with PCOS have elevated levels of sex steroid precursors, estrogens, androgens, and glucuronidated androgen metabolites as measured with a specific and sensitive mass spectrometry-based technique. The combination of elevated estrone (>50 pg/ml) and free testosterone (>3.3 pg/ml) appeared to discriminate with high sensitivity and specificity between women with and without PCOS.

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Lower insulin sensitivity differentiates hirsute from non-hirsute Sicilian women with polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje.1.02290 ◽

2006 ◽

Vol 155 (6) ◽

pp. 859-865 ◽

Cited By ~ 18

Author(s):

Marco C Amato ◽

Aldo Galluzzo ◽

Simona Merlino ◽

Antonina Mattina ◽

Pierina Richiusa ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Free Testosterone ◽

Total Testosterone ◽

Obese Women ◽

Ovary Syndrome ◽

The Metabolic Syndrome ◽

Matsuda Index

Objective: It is well known that hyperandrogenism and insulin-resistance with or without compensatory hyperinsulinism are closely associated, but the Rotterdam Consensus has concluded that principally obese women with polycystic ovary syndrome (PCOS) should be evaluated for the metabolic syndrome. Our aim was to study insulin sensitivity in PCOS women with hirsutism regardless of obesity. Methods: Clinical characteristics, sex hormones and fasting- and after OGTT-glycemia and insulinemia, homeostatic model of insulin resistance (HOMA IR), and Matsuda index of insulin sensitivity were analyzed in 130 women with PCOS. Hirsutism has been evaluated through the Ferriman–Gallwey (FG) map scoring system. Results: PCOS women with hirsutism (57.7% of participants) showed significant higher values of total testosterone levels (P = 0.016), free testosterone (P = 0.027), DHEA sulfate (P = 0.017), and Δ4androstenedione (P = 0.018). They had similar body mass index (BMI) (P = 0.073) and were significantly less insulin sensitive (P = 0.002) than those without hirsutism (42.3% of participants). In women with PCOS and hirsutism, there was a significant correlation between FG score and insulin-sensitivity indexes (HOMA IR, ρ = 0.33, P = 0.005; Matsuda index, ρ = −0.34, P = 0.003) but not with the androgen levels. Moreover, women with hirsutism showed a significantly greater insulin (P = 0.019), C-peptide (P = 0.002), and glucose (P = 0.024) areas under the curve (auc2h). Conclusions: Our study suggests that the increased responsiveness of the pilo-sebaceous unit to androgens seems to be influenced by insulin sensitivity and that insulin resistance should be assessed in all hirsute women with PCOS regardless of their BMI, as insulin resistance was found in hirsute women irrespective of whether they were overweight or obese.

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Plasma levels of pentraxin-3, an inflammatory protein involved in fertility, are reduced in women with polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje-13-0761 ◽

2014 ◽

Vol 170 (3) ◽

pp. 401-409 ◽

Cited By ~ 9

Author(s):

Flavia Tosi ◽

Daniela Di Sarra ◽

Cecilia Bonin ◽

Francesca Zambotti ◽

Marlene Dall'Alda ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Equilibrium Dialysis ◽

Free Testosterone ◽

Cross Sectional Study ◽

Pentraxin 3 ◽

Ovary Syndrome ◽

Cross Sectional ◽

Glucose Clamp Technique ◽

Serum Crp

ObjectivePentraxin-3 (PTX3), like C-reactive protein (CRP), is an acute-phase protein that belongs to the pentraxin superfamily. Moreover, it is expressed in the cumulus oophorus and appears to be involved in female fertility. The aim of the present study was to assess whether PTX3 levels are altered in polycystic ovary syndrome (PCOS) women and whether they show any relationship with the main features of these subjects.DesignA cross-sectional study was conducted at the outpatient clinic of an academic centre.MethodsA total of 66 women affected with PCOS and 51 healthy controls were studied. Plasma PTX3 and serum CRP were measured by ELISA. Androgens were measured by liquid chromatography–mass spectrometry and free testosterone was measured by equilibrium dialysis. In PCOS women, insulin sensitivity was assessed by the glucose clamp technique.ResultsAdjusting for age and BMI, plasma PTX3 was reduced in PCOS women (P=0.036), in contrast with serum CRP, which was increased (P=0.004). In multiple regression analysis, serum androgens and other endocrine and ovarian features of PCOS were predictors of PTX3 levels, whereas body fat was the main independent predictor of CRP concentrations.ConclusionsPlasma PTX3 levels were reduced in PCOS women and independently associated with hyperandrogenism and other endocrine and ovarian features of PCOS.

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