scholarly journals ELEVATED SERUM TESTOSTERONE (T) TO ANDROSTENEDIONE (A4) RATIO AS A BIOMARKER OF ALDO-KETO REDUCTASE 1C3 (AKR1C3) ACTIVITY ACCOMPANIES IMPROVED METABOLIC FUNCTION IN NORMAL-WEIGHT POLYCYSTIC OVARY SYNDROME (PCOS) WOMEN

2021 ◽  
Vol 116 (3) ◽  
pp. e120-e121
Author(s):  
Ayli Tulberg ◽  
Megan McNamara ◽  
Rajanigandha Naik ◽  
David H. Abbott ◽  
Tristan R. Grogan ◽  
...  
Author(s):  
Daniel A Dumesic ◽  
Ayli Tulberg ◽  
Megan McNamara ◽  
Tristan R Grogan ◽  
David H Abbott ◽  
...  

Abstract Context Increased aldo-keto reductase 1C3 (AKR1C3)-mediated conversion of androstenedione (A4) to testosterone (T) promotes lipid storage in subcutaneous (SC) abdominal adipose in overweight/obese polycystic ovary syndrome (PCOS) women. Objective To examine whether an elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts metabolic function in normal-weight PCOS women. Design Prospective cohort study. Setting Academic center. Patients Nineteen normal-weight PCOS women; 21 age- and body mass index-matched controls. Intervention(s) Circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, SC abdominal fat biopsy. Main Outcome Measure(s) Serum T/A4 ratios, hormone/metabolic measures and AKR1C3 expression of adipocytes matured in vitro were compared between female types; serum T/A4 ratios were correlated with serum lipids, adipose insulin resistance (adipose-IR), homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (Si). Results Increased serum T/A4 ratios (P=0.040) and log adipose-IR values (P=0.002) in PCOS women versus controls were accompanied by AKR1C3 mRNA overexpression of PCOS adipocytes matured in vitro (P=0.016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TG: R=-0.65, P=0.002) and the TG index (R=-0.57, P=0.011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R=-0.57, P=0.013) and TG index (R=-0.50, P=0.036), respectively, without significant relationships with other metabolic measures. Conclusion An elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts healthy metabolic function in normal-weight PCOS women.


2003 ◽  
Vol 88 (12) ◽  
pp. 5957-5962 ◽  
Author(s):  
Pascal Pigny ◽  
Emilie Merlen ◽  
Yann Robert ◽  
Christine Cortet-Rudelli ◽  
Christine Decanter ◽  
...  

Abstract The serum level of anti-Mullerian hormone (AMH), a product from granulosa cells involved in follicle growth, has been shown to correlate tightly with the small antral follicle number (FN) at ultrasonography (U/S) in women who do not have polycystic ovary syndrome (PCOS). Because PCOS is associated with a 2- to 3-fold increase in growing FN, we investigated whether an increased AMH serum level correlates to other hormonal and/or U/S features of PCOS. Serum AMH has been assayed in 104 women (59 symptomatic PCOS, 45 controls) between d 2 and 7 after the last either spontaneous or progestin-induced (in PCOS) menstrual period. Mean serum AMH level was markedly increased in the PCOS group (47.1 ± 22.9 vs. 20.8 ± 11.6 pmol/liter in controls; P < 0.0001), an increase in the same order of magnitude as the one of the FN in the 2- to 5-mm range at U/S (12.8 ± 8.3 vs. 4.8 ± 1.9; P < 0.0001, respectively). The ratio AMH/FN was similar between the two groups (4.8 ± 3.4 vs. 4.8 ± 2.9; P = 0.55). By simple regression, both in PCOS and controls, the AMH level was positively related to the 2- to 5-mm FN at U/S (P < 0.0001 and P < 0.03, respectively), but not to the 6- to 9-mm FN, and was negatively correlated to the serum FSH level (P < 0.02 and P < 0.04, respectively). AMH was also positively related to the serum testosterone and androstenedione levels, in PCOS exclusively (P < 0.0005 and <0.002, respectively). No relationship was found between AMH and age, serum estradiol, inhibin B, and LH levels in both groups. After multiple regression only the 2- to 5-mm FN remained significantly related to AMH in PCOS whereas testosterone, androstenedione, and FSH were no longer. In conclusion, the assay of the serum AMH may represent an important breakthrough in the diagnosis and in the understanding of PCOS. Our data suggest that the increase of AMH serum level in PCOS is the consequence of the androgen-induced excess in small antral FN and that each follicle produces a normal amount of AMH. We hypothesize that an increased AMH tone within the cohort could be involved in the follicular arrest of PCOS, by interacting negatively with FSH at the time of selection.


2015 ◽  
Vol 83 (6) ◽  
pp. 895-901 ◽  
Author(s):  
Elisabetta Bacchi ◽  
Carlo Negri ◽  
Daniela Di Sarra ◽  
Flavia Tosi ◽  
Cantor Tarperi ◽  
...  

2013 ◽  
Vol 168 (6) ◽  
pp. 871-877 ◽  
Author(s):  
Dimitrios Panidis ◽  
Konstantinos Tziomalos ◽  
Efstathios Papadakis ◽  
Panagiotis Chatzis ◽  
Eleni A Kandaraki ◽  
...  

ObjectiveHirsutism is frequently present in patients with polycystic ovary syndrome (PCOS) and is a major sign of hyperandrogenism. However, other disorders frequently present in PCOS, particularly abdominal obesity and insulin resistance (IR), have also been implicated in the development of hirsutism in this population but relevant data are limited. We aimed to define the determinants of the presence of hirsutism in PCOS.DesignObservational study.MethodsWe studied 1297 patients with PCOS (age 24.3±5.8 years, BMI 26.8±6.9 kg/m2). Hirsutism was defined as a modified Ferriman–Gallwey score ≥8.ResultsWomen with hirsutism were younger, had greater BMI, and had higher levels of circulating androgens than women without hirsutism; markers of IR did not differ between the two groups after adjustment for age and BMI. The prevalence of hirsutism progressively declined with age, was lower in normal-weight women than in overweight and obese women, and was comparably prevalent in the hyperandrogenemic phenotypes of PCOS. In binary logistic regression analysis, independent predictors of the presence of hirsutism were younger age, larger waist circumference (W), and higher serum testosterone levels. In stepwise linear regression analysis, the Ferriman–Gallwey score independently correlated with age, W, free androgen index, and serum Δ4-androstenedione and DHEAS levels.ConclusionsBesides hyperandrogenemia, abdominal obesity, and young age are independently associated with the presence of hirsutism. In contrast, the relationship between IR and hirsutism appears to be mediated by the more severe obesity of insulin-resistant patients with PCOS.


2011 ◽  
Vol 165 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Ekaterini Koiou ◽  
Konstantinos Tziomalos ◽  
Ilias Katsikis ◽  
Emmanuil Kalaitzakis ◽  
Eleni A Kandaraki ◽  
...  

ObjectiveWomen with polycystic ovary syndrome (PCOS) appear to have higher cardiovascular risk than healthy population. Patients diagnosed with PCOS according to the 1990 criteria have a more adverse metabolic profile than those diagnosed with the 2003 criteria. Platelet-derived microparticles (PMPs) appear to contribute to atherosclerosis but have not been assessed in PCOS. The aim of this study was to determine plasma PMPs in PCOS patients.DesignA cross-sectional study.MethodsWe assessed plasma PMPs in 76 normal weight women with PCOS (39 belonging to the phenotypes 1 and 2 (group I) and 37 belonging to the phenotypes 3 and 4 (group II)) and 21 healthy normal weight women.ResultsMarkers of obesity and insulin resistance did not differ between women with PCOS and controls. Serum testosterone levels and the free androgen index (FAI) were higher in group I than in group II and controls (P<0.001 for all comparisons) but did not differ between the latter two groups. Plasma PMPs were higher in group I than in controls (P=0.018) but did not differ between group II and controls or between groups I and II. In the total study population (n=97), plasma PMPs correlated with serum testosterone levels (r=0.207, P=0.042) and the FAI (r=0.207, P=0.042).ConclusionsPlasma PMPs are elevated in women with phenotypes 1 and 2 of PCOS compared with healthy controls, but not in women with phenotypes 3 and 4. Hyperandrogenemia, which is more pronounced in phenotypes 1 and 2, appears to be implicated in the increase in plasma PMPs.


1997 ◽  
pp. 670-674 ◽  
Author(s):  
Y Sahin ◽  
F Kelestimur

OBJECTIVE: To determine the frequency of late-onset adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) and 11 beta-hydroxylase (11 beta-OH) deficiency in women with clinical and biochemical features of polycystic ovary syndrome (PCOS). DESIGN: Eighty-three consecutively selected women with PCOS and eighteen normal women were included in the study. METHODS: Ultrasound, clinical and hormonal parameters were used to define PCOS. Basal FSH, LH, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and cortisol levels were measured. Serum 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (11-DOC) levels were also measured before, 30 and 60 min after a single bolus injection of 0.25 mg ACTH (1-24) at 0900 h during the mid-follicular phase of the cycle. ACTH-stimulated 17-OHP levels > 30 nmol/l were considered as the criteria of 21-OH deficiency. The diagnosis 11 beta-OH deficiency was made if the adrenal 11-DOC response to ACTH stimulation exceeded threefold the 95th percentile of controls. RESULTS: Basal serum testosterone, free testosterone, androstenedione, DHEA-S, cortisol and 11-DOC levels were significantly higher in PCOS than in control subjects. ACTH-stimulated 17-OHP (P < 0.05) and 11-DOC (P < 0.0005) levels were found to be significantly higher in patients with PCOS than in controls. Seven (8.4%) patients had an 11-DOC response to ACTH higher than threefold the 95th percentile of controls, while no patients showed evidence of 21-OH deficiency. CONCLUSIONS: We have found that 8.4% of the women with clinical and biochemical features of PCOS could be presumed to have 11 beta-OH deficiency. No patients among the women with PCOS showed evidence of 21-OH deficiency. 11 beta-OH deficiency is unexpectedly more common than 21-OH deficiency in women with PCOS.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Luis Hoyos ◽  
Karen Leung ◽  
Tristan Grogan ◽  
David Abbott ◽  
Gregorio Chazenbalk ◽  
...  

Author(s):  
Somnath Singh Raghuvanshi ◽  
Anirban Sinha ◽  
Animesh Maiti ◽  
Partha Pratim Chakraborty ◽  
Asish Kumar Basu ◽  
...  

Background: Ovarian steroidogenesis requires gonadotropin stimulation, Luteinizing Hormone (LH) is a key factor in the hyperandrogenaemia of the polycystic ovary syndrome. Progesterone is the primary regulator of Gonadotropin-Releasing Hormone (GnRH) pulse frequency; however, in the polycystic ovary syndrome, the GnRH pulse generator is relatively resistant to the negative feedback effects of progesterone.  Study aims to evaluate the association of Anti-mullerian hormone with serum androgen and gonadotropin level in adolescents and young women of Polycystic Ovary Syndrome (PCOS).Methods: This was a single centre observational Cross-sectional study carried out in the department of Endocrinology and metabolism, Medical College, Kolkata from March 2017 to January 2019. Total number of study subjects were 207 out of which 138 were cases.Results: The AMH had strong positive correlation with serum testosterone in both case and control groups (r 0.542, p<0.001 and r 0.57, p<0.001) respectively .After the adjustment of age and BMI , the AMH moderately positive  but extremely significant correlation with serum testosterone as compare to control.Conclusions: Hyperandrogenaemia and higher ratio of LH and FSH associated with higher serum AMH level is associated with the higher serum AMH in polycystic ovarian syndrome.


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