scholarly journals Hyperandrogenism and menstrual imbalance are the best predictors of metformin response in PCOS patients

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Emanuele Garzia ◽  
Valentina Galiano ◽  
Giovanni Marfia ◽  
Stefania Navone ◽  
Enzo Grossi ◽  
...  

Abstract Background Moving from the correlation between insulin-resistance and PCOS, metformin has been administered in some PCOS women improving ovulatory and metabolic functions and decreasing androgen levels. Inconsistency and unpredictability of response to metformin limit its extensive use. Aim of this study was to identify reliable predictors of response to metformin therapy for weight loss and reduction in plasma androgen levels using ANNs (artificial neural networks). Methods One hundred eight consecutive women with PCOS (ESHRE/ASRM 2003 Rotterdam criteria) treated with metformin 1500 mg/day, at inclusion and every 6 months underwent to a complete clinical, endocrine/metabolic assessment and ultrasonographic evaluation. Therapy outcomes were BMI reduction (≥1 kg/m2) in overweight/obese and free-androgen-index (FAI) decrease (≥1%) in hyperandrogenemic women. Semantic connectivity maps (SCMs) were obtained through Auto-CM, a fourth generation ANN, to compare patients’ baseline clinical features to the treatment outcomes. Multivariate logistic regression analysis was used to assess the major predictor in drop-out patients and the associated risk. Results At 6 months 54 out of 103 (52,4%) obese patients showed BMI reduction and 45 out of 89 (50,6%) hyperandrogenemic women showed FAI decrease. The further response rates at 12 months were 30,6 and 47%, respectively. SCMs showed a clear polarization for both the outcomes with elevated accuracy. Treatment responsiveness resulted strictly related to oligo-amenorrhea and hyperandrogenemia at baseline. In addition, lower serum testosterone levels at baseline were found to be the major predictor of treatment discontinuation. Conclusions In women with PCOS, menstrual pattern imbalance and ovarian androgens excess are the best predictors of metformin response. They may pave the way for a rethinking of the criteria for evaluating hyperandrogenism in order to better define the large population included in the diagnosis of PCOS. Baseline plasma testosterone level can serve as a sensitive marker to predict treatment compliance.

2011 ◽  
Vol 140 (7) ◽  
pp. 1277-1285 ◽  
Author(s):  
C. H. CHEN ◽  
H. J. WEN ◽  
P. C. CHEN ◽  
S. J. LIN ◽  
T. L. CHIANG ◽  
...  

SUMMARYPneumonia is an important cause of mortality and morbidity in infants. However, information of risk factors for pneumonia in children aged <6 months is limited. This study aimed to evaluate the risk factors and their contribution to infantile pneumonia in a large population-based survey. Of 24 200 randomly sampled main caregivers invited, 21 248 (87·8%) participated in this study. A structured questionnaire was used to interview the main caregivers. Information regarding whether hospitalization was required, family environment, and medical history were obtained. The prevalence of pneumonia was 0·62% in our study cohort. Multivariate logistic regression analysis showed that preterm birth, congenital cardiopulmonary disease, antibiotic use during pregnancy, maternal overweight, daily prenatal exposure to environmental tobacco smoke, maternal smoking during pregnancy, and visible mould on walls at home are risk factors associated with infantile pneumonia. Further study is warranted to investigate the causality and mechanisms of these novel factors.


2020 ◽  
Vol 102 (6) ◽  
pp. 1225-1233
Author(s):  
Deepak S Hiremath ◽  
Elizabeth C Geerling ◽  
Lan Hai ◽  
Prema Narayan

Abstract Androgens are essential for penile development and for maintaining penile structural and functional integrity. Loss of androgen levels or function results in a decrease in smooth muscle content, accumulation of adipocytes in the corpora cavernosa, and inhibition of erectile function. Our previous studies with a mouse model (KiLHRD582G) of constitutive luteinizing hormone receptor activity also showed structural abnormalities in the penis caused by a decrease in smooth muscle content, accumulation of chondrocytes, and sexual dysfunction. As KiLHRD582G mice exhibit very high levels of testosterone at all postnatal ages, the goal of this study was to determine if the elevated androgen levels were responsible for the morphological changes in the penis. Implantation of testosterone capsules in wild-type mice at neonatal (2 weeks) and postpubertal (5 weeks) ages resulted in the accumulation of chondrocytes in the corpora cavernosa of the adult animals. Mice implanted with testosterone capsules at 2 weeks of age exhibited a 4-fold increase in serum testosterone with a 1.5-fold loss of smooth muscle at 24 weeks of age. Collagen content was unchanged. Only 57% of testosterone implanted mice were fertile at 24 weeks of age. Mice implanted with testosterone capsules at 5 weeks of age showed no decrease in smooth muscle content at 24 weeks, although serum testosterone levels were elevated 5-fold. Implantation with dihydrotestosterone also resulted in chondrocyte accumulation and a 2-fold loss in smooth muscle content. Together, these studies demonstrate that supraphysiological levels of androgens cause structural changes in the penile corpora cavernosa and impair fertility.


Biology ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 49
Author(s):  
Enoka P. Kudavidanage ◽  
D. M. I. Dissanayake ◽  
W. L. Rangi Keerthirathna ◽  
N. Lasni Wathima Nishshanke ◽  
L. Dinithi C. Peiris

Pesticides are known to result in toxic insult. We aimed to evaluate Judo 40, the commercial formulation of chlorpyrifos on the neurological activities, fertility, and hormone levels of male rats. Male Wistar rats were treated orally with 1 mL of 20 or 50 mg/kg Judo 40. The doses were administered four times, twice a day. Sexual and exploratory behavior indices, fertility indices, serum androgen levels, blood acetylcholinesterase (BChE) levels, and neurological and muscular effects were evaluated. Serum testosterone and luteinizing hormone were significantly reduced in the rats receiving 50 mg/kg Judo 40. A reduction in viable implantation sites and live pups born were evident in the female rats mated with the male rats treated with the highest dose. Similarly, in the rats treated with the highest dose of Judo 40, a significant reduction in plasma BChE enzyme was observed. According to the results, prolonged Judo 40 exposure can cause impairment of the neurological alterations and sex hormones leading to impaired fertility. Therefore, chemical handlers should be educated on protection and risk minimization.


2012 ◽  
Vol 27 (6) ◽  
pp. 471-474 ◽  
Author(s):  
Manal K. Al Kindi ◽  
Faiza S. Al Essry ◽  
Fatma S. Al Essry ◽  
Waad-Allah S. Mula-Abed

1978 ◽  
Vol 89 (4) ◽  
pp. 770-779 ◽  
Author(s):  
G. Pelardy ◽  
P. Delost

ABSTRACT Plasma and testicular testosterone, androstenedione and dihydrotestosterone concentrations have been estimated by radioimmunoassay in the male foetus and newborn guinea-pigs between day 62 of pregnancy to day 12 of post-natal life. The prenatal period is characterized by low plasma androgen levels and high testosterone and androstenedione testicular content. After birth there is a peak of plasma testosterone concentration on day 3 concomitant with a release of testicular androgens; no similar increase of androstenedione or DHT is observed in plasma. This peak in plasma testosterone is testis dependent because it disappears after castration; it is also light dependent at birth. The investigations on testosterone and androstenedione peripheral metabolism have shown that day 3 after parturition is a "critical period" in the evolution of the metabolic clearance rate, the production rate and the conversion rate of these two androgens. The neonatal increase in plasma testosterone may be accounted for by the variations in these metabolic parameters and may have an influence upon certain sexual target organs, especially upon the vas deferens, the androgens content of which increases during the same "critical period".


1986 ◽  
Vol 110 (3) ◽  
pp. 517-523 ◽  
Author(s):  
P. Shrenker ◽  
R. Stegar ◽  
A. Bartke

ABSTRACT From day 1 post partum to postnatal day 5, lactating female mice were given daily oral doses of 25 μl sesame oil, 0·5 mg tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo(b,d)pyran-1-ol (Δ9-tetrahydrocannabinol; THC)/kg or 50 mg THC/kg in 25 μl oil. Additionally, the pups were given 20 μl oil, 10 μg testosterone or 20 μg testosterone in 20 μl oil s.c. from days 1 to 5 of age. This regimen resulted in nine treatment groups. At 60 days of age, all males were castrated and their testes weighed. After castration, each mouse was implanted s.c. with a 5 mm length of testosterone-filled silicone elastomer capsule. When adult they were tested for male copulatory behaviour. Following behavioural testing the animals were bled by cardiac puncture for measurement of plasma testosterone levels, and their hypothalami removed and assayed for dopamine, noradrenaline, 5-hydroxytryptamine (5-HT) and LH-releasing hormone (LHRH). In addition, another two groups of pregnant females were given daily oral doses of 0·5 or 50 mg THC/kg or oil during the first 3 or 5 days of lactation. The male pups were either decapitated for collection of trunk blood or homogenized for determination of serum or whole body testosterone concentrations. Neonatal administration of THC altered adult male sexual responses and had no effect on hypothalamic noradrenaline, 5-HT and LHRH concentrations. There were large increases in serum testosterone concentrations in neonates after maternal THC treatment, although these differences were not significant. Additionally, THC did not influence the testosterone content of neonatal tissue or the testosterone concentration of adult plasma. These results suggest strongly that the effect of THC on male sexual responses is not mediated by its effect on adult hypothalamic neurotransmitter concentrations. Some other potential mechanisms are discussed. J. Endocr. (1986) 110, 517–523


2015 ◽  
Vol 8 ◽  
pp. CMED.S27700 ◽  
Author(s):  
Entesar O.A. El Saghier ◽  
Salah E. Shebl ◽  
Olfat A. Fawzy ◽  
lhab M. Eltayeb ◽  
Lamya M.A. Bekhet ◽  
...  

Background The association between type 2 diabetes mellitus (T2DM) and low total serum testosterone (LST) has been identified in several cross-sectional studies. Objectives To assess the prevalence of androgen deficiency and erectile dysfunction (ED) and their relation to glycemic control within a sample of Egyptian men with T2DM. Research Design and Methods A cross-sectional study including 70 men having T2DM. Their ages ranged from 30 to 50 years. They were evaluated for symptoms of androgen deficiency and ED, using a validated Arabic-translated Androgen Deficiency in Aging Males questionnaire and five-items version of the International Index of Erectile Function-5, respectively. Total testosterone (TT), glycated hemoglobin (HbA1c), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin were measured for all study subjects. Penile hemodynamics was assessed using penile duplex study for subjects who gave history of ED. Results LST was found in 40% of studied men, and 92.9% of them reported overt symptoms of androgen deficiency. ED was detected in 85.7% of those with LST, as opposed to 31.0% of those with normal TT ( P < 0.000). TT was lower in diabetic men with ED compared to those without ED (12.04 ± 5.36 vs 17.11 ± 7.11 nmol/L, P < 0.001). Significant negative correlation was found between TT and age, body mass index, waist circumference, systolic and diastolic blood pressures, and HBA1c ( P < 0.00). FSH, LH, and prolactin levels were within the normal reference range in all subjects. HbA1c was higher in patients who had LST with ED, compared to those with normal TT and without ED. However, multivariate logistic regression analysis did not reveal a significant association between HBA1c and LST levels. Conclusion LST, symptoms of androgen deficiency, and ED are common in the studied sample of Egyptian men with T2DM. Inappropriately normal FSH and LH in face of LST may denote a state of hypogonadotropic hypogonadism. HBA1c was found to be more significantly associated with ED than with LST.


2014 ◽  
Vol 99 (11) ◽  
pp. 4328-4335 ◽  
Author(s):  
Stéphane Bermon ◽  
Pierre Yves Garnier ◽  
Angelica Lindén Hirschberg ◽  
Neil Robinson ◽  
Sylvain Giraud ◽  
...  

Objective: Prior to the implementation of the blood steroidal module of the Athlete Biological Passport, we measured the serum androgen levels among a large population of high-level female athletes as well as the prevalence of biochemical hyperandrogenism and some disorders of sex development (DSD). Methods and Results: In 849 elite female athletes, serum T, dehydroepiandrosterone sulphate, androstenedione, SHBG, and gonadotrophins were measured by liquid chromatography-mass spectrometry high resolution or immunoassay. Free T was calculated. The sampling hour, age, and type of athletic event only had a small influence on T concentration, whereas ethnicity had not. Among the 85.5% that did not use oral contraceptives, 168 of 717 athletes were oligo- or amenorrhoic. The oral contraceptive users showed the lowest serum androgen and gonadotrophin and the highest SHBG concentrations. After having removed five doped athletes and five DSD women from our population, median T and free T values were close to those reported in sedentary young women. The 99th percentile for T concentration was calculated at 3.08 nmol/L, which is below the 10 nmol/L threshold used for competition eligibility of hyperandrogenic women with normal androgen sensitivity. Prevalence of hyperandrogenic 46 XY DSD in our athletic population is approximately 7 per 1000, which is 140 times higher than expected in the general population. Conclusion: This is the first study to establish normative serum androgens values in elite female athletes, while taking into account the possible influence of menstrual status, oral contraceptive use, type of athletic event, and ethnicity. These findings should help to develop the blood steroidal module of the Athlete Biological Passport and to refine more evidence-based fair policies and recommendations concerning hyperandrogenism in female athletes.


2021 ◽  

Background: Both endothelial dysfunction and low circulating androgen levels predict cardiovascular disease in men. Endothelial function evaluation is commonly performed by measuring flow-mediated vasodilatation of the brachial artery. However, studies have suggested that compared with evaluation of large arteries, microvascular function evaluation of peripheral arteries is a better predictor of increased cardiovascular disease risks. Although circulating levels of androgens, such as testosterone and dehydroepiandrosterone sulfate (DHEA-S), positively correlate with cardiovascular function, the association between circulating androgen levels and microvascular function is unknown. In this study, we investigated whether serum androgen levels correlate with microvascular endothelial function in men. Methods: The study included 105 Japanese men (age 59 ± 1 years) in whom we measured serum testosterone and DHEA-S levels. The reactive hyperemia index (RHI) determined by the Endo-PAT system (finger plethysmography) was used to evaluate microvascular endothelial function. Results: Serum testosterone levels were significantly correlated with the RHI (r = 0.32, P < 0.01). The association between serum testosterone levels and the RHI remained significant even after adjustment for confounders, including age and body mass index (β = 0.31, P < 0.01). Notably, serum DHEA-S levels were not associated with the RHI (r = 0.01, n.s.). Conclusion: This study showed that serum testosterone levels were positively correlated with microvascular endothelial function in men. These results suggest that endogenous testosterone level is one of the determinants of microvascular endothelial function and may become a biomarker reflecting lifestyle modifications-induced improvement in cardiovascular function in men.


2006 ◽  
Vol 9 (2) ◽  
pp. 2-5
Author(s):  
I A PRONChENKO ◽  
V P BUZULINA ◽  
N A TOMILINA ◽  
R N VEDERNIKOVA ◽  
I P ERMAKOVA

Lumbal spine and hip bone mineral density (BMD), bone turnover markers [bone alkaline phosphatase (bALP), osteocalcin (OC), aminoterminal procollagen I propeptide, bone acid phosphatase (bACP), ß-crosslaps (CTX)], sex hormones [testosterone, estradiol (E2), sex hormone-binding globulin (SHBG), free androgen index (FAI), free estrogen index (FEI)], parathyroid hormone (PTH), osteoprotegerin (OPG) and insulin-like growth factor-1 (IGF-1)] were determined in 39 men in age 42±10 years (33 with well renal function and 6 - with renal failure (RF) 44±26 months following KT receiving triple immunosuppressive therapy (CysA, prednisolone and azathioprine). Increased CTX, bACP, OC and decreased bALP so as BMD were associated in men following KT with low testosterone, SHBG and IGF-1 and high E2, OPG and PTH. There was more degree of bone turnover disturbances, decreased BMD, PTH hypersecretion and low FAI in RF. There were significant positive relationships between serum testosterone and E2, FEI and FAI, bALP and E2, bALP and FEI, femur BMD and FAI, femur BMD and FEI, OPG and E2, IGF-1 and PTH. There were significant inverse correlations between serum CTX and FAI, CTX and FEI, hip (spine) BMD and SHBG, hip (spine) BMD and PTH so as between PTH and FAI, PTH and FEI. So bone turnover disturbances, hip BMD losses and PTH hypersecretion in men at late time following KT associated with sex hormone deficiency. Predictor of high bone turnover and as vertebral as femur bone losses after KT besides PTH hypersecretion was serum SHBG. Decreased IGF-1 was the reason of bone forming suppression and possibly was following cyclosporine hepatotoxicity. OPG increasing was associated partly with high estradiol and was compensatory to attenuation of bone resorption and bone losses.


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