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1
Yarnold, Paul R., Gary J. Martin, Robert C. Soltysik, and Steven D. Nightingale. "Androgyny Predicts Empathy for Trainees in Medicine." Perceptual and Motor Skills 77, no. 2 (October 1993): 576–78. http://dx.doi.org/10.2466/pms.1993.77.2.576.
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Data from 65 medical students and residents support the hypothesis that scores on a measure of androgyny are predictive of those on an index of empathy but relatively modest predictive accuracy was observed for sympathetic responses. Further exploration is suggested.
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Pavlova, T. S., and A. B. Kholmogorova. "Gender factors of social anxiety in adolescence." Psychological-Educational Studies 6, no. 1 (2014): 169–79. http://dx.doi.org/10.17759/psyedu.2014060119.
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Social anxiety in adolescence is one of the most important factors of social and psychological maladjustment. The data of Russian and international research of the differences in the severity of social anxiety in boys and girls is not uniform. In a study conducted by the authors, participants were 183 adolescents aged 12-16 years (90 boys and 93 girls), students of VII-X grades. We measured the level of social anxiety and defined the type of gender identity. The results showed that biological sex does not influence the severity of social anxiety: there were no differences in this indicator between boys and girls. The factor influencing the level of social anxiety was gender identity, and gender identity types (masculinity, femininity, androgyny) have approximately the same distributions in both boys and girls. The level of social anxiety shows inversed connection with level of masculinity in adolescents of both sexes and direct connection with femininity index. The magnitude of the gap between the real and the ideal of masculinity of the Self is more pronounced in adolescents with social anxiety disorder.
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Vitulli, William F., and Jane M. Barbin. "Humor-Value Assessment as a Function of Sex, Age, and Education." Psychological Reports 69, no. 3_suppl (December 1991): 1155–64. http://dx.doi.org/10.2466/pr0.1991.69.3f.1155.
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A sense of humor may be related to our survival, yet the value one places on humor is typically not very explicit. Sex, age, and education were selected as variables to examine how participants would respond to Vitulli's Humor Rating Scale. 217 volunteers (108 men and 109 women) were distributed among four levels of education: Grade 8, high school, college, and a combined sample of graduate students and professors. The rating scale measured attitudes toward male-oriented humor, female-oriented humor, general humor values, and an index of “differentiation of humor by gender.” Significant interactions between sex and humor scales and between educational levels and humor scales were found in a 2 × 4 × 4 factorial (split-plot) design. Scheffé tests of multiple comparisons between sample means showed significant sex differences on the male-oriented scale and on the differentiation scale. Significant differences between educational levels occurred on the male- and female-oriented scales, as well as on the differentiation scale. The ‘egalitarian hypothesis’ and the ‘androgyny hypothesis’ were evaluated to assess under what conditions they do or do not account for the data.
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O’Reilly, Michael W., Punith Kempegowda, Carl Jenkinson, Angela E. Taylor, Jonathan L. Quanson, Karl-Heinz Storbeck, and Wiebke Arlt. "11-Oxygenated C19 Steroids Are the Predominant Androgens in Polycystic Ovary Syndrome." Journal of Clinical Endocrinology & Metabolism 102, no. 3 (November 30, 2016): 840–48. http://dx.doi.org/10.1210/jc.2016-3285.
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Abstract Context: Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), but the exact origin of hyperandrogenemia remains a matter of debate. Recent studies have highlighted the importance of the 11-oxygenated C19 steroid pathway to androgen metabolism in humans. In this study, we analyzed the contribution of 11-oxygenated androgens to androgen excess in women with PCOS. Methods: One hundred fourteen women with PCOS and 49 healthy control subjects underwent measurement of serum androgens by liquid chromatography-tandem mass spectrometry. Twenty-four–hour urinary androgen excretion was analyzed by gas chromatography-mass spectrometry. Fasting plasma insulin and glucose were measured for homeostatic model assessment of insulin resistance. Baseline demographic data, including body mass index, were recorded. Results: As expected, serum concentrations of the classic androgens testosterone (P < 0.001), androstenedione (P < 0.001), and dehydroepiandrosterone (P < 0.01) were significantly increased in PCOS. Mirroring this, serum 11-oxygenated androgens 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone, and 11-ketotestosterone were significantly higher in PCOS than in control subjects, as was the urinary 11-oxygenated androgen metabolite 11β-hydroxyandrosterone. The proportionate contribution of 11-oxygenated to total serum androgens was significantly higher in patients with PCOS compared with control subjects [53.0% (interquartile range, 48.7 to 60.3) vs 44.0% (interquartile range, 32.9 to 54.9); P < 0.0001]. Obese (n = 51) and nonobese (n = 63) patients with PCOS had significantly increased 11-oxygenated androgens. Serum 11β-hydroxyandrostenedione and 11-ketoandrostenedione correlated significantly with markers of insulin resistance. Conclusions: We show that 11-oxygenated androgens represent the majority of circulating androgens in women with PCOS, with close correlation to markers of metabolic risk.
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Honour, John W., Richard Jones, Sam Leary, Jean Golding, Ken K. Ong, and David B. Dunger. "Relationships of Urinary Adrenal Steroids at Age 8 Years with Birth Weight, Postnatal Growth, Blood Pressure, and Glucose Metabolism." Journal of Clinical Endocrinology & Metabolism 92, no. 11 (November 1, 2007): 4340–45. http://dx.doi.org/10.1210/jc.2007-0851.
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Abstract Introduction: Overactivity of the hypothalamic-pituitary-adrenal axis through a program set by early growth patterns is hypothesized to lead to central obesity, insulin resistance, and hypertension. We therefore examined links between adrenal steroid production and birth weight, rapid early growth, and body mass index (BMI), blood pressure, waist circumference, and resistance to insulin in early childhood through the action of adrenal steroids. Methods: Timed overnight urine samples were collected in 461 children from a large representative birth cohort. In total 244 boys and 188 girls aged 8.2–8.4 yr completed the protocol. The excretion rates of individual steroids were measured to determine total androgen and cortisol metabolites. Indices of activity of 5α-androgen reduction of androgens and cortisol metabolites and 11β-hydroxy steroid dehydrogenase activity were calculated. Results: In both boys and girls, total urinary androgen and cortisol metabolites were positively related to current height, weight, BMI, and waist circumference. Girls had higher urine androgen metabolite levels and 5α-androgen indexes than boys, and in girls higher androgen metabolite excretion was associated with lower birth weight and faster postnatal weight gain. After adjustment for current BMI, total cortisol metabolites and 11β-hydroxy steroid dehydrogenase index were not related to birth weight or postnatal weight gain in either sex. Conclusions: These data confirm early growth associations in this cohort seen with plasma levels of adrenal androgens at age 8 yr, at least in girls. Larger studies and follow-up during puberty are needed to exclude the possibility of programming of cortisol metabolism by early growth.
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de Medeiros, Sebastião Freitas, Bruna Barcelo Barbosa, Ana Karine Lin Winck Yamamoto de Medeiros, Matheus Antônio Souto de Medeiros, and Márcia Marly Winck Yamamoto. "Differential Effects of Various Androgens on Polycystic Ovary Syndrome." Hormone and Metabolic Research 53, no. 05 (April 20, 2021): 341–49. http://dx.doi.org/10.1055/a-1422-3243.
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AbstractThe hyperandrogenism in polycystic ovary syndrome (PCOS) is associated with the risk for the future development of the cardiovascular disease. The objective of the study is to verify whether different androgens have the same harmful effect. This cross-sectional study enrolled 823 women with PCOS: 627 (76.2%) with biochemical hyperandrogenism and 196 (23.8%) with normal androgen levels. The role of individual androgen was evaluated using univariate and multivariate logistic regression. In normoandrogenemic PCOS (NA-PCOS), free androgen index (FAI) predicted significant abnormality in visceral adipose index (VAI, OR=9.2, p=0.002) and dehydroepiandrosterone (DHEA) predicted against alteration in β-cell function (OR=0.5, p=0.007). In hyperandrogenemic PCOS (HA-PCOS), FAI predicted derangements in waist triglyceride index (WTI), VAI, and lipid accumulation product (LAP) (OR ranging from 1.6 to 5.8, p<0.05). DHEA weakly predicted against VAI (OR 0.7, p=0.018), dehydroepiandrosterone sulfate (DHEAS) tended to predict against the conicity index (OR=0.7, p=0.037). After multiple regression, FAI retained significant strength to predict various anthropometric and metabolic abnormalities (OR ranging from 1.1 to 3.0, p<0.01), DHEA was kept as a protector factor against WTI, LAP, and VAI (OR ranging from 0.6 to 0.9; p<0.01) and DHEAS against the conicity index (OR=0.5, p<0.001). In conclusion, the free androgen index was the most powerful predictor of anthropometric and metabolic abnormalities of polycystic ovary syndrome. Conversely, DHEA and DHEAS demonstrated protective effects against disorders in some markers of obesity and abnormal metabolism.
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Bernini, G. P., M. Sgro’, A. Moretti, G. F. Argenio, C. O. Barlascini, R. Cristofani, and A. Salvetti. "Endogenous Androgens and Carotid Intimal-Medial Thickness in Women." Journal of Clinical Endocrinology & Metabolism 84, no. 6 (June 1, 1999): 2008–12. http://dx.doi.org/10.1210/jcem.84.6.5824.
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The influence of endogenous androgens on atherosclerotic disease in women is unknown. In this study involving 101 pre- and postmenopausal females, we evaluated the relationship between serum androgen levels and both carotid artery intimal-medial thickness (IMT) and major cardiovascular risk factors. In addition to evaluation of blood pressure, body mass index, and waist-to-hip ratio, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), total testosterone (TTS), free testosterone (FTS), insulin, cholesterol (total and high density lipoproteins), triglycerides, and glucose were measured. All women underwent carotid ultrasonography. Spearman correlation coefficients showed that serum DHEA-S and A levels were negatively related (P < 0.03–0.0004) to several IMT measures. Higher tertiles of DHEA-S, A, and FTS corresponded to significantly lower measures of carotid thickness. DHEA-S, and all androgens were inversely related to age (P < 0.03 or less), showing no unfavorable association with major cardiovascular risk factors. In contrast, serum DHEA-S was negatively associated with WHR (P < 0.02), while A was negatively associated with body mass index (P < 0.02). Stepwise multiple regression analysis indicated that A and FTS showed an inverse association with IMT measures (P< 0.05–0.001). In conclusion, our data indicate that in women serum DHEA-S and androgens decline with age and that normal hormonal levels are not associated with major cardiovascular risk factors. They also show that higher DHEA-S and androgen concentrations are related to lower carotid wall thickness; for A this association is independent of cardiovascular risk factors. Our results suggest that, in the physiological range, DHEA-S and androgens in women are correlated with lower risk of carotid artery atherosclerosis.
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Vandenput, Liesbeth, Dan Mellström, Mattias Lorentzon, Charlotte Swanson, Magnus K. Karlsson, John Brandberg, Lars Lönn, et al. "Androgens and Glucuronidated Androgen Metabolites Are Associated with Metabolic Risk Factors in Men." Journal of Clinical Endocrinology & Metabolism 92, no. 11 (November 1, 2007): 4130–37. http://dx.doi.org/10.1210/jc.2007-0252.
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Abstract Context: Androgens are associated with metabolic risk factors in men. However, the independent impact of androgens and androgen metabolites on metabolic risk factors in men is unclear. Objective: Our objective was to determine the predictive value of serum levels of androgens and glucuronidated androgen metabolites for metabolic risk factors. Design and Study Subjects: We conducted a population-based study of two Swedish cohorts (1068 young adult and 1001 elderly men). Main Outcome Measures: We measured correlation of serum dihydrotestosterone (DHT), testosterone (T), and glucuronidated androgen metabolites with fat mass, fat distribution, serum lipids, and insulin resistance. Results: Both DHT and T were negatively associated with different measures of fat mass in both cohorts (P < 0.001). Further statistical analysis indicated that DHT, but not T, was independently negatively associated with different measures of fat mass and insulin resistance (P < 0.001). The glucuronidated androgen metabolite androstane-3α,17β-diol-17glucuronide (17G) was independently positively associated with fat mass (P < 0.001). Most importantly, the 17G to DHT ratio was strongly correlated, not only with fat mass but also with central fat distribution, intrahepatic fat, disturbed lipid profile, insulin resistance, and diabetes, explaining a substantial part of the total variance in total body fat (12% in young adult men, 15% in elderly men), the homeostasis model assessment index (10%), and high-density lipoprotein cholesterol (7%). Conclusion: Our findings demonstrate that 17-glucuronidation of the DHT metabolite androstane-3α,17β-diol is strongly associated with several metabolic risk factors in men. Future longitudinal studies are required to determine the possible impact of the 17G to DHT ratio as a metabolic risk factor in men.
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Puurunen, Johanna, Terhi Piltonen, Päivi Jaakkola, Aimo Ruokonen, Laure Morin-Papunen, and Juha S. Tapanainen. "Adrenal Androgen Production Capacity Remains High up to Menopause in Women with Polycystic Ovary Syndrome." Journal of Clinical Endocrinology & Metabolism 94, no. 6 (June 1, 2009): 1973–78. http://dx.doi.org/10.1210/jc.2008-2583.
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Abstract Introduction: Hyperandrogenism is one of the main features of polycystic ovary syndrome (PCOS). Of circulating androgens, 50% of androstenedione and testosterone are of ovarian and adrenal origin, whereas dehydroepiandrosterone (DHEA) and DHEA sulfate are almost uniquely of adrenal origin. Our previous studies have indicated that ovarian androgen production capacity is enhanced in women with PCOS, and it remains high until late reproductive age. To study whether this also applies to adrenal androgen production, ACTH tests were performed in healthy women and in women with PCOS. Materials: Sixty-nine healthy women (aged 19–62 yr; body mass index 19.2–35.0 kg/m2) and 58 women with previously diagnosed PCOS (aged 18–59 yr; body mass index 19.0–42.9 kg/m2) participated in the study. Methods: The subjects underwent ACTH stimulation tests, and serum cortisol, 17-hydroxyprogesterone, androstenedione, testosterone, DHEA, and DHEA sulfate levels were analyzed at 0, 30, and 60 min. Results: Basal and ACTH-stimulated levels of most adrenal androgens decreased in healthy women with age, whereas in women with PCOS, only the concentrations of basal serum 17-hydroxyprogesterone decreased, and all areas under the curve (AUCs) remained unchanged and significantly higher (except for DHEA) than those in control women. Likewise, at the menopausal transition, pre- and postmenopausal women with PCOS exhibited mainly unchanged and higher basal androgen and AUC levels. Conclusions: Similarly to ovarian endocrine function, serum adrenal steroid levels and adrenal steroid production capacity remain enhanced at least up to menopause in women with PCOS.
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Raivio, Taneli, Jorma Toppari, Marko Kaleva, Helena Virtanen, Anne-Maarit Haavisto, Leo Dunkel, and Olli A. Jänne. "Serum Androgen Bioactivity in Cryptorchid and Noncryptorchid Boys during the Postnatal Reproductive Hormone Surge." Journal of Clinical Endocrinology & Metabolism 88, no. 6 (June 1, 2003): 2597–99. http://dx.doi.org/10.1210/jc.2002-021676.
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The first postnatal months of life in boys are characterized by activation of the hypothalamic-pituitary-testicular axis that results in the well depicted surge of reproductive hormones. Serum testosterone levels at that time are high, but infants do not display signs of virilization, and subsequently there is only indirect evidence that circulating androgens during the surge are biologically active. We used a recombinant cell bioassay to determine serum androgen bioactivity in 80 3-month-old boys born after full-term pregnancies (37–42 wk) in whom localization of the testes was determined by palpation after birth and at a mean age of 3 months. At that age, serum androgen bioactivity ranged from less than 0.8 to 1.9 nm testosterone equivalents and correlated with serum testosterone concentration (r = 0.71; P < 0.0001; n = 34), free androgen index (r = 0.80; P < 0.0001; n = 34), age (r = −0.29; P < 0.01; n = 80), and localization of the testes (r = −0.24; P < 0.05; n = 80). Moreover, all boys in this study with detectable androgen bioactivity (n = 26) had testes located in scrotal or high scrotal position (n = 64), whereas all boys (n = 16) with at least 1 suprascrotal, inguinal, or nonpalpable testis had nonmeasurable androgen bioactivity in serum (P < 0.01). We conclude that 3-month-old boys are exposed to biological effects of androgens during the postnatal activation of the hypothalamic-pituitary-testicular axis, and that this exposure may be reduced in boys with at least 1 testis located superior to the scrotum.
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Kaaks, R., S. Rinaldi, T. J. Key, F. Berrino, P. H. M. Peeters, C. Biessy, L. Dossus, et al. "Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition." Endocrine-Related Cancer 12, no. 4 (December 2005): 1071–82. http://dx.doi.org/10.1677/erc.1.01038.
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Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids — notably androgens and oestrogens — promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual well-being. We have conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (Δ4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroids –the androgens as well as the oestrogens – elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk estimates (95% confidence intervals) between the top and bottom quintiles of the exposure distribution were: DHEAS 1.69 (1.23–2.33), androstenedione 1.94 (1.40–2.69), testosterone 1.85 (1.33–2.57) and free testosterone 2.50 (1.76–3.55). For the oestrogens, relative risk estimates were: oestrone 2.07 (1.42–3.02), oestradiol 2.28 (1.61–3.23) and free oestradiol (odds ratios 2.13 (1.52–2.98)). Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.
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Skiba, Marina A., Robin J. Bell, Rakibul M. Islam, David J. Handelsman, Reena Desai, and Susan R. Davis. "Androgens During the Reproductive Years: What Is Normal for Women?" Journal of Clinical Endocrinology & Metabolism 104, no. 11 (August 7, 2019): 5382–92. http://dx.doi.org/10.1210/jc.2019-01357.
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Abstract Objective Whether serum androgen levels can identify women with “androgen insufficiency” or “androgen excess” is unresolved; thus, what constitutes “normal” remains uncertain. We sought to determine whether androgens, including 11-oxygenated C19 steroids, vary with age, menstrual cycle, or body mass index (BMI), during the reproductive years. Design and Setting Cross-sectional study recruited from eastern Australian states. Participants A total of 588 women, aged 18 to 39 years, who were not pregnant, lactating, or using systemic hormone therapy, with regular menstrual cycles and no previous diagnosis of polycystic ovarian syndrome. Main Outcome Measures Sex steroids measured using liquid chromatography-tandem mass spectrometry. Results Testosterone and androstenedione concentrations were significantly higher during the menstrual cycle mid- and luteal phases than in the early follicular phase, with median values across the cycle of 0.34 nmol/L (range, 0.04 to 1.01) and 1.97 nmol/L (range, 0.53 to 7.89), respectively. No cyclical variations were found in dehydroepiandrosterone (DHEA; 4.91 nmol/L; range, 0.08 to 23.51), 11-ketoandrostenedione (11KA; 7.99 nmol/L; range, 0.07 to 31.67), or 11-ketotestosterone (11KT; 1.27 nmol/L; range, 0.03 to 7.61). Overweight women had lower median testosterone (P < 0.05), DHEA (P < 0.05), and 11KA (P < 0.01) levels than normal-weight women. All C19 steroids were significantly lower (P < 0.01) in those aged 35 to 39 years than in those aged 18 to 25 years. The median 11KA/androstenedione (4.3:1) and 11KT/testosterone (3.9:1) ratios did not change with age, after adjustment for BMI and cycle stage. Conclusions We have demonstrated that 11KA and 11KT are stable across the menstrual cycle and make major quantitative contributions to the circulating androgen pool. All C19 androgens declined with age before menopause; hence, age-specific reference ranges are required for the interpretation of androgen levels in premenopausal women.
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Wang, Yuying, Xiaojing Guo, Wendi Xu, Jie Cai, Yi Zhang, Chunhua Wu, Shengxian Li, Yun Sun, Wei Liu, and Tao Tao. "ROLE OF ANDROGEN IN LIVER FAT CONTENT IN WOMEN: METABOLICALLY ADVANTAGEOUS OR DISADVANTAGEOUS?" Endocrine Practice 26, no. 9 (September 2020): 1003–16. http://dx.doi.org/10.4158/ep-2019-0407.
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Objective: Androgens have a controversial effect on liver fat content (LFC) in androgen-excess females and androgen-deficient males. Polycystic ovarian syndrome (PCOS) is often associated with hyperandrogenism and nonalcoholic fatty liver disease. The aim of this study was to explore the association between hyperandrogenemia and increased liver fat content in women with PCOS, independent of other metabolic parameters. Methods: This case series study included 501 women with PCOS and 112 aged-matched controls in the outpatient department of a tertiary hospital. Anthropometric measurements, hepatic and renal function, glucose and lipid metabolism parameters, and sex hormones were examined in these women. LFC was measured by quantitative ultrasonography. Results: Women with hyperandrogenism ( P<.001), an oligomenorrhoea/anovulation phenotype ( P = .0064), and a diagnosis of PCOS ( P<.001) had higher LFC. Androgen level is an important factor among the 9 independent risk factors of LFC ( P = .0239) and may have a dimorphic impact on LFC. In all women, when the free androgen index (FAI) was less than 41.94, LFC increased with the elevated FAI; when the FAI was greater than 41.94, LFC decreased with the elevated FAI ( P<.001). In women with PCOS, receiver operating characteristic curve analysis demonstrated that LFC could at least partially predict impaired glucose regulation, impaired lipid metabolism, and insulin resistance ( P<.0001 for all). Conclusion: Androgen level is associated with LFC in dimorphic directions. LFC may be a predictive factor of insulin resistance, impaired glucose regulation, and impaired lipid metabolism in women with PCOS. Abbreviations: A2 = androstenedione; AUC = area under curve; BioT = bioactive testosterone; BMI = body mass index; DHEAS = sulfated dehydroepiandrosterone; FAI = free androgen index; FBG = fasting blood glucose; FFA = free fatty acid; FT = free testosterone; HA = hyperandrogenism; LFC = liver fat content; LH = luteinizing hormone; MRS = proton magnetic resonance; NAFLD = nonalcoholic fatty liver disease; ROC = receiver operator characteristic; SHBG = sex hormone binding globulin; T = total testosterone; T2DM = type 2 diabetes mellitus
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Nguyen, T.-V., P. Monnier, G. Muckle, S. Sathyanarayana, E. Ouellet, M. P. Velez, L. Dodds, and T. E. Arbuckle. "Androgenic and estrogenic indices in human newborns and infants: the MIREC-ID study." Journal of Developmental Origins of Health and Disease 10, no. 5 (March 11, 2019): 578–86. http://dx.doi.org/10.1017/s2040174419000059.
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AbstractPrenatal sex steroid exposure plays an important role in determining child development. Yet, measurement of prenatal hormonal exposure has been limited by the paucity of newborn/infant data and the invasiveness of fetal hormonal sampling. Here we provide descriptive data from the MIREC-ID study (n=173 girls; 162 boys) on a range of minimally invasive physical indices thought to reflect prenatal exposure to androgens [anogenital distances (AGDs); penile length/width, scrotal/vulvar pigmentation], to estrogens [vaginal maturation index (VMI) – the degree of maturation of vaginal wall cells] or to both androgens/estrogens [2nd-to-4th digit ratio (2D:4D); areolar pigmentation, triceps/sub-scapular skinfold thickness, arm circumference]. VMI was found to be associated with triceps skinfold thickness (β=0.265, P=0.005), suggesting that this marker may be sensitive to estrogen levels produced by adipose tissue in girls. Both estrogenic and androgenic markers (VMI: β=0.338, P=0.031; 2D:4D – right: β=−0.207, P=0.040; left: β=−0.276, P=0.006; AGD-fourchette − β=0.253, P=0.036) were associated with areolar pigmentation in girls, supporting a role for the latter as an index of both androgen and estrogen exposure. We also found AGD-penis (distance from the anus to the penis) to be associated with scrotal pigmentation (β=0.290, P=0.048), as well as right arm circumference (β=0.462, P<0.0001), supporting the notion that these indices may be used together as markers of androgen exposure in boys. In sum, these findings support the use of several physical indices at birth to convey a more comprehensive picture of prenatal exposure to sex hormones.
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Scott, Hayley M., Gary R. Hutchison, Matthew S. Jobling, Chris McKinnell, Amanda J. Drake, and Richard M. Sharpe. "Relationship between Androgen Action in the “Male Programming Window,” Fetal Sertoli Cell Number, and Adult Testis Size in the Rat." Endocrinology 149, no. 10 (June 19, 2008): 5280–87. http://dx.doi.org/10.1210/en.2008-0413.
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Fetal androgen action is an important determinant of Sertoli cell (SC) number at birth. Androgens “program” reproductive tract development in rats between embryonic d (e) 15.5 and e17.5 (“male programming window”), and this is reflected for life by anogenital distance (AGD). We investigated if androgen regulation of SC number/proliferation was also programmed by androgens in this window. Pregnant rats were treated in various fetal time windows with vehicle (control) or 500 mg/kg·d di(n-butyl) phthalate (DBP), which suppresses fetal intratesticular testosterone (ITT). ITT and SC number/proliferation index were determined at e17.5 or e21.5; AGD was also determined at e21.5. In controls, SC number increased 11-fold and ITT by 10-fold from e17.5–e21.5. In animals exposed daily to DBP from e13.5, SC number was reduced by approximately 50% at e21.5, but increased 6-fold, as did ITT, from e17.5–e21.5; DBP had no effect on ITT at e15.5, reduced ITT by 50% at e17.5, and by more than 75% at e19.5–21.5. DBP exposure just in the male programming window did not alter SC number at e17.5 or 21.5 but reduced AGD. DBP treatment beyond e19.5 caused major reductions in SC number/proliferation index and ITT at e21.5. Only DBP treatments that included the male programming window led to reduced AGD at e21.5, but SC number was clearly not programmed in this window. Nevertheless, testis weight correlated highly (P < 0.001) with AGD at e21.5, and postnatal d 25 and 90 in animals exposed in utero to vehicle or DBP (e13.5–e21.5). Thus, AGD may predict adult testis size but probably not through a direct relationship with SC number.
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Balvočius, Antanas. "Vyrų sutrikusios lytinės funkcijos androgeniniai aspektai." Lietuvos chirurgija 3, no. 4 (January 1, 2005): 0. http://dx.doi.org/10.15388/lietchirur.2005.4.2302.
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Antanas BalvočiusTarptautinis medicinos centras Union Clinic Vilnius,Tilto g. 1/2, VilniusEl paštas: balvociusa@delfi.lt Įvadas / tikslas Lytinių steroidinių hormonų endokrininiai sutrikimai neigiamai paveikia vyrų lytinę funkciją. Straipsnio tikslas – pateikti pagyvenusių vyrų lytinės disfunkcijos tyrimų ir gydymo rezultatus, apžvelgti mokslinę literatūrą apie endokrininę vyrų lytinės disfunkcijos patofiziologiją, diagnostiką ir gydymą. Ligoniai ir metodai Nuo lytinės disfunkcijos gydyti 64 pagyvenę (50–75 metų, vidutinis amžius 59 metai) vyrai. Erekcijos sutrikimai pagal TEFR-5 skalę svyravo nuo 11 iki 21 balo (vidutiniškai 15,5). Testosterono (T) kraujo serume buvo nuo 15,8 iki 4,6 nmol/L. Mažiau kaip 11 nmol/L rasta 44 vyrams (69%). Pavartoję FDE-5 inhibitorių, erekcijos kokybe buvo nepatenkinti iš 64 net 46 ligoniai, iš jų 35 ligoniams buvo taikytas kombinuotasis gydymas: 250 mg testosterono injekcijos į raumenis kas trys savaitės ir 5-fosfodiesterazės inhibitorius 1 valandą prieš lytinius santykius. Po 3 mėn. lytinės funkcijos pagal TEFR-5 skalę didesnis kaip 21 balas buvo 30 ligonių (85,7%). Rezultatai Hipogonadizmas yra klinikinis ir biocheminis sindromas, pasižymintis nepakankama androgenų koncentracija serume, dėl to gali sumažėti lytinė trauka, pablogėti erekcijos ir gyvenimo kokybė. Jei yra klinikinių indikacijų skirti androgenų terapiją, ja testosterono koncentracija turi būti palaikoma neviršijant fiziologinių ribų. Egzistuoja terapinis sinergizmas, kai esant hipogonadizmui taikomas kombinuotasis gydymas testosteronu ir 5-fosfodiesterazės inhibitoriais. Prieš terapiją ir reguliariai po jos būtina atlikti prostatos digitalinę rektalinę apžiūrą ir nustatyti prostatos specifinius antigenus kraujo serume. Androgenų terapija gali būti trumpalaikė arba ilgalaikė. Pastarajai reikia reguliariai ir dažnai stebėti pacientą, palankų bei šalutinį terapijos atsaką. Išvados Gydant pagyvenusių vyrų lytinę disfunkciją būtina atsižvelgti ir į steroidinių hormonų kiekį kraujo serume bei androgenų terapijos galimybes. Kombinuotąjį gydymą testosteronu ir 5-fosfodiesterazės inhibitoriais reikėtų skirti tiems erekcijos sutrikimų turintiems pacientams, kuriems nepakankamai padeda gydymas vien 5-fosfodiesterazės inhibitoriais. Reikšminiai žodžiai: lytinė disfunkcija; androgenai; andropauzė; testosteronas; prolaktinas dihidrotestosteronas, 5-fosfodiesterazės inhibitoriai, hormonų terapija Androgen aspects of male sexual dysfunction Antanas BalvočiusInternational Medical Center Union Clinic Vilnius,Tilto str. 1/2, Vilnius, LithuaniaE-mail: balvociusa@delfi.lt Background / objective Steroid hormone endocrine disturbances have an adverse impact on sexual function in men. The aim of the article was to present findings of the study on sexual dysfunction in elderly men and results of their treatment together with a review of the literature on pathologic physiology, diagnostics and therapy of male endocrine sexual dysfunction. Patients and methods Sixty four elderly men (aged 50 to 75, mean age 59 years) were treated for sexual dysfunction. The score of erectile disturbances according to International Index of Erectile Function TEFR-5scale ranged from 11 to 21 (mean, 15.5). The blood testosterone (T) level was 15.8 to 4.6 nmol/l. The level lower than 11 nmol/l was found in 44 (69%) patients. Only 46 of 64 patients were not satisfied with the quality of erection after administration of PDE-5 inhibitors. A combined therapy was applied for 35 of 46 patients with a low T level: intramuscular T 250 mg injections three times a week and a FED-5 inhibitor one hour before sexual intercourse. Sexual function of >21 as assessed by TEFR-5 scale was determined for 30 (85.7%) patients after three months. Results Hypogonadism is a clinical and biochemical syndrome characterised by an insufficient serum androgen level, which may result in a decreased libido, lower quality of erection and decreased quality of life. If clinical indications for androgen therapy are present, it shall maintain the level of testosterone within the physiological limits. Therapeutic synergism is observed when a combined treatment including testosterone and phosphodiesterase-5 inhibitors is applied in hypogonadic men. Digital rectal examination of prostate and determination of values of blood serum prostate specific antigens are indispensable before the initiation of therapy and must be performed regularly afterwards. Androgen therapy may be short-term or long-term, and requires regular and frequent monitoring and observation for favourable and side response to the treatment. Conclusions The level of blood serum steroid hormones should be taken into account and the possibilities for androgen therapy considered in the therapy of sexual dysfunctions in elderly men. A combined treatment of erectile disorders with testosterone and phosphodiesterease-5 inhibitors should be administered to the patients in whom the treatment with phosphodiesterease-5 inhibitors alone is not helpful. Keywords: sexual dysfunction, androgens, andropause, testosterone, prolactin, dihydrotestosterone, phosphodiesterease-5 inhibitors, hormone therapy
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Ebeling, P., U.-H. Stenman, M. Seppälä, and V. A. Koivisto. "Acute hyperinsulinemia, androgen homeostasis and insulin sensitivity in healthy man." Journal of Endocrinology 146, no. 1 (July 1995): 63–69. http://dx.doi.org/10.1677/joe.0.1460063.
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Abstract The acute effects of hyperinsulinemia on androgen homeostasis and a possible association of androgens to insulin sensitivity, serum lipids and lipoproteins and to lipid oxidation were examined in 19 healthy males (27 ± 1 yrs, body mass index 24 ± 1 kg/m2). In each subject, a 240 min euglycemic hyperinsulinemic clamp was performed and glucose and lipid oxidation were determined by indirect calorimetry. During hyperinsulinemia serum sex hormone-binding globulin (SHBG) concentration decreased by 5% (P<0·01), insulin-like growth factor binding protein (IGFBP-1) by 88% (P<0·001) and dehydroepiandrosterone sulphate (DHEAS) by 12% (P<0·001), with no change in total or free testosterone concentrations. In the basal state, IGFBP-1 and C-peptide were inversely related (r= −0·54, P<0·05). Fasting concentrations of serum free testosterone (r=0·59, P<0·01) and DHEAS (r=0·47, P<0·05) correlated positively with serum free fatty acid (FFA) concentrations during hyperinsulinemia, but not with fasting FFA level. Lipid oxidation rate in the basal state correlated positively to the decline in SHBG (r=0·61, P<0·01) and DHEAS concentrations (r=0·62, P<0·01) during hyperinsulinemia. While the fasting serum high density lipoprotein cholesterol level correlated positively with the insulin-induced decline in DHEAS level (r=0·58, P<0·01), no associations were found between serum androgens and total cholesterol, low density lipoprotein cholesterol or triglyceride concentrations. Insulin sensitivity was not related to SHBG, IGFBP-1, DHEAS or testosterone concentrations. It is concluded that, in the healthy man with normal androgen homeostasis, (1) acute hyperinsulinemia decreases SHBG, IGFBP-1 and DHEAS concentrations, (2) the relative insulin-induced decline of IGFBP-1 level is 18-fold greater than that of the SHBG level, (3) androgens may maintain lipolysis during hyperinsulinemia and (4) there is no association between physiological androgen concentrations and insulin sensitivity. Journal of Endocrinology (1995) 146, 63–69
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Hersberger, Martin, Jörg Muntwyler, Harald Funke, Jacqueline Marti-Jaun, Helmut Schulte, Gerd Assmann, Thomas F. Lüscher, and Arnold von Eckardstein. "The CAG Repeat Polymorphism in the Androgen Receptor Gene Is Associated with HDL-Cholesterol but Not with Coronary Atherosclerosis or Myocardial Infarction." Clinical Chemistry 51, no. 7 (July 1, 2005): 1110–15. http://dx.doi.org/10.1373/clinchem.2005.049262.
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Abstract Background: Age-adjusted morbidity and mortality rates from coronary heart disease (CHD) are higher in men than in women. Androgens are suspected to be responsible for the male disadvantage. The genomic effect of androgens is mediated by the androgen receptor (AR), which has a polymorphic CAG repeat in exon 1. The number of repeats is inversely related to the transcriptional activity of the AR on target genes. Methods: We investigated the association of this CAG repeat polymorphism with CHD and myocardial infarction (MI) in 2 independent case–control studies involving 544 Caucasian men. Results: The number of CAG repeats in the AR gene correlated significantly with HDL-cholesterol (HDL-C) in controls (r = 0.21; P = 0.015). This effect was independent of triglycerides, body mass index, alcohol intake, smoking, and age in a multiple regression model (R2 = 50%). Despite decreased HDL-C, lower CAG repeat numbers were not associated with increased risk for CHD (odds ratio = 0.82; 95% confidence interval, 0.50–1.36; P = 0.44) or MI in carriers of AR genes with lower CAG repeat numbers (odds ratio = 0.72; 95% confidence interval, 0.37–1.39; P = 0.33). Conclusions: Shorter, more androgenic AR alleles with fewer CAG repeats are associated with lower HDL-C, but not with an increased risk for CHD or MI, which argues against a detrimental androgen effect on cardiovascular risk under physiologic conditions.
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Cunningham, Sean K., Therese Loughlin, Marie Culliton, and T. Joseph McKenna. "The Relationship between Sex Steroids and Sex-Hormone-Binding Globulin in Plasma in Physiological and Pathological Conditions." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 22, no. 5 (September 1985): 489–97. http://dx.doi.org/10.1177/000456328502200504.
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Physiological and many pathological changes in plasma sex-hormone-binding globulin (SHBG) levels have been attributed to the opposing effects of androgens which lower, and oestrogens which elevate, levels. We examined four clinical situations in which changes in SHBG levels may not be explained by sex steroid alterations. (1) Dexamethasone caused an increase in SHBG levels in hyperandrogenaemic hirsute women whether or not androgens were suppressed. (2) In male patients with untreated isolated gonadotrophin deficiency there was a highly significant correlation between SHBG levels and age, but there was no relationship between the levels of SHBG and those of plasma testosterone, androstenedione or DHEAS. (3) Two 46-XY siblings, phenotypic female subjects with complete androgen insensitivity, demonstrated a marked decline in SHBG levels between the ages of 9–13 and 12–16 years. (4) SHBG was suppressed in obese oligomenorrhoeic women while plasma concentrations of testosterone, androstenedione and oestradiol were normal and that of oestrone was elevated; however, the testosterone: SHBG ratio, an index of free testosterone, was elevated. These observations indicate that the decline in SHBG levels which normally occurs in men during the second decade of life is independent of androgen activity and is under the influence of as yet unidentified factors. Glucocorticoids in small doses increase SHBG levels independently of sex steroid alterations while elevated free testosterone concentration may contribute to suppression of SHBG in obesity.
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Pepersack, Thierry, Camelia Rossi, Françoise Dupuis, André Lefevre, Michel Vanhaeverbeek, and Willy Dekoninck. "Hormonal status and clinical relevance of hirsutism in elderly women." Acta Endocrinologica 129, no. 4 (October 1993): 307–10. http://dx.doi.org/10.1530/acta.0.1290307.
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Hirsutism is a common condition of elderly women, but its aethiopathogeny and its clinical implications remain unclear. We therefore studied circulating androgen concentrations in elderly women. In addition, this study aims to define a possible relationship between hirsutism and anthropometric determinations, bone mass and serum lipids. Androgen levels were determined at basal state, after adrenocorticotrophin (ACTH) stimulation and after dexamethasone administration in 10 hirsute elderly women and compared to 10 age-matched non-hirsute women. Anthropometric determinations included measurements of skinfold thickness and body mass index. Spinal bone mass density was assessed using dual photon absorptiometry. Hirsute women presented significantly higher levels of testosterone than controls (1.49±0.38 vs 0.59±0.05 nmol/l, mean±sem; p<0.05) and dihydrotestosterone (0.54±0.07 vs 0.32±0.03; p<0.02). 1 7-hydroxyprogesterone levels after ACTH stimulation tended to be higher in hirsute women than in controls. No differences were observed between the two groups in serum oestrogen concentrations, plasma lipid pattern or bone mineral density. Hirsute women had a lower body mass index and lower calculated percentage body fat than the control group. We conclude that: (i) hirsutism of elderly women is associated with increased androgen levels, probably from adrenal origin; (ii) in some cases, enhanced response in 17-hydroxyprogesterone after ACTH stimulation suggests a partial adrenal 21-hydroxylase deficiency; (iii) hirsute women present anthropometric characteristics compatible with the known anabolic effect of androgens on fat-free mass.
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Quinkler, Marcus, Binayak Sinha, Jeremy W. Tomlinson, Iwona J. Bujalska, Paul M. Stewart, and Wiebke Arlt. "Androgen generation in adipose tissue in women with simple obesity – a site-specific role for 17β-hydroxysteroid dehydrogenase type 5." Journal of Endocrinology 183, no. 2 (November 2004): 331–42. http://dx.doi.org/10.1677/joe.1.05762.
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Women with polycystic ovary syndrome (PCOS) have high circulating androgens, thought to originate from ovaries and adrenals, and frequently suffer from the metabolic syndrome including obesity. However, serum androgens are positively associated with body mass index (BMI) not only in PCOS, but also in simple obesity, suggesting androgen synthesis within adipose tissue. Thus we investigated androgen generation in human adipose tissue, including expression of 17β-hydroxysteroid dehydrogenase (17β-HSD) isozymes, important regulators of sex steroid metabolism. Paired omental and subcutaneous fat biopsies were obtained from 27 healthy women undergoing elective abdominal surgery (age range 30–50 years; BMI 19.7–39.2 kg/m2). Enzymatic activity assays in preadipocyte proliferation cultures revealed effcient conversion of androstenedione to testosterone in both subcutaneous and omental fat. RT-PCR of whole fat and preadipocytes of subcutaneous and omental origin showed expression of 17β-HSD types 4 and 5, but no relevant expression of 17β-HSD types 1, 2, or 3. Microarray analysis confirmed this expression pattern (17β-HSD5>17β-HSD4) and suggested a higher expression of 17β-HSD5 in subcutaneous fat. Accordingly, quantitative real-time RT-PCR showed significantly higher expression of 17β-HSD5 in subcutaneous compared with omental fat (P<0.05). 17β-HSD5 expression in subcutaneous, but not omental, whole fat correlated significantly with BMI (r=0.51, P<0.05). In keeping with these findings, 17β-HSD5 expression in subcutaneous fat biopsies from six women taking part in a weight loss study decreased significantly with weight loss (P<0.05). A role for 17β-HSD5 in adipocyte differentiation was further supported by the observed increase in 17β-HSD5 expression upon differentiation of stromal preadipocytes to mature adipocytes (n=5; P<0.005), which again was higher in cells of subcutaneous origin. Functional activity of 17β-HSD5 also significantly increased with differentiation, revealing a net gain in androgen activation (androstenedione to testosterone) in subcutaneous cultures, contrasting with a net gain in androgen inactivation (testosterone to androstenedione) in omental cultures. Thus, human adipose tissue is capable of active androgen synthesis catalysed by 17β-HSD5, and increased expression in obesity may contribute to circulating androgen excess.
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Olsen, Nancy J., Ann L. Benko, and William J. Kovacs. "Variation in the androgen receptor gene exon 1 CAG repeat correlates with manifestations of autoimmunity in women with lupus." Endocrine Connections 3, no. 2 (June 2014): 99–109. http://dx.doi.org/10.1530/ec-14-0039.
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Clinical and experimental evidence support a role for gonadal steroids in modulating the expression and course of autoimmune diseases such as lupus. Whether or not inherited variation in sensitivity to circulating androgenic hormones could influence the manifestations of such disease is, however, unknown. We sought to determine whether differences in androgen sensitivity conferred by variation in the exon 1 CAG repeat region of the androgen receptor (AR) gene were associated with differences in the clinical or humoral immune manifestations of lupus in a cohort of female subjects. We found that shorter AR CAG repeat lengths in lupus subjects correlated with a higher Systemic Lupus Erythematosus Disease Activity Index score, higher ANA levels, and expression of a broader array of IgG autoantibodies. Our findings of more severe clinical manifestations and more exuberant humoral autoimmunity in women with a shorter AR exon 1 CAG repeat length suggest a role for genetically determined sensitivity to androgens as a modulator of autoimmune processes.
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Tsilchorozidou, Tasoula, John W. Honour, and Gerard S. Conway. "Altered Cortisol Metabolism in Polycystic Ovary Syndrome: Insulin Enhances 5α-Reduction But Not the Elevated Adrenal Steroid Production Rates." Journal of Clinical Endocrinology & Metabolism 88, no. 12 (December 1, 2003): 5907–13. http://dx.doi.org/10.1210/jc.2003-030240.
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Abstract Androgen excess in women with polycystic ovary syndrome (PCOS) may be ovarian and/or adrenal in origin, and one proposed contributing mechanism is altered cortisol metabolism. Increased peripheral metabolism of cortisol may occur by enhanced inactivation of cortisol by 5α-reductase (5α-R) or impaired reactivation of cortisol from cortisone by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) resulting in decreased negative feedback suppression of ACTH secretion maintaining normal plasma cortisol concentrations at the expense of androgen excess. We have tested whether any enzyme dysregulation was related to circulating insulin or androgen concentrations in women with PCOS and have sought to clarify their relationship with obesity. First, to avoid obesity-related effects on cortisol metabolism, 18 lean women with PCOS were compared with 19 lean controls who were closely matched for body mass index (BMI). Second, the impact of obesity was studied in a cross-section of 42 PCOS women of a broad range of BMI. We measured 24-h urinary excretion of steroid metabolites by gas chromatography/mass spectrometry and fasting metabolic and hormone profiles. Urinary excretion of androgens [androsterone (P = 0.003), etiocholanolone (P = 0.02), and C19 steroid sulfates (P = 0.009)], cortisone metabolites [tetrahydrocortisone (THE) (P = 0.02), α-cortolone (P < 0.001), β-cortol + β-cortolone (P < 0.001), cortolones (P < 0.001), and E metabolites (P < 0.001)], and TCM (P = 0.002) were raised in lean PCOS subjects when compared with controls. A significantly higher 5α-tetrahydrocortisol (5α-THF)/5β-THF ratio (P = 0.04) and a significantly lower α-THF + THF + α-cortol/THE + cortolones ratio (P = 0.01) were found in lean PCOS women compared with lean controls, indicating both enhanced 5α-R and reduced 11β-HSD1 activities. A decreased THE/cortolones ratio (P = 0.03) was also found in lean PCOS women compared with lean controls, indicating increased 20 α/β-HSD activity. In the group of 42 PCOS subjects, measures of 5α/5β reduction were positively correlated with the homeostasis model insulin resistance index (HOMA-R): α-THF/THF and HOMA-R (r = 0.34; P = 0.03), androsterone/etiocholanolone and HOMA-R (r = 0.32; P = 0.04), and total 5α /total 5β and HOMA-R (r = 0.37; P = 0.02). A positive correlation was also found between measures of 5α-R and BMI (r = 0.37; P = 0.02). No correlation was found between measures of 11β-HSD1 activity and indices of insulin sensitivity or BMI. We have demonstrated that there is an increased production rate of cortisol and androgens as measured in vivo in lean PCOS women. Insulin seems to enhance 5α reduction of steroids in PCOS but was not associated with the elevated cortisol production rate. The changes in 5α-R, 11β-HSD1, and 20α/β-HSD enzyme activities observed in PCOS may contribute to the increased production rates of cortisol and androgens, supporting the concept of a widespread dysregulation of steroid metabolism. This dysregulation does not seem to be the primary cause of PCOS because no correlation was found between serum androgen levels or urinary excretion of androgens with measurements of either 5α-R or 11β-HSD1 activities.
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Andræ, Frida, David Abbott, Solhild Stridsklev, Anne Vibeke Schmedes, Ingrid Hov Odsæter, Eszter Vanky, and Øyvind Salvesen. "Sustained Maternal Hyperandrogenism During PCOS Pregnancy Reduced by Metformin in Non-obese Women Carrying a Male Fetus." Journal of Clinical Endocrinology & Metabolism 105, no. 12 (September 1, 2020): 3762–70. http://dx.doi.org/10.1210/clinem/dgaa605.
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Abstract Context Large, longitudinal studies on androgen levels in pregnant women with polycystic ovary syndrome (PCOS) are lacking. While metformin has a mild androgen-lowering effect in non-pregnant women with PCOS, its effects on maternal androgen levels in pregnancy are less well understood. Objective To describe androgen patterns in pregnant women with PCOS and in healthy control women, and to explore the potential effects of metformin on maternal androgen levels in PCOS. Design and Setting A post hoc analysis from a randomized, placebo-controlled, multicenter study carried out at 11 secondary care centers and a longitudinal single-center study on healthy pregnant women in Norway. Participants A total of 262 women with PCOS and 119 controls. Intervention The participants with PCOS were randomly assigned to metformin (2 g daily) or placebo, from first trimester to delivery. Main Outcome Measures Androstenedione (A4), testosterone (T), sex-hormone binding globulin (SHBG), and free testosterone index (FTI) at 4 time points in pregnancy. Results Women with PCOS versus healthy controls had higher A4, T, and FTI, and lower SHBG at all measured time points in pregnancy. In the overall cohort of women with PCOS, metformin had no effect on A4, T, SHBG, and FTI. In subgroup analyses, metformin reduced A4 (P = 0.019) in nonobese women. Metformin also reduced A4 (P = 0.036), T (P = 0.023), and SHBG (P = 0.010) levels through pregnancy in mothers with a male fetus. Conclusion Metformin had no effect on maternal androgens in PCOS pregnancies. In subgroup analyses, a modest androgen-lowering effect was observed in nonobese women with PCOS. In PCOS women carrying a male fetus, metformin exhibited an androgen-lowering effect.
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Leão, Lenora M. Camarate S. M., Mônica Peres C. Duarte, Dalva Margareth B. Silva, Paulo Roberto V. Bahia, Cláudia Medina Coeli, and Maria Lucia Fleiuss de Farias. "Influence of methyltestosterone postmenopausal therapy on plasma lipids, inflammatory factors, glucose metabolism and visceral fat: a randomized study." European Journal of Endocrinology 154, no. 1 (January 2006): 131–39. http://dx.doi.org/10.1530/eje.1.02065.
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Background: There has been a growing interest in treating postmenopausal women with androgens. However, hyperandrogenemia in females has been associated with increased risk of cardiovascular disease. Objective: We aimed to assess the effects of androgen replacement on cardiovascular risk factors. Design: Thirty-seven postmenopausal women aged 42–62 years that had undergone hysterectomy were prospectively enrolled in a double-blind protocol to receive, for 12 months, percutaneous estradiol (E2) (1 mg/day) combined with either methyltestosterone (MT) (1.25 mg/day) or placebo. Methods: Along with treatment, we evaluated serum E2, testosterone, sex hormone-binding globulin (SHBG), free androgen index, lipids, fibrinogen, and C-reactive protein; glucose tolerance; insulin resistance; blood pressure; body-mass index; and visceral and subcutaneous abdominal fat mass as assessed by computed tomography. Results: A significant reduction in SHBG (P < 0.001) and increase in free testosterone index (P < 0.05; Repeated measures analysis of variance) were seen in the MT group. Total cholesterol, triglycerides, fibrinogen, and systolic and diastolic blood pressure were significantly lowered to a similar extent by both regimens, but high-density lipoprotein cholesterol decreased only in the androgen group. MT-treated women showed a modest rise in body weight and gained visceral fat mass relative to the other group (P < 0.05), but there were no significant detrimental effects on fasting insulin levels and insulin resistance. Conclusion: This study suggests that the combination of low-dose oral MT and percutaneous E2, for 1 year, does not result in expressive increase of cardiovascular risk factors. This regimen can be recommended for symptomatic postmenopausal women, although it seems prudent to perform baseline and follow-up lipid profile and assessment of body composition, especially in those at high risk of cardiovascular disease.
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Piltonen, Terhi, Riitta Koivunen, Antti Perheentupa, Laure Morin-Papunen, Aimo Ruokonen, and Juha S. Tapanainen. "Ovarian Age-Related Responsiveness to Human Chorionic Gonadotropin in Women with Polycystic Ovary Syndrome." Journal of Clinical Endocrinology & Metabolism 89, no. 8 (August 1, 2004): 3769–75. http://dx.doi.org/10.1210/jc.2003-031851.
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Ovarian steroid secretion capacity starts to decline as early as around the age of 30 yr. Whether an age-related decrease in androgen secretion, as in normal women, also occurs in women with polycystic ovary syndrome (PCOS) and whether the enhanced androgen production in PCOS remains throughout the fertile period of life are not known. The aim of this study was to determine the age-related serum basal and gonadotropin-stimulated androgen levels in women with PCOS and to compare the results with those obtained from our previous study in healthy women with normal ovaries. Human chorionic gonadotropin (hCG) stimulation tests were carried out among 42 women with PCOS (age, 16–44 yr; body mass index, 31.02 ± 1.1 kg/m2). An im injection of 5000 IU hCG was given 2–4 d after spontaneous or progestin-induced menstrual bleeding, and blood samples for LH, FSH, inhibin B, 17-hydroxyprogesterone, androstenedione (A), testosterone (T), and estradiol assays were collected at 0, 24, 48, and 96 h. In women with PCOS, basal serum T and A levels were about 50% higher than in healthy women. The responses of A and T to hCG [area under the curve (AUC), 96 h)] were significantly higher in women with PCOS than in normal women [A, 1183.6 ± 60 (±se) vs. 814.4 ± 39 (P ≤ 0.001); T, 192.9 ± 12 vs. 117.4 ± 6; P ≤ 0.001]. In PCOS women, the hCG-stimulated A levels correlated negatively with age (AUC of A: r = −0.044; P = 0.004), and a similar trend was also observed in AUC T levels (AUC of T: r = −0.125, P = 0.425). Despite the higher androgen secretion capacity in PCOS, the basal and hCG-stimulated serum estradiol levels were similar to those observed in normal women. LH correlated positively with age, but basal FSH and inhibin B levels remained unchanged. In conclusion, in PCOS basal serum levels of androgens and ovarian androgen secretion capacity are markedly increased and remain high throughout the reproductive years, although the decreasing ovarian capacity to release androgens in response to hCG stimulation seen in healthy women also occurs in PCOS.
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Swanson, Charlotte, Dan Mellström, Mattias Lorentzon, Liesbeth Vandenput, Jenny Jakobsson, Anders Rane, Magnus Karlsson, et al. "The Uridine Diphosphate Glucuronosyltransferase 2B15 D85Y and 2B17 Deletion Polymorphisms Predict the Glucuronidation Pattern of Androgens and Fat Mass in Men." Journal of Clinical Endocrinology & Metabolism 92, no. 12 (December 1, 2007): 4878–82. http://dx.doi.org/10.1210/jc.2007-0359.
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Abstract Context: Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT)2B15 and UGT2B17 glucuronidate androgens and their metabolites. Objective: Our objective was to determine in vivo whether the UGT2B15 D85Y and the UGT2B17 deletion polymorphisms predict androgen glucuronidation and body composition. Participants: Two population-based cohorts including young adult (n = 1068; age = 18.9 yr) and elderly (n = 1001; age = 75.3 yr) men were included in the study. Main Outcome Measures: Serum and urine levels of testosterone (T) and dihydrotestosterone (DHT) were measured by gas chromatography-mass spectrometry, and serum levels of the major glucuronidated androgen metabolites androstane-3α,17β-diol(androstanediol)-3-glucuronide, androstanediol-17-glucuronide, and androsterone-glucuronide were measured by liquid chromatography-tandem mass spectrometry. Body composition was measured by dual-energy x-ray absorptiometry. Results: Both the UGT2B15 D85Y and the UGT2B17 deletion polymorphisms were associated with serum levels of androstanediol-17-glucuronide (P < 0.001) but not with levels of androstanediol-3-glucuronide or androsterone-glucuronide in both cohorts. Glucuronidation of T and DHT was associated with the UGT2B17 deletion but not with the UGT2B15 D85Y polymorphism, suggested by strong associations between the deletion polymorphism and urine levels of these two hormones. Both polymorphisms were associated with several different measures of fat mass (P < 0.01). The UGT2B17 deletion polymorphism was associated with insulin sensitivity (P < 0.05) as indicated by the homeostasis model assessment index. Conclusions: The UGT2B15 D85Y and the UGT2B17 deletion polymorphisms are both predictors of the glucuronidation pattern of androgens/androgen metabolites. Our findings indicate that UGT2B17 is involved in 17-glucuronidation of mainly T but also of DHT and androstanediol and that UGT2B15 is involved in the 17-glucuronidation of androstanediol. Furthermore, these two polymorphisms are predictors of fat mass in men.
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de Medeiros, Sebastião Freitas, Matheus Antonio Souto de Medeiros, Bruna Barcelo Barbosa, and Márcia Marly Winck Yamamoto. "Relationship of Biological Markers of Body Fat Distribution and Corticosteroidogenic Enzyme Activities in Women with Polycystic Ovary Syndrome." Hormone and Metabolic Research 51, no. 10 (October 2019): 639–48. http://dx.doi.org/10.1055/a-0975-9207.
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AbstractThe aim of the study is to determine the impact of different anthropometric measurements of fat distribution on baseline sex-steroid concentrations and corticosteroidogenic enzyme activity in women with polycystic ovary syndrome compared to those with regular menstrual cycles. The current cross-sectional study included 106 normal cycling controls and 268 polycystic ovary syndrome patients. Patients with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided in normoandrogenemic (n=91) and hyperandrogenemic (n=177). Anthropometric, biochemical, and hormone parameters were assessed and correlated with corticosteroidogenic enzyme activities in all three groups. Corticosteroidogenic enzyme activities were calculated using product-to-precursor ratios. Regarding sex-steroids individually, anthropometric parameters correlated with the concentrations of several androgens in polycystic ovary syndrome patients, most of them in patients with biochemical hyperandrogenism. The androgen precursors androstenedione, 17-hydroxyprogesterone, and dehydroepiandrosterone were less correlated with anthropometric parameters. The 17,20 lyase activity, in both Δ4 and Δ5 pathways, correlated with several anthropometric measurements in normo- and hyperandrogenemic polycystic ovary syndrome patients. The 17,20 lyase enzyme activity (Δ4 pathway) also correlated with conicity index, visceral adiposity index, and lipid accumulation product in the control group. 17-Hydroxylase activity positively correlated with waist-height ratio in both polycystic ovary syndrome groups. In contrast, 17-hydroxilase negatively correlated with the conicity index. Anthropometric markers of adiposity are associated with androgen levels and their precursors in blood. Body fat distribution correlates with the activities of some steroidogenic enzyme in both normo-and hyperandrogenemic polycystic ovary syndrome phenotypes. The molecular mechanisms involved in these associations are largely unclear and more investigations are required.
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Mesinovic, Jakub, Helena J. Teede, Soulmaz Shorakae, Gavin W. Lambert, Elisabeth A. Lambert, Negar Naderpoor, and Barbora de Courten. "The Relationship between Vitamin D Metabolites and Androgens in Women with Polycystic Ovary Syndrome." Nutrients 12, no. 5 (April 26, 2020): 1219. http://dx.doi.org/10.3390/nu12051219.
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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, with hyperandrogenism present in up to 90% of affected women. Some evidence suggests a link between vitamin D deficiency and PCOS features via insulin resistance and inflammation. Our aim was to explore the relationship between biochemical markers of vitamin D status and androgens in women with PCOS. This cross-sectional study used bio-banked samples from 46 pre-menopausal women with PCOS (mean ± SD: age 30 ± 6 years; BMI 29 ± 6 kg/m2). We measured 25-hydroxyvitamin D (25[OH]D), vitamin D-binding protein (DBP), total testosterone, sex hormone-binding globulin (SHBG), and calculated the free androgen index (FAI) and bioavailable and free 25(OH)D. Fasting glucose and insulin were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) and body fat percentage was determined via dual energy x-ray absorptiometry. High-sensitivity C-reactive protein (hs-CRP) was measured as a marker of inflammation. DBP was positively associated with total 25(OH)D and expectedly, negatively associated with free 25(OH)D. There were no associations between vitamin D metabolites and total testosterone, SHBG or FAI, even after adjusting for age, body fat percentage, HOMA-IR and hs-CRP. We found no associations between vitamin D metabolites and androgens in women with PCOS. Studies that have identified a vitamin D–androgen link have largely relied on methodology with numerous pitfalls; future studies should exclusively use gold-standard measures to confirm these findings in this population.
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Zachurzok, Agnieszka, Grazyna Deja, Aneta Gawlik, Agnieszka Drosdzol-Cop, Katarzyna Klimek, and Ewa Malecka-Tendera. "Lipid Profile in Adolescent Girls with Type 1 Diabetes Mellitus and Hyperandrogenemia." International Journal of Endocrinology 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/9473158.
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Study Objectives. The study aim was to evaluate whether hyperandrogenemia in adolescent girls with type 1 diabetes mellitus (T1DM) may adversely influence lipid profile.Design and Participants. Lipid levels in 16 diabetic girls with biochemical hyperandrogenemia (T1DM-H) aged 16.3 ± 1.2 years were compared to 38 diabetic girls with normal androgen levels (T1DM-N) aged 15.8 ± 1.2 years. 15 healthy girls served as controls (CG). In all patients, anthropometric measurements were done, and androgens and SHBG were assessed.Results. In T1DM-H, total cholesterol (TC) and low density cholesterol (LDL-ch) were significantly higher than in CG (196.1 ± 41.2 versus 162.7 ± 31.7 mg/dL,p=0.01; 117.3 ± 33.1 versus 91.3 ± 27.8 mg/dL,p=0.01, resp.). Their LDL-ch, non-high density cholesterol (non-HDL-ch) concentrations, and LDL/HDL ratio were also significantly higher than in T1DM-N (117.3 ± 33.1 versus 97.7 ± 26.7 mg/dL,p=0.03; 137.3 ± 42.9 versus 113.3 ± 40.4 mg/dL,p=0.04; 2.8 ± 3.7 versus 1.6 ± 0.5,p=0.04, resp.). In stepwise multiple linear regression, free androgen index (FAI) and waist-to-hip ratio (WHR) were associated with TC (R2=0.4,p<0.0006), non-HDL-ch (R2=0.4,p<0.0003), and LDL-ch (R2=0.4,p<0.0008). Triglycerides and LDL/HDL ratio were (R2=0.7,p<0.0001,R2=0.6,p<0.0003resp.) related to testosterone, FAI, WHR, and mean HbA1c.Conclusion. Lipid profile in diabetic adolescent girls is adversely influenced by the androgens level, particularly in the group with higher WHR and poorer glycemic control.
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Autio, Karen A., Josef J. Fox, Coursen Walker Schneider, Heiko Schöder, John Humm, Dana E. Rathkopf, Susan F. Slovin, et al. "Evaluating 18F-16B-fluoro-5α-dihydrotestosterone (FDHT) and FDG-PET as a measure of disease progression in metastatic castration resistant prostate cancer (mCRPC)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 5090. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.5090.
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5090 Background: Prostate Cancer Working Group 2 defines radiographic progression as new lesions on bone scan. Molecular imaging has potential as a biomarker that reflects both alterations in disease burden and tumor biology. FDG and FDHT PET capture glycolytic activity and androgen receptor (AR) expression and tracer binding, respectively. We examined these tracers in mCRPC patients (pts) at progression (POD) to determine patterns of relapse. Methods: mCRPC pts simultaneously enrolled in imaging and therapeutic clinical trials had FDG and/or FDHT PET scans performed at baseline (BL) and within 4 weeks of treatment (rx) discontinuation for protocol-defined POD. BL characteristics, rx, SUVmax, SUVmaxavg (average of 5 index lesions), and presence of new lesion(s) at POD were collected. ΔSUV was calculated relative to BL. Results: 44 mCRPC pts (86 BL PET scans, 84 scans at POD) receiving novel anti-androgens (eg, enzalutamide) (n=18), abiraterone (abi) (n=10), chemotherapy-based rx (n=5), prednisone (n=4), or other targeted rx (n=7) were included. Of those with PET POD, 75% (24/32) had > 1 new lesion on FDG-PET and 96% (25/26) had > 1 new lesion on FDHT. New lesions on FDHT were seen in 33% (6/18) of pts on novel anti-androgens as compared with 100% (10/10) on abi. Presence of a new FDG avid lesion was similar for both anti-androgens and abi (56% vs 60%). Conclusions: POD on FDG/FDHT is more frequently detected by a new lesion rather than ΔSUV in existing index lesions. This is possibly an underestimate of change as the BL scan and not the post-rx nadir scan were used as a comparator. AR and glycolytic activity at POD may be dependent on individual and treatment factors. Notably, a third of pts on anti-androgens had a new FDHT avid lesion at POD. Full lesional analysis of metastases may enhance our understanding of tumor biology at POD. Clinical trial information: NCT00588185. [Table: see text]
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Ponjee, Gabriëlle A. E., Hans A. M. de Rooy, and Huib L. Vader. "Androstanediolglucuronide: A parameter for peripheral androgen activity before and during therapy with cyproterone acetate." Acta Endocrinologica 124, no. 4 (April 1991): 411–16. http://dx.doi.org/10.1530/acta.0.1240411.
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Abstract. Serum 5α-androstane-3α,17β-diolglucuronide (3α-AdiolG) levels were measured and the degree of hirsutism was scored in female outpatients complaining of excessive hair growth before and during treatment with cyproterone acetate. In a group of 16 patients with idiopathic hirsutism and in a group of 9 patients with either polycystic ovary syndrome and hirsutism or 21-hydroxylase deficiency and hirsutism, the serum 3α-AdiolG levels were significantly increased (p<0.01) as compared with the serum 3α-AdiolG level in a control group of 13 apparently healthy women: 3α-AdiolG levels, median (range), being 5.3 (2.3-7.8) nmol/l, 8.5 (4.1-10.4) nmol/l, and 2.9 (1.5-5.2) nmol/l, respectively. In contrast to a previous report, no correlation was found between the serum 3α-AdiolG levels and the Quetelet Index (N=18, R=0.42, p>0.05), indicating an apparent ineffectiveness of the excessive androgen turnover in fat tissue. The use of the anti-androgen drug cyproterone acetate alone or in combination with ethinylestradiol in reverse sequential therapy did lower the 3α-AdiolG levels significantly (p<0.01) together with a significant decrease (p<0.01) in hirsutism score. From the results of this study we therefore conclude that 3α-AdiolG can be used as a parameter for peripheral androgen action before and during treatment with anti-androgens.
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Khaw, Kay-Tee, and Elizabeth Barrett-Connor. "Fasting Plasma Glucose Levels and Endogenous Androgens in Non-Diabetic Postmenopausal Women." Clinical Science 80, no. 3 (March 1, 1991): 199–203. http://dx.doi.org/10.1042/cs0800199.
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1. The clinical association between glucose intolerance, hyperinsulinaemia, insulin resistance and hyperandrogenism is well recognized in premenopausal women with polycystic ovarian disease. We examined the hypothesis that fasting plasma glucose levels might be related to endogenous androgen levels in postmenopausal women in the absence of overt clinical disease. 2. In a Southern Californian cohort of 848 non-diabetic postmenopausal women aged 50–79 years, fasting plasma glucose levels positively correlated with levels of the endogenous androgens dehydroepiandrosterone sulphate and free testosterone and negatively with sex-hormone-binding globulin across the whole range of glucose and hormone levels. Mean dihydroepiandro-sterone sulphate and free testosterone levels were 16% and 46% higher, respectively, and mean sex-hormone-binding globulin levels 27% lower in the top compared with the bottom quartile of fasting plasma glucose levels. This relationship was independent of age, body mass index, cigarette smoking habit and exogenous oestrogen use. 3. These findings raise questions about the possible physiological role of androgens in the regulation of glucose metabolism and insulin resistance and, possibly, in the mediation of the some of the cardiovascular consequences of diabetes in women.
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Nóbrega, Rafael Henrique, Roberto Daltro Vidal de Souza Morais, Diego Crespo, Paul P. de Waal, Luiz Renato de França, Rüdiger W. Schulz, and Jan Bogerd. "Fsh Stimulates Spermatogonial Proliferation and Differentiation in Zebrafish via Igf3." Endocrinology 156, no. 10 (July 24, 2015): 3804–17. http://dx.doi.org/10.1210/en.2015-1157.
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Growth factors modulate germ line stem cell self-renewal and differentiation behavior. We investigate the effects of Igf3, a fish-specific member of the igf family. Fsh increased in a steroid-independent manner the number and mitotic index of single type A undifferentiated spermatogonia and of clones of type A differentiating spermatogonia in adult zebrafish testis. All 4 igf gene family members in zebrafish are expressed in the testis but in tissue culture only igf3 transcript levels increased in response to recombinant zebrafish Fsh. This occurred in a cAMP/protein kinase A-dependent manner, in line with the results of studies on the igf3 gene promoter. Igf3 protein was detected in Sertoli cells. Recombinant zebrafish Igf3 increased the mitotic index of type A undifferentiated and type A differentiating spermatogonia and up-regulated the expression of genes related to spermatogonial differentiation and entry into meiosis, but Igf3 did not modulate testicular androgen release. An Igf receptor inhibitor blocked these effects of Igf3. Importantly, the Igf receptor inhibitor also blocked Fsh-induced spermatogonial proliferation. We conclude that Fsh stimulated Sertoli cell production of Igf3, which promoted via Igf receptor signaling spermatogonial proliferation and differentiation and their entry into meiosis. Because previous work showed that Fsh also released spermatogonia from an inhibitory signal by down-regulating anti-Müllerian hormone and by stimulating androgen production, we can now present a model, in which Fsh orchestrates the activity of stimulatory (Igf3, androgens) and inhibitory (anti-Müllerian hormone) signals to promote spermatogenesis.
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Markopoulos, Marios C., George Valsamakis, Evangelia Kouskouni, Anastassios Boutsiadis, Ioannis Papassotiriou, George Creatsas, and George Mastorakos. "Study of carbohydrate metabolism indices and adipocytokine profile and their relationship with androgens in polycystic ovary syndrome after menopause." European Journal of Endocrinology 168, no. 1 (January 2013): 83–90. http://dx.doi.org/10.1530/eje-12-0550.
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ObjectiveHyperandrogenism, insulin resistance, and altered adipocytokine levels characterize polycystic ovary syndrome (PCOS) women of reproductive age. Hyperandrogenism persists in postmenopausal PCOS women. In the latter, this study aimed at investigating carbohydrate metabolism, adipocytokines, androgens, and their relationships.Subjects and methodsBlood sampling from overweight postmenopausal women (25 PCOS and 24 age- and BMI-matched controls) at baseline and during oral glucose tolerance test for measurement of insulin and glucose levels, baseline leptin, adiponectin, visfatin, retinol-binding protein 4, lipocalin-2, androgen, and high-sensitivity C-reactive protein (hs-CRP) levels and for calculation of insulin sensitivity (glucose-to-insulin ratio (G/I), quantitative insulin sensitivity check index, and insulin sensitivity index (ISI)), resistance (homeostasis mathematical model assessment-insulin resistance (HOMA-IR)), secretion (Δ of the area under the curve of insulin (ΔAUCI), first-phase insulin secretion (1st PHIS), and second-phase insulin secretion (2nd PHIS)), and free androgen indices (FAI).ResultsPCOS women had higher insulin secretion indices, hs-CRP, androgen, and FAI levels than controls without differing in baseline glucose, insulin and adipocytokines levels, insulin sensitivity, and resistance indices. In PCOS women, FAI levels correlated positively with baseline insulin, ΔAUCI, HOMA-IR, and ΔAUCG and negatively with G/I; hs-CRP levels correlated positively with ΔAUCI and negatively with ISI. PCOS status, waist circumference, and 17-hydroxyprogesterone (17-OHP) levels were positive predictors for ΔAUCI. In all women, waist circumference was a negative predictor for ISI; 17-OHP and FAI levels were positive predictors respectively for baseline insulin levels and for 1st PHIS and 2nd PHIS.ConclusionsEarly postmenopausal PCOS women are characterized by hyperinsulinemia but attenuated insulin resistance. PCOS status and waist circumference are predictors of hyperinsulinemia while insulin sensitivity correlates negatively with FAI. The differences reported in adipocytokine levels between PCOS and non-PCOS women in reproductive years seem to disappear after menopause.
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Koltun, Kristen J., Nancy I. Williams, Jennifer L. Scheid, and Mary Jane De Souza. "Discriminating hypothalamic oligomenorrhea/amenorrhea from hyperandrogenic oligomenorrhea/amenorrhea in exercising women." Applied Physiology, Nutrition, and Metabolism 45, no. 7 (July 2020): 707–14. http://dx.doi.org/10.1139/apnm-2019-0640.
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The mechanism underlying oligo/amenorrhea in exercising women is often presumed as hypothalamic inhibition secondary to energy deficiency; however, hyperandrogenism may provide an alternative mechanism in some exercising women. Our purpose was to compare reproductive, metabolic, and androgen profiles of exercising women with eumenorrheic, ovulatory menstrual cycles (n = 91), oligo/amenorrhea without evidence of hyperandrogenism (Oligo/Amen; n = 83), and oligo/amenorrhea with evidence of hyperandrogenism (Oligo/Amen-HA; n = 17), and determine the prevalence of oligo/amenorrhea with evidence of hyperandrogenism in exercising women. Self-reported menstrual history and quantification of daily estrogen and progesterone urinary metabolites determined reproductive status. Resting energy expenditure, body composition, and metabolic hormone concentrations determined metabolic status. Serum androgens and calculated free androgen index (FAI) determined androgen status. Groups were similar in age (22.4 ± 0.3 years), height (165.1 ± 0.5 cm), resting energy expenditure (1198.4 ± 12.0 kcal/day), and total triiodothyronine (85.0 ± 1.5 ng/dL) concentration. Oligo/Amen-HA had greater weight (60.0 ± 1.6, 56.1 ± 0.7 kg), body mass index (22.3 ± 0.4, 20.6 ± 0.2 kg/m2), percentage body fat (27.3% ± 1.4%, 24.4% ± 0.6%), fat mass (16.2 ± 1.0, 13.8 ± 0.4 kg), insulin (5.8 ± 0.7, 4.2 ± 0.3 μIU/mL), leptin (12.2 ± 2.3, 6.6 ± 0.7 ng/mL), FAI (6.1 ± 0.3, 1.7 ± 0.1), and luteinizing hormone/follicle-stimulating hormone (1.9 ± 0.3, 1.3 ± 0.2) compared with Oligo/Amen, respectively. In our sample, 17% of those with oligo/amenorrhea had concurrent hyperandrogenism. This study supports that oligo/amenorrhea in some exercising women is related to hyperandrogenism. Novelty Caution must be utilized when discriminating hypothalamic oligo/amenorrhea from hyperandrogenic oligo/amenorrhea. In our sample, 17% of those with presumed hypothalamic oligo/amenorrhea had concurrent hyperandrogenism. Exercise and/or mild energy deficiency may be protective against developing severe hyperandrogenic symptoms.
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Carlsen, S. M., G. Jacobsen, and P. Romundstad. "Maternal testosterone levels during pregnancy are associated with offspring size at birth." European Journal of Endocrinology 155, no. 2 (August 2006): 365–70. http://dx.doi.org/10.1530/eje.1.02200.
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Objective: Animal studies have indicated that maternal androgen levels influence the intrauterine environment and development of the offspring. Human data are missing. We therefore investigated the possible association between maternal androgens and offspring size at birth in humans. Design: A random sample of parous Caucasian women (n = 147) was followed prospectively through pregnancy. Methods: Maternal serum levels of dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone and sex hormone-binding globulin (SHBG) were measured at gestational weeks 17 and 33. The main outcome measures were weight and length at birth. Associations between maternal androgen levels and offspring birth weight and length were investigated using multiple linear regression modeling adjusted for potential confounding by maternal height, pre-pregnancy body mass index, smoking, parity, offspring gender and gestational age at birth. Results: Elevated maternal testosterone levels at week 17 and 33 were both associated with lower birth weights and lengths. Accordingly, at week 17, an increase in maternal testosterone levels from the 25th to the 75th percentile was associated with a decrease in birth weight by 160 g (95% confidence interval (CI); 29–290 g), while at week 33 that estimate was 115 g (95% CI; 21–207 g). No similar associations were observed for DHEAS, androstenedione or SHBG. Conclusions: Elevated maternal testosterone levels during human pregnancy are associated with growth restriction in utero. Our results support animal studies, which have indicated that maternal androgen levels influence intrauterine offspring environment and development.
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Shetelig Løvvik, Tone, Solhild Stridsklev, Sven M. Carlsen, Øyvind Salvesen, and Eszter Vanky. "Cervical Length and Androgens in Pregnant Women With Polycystic Ovary Syndrome: Has Metformin Any Effect?" Journal of Clinical Endocrinology & Metabolism 101, no. 6 (June 1, 2016): 2325–31. http://dx.doi.org/10.1210/jc.2015-3498.
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Abstract Context: Women with polycystic ovary syndrome (PCOS) have increased risk of preterm delivery. Shortening of the cervix is a sign of preterm delivery. Objective: This study aimed to investigate potential effect of metformin on cervical length and whether androgen levels correlate with cervical length in PCOS pregnancies. Design and Setting: This was a sub-study of a randomized, placebo-controlled, multicenter study (The PregMet study) performed at 11 secondary or tertiary centers from 2005 to 2009. Participants: Two-hundred sixty-one pregnancies of 245 women with PCOS, age 18–42 years participated. Interventions: Participants were randomly assigned to metformin or placebo from first trimester to delivery. Outcome Measurements: We compared cervical length and androgen levels in metformin and placebo groups at gestational weeks 19 and 32. We also explored whether cervical length correlated with androgen levels. Results: We found no difference in cervical length between the metformin and the placebo groups at gestational week 19 and 32. Dehydroepiandrosterone (DHEAS) tended to be higher in the metformin group. There were no correlations between androgens and cervical length at week 19. At gestational week 32, androstenedione (P = .02) and DHEAS (P = .03) showed a trend toward negative correlation to cervical length. High androstenedione level correlated with shortening of cervical length from week 19 to 32 when adjusted for confounders (P = .003). T (P = .03), DHEAS (P = .02), and free testosterone index (P = .03) showed a similar trend. Conclusion: Metformin in pregnancy did not affect cervical length in women with PCOS. High maternal androgen levels correlated with cervical shortening from the second to the third trimester of pregnancy, as a sign of cervical ripening.
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Lovering, Richard M., and William A. Romani. "Effect of testosterone on the female anterior cruciate ligament." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 289, no. 1 (July 2005): R15—R22. http://dx.doi.org/10.1152/ajpregu.00829.2004.
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Injuries to the anterior cruciate ligament (ACL) result in immediate and long-term morbidity and expense. Young women are more likely to sustain ACL injuries than men who participate in similar athletic and military activities. Although significant attention has focused on the role that female sex hormones may play in this disparity, it is still unclear whether the female ACL also responds to androgens. The purpose of this study was to determine whether the female ACL was an androgen-responsive tissue. To identify and localize androgen receptors in the female ACL, we used Western blotting and immunofluorescent labeling, respectively, of ACL tissue harvested during surgery from young women ( n = 3). We then measured ACL stiffness and assessed total testosterone (T) and free [free androgen index (FAI)] testosterone concentrations, as well as relative estradiol to testosterone ratios (E2/T and E2/FAI) at three consecutive menstrual stages ( n = 20). There were significant rank-order correlations between T (0.48, P = 0.031), FAI (0.44, P = 0.053), E2/T (−0.71, P < 0.001), E2/FAI (−0.63, P = 0.003), and ACL stiffness near ovulation. With the influences of the other variables controlled, there were significant negative partial rank-order correlations between ACL stiffness and E2/T (−0.72, P < 0.001) and E2/FAI (−0.59, P = 0.012). The partial order residuals for T and FAI were not significant. These findings suggest that the female ACL is an androgen-responsive tissue but that T and FAI are not independent predictors of ACL stiffness near ovulation. Instead, the relationship between T, FAI, and ACL stiffness was likely influenced by another hormone or sex hormone binding globulin.
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DOCKERY, Frances, Christopher J. BULPITT, Sanjiv AGARWAL, Mandy DONALDSON, and Chakravarthi RAJKUMAR. "Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia." Clinical Science 104, no. 2 (January 17, 2003): 195–201. http://dx.doi.org/10.1042/cs1040195.
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The role of androgens in cardiovascular disease is uncertain. We aimed to determine the vascular effects of androgen suppression in men with prostate cancer. Arterial stiffness (or ‘compliance’) was measured in 16 men (71±9 years, mean±S.D.) prior to, and 3 months after, complete androgen suppression with gonadotrophin-releasing hormone analogues as treatment for prostate cancer. Fifteen control men (70±7 years) also had arterial stiffness studies at baseline and 3 months later. Two measures of arterial stiffness were employed: systemic arterial compliance (SAC) was measured by simultaneous recording of aortic flow and carotid artery pressure (‘area method’), and pulse wave velocities (PWVs) were recorded with the ‘Complior’ system. The 16 cases underwent glucose-tolerance and fasting-lipids tests on both visits. After 3 months of testosterone suppression, there was a significant fall in SAC, which was not seen in the controls [mean change±S.E.M., -0.26±0.09a.c.u. (arbitrary compliance unit) in the cases versus +0.06±0.11 in the controls; P = 0.03). Central, but not peripheral, PWVs tended to increase in the cases (mean change±S.E.M. for aorto-femoral PWV, +0.5±0.4m/s for cases versus -0.3±0.3m/s for controls; P = 0.08). After testosterone suppression, fasting insulin levels increased from 6.89±4.84m-units/l to 11.34±8.16m-units/l (mean±S.D.), total cholesterol increased from 5.32±0.77mmol/l to 5.71±0.82mmol/l and high-density lipoprotein cholesterol increased from 1.05±0.24mmol/l to 1.26±0.36mmol/l; P<0.005 for all. No significant change occurred in body-mass index, serum glucose, low-density lipoprotein cholesterol or triacylglycerol (triglyceride) levels. Our results indicate that loss of androgens in men leads to an increase in aortic stiffness and serum insulin levels, and may therefore adversely affect cardiovascular risk.
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Choi, Ji-Hun, Eun-Jung Rhee, Kye-Hyun Kim, Hee-Yeon Woo, Won-Young Lee, and Ki-Chul Sung. "Plasma omentin-1 levels are reduced in non-obese women with normal glucose tolerance and polycystic ovary syndrome." European Journal of Endocrinology 165, no. 5 (November 2011): 789–96. http://dx.doi.org/10.1530/eje-11-0375.
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ObjectiveOmentin-1 is a novel adipokine that increases insulin sensitivity and is expressed in visceral adipose tissue. The aim of this study was to determine the metabolic parameters that influence plasma omentin-1 levels in women with polycystic ovary syndrome (PCOS).Design and methodsA cross-sectional study was performed in 87 women with PCOS and 53 body mass index (BMI)-matched healthy controls including 39 non-obese, normal-weight (NW) PCOS women with normal glucose tolerance (NGT) and 44 BMI- and homeostasis model assessment (HOMA)-matched controls. Indices of insulin sensitivity, metabolic variables, circulating androgen levels, serum adiponectin, and omentin-1 levels were measured. A 75 g oral glucose tolerance test was performed in all participants.ResultsPlasma omentin-1 levels were significantly lower in women with PCOS compared with those in BMI-matched controls (P<0.001). A significantly lower level of plasma omentin-1 was observed in non-obese women with PCOS and NGT compared with that in BMI- and HOMA-matched controls (P<0.001). Omentin-1 level was negatively correlated with BMI, indices of insulin sensitivity, and circulating androgens and was associated with greater 2 h postprandial glucose, C-peptide, and insulin levels compared with fasting values. Within the NW and NGT groups, omentin-1 levels remained negatively correlated with BMI, 2 h postprandial C-peptide, and circulating androgens and demonstrated a negative linear trend according to quartile of free testosterone (P=0.028).ConclusionsPlasma levels of omentin-1 were reduced in non-obese women with PCOS and NGT. Postprandial hyperinsulinemia and hyperglycemia contributed more to lower omentin-1 levels than did fasting values in the setting of PCOS. Increased androgen levels contributed to decreased omentin-1 levels in women with PCOS.
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van Hooff, M. H. A., F. J. Voorhorst, M. B. H. Kaptein, R. A. Hirasing, C. Koppenaal, and J. Schoemaker. "Insulin, Androgen, and Gonadotropin Concentrations, Body Mass Index, and Waist to Hip Ratio in the First Years after Menarche in Girls with Regular Menstrual Cycles, Irregular Menstrual Cycles, or Oligomenorrhea1." Journal of Clinical Endocrinology & Metabolism 85, no. 4 (April 1, 2000): 1394–400. http://dx.doi.org/10.1210/jcem.85.4.6543.
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Data on changes in hormone concentrations during the first years after menarche are scarce. We studied the relation between gynecological age (age minus age at menarche), hormone concentrations, and body measurements from the 1st to the 6th yr after menarche in 229 observations of girls with regular menstrual cycles, 157 observations of girls with irregular menstrual cycles, and 104 observations of girls with oligomenorrhea. Body Mass Index, waist circumference, hip circumference, LH, androstenedione, testosterone, and dehydro-epiandrosterone sulphate increased significantly (linear regression, P < 0.05) by gynecological age in all menstrual cycle pattern groups. For PRL and estradiol a significant increase with gynecological age was only documented in the regular menstrual cycle group and for waist to hip ratio only in the irregular menstrual cycle group. No significant correlation could be documented between gynecological age and overnight fasting insulin concentrations or glucose to insulin ratio. We found no significant correlation between insulin concentrations or glucose to insulin ratio and androgen concentrations. Significant positive correlations were found between LH and androgens. LH and androgen levels increase during the first years after menarche, and reference values should be adjusted for gynecological age. In these years, no significant correlation between hyperinsulinemia and hyperandrogenemia could be documented.
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Abruzzese, Giselle Adriana, Maria Florencia Heber, Silvana Rocío Ferreira, María José Ferrer, and Alicia Beatriz Motta. "Prenatal androgen exposure affects ovarian lipid metabolism and steroid biosynthesis in rats." Journal of Endocrinology 247, no. 3 (December 2020): 239–50. http://dx.doi.org/10.1530/joe-20-0304.
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Prenatal androgen exposure affects reproductive functions and has been proposed as an underlying cause of polycystic ovary syndrome (PCOS). In this study, we aimed to investigate the impact of prenatal androgen exposure on ovarian lipid metabolism and to deepen our understanding of steroidogenesis regulation during adulthood. Pregnant rats were hyperandrogenized with testosterone and female offspring were studied when adult. This treatment leads to two different phenotypes: irregular ovulatory and anovulatory animals. Our results showed that prenatally hyperandrogenized (PH) animals displayed altered lipid and hormonal profile together with alterations in steroidogenesis and ovarian lipid metabolism. Moreover, PH animals showed alterations in the PPARg system, impaired mRNA levels of cholesterol receptors (Ldlr and Srb1) and decreased expression of the rate-limiting enzyme of de novo cholesterol production (Hmgcr). Anovulatory PH animals presented an increase of ovarian cholesteryl esters levels and lipid peroxidation index. Together with alterations in cholesterol metabolism, we found an impairment of the steroidogenic pathway in PH animals in a phenotype-specific manner. Regarding fatty acid metabolism, our results showed, in PH animals, an altered expression of Srebp1 and Atgl, which are involved in fatty acid metabolism and triglycerides hydrolysis, respectively. In conclusion, fatty acid and cholesterol metabolism, which are key players in steroidogenesis acting as a source of energy and substrate for steroid production, were affected in animals exposed to androgens during gestation. These results suggest that prenatal androgen exposure leads to long-term effects that affect ovary lipid metabolism and ovarian steroid formation from the very first steps.
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Kim, Jae Hyun, Young Ah Lee, Youn-Hee Lim, Kyunghoon Lee, Bung-Nyun Kim, Johanna Inhyang Kim, Yun-Chul Hong, Sei Won Yang, Junghan Song, and Choong Ho Shin. "Changes in Adrenal Androgens and Steroidogenic Enzyme Activities From Ages 2, 4, to 6 Years: A Prospective Cohort Study." Journal of Clinical Endocrinology & Metabolism 105, no. 10 (August 4, 2020): 3265–72. http://dx.doi.org/10.1210/clinem/dgaa498.
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Abstract Context The levels of adrenal androgens are increased through the action of steroidogenic enzymes with morphological changes in the adrenal zona reticularis. Objective We investigated longitudinal changes in androgen levels and steroidogenic enzyme activities during early childhood. Design and Participants From a prospective children’s cohort, the Environment and Development of Children cohort, 114 boys and 86 girls with available blood samples from ages 2, 4, and 6 years were included. Outcome Measurements Serum concentrations of adrenal androgens using liquid chromatography-tandem mass spectrometry and steroidogenic enzyme activity calculated by the precursor/product ratio. Results During ages 2 to 4 years, 17,20-lyase and dehydroepiandrosterone (DHEA) sulfotransferase activities increased (P < 0.01 for both in boys). During ages 4 to 6 years, 17,20-lyase activity persistently increased, but 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD activities decreased (P < 0.01 for all). Serum DHEA sulfate (DHEA-S) levels persistently increased from 2, 4, to 6 years, and DHEA, 17-hydroxyprogesterone, and androstenedione levels increased during ages 4 to 6 years (P < 0.01 for all). Serum DHEA-S levels during early childhood were associated with body mass index z-scores (P = 0.001 in only boys). Conclusion This study supports in vivo human evidence of increased 17,20-lyase and DHEA sulfotransferase activities and decreased 3β-HSD activity during early childhood.
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Silveira, Diosely C., Elizabeth A. P. de Souza, José F. Carvalho, and Carlos A. M. Guerreiro. "Interictal hyposexuality in male patients with epilepsy." Arquivos de Neuro-Psiquiatria 59, no. 1 (March 2001): 23–28. http://dx.doi.org/10.1590/s0004-282x2001000100006.
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The purpose of this study was to compare the serum levels of androgens between hyposexual and non-hyposexual patients with epilepsy. Adult male patients with epilepsy were investigated. Serum levels of testosterone (T) and free-T, estradiol, and sex hormone binding globulin (SHBG) were measured and the free androgen index (FAI) was calculated. While there were no differences between hyposexual and non-hyposexual patients in the serum levels of T, free-T, and estradiol, or to the FAI, the serum levels of SHBG were significantly higher in hyposexual patients than in non-hyposexual patients. Thus, the effects of increased SHBG upon serum levels of testosterone biologically active in patients with epilepsy and hyposexuality were not detected by the methods used in this study. Four (44%) of nine hyposexual patients who were re-evaluated after two years follow-up improved sexual performance. Thus, clinical treatment that results in good seizure control may improve sexual performance in some patients with epilepsy.
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Cree-Green, Melanie, Bradley R. Newcomer, Gregory Coe, Lindsey Newnes, Amy Baumgartner, Mark S. Brown, Laura Pyle, Jane E. Reusch, and Kristen J. Nadeau. "Peripheral insulin resistance in obese girls with hyperandrogenism is related to oxidative phosphorylation and elevated serum free fatty acids." American Journal of Physiology-Endocrinology and Metabolism 308, no. 9 (May 1, 2015): E726—E733. http://dx.doi.org/10.1152/ajpendo.00619.2014.
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Hyperandrogenic syndrome (HAS) is associated with insulin resistance (IR) and type 2 diabetes. Muscle IR in type 2 diabetes is linked with defects in mitochondrial oxidative capacity. In vivo muscle mitochondrial function has not been studied in HAS, especially in youth, who are early in the disease process. Our goal was to measure muscle mitochondrial oxidative function and peripheral IR in obese youth with HAS. Obese girls without HAS [ n = 22, age 15(13,17) yr, BMI Z-score 2.05 ± 0.37] and with HAS [ n = 35, age 15(14,16) yr, BMI Z-score 2.18 ± 0.30] were enrolled. Mitochondrial function was assessed with31phosphorus MR spectroscopy before, during, and after near-maximal isometric calf exercise, and peripheral IR was assessed with an 80 mU·m−2·min−1hyperinsulinemic euglycemic clamp. Girls with HAS had higher androgens [free androgen index 7.9(6.6,15.5) vs. 3.5(3.0,4.0), P < 0.01] and more IR [glucose infusion rate 9.4(7.0, 12,2) vs. 14.5(13.2,15.8) mg·kg lean−1·min−1, P < 0.01]. HAS girls also had increased markers of inflammation including CRP, platelets, and white blood cell count and higher serum free fatty acids during hyperinsulinemia. Mitochondrial oxidative phosphorylation was lower in HAS [0.11(0.06,0.19) vs. 0.18(0.12,0.23) mmol/s, P < 0.05], although other spectroscopy markers of mitochondrial function were similar between groups. In multivariate analysis of the entire cohort, IR related to androgens, oxidative phosphorylation, and free fatty acid concentrations during hyperinsulinemia. These relationships were present in just the HAS cohort as well. Obese girls with HAS have significant peripheral IR, which is related to elevated androgens and free fatty acids and decreased mitochondrial oxidative phosphorylation. These may provide future options as targets for therapeutic intervention.
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Isidori, Andrea M., Massimiliano Caprio, Felice Strollo, Costanzo Moretti, Gaetano Frajese, Aldo Isidori, and Andrea Fabbri. "Leptin and Androgens in Male Obesity: Evidence for Leptin Contribution to Reduced Androgen Levels*." Journal of Clinical Endocrinology & Metabolism 84, no. 10 (October 1, 1999): 3673–80. http://dx.doi.org/10.1210/jcem.84.10.6082.
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Abstract Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8–55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = −0.51 and r = −0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU im) was 30–40% lower than in controls and inversely correlated with leptin levels (r = −0.45 and r = −0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.
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Wilke, T. J., and D. J. Utley. "Total testosterone, free-androgen index, calculated free testosterone, and free testosterone by analog RIA compared in hirsute women and in otherwise-normal women with altered binding of sex-hormone-binding globulin." Clinical Chemistry 33, no. 8 (August 1, 1987): 1372–75. http://dx.doi.org/10.1093/clinchem/33.8.1372.
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Abstract We compared the clinical value of information on free testosterone as measured with the Coat-A-Count (Diagnostic Products Corp.) radioimmunoassay kit involving a ligand analog with that of total testosterone, the free-androgen index, and free testosterone calculated from concentrations of testosterone, sex-hormone-binding globulin, and albumin, in hirsute women, pregnant women, oral-contraceptive users, women with thyroid disease, and epileptic women taking phenytoin. Total testosterone, the free-androgen index, calculated free testosterone, and free testosterone by RIA were increased in 41-68% of hirsute women. Values for free testosterone increased in the first and third trimesters of pregnancy but remained within normal limits in all non-hirsute groups. Total testosterone was increased in patients having increased sex-hormone-binding globulin, whereas the free-androgen index and, to a lesser extent, calculated free testosterone were significantly decreased. Free testosterone measured by analog RIA not only has greater diagnostic efficiency than total testosterone, it also is technically simpler to determine than the free-androgen index and calculated free testosterone.
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Janner, Marco, Grit Sommer, Michael Groessl, and Christa E. Flück. "Premature Adrenarche in Girls Characterized By Enhanced 17,20-Lyase and 17β-Hydroxysteroid Dehydrogenase Activities." Journal of Clinical Endocrinology & Metabolism 105, no. 12 (August 31, 2020): e4439-e4451. http://dx.doi.org/10.1210/clinem/dgaa598.
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Abstract Context Girls with premature adrenarche (PA) may have a higher risk of developing polycystic ovary syndrome (PCOS) and metabolic syndrome. The biological purpose of adrenarche is unknown and the role of novel biosynthetic pathways remains unclear. Objective To compare the urinary steroid metabolome and enzyme activities of girls with PA to age-matched control girls and to published steroid values of girls with normal adrenarche and of women with PCOS and their newborn daughters. Design Prospective observational study from 2009 to 2014. Setting Academic pediatric endocrinology referral center. Participants Twenty-three girls with PA and 22 healthy, age-matched girls. Main Outcome Measures Steroid metabolites in 24-hour urine samples, including 4 progesterones, 5 corticosterones, aldosterone, 13 androgens, 2 estrogens, 14 glucocorticoids, and enzyme activities represented by metabolite ratios. Results Girls with PA had a higher body mass index (mean standard deviation scores 0.9 vs -0.3, P = 0.013). Androgen excretion was higher in PA girls than in control girls (median 3257 nmol/24 hours vs 1627 nmol/24 hours, P < 0.001), in particular metabolites from alternate androgen pathways. The amount of progesterone, corticosterone, aldosterone, estrogen, and cortisol metabolites were similar between groups. Activities of 17β-hydroxysteroid-dehydrogenase and of 17,20-lyase were higher in girls with PA. Activities of 3β-hydroxysteroid-dehydrogenase, 21-hydroxylase, and 5α-reductase activity were not different between groups, in contrast to published results on girls with normal adrenarche or PCOS females. Conclusions Metabolites and enzymes involved in alternate androgen pathways appear to be markers of PA. Prospective studies should assess whether steroid production in PA also differs from adrenarche at normal timing and persists into adulthood.
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Grassi, Giorgia, Elisa Polledri, Silvia Fustinoni, Iacopo Chiodini, Ferruccio Ceriotti, Simona D’Agostino, Francesca Filippi, et al. "Hyperandrogenism by Liquid Chromatography Tandem Mass Spectrometry in PCOS: Focus on Testosterone and Androstenedione." Journal of Clinical Medicine 10, no. 1 (December 31, 2020): 119. http://dx.doi.org/10.3390/jcm10010119.
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The identification of hyperandrogenism in polycystic ovary syndrome (PCOS) is concerning because of the poor accuracy of the androgen immunoassays (IA) and controversies regarding which androgens should be measured. The aim of our study was to evaluate the impact of the assessment of testosterone (T) and androstenedione (A) by liquid chromatography in tandem with mass spectrometry (LC/MS-MS), in the diagnosis of PCOS. We evaluated 131 patients referred for suspected PCOS. Fourteen patients in total were excluded, some because of other diagnosis (n = 7) or incomplete diagnostic workup (n = 7). We measured T and A both by IA and LC-MS/MS in the 117 subjects included. We calculated free T (fT) by the Vermeulen formula and recorded clinical and metabolic data. 73 healthy females served as controls to derive immunoassays (IA) and LC-MS/MS reference intervals for T, fT and A. PCOS was confirmed in 90 subjects by IA and in 93 (+3.3%) by LC-MS/MS. The prevalence of biochemical hyperandrogenism in PCOS by LC-MS/MS increased from 81.7% to 89.2% if A was also considered. The most frequently elevated androgens were fT (73.1%) and A (64.5%) and they had similar levels of accuracy in differentiating PCOS and controls (0.34 ng/dL, Sn 91% Sp 89%; 1.16 ng/mL, Sn 91% Sp 88%, respectively). Free testosterone correlated with body mass index (BMI), homeostatic model assessment (HOMA)-index, glycated hemoglobin (HbA1c), and sex-binding globulin (SHBG). The results confirm that LC-MS/MS is slightly more sensitive than IA in the diagnosis of PCOS with LC-MS/MS detecting higher levels of fT and A. Moreover, assessment of fT and A by LC-MS/MS had a similar level of accuracy in discriminating between PCOs and control subjects. Lastly, fT by LC-MS/MS correlates with adverse metabolic parameters.