Androgens During the Reproductive Years: What Is Normal for Women?

2019 ◽  
Vol 104 (11) ◽  
pp. 5382-5392 ◽  
Author(s):  
Marina A Skiba ◽  
Robin J Bell ◽  
Rakibul M Islam ◽  
David J Handelsman ◽  
Reena Desai ◽  
...  

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.

2019 ◽  
Vol 105 (3) ◽  
pp. 754-768 ◽  
Author(s):  
Hanne Frederiksen ◽  
Trine Holm Johannsen ◽  
Stine Ehlern Andersen ◽  
Jakob Albrethsen ◽  
Selma Kløve Landersoe ◽  
...  

Abstract Context The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low concentrations. Objective To establish sex-specific reference ranges for estrone (E1) and estradiol (E2) throughout life and to evaluate sex-differences using the state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantification of E1, E2, and estriol (E3). Design LC-MS/MS method development and construction of estrogen reference ranges. Settings Population-based cross-sectional cohorts from the greater Copenhagen and Aarhus areas. Participants Healthy participants aged 3 months to 61 years (n = 1838). Results An isotope diluted LC-MS/MS method was developed and validated for measurements of serum E1, E2, and E3. Limits of detections (LODs) were 3 pmol/L (E1), 4 pmol/L (E2), and 12 pmol/L (E3), respectively. This sensitive method made it possible to differentiate between male and female concentration levels of E1 and E2 in children. In girls, E2 levels ranged from &lt;LOD to 100 pmol/L during mini-puberty, whereas it was ≤20 pmol/L during childhood. E1 and E2 increased with age and pubertal breast stage and varied during the menstrual cycle; E1 was lower than E2 in girls and premenopausal women, and higher than E2 in postmenopausal women. In boys, E1 and E2 increased with age and pubertal stage, whereas little changes with age were observed in men. High E3 concentrations were confirmed in pregnant women. Conclusion Reference ranges of simultaneous quantification of E1 and E2 by this novel specific and highly sensitive LC-MS/MS method provide an invaluable tool in clinical practice and in future research studies.


Author(s):  
Vichit Supornsilchai ◽  
Chutima Jantarat ◽  
Wichit Nosoognoen ◽  
Sopon Pornkunwilai ◽  
Suttipong Wacharasindhu ◽  
...  

AbstractReports on the secular trend of pubertal onset indicate a recent earlier start especially in girls. Bisphenol A (BPA), which posses estrogenic activity, might be a cause of advanced puberty. The objective of the study was to determine the association between BPA and advanced puberty.A cross-sectional study was conducted in patients with advanced puberty (n=41) compared to age-matched controls (n=47). Anthropometric measurements, estradiol, basal and gonadotropin releasing hormone (GnRH)-stimulated follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, uterine sizes, ovarian diameters and bone ages were obtained. Urinary BPA concentrations were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MSMS) with the lower limit of quantification (LLOQ) of 0.05 ng/mL.The median adjust-BPA concentration in advanced puberty group was higher than in control groups [1.44 vs. 0.59 μg/g creatinine (Cr): p<0.05]. We also found that the median adjust-BPA concentration in girls with advanced puberty who were overweight/obese, was greater than in the normal pubertal overweight/obese girls (1.74 vs. 0.59 μg/g Cr: p<0.05), and was in the same trend among normal weight girls with advanced and normal puberty (0.83 vs. 0.49 μg/g Cr: p=0.09), but not statistically significant.The present findings suggest that BPA exposure appears to be related to an earlier age at onset of puberty especially in obese girls.


2021 ◽  
Vol 28 (1) ◽  
pp. e100419
Author(s):  
Haoran Xu ◽  
Louis Agha-Mir-Salim ◽  
Zachary O’Brien ◽  
Dora C Huang ◽  
Peiyao Li ◽  
...  

BackgroundDespite wide usage across all areas of medicine, it is uncertain how useful standard reference ranges of laboratory values are for critically ill patients.ObjectivesThe aim of this study is to assess the distributions of standard laboratory measurements in more than 330 selected intensive care units (ICUs) across the USA, Amsterdam, Beijing and Tarragona; compare differences and similarities across different geographical locations and evaluate how they may be associated with differences in length of stay (LOS) and mortality in the ICU.MethodsA multi-centre, retrospective, cross-sectional study of data from five databases for adult patients first admitted to an ICU between 2001 and 2019 was conducted. The included databases contained patient-level data regarding demographics, interventions, clinical outcomes and laboratory results. Kernel density estimation functions were applied to the distributions of laboratory tests, and the overlapping coefficient and Cohen standardised mean difference were used to quantify differences in these distributions.ResultsThe 259 382 patients studied across five databases in four countries showed a high degree of heterogeneity with regard to demographics, case mix, interventions and outcomes. A high level of divergence in the studied laboratory results (creatinine, haemoglobin, lactate, sodium) from the locally used reference ranges was observed, even when stratified by outcome.ConclusionStandardised reference ranges have limited relevance to ICU patients across a range of geographies. The development of context-specific reference ranges, especially as it relates to clinical outcomes like LOS and mortality, may be more useful to clinicians.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Asim Mumtaz ◽  
Fauzia Sadiq ◽  
Saima Zaki ◽  
Hijab Batool ◽  
Muhammad Ibrahim ◽  
...  

Abstract Background The significance of investigation for diagnosing and managing thyroid dysfunction in pregnant females has been extensively documented in the medical literature. This study aimed to determine trimester-specific reference ranges for thyroid-stimulating hormones (TSH), free T3 (FT3), and free T4 (FT4) in apparently healthy pregnant women attending tertiary care hospitals in Lahore. Methods This cross-sectional study was conducted at two tertiary care Hospitals in Lahore, Pakistan. In this multi-centric study, 500 pregnant females were initially enrolled from September 2019 to December 2019 who fulfilled the inclusion criteria. For measurement of serum FT3, FT4, thyroid stimulating hormone (TSH), anti-thyroid peroxidase (anti-TPO), and thyroglobulin antibodies, 5 ml of the blood sample was drawn, under aseptic conditions, from each subject using Maglumi 800 chemiluminescence immunoassay (CLIA) system. Results Out of 500 subjects, 23 subjects with positive anti-TPO, 19 subjects with anti-TG antibodies, and 12 subjects due to less volume of serum yielded from whole blood (serum less than 3 ml) were excluded from the analysis. Ten samples were hemolyzed and not included in the analysis. A total of 436 samples were examined for analysis. Of the remaining 436 subjects, 133 (30.5%) were from 1st trimester, 153 (35.1%) from 2nd trimester, and 150 (34.4%) from 3rd trimester. As the data were non-normal, the 2.5th, 50th, and 97.5th percentiles were calculated to express each group's results. Trimester specific range of TSH 0.168-4.294, 0.258-4.584 and 0.341-4.625 mIU/mL, FT31.857-4.408, 1.958-4.621 and 2.025-4.821 pmol/L and FT4 8.815-18.006, 8.306-17.341 and 7.402-17.292 pmol/L. Conclusion In this study, we established a trimester-specific reference range for our local population's thyroid function test. The results of this study have complemented the results of previous studies.


2019 ◽  
Vol 104 (12) ◽  
pp. 6291-6300 ◽  
Author(s):  
Susan R Davis ◽  
Robin J Bell ◽  
Penelope J Robinson ◽  
David J Handelsman ◽  
Tom Gilbert ◽  
...  

Abstract Context There is a lack of understanding of what is normal in terms of sex steroid levels in older women. Objective To determine whether sex steroid levels vary with age in and establish reference ranges for women >70 years of age. Design and Setting Cross-sectional, community-based study. Participants Included 6392 women ≥70 years of age. Main Outcome Measures Sex steroids measured by liquid chromatography–tandem mass spectrometry. A reference group, to establish sex steroid age-specific reference ranges, excluded women using systemic or topical sex steroid, antiandrogen or glucocorticoid therapy, or an antiglycemic agent. Results The reference group of 5326 women had a mean age of 75.1 (±4.2) years, range of 70 to 94.7 years. Median values (range) were 181.2 pmol/L (3.7 to 5768.9) for estrone (E1), 0.38 nmol/L (0.035 to 8.56) for testosterone (T), 2.60 nmol/L (0.07 to 46.85) for dehydroepiandrosterone (DHEA), and 41.6 nmol/L (2.4 to 176.6) for SHBG. Estradiol and DHT were below method sensitivity in 66.1% and 72.7% of the samples, respectively. Compared with women aged 70 to 74 years, women aged ≥85 years had higher median levels of E1 (11.7%, P = 0.01), T (11.3%, P = 0.02), and SHBG (22.7%, P < 0.001) and lower DHEA (30% less, P < 0.001). Women with overweight and obesity had higher E1 (P < 0.001) and T (P < 0.03) and lower SHBG (P < 0.001) than did women with normal body mass index. Smokers had 17.2% higher median T levels (P = 0.005). Conclusion From the age of 70 years, T and E1 increase with age, despite a steady decline in DHEA. Whether E1 and T are biomarkers for longevity or contribute to healthy aging merits investigation.


PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0119103 ◽  
Author(s):  
Luís Guedes-Martins ◽  
Rita Gaio ◽  
Joaquim Saraiva ◽  
Sofia Cerdeira ◽  
Liliana Matos ◽  
...  

2021 ◽  
Author(s):  
Asim Mumtaz ◽  
Fauzia Sadiq ◽  
Saima Zaki ◽  
Hijab Batool ◽  
Muhammad Ibrahim ◽  
...  

Abstract Background: The significance of investigation for diagnosing and managing thyroid dysfunction in pregnant females has been extensively documented in the medical literature. This study aimed to determine trimester-specific reference ranges for thyroid-stimulating hormones (TSH), Free T3 (FT3), and free T4 (FT4) in apparently healthy pregnant women attending tertiary care hospitals in Lahore. Methods: This cross-sectional study was conducted at two tertiary care Hospitals in Lahore, Pakistan. In this multi-centric study, initially, 500 pregnant females were enrolled from September 2019 to December 2019 who fulfilled the inclusion criteria. For measurement of serum freeT3, free T4, TSH, anti-TPO, and Thyroglobulin antibodies, 5 ml of the blood sample was drawn, under aseptic conditions, from each subject using Maglumi 800 chemiluminescence immunoassay (CLIA) system. Results: Out of 500 subjects, 23 subjects with positive anti-TPO, 19 subjects with anti-TG antibodies, and 12 subjects due to less volume of serum yielded from whole blood (serum less than 3 ml) were excluded from the analysis. Ten samples were hemolyzed and not included in the analysis. A total of 436 samples were examined for analysis. Of the remaining 436 subjects, 133 (30.5%) were from 1st Trimester, 153 (35.1%) from 2nd Trimester, and 150 (34.4%) from 3rd Trimester. As the data were non-normal, the 2.5th, 50th and 97.5th percentiles were calculated to express each group's results. Trimester specific range of TSH 0.168-4.294, 0.258-4.584 and 0.341-4.625, FT3 1.857-4.408, 1.958-4.621 and 2.025-4.821 pg/mL and FT4 8.815-18.006, 8.306-17.341 and 7.402-17.292 pg/mL. Conclusion: In this study, we established a trimester-specific reference range for our local population's thyroid function test. The results of this study have complemented the results of previous studies.


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