Objective:
The objective of the study was to evaluate the current state of clinical assays for estradiol in the context of their applications.
Participants:
The participants were appointed by the ...Council of The Endocrine Society and charged with attaining the objective using published data and expert opinion.
Evidence:
Data were gathered from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), and the clinical and laboratory experience of the participants.
Consensus Process:
The statement was an effort of the committee and was reviewed by each member. The Clinical Affairs Committee, the Council of The Endocrine Society, and JCEM reviewers reviewed the manuscript and made recommendations.
Conclusions:
The measurement of estradiol in biological fluids is important in human biology from cradle to grave. In addition to its centrality in sexual development, it has significant effects on skin, blood vessels, bone, muscle, coagulation, hepatic cells, adipose tissue, the kidney, the gastrointestinal tract, brain, lung, and pancreas. Alterations in its plasma concentration have been implicated in coronary artery disease, stroke, and breast cancer. Although modern immunoassays and liquid chromatography/tandem mass spectrometry-based methods for estradiol are reasonably well suited to the diagnosis and management of infertility (nonetheless, imprecision and method-to-method differences remain problematic), the very low concentrations that appear to be crucial in nonreproductive tissues are a separate and more difficult issue. Such levels of estradiol are too low to be routinely measured accurately or precisely, and further evolution of analytical methods and the way in which estradiol is standardized is needed.
Objective:
The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding ...of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period.
Methods:
Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus.
Results:
STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage -3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage -1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics.
Conclusions:
STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified.
Abstract
Background
A test that helps predict the time to the final menstrual period (FMP) has been sought for many years.
Objective
To assess the ability of antimullerian hormone (AMH) measurements ...to predictions the time to FMP.
Design
Prospective longitudinal cohort study.
Setting
The Study of Women’s Health Across the Nation.
Participants and Measurements
AMH and FSH were measured in 1537 pre- or early perimenopausal women, mean age 47.5 ± 2.6 years at baseline, then serially until 12 months of amenorrhea occurred. AMH was measured using a 2-site ELISA with a detection limit of 1.85 pg/mL.
Main Outcome Measure
Areas under the receiver operating curves (AUC) for AMH-based and FSH-based predictions of time to FMP, stratified by age. Probabilities that women would undergo their FMP in the next 12, 24, or 36 months across a range of AMH values were assessed.
Results
AUCs for predicting that the FMP will occur within the next 24 months were significantly greater for AMH-based than FSH-based models. The probability that a woman with an AMH <10 pg/mL would undergo her FMP within the next 12 months ranged from 51% at h<48 years of age to 79% at ≥51 years. The probability that a woman with an AMH >100 pg/mL would not undergo her FMP within the next 12 months ranged from 97% in women <48 years old to 90% in women ≥51 years old.
Conclusions
AMH measurement helps estimate when a woman will undergo her FMP, and, in general, does so better than FSH.
The objective of the study was to evaluate the current state of clinical assays for total and free testosterone.
The five participants were appointed by the Council of The Endocrine Society and ...charged with attaining the objective using published data and expert opinion.
Data were gleaned from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), the College of American Pathologists, and the clinical and laboratory experiences of the participants.
The statement was an effort of the committee and was reviewed in detail by each member. The Council of The Endocrine Society reviewed a late draft and made specific recommendations.
Laboratory proficiency testing should be based on the ability to measure accurately and precisely samples containing known concentrations of testosterone, not only on agreement with others using the same method. When such standardization is in place, normative values for total and free testosterone should be established for both genders and children, taking into account the many variables that influence serum testosterone concentration.
OBJECTIVE: The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding ...of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period. METHOD(S): Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus. RESULT(S): STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage −3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage −1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics. CONCLUSION(S): STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified.
Both FSH and LH circulate as 2 glycoforms, differing in number of glycans: low-N-glycosylated glycoforms, FSHtri and LHdi, and fully N-glycosylated glycoforms, FSHtetra and LHtri.
To determine the ...half-lives of endogenous circulating gonadotropin glycoforms in women during GnRH receptor blockade.
Serum samples were collected in 8 healthy women before and up to 20 hours after administration of the NAL-GLU GnRH antagonist. Three women were in early follicular phase, 2 at mid-cycle phase, and 3 were postmenopausal.
The half-life of each glycoform was estimated by monoexponential decay for FSH (n = 8) and LH (n = 5). Data were analyzed using paired t tests.
Half-lives in the circulation of low-N-glycosylated glycoforms of both FSH and LH were shorter than those of the fully N-glycosylated glycoforms (mean; range, FSHtri 343; 116-686 minutes vs FSHtetra 757; 436-1038, minutes, P = 0.0003; LHdi 125, 84-198 minutes vs LHtri 164, 107-235 minutes, P = 0.004). The half-lives of low-and fully N-glycosylated forms of LH were shorter than the corresponding half-lives of FSH glycoforms, P = 0.0008.
For both FSH and LH, low-N-glycosylated glycoforms disappeared from the circulation faster than the fully N-glycosylated. The half-lives of low and fully N-glycosylated forms of LH were shorter than the corresponding half-lives of FSH. The estimated values for half-life in the circulation of total FSH and total LH will depend on the relative amounts of the 2 glycoforms of each hormone and their individual disappearance rates in circulation.
The divergence in analytical quality of serum/plasma 25-hydroxy-vitamin D analysis calls for defining specifications for a reference measurement system.
Fundamentally, in a reference measurement ...system, there should be a relationship between the analytical specifications for higher- (reference) and lower-order (routine) measurements. Therefore, when setting specifications, we started with limits for routine imprecision (CV
rou) and bias (
B
rou) using 4 models: (1) the misclassifications in diagnosis, (2) biological variation data (reference interval (RI) and monitoring), (3) expert recommendations, and (4) state-of-the-art performance. Then, we used the derived goals to tailor those for reference measurements and certified reference materials (CRMs) for calibration by setting the limits for CV
ref at 0.5 CV
rou,
B
ref at 0.33
B
rou
, max. uncertainty (
U
max) at 0.33
B
ref.
The established specifications ranged between CV
rou
≤
22%,
B
rou
≤
10%, CV
ref
≤
11%,
B
ref
≤
3.3%,
U
max 1.1% (model 3) and CV
rou
≤
4%,
B
rou
≤
2.6%, CV
ref
≤
2%,
B
ref
≤
0.9%,
U
max 0.3% (model 2, monitoring).
Model 2 (monitoring) gave the most stringent goals, model 3, the most liberal ones. Accounting for state-of-the-art performance and certification capabilities, we used model 2 (RI) to recommend achievable goals: for routine testing, CV
rou
≤
10%,
B
rou
≤
5%, for reference measurements, CV
ref
≤
5%,
B
ref
≤
1.7%, and for CRMs,
U
max 0.6%.
The utility of aminoterminal pro-brain natriuretic peptide (NT-proBNP) testing in the emergency department to rule out acute congestive heart failure (CHF) and the optimal cutpoints for this use are ...not established. We conducted a prospective study of 600 patients who presented in the emergency department with dyspnea. The clinical diagnosis of acute CHF was determined by study physicians who were blinded to NT-proBNP results. The primary end point was a comparison of NT-proBNP results with the clinical assessment of the managing physician for identifying acute CHF. The median NT-proBNP level among 209 patients (35%) who had acute CHF was 4,054 versus 131 pg/ml among 390 patients (65%) who did not (p <0.001). NT-proBNP at cutpoints of >450 pg/ml for patients <50 years of age and >900 pg/ml for patients ≥50 years of age were highly sensitive and specific for the diagnosis of acute CHF (p <0.001). An NT-proBNP level <300 pg/ml was optimal for ruling out acute CHF, with a negative predictive value of 99%. Increased NT-proBNP was the strongest independent predictor of a final diagnosis of acute CHF (odds ratio 44, 95% confidence interval 21.0 to 91.0, p <0.0001). NT-proBNP testing alone was superior to clinical judgment alone for diagnosing acute CHF (p = 0.006); NT-proBNP plus clinical judgment was superior to NT-proBNP or clinical judgment alone. NT-proBNP measurement is a valuable addition to standard clinical assessment for the identification and exclusion of acute CHF in the emergency department setting.
The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the ...critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period.
Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus.
STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage -3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage -1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics.
STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified.
Abstract
Context
Accurate diagnosis of adrenal insufficiency is critical because there are risks associated with overdiagnosis and underdiagnosis. Data using liquid chromatography tandem mass ...spectrometry (LC/MS/MS) free cortisol (FC) assays in states of high or low cortisol-binding globulin (CBG) levels, including cirrhosis, critical illness, and oral estrogen use, are needed.
Design
Cross-sectional.
Objective
Determine the relationship between CBG and albumin as well as total cortisol (TC) and FC in states of normal and abnormal CBG. Establish the FC level by LC/MS/MS that best predicts TC of <18 μg/dL (497 nmol/L) (standard adrenal insufficiency diagnostic cutoff) in healthy individuals.
Subjects
This study included a total of 338 subjects in four groups: healthy control (HC) subjects (n = 243), patients with cirrhosis (n = 38), intensive care unit patients (ICU) (n = 26), and oral contraceptive (OCP) users (n = 31).
Main Outcome Measure(s)
FC and TC by LC/MS/MS, albumin by spectrophotometry, and CBG by ELISA.
Results
TC correlated with FC in the ICU (R = 0.91), HC (R = 0.90), cirrhosis (R = 0.86), and OCP (R = 0.70) groups (all P < 0.0001). In receiver operator curve analysis in the HC group, FC of 0.9 μg/dL (24.8 nmol/L) predicted TC of <18 μg/dL (497 nmol/L; 98% sensitivity, 91% specificity; AUC, 0.98; P < 0.0001). Decreasing the cutoff to 0.7 μg/dL led to a small decrease in sensitivity (92%) with similar specificity (91%).
Conclusions
A cutoff FC of <0.9 μg/dL (25 nmol/L) in this LC/MS/MS assay predicts TC of <18 μg/dL (497 nmol/L) with excellent sensitivity and specificity. This FC cutoff may be helpful in ruling out adrenal insufficiency in patients with binding globulin derangements.
In healthy subjects, plasma free cortisol of 0.9 μg/dL best predicted total cortisol of <18 μg/dL and could aid in the diagnosis of adrenal insufficiency in states of altered binding globulins.
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