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The Journal of Clinical Endocrinology... Oct 2023Crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist, has been shown to reduce elevated adrenal androgens and precursors in adults with congenital...
CONTEXT
Crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist, has been shown to reduce elevated adrenal androgens and precursors in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), a rare autosomal recessive disorder characterized by cortisol deficiency and androgen excess due to elevated adrenocorticotropin.
OBJECTIVE
To evaluate the safety, tolerability, and efficacy of crinecerfont in adolescents with 21OHD CAH.
METHODS
This was an open-label, phase 2 study (NCT04045145) at 4 centers in the United States. Participants were males and females, 14 to 17 years of age, with classic 21OHD CAH. Crinecerfont was administered orally (50 mg twice daily) for 14 consecutive days with morning and evening meals. The main outcomes were change from baseline to day 14 in circulating concentrations of ACTH, 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone.
RESULTS
8 participants (3 males, 5 females) were enrolled; median age was 15 years and 88% were Caucasian/White. After 14 days of crinecerfont, median percent reductions from baseline to day 14 were as follows: ACTH, -57%; 17OHP, -69%; and androstenedione, -58%. In female participants, 60% (3/5) had ≥50% reduction from baseline in testosterone.
CONCLUSION
Adolescents with classic 21OHD CAH had substantial reductions in adrenal androgens and androgen precursors after 14 days of oral crinecerfont administration. These results are consistent with a study of crinecerfont in adults with classic 21OHD CAH.
Topics: Male; Adult; Humans; Female; Adolescent; Androgens; Adrenal Hyperplasia, Congenital; Androstenedione; 17-alpha-Hydroxyprogesterone; Testosterone; Adrenocorticotropic Hormone
PubMed: 37216921
DOI: 10.1210/clinem/dgad270 -
Clinical Endocrinology Aug 2023Monitoring of hormone replacement therapy represents a major challenge in the management of congenital adrenal hyperplasia (CAH). In the absence of clear guidance and... (Review)
Review
Monitoring of hormone replacement therapy represents a major challenge in the management of congenital adrenal hyperplasia (CAH). In the absence of clear guidance and standardised monitoring strategies, there is no consensus among clinicians regarding the relevance of various biochemical markers used in practice, leading to wide variability in their application and interpretation. In this review, we summarise the published evidence on biochemical monitoring of CAH. We discuss temporal variations of the most commonly measured biomarkers throughout the day, the interrelationship between different biomarkers, as well as their relationship with different glucocorticoid and mineralocorticoid treatment regimens and clinical outcomes. Our review highlights significant heterogeneity across studies in both aims and methodology. However, we identified key messages for the management of patients with CAH. The approach to hormone replacement therapy should be individualised, based on the individual hormonal profile throughout the day in relation to medication. There are limitations to using 17-hydroxyprogesterone, androstenedione and testosterone, and the role of additional biomarkers such 11-oxygenated androgens which are more disease specific should be further established. Noninvasive monitoring via salivary and urinary steroid measurements is becoming increasingly available and should be considered, especially in the management of children with CAH. Additionally, this review indicates the need for large scale longitudinal studies analysing the interrelation between different monitoring strategies used in clinical practice and health outcomes in children and adults with CAH.
PubMed: 37608608
DOI: 10.1111/cen.14960 -
Chemosphere Aug 2023Wastewater monitoring and epidemiology have seen renewed interest during the recent COVID-19 pandemic. As a result, there is an increasing need to normalize... (Review)
Review
Wastewater monitoring and epidemiology have seen renewed interest during the recent COVID-19 pandemic. As a result, there is an increasing need to normalize wastewater-derived viral loads in local populations. Chemical tracers, both exogenous and endogenous compounds, have proven to be more stable and reliable for normalization than biological indicators. However, differing instrumentation and extraction methods can make it difficult to compare results. This review examines current extraction and quantification methods for ten common population indicators: creatinine, coprostanol, nicotine, cotinine, sucralose, acesulfame, androstenedione 5-hydroindoleacetic acid (5-HIAA), caffeine, and 1,7-dimethyluric acid. Some wastewater parameters such as ammonia, total nitrogen, total phosphorus, and daily flowrate were also evaluated. The analytical methods included direct injection, dilute and shoot, liquid/liquid, and solid phase extraction (SPE). Creatine, acesulfame, nicotine, 5-HIAA and androstenedione have been analysed by direct injection into LC-MS; however, most authors prefer to include SPE steps to avoid matrix effects. Both LC-MS and GC-MS have been successfully used to quantify coprostanol in wastewater, and the other selected indicators have been quantified successfully with LC-MS. Acidification to stabilize the sample before freezing to maintain the integrity of samples has been reported to be beneficial. However, there are arguments both for and against working at acidic pHs. Wastewater parameters mentioned earlier are quick and easy to quantify, but the data does not always represent the human population effectively. A preference for population indicators originating solely from humans is apparent. This review summarises methods employed for chemical indicators in wastewater, provides a basis for choosing an appropriate extraction and analysis method, and highlights the utility of accurate chemical tracer data for wastewater-based epidemiology.
Topics: Humans; Wastewater; Nicotine; RNA, Viral; SARS-CoV-2; Hydroxyindoleacetic Acid; Androstenedione; Cholestanol; Pandemics; Water Pollutants, Chemical; COVID-19; Solid Phase Extraction; Indicators and Reagents
PubMed: 37201600
DOI: 10.1016/j.chemosphere.2023.138682 -
Biomedicines Feb 2024Hair loss is a common clinical condition connected with serious psychological distress and reduced quality of life. Hormones play an essential role in the regulation of... (Review)
Review
Hair loss is a common clinical condition connected with serious psychological distress and reduced quality of life. Hormones play an essential role in the regulation of the hair growth cycle. This review focuses on the hormonal background of hair loss, including pathophysiology, underlying endocrine disorders, and possible treatment options for alopecia. In particular, the role of androgens, including dihydrotestosterone (DHT), testosterone (T), androstenedione (A4), dehydroepiandrosterone (DHEA), and its sulfate (DHEAS), has been studied in the context of androgenetic alopecia. Androgen excess may cause miniaturization of hair follicles (HFs) in the scalp. Moreover, hair loss may occur in the case of estrogen deficiency, appearing naturally during menopause. Also, thyroid hormones and thyroid dysfunctions are linked with the most common types of alopecia, including telogen effluvium (TE), alopecia areata (AA), and androgenetic alopecia. Particular emphasis is placed on the role of the hypothalamic-pituitary-adrenal axis hormones (corticotropin-releasing hormone, adrenocorticotropic hormone (ACTH), cortisol) in stress-induced alopecia. This article also briefly discusses hormonal therapies, including 5-alpha-reductase inhibitors (finasteride, dutasteride), spironolactone, bicalutamide, estrogens, and others.
PubMed: 38540126
DOI: 10.3390/biomedicines12030513 -
Human Reproduction (Oxford, England) Nov 2023What is the relationship of sex steroid levels with sexual function in women with and without polycystic ovary syndrome (PCOS)? (Observational Study)
Observational Study
STUDY QUESTION
What is the relationship of sex steroid levels with sexual function in women with and without polycystic ovary syndrome (PCOS)?
SUMMARY ANSWER
Women with PCOS reported more sexual dysfunction and more sexual distress compared to those without PCOS, but only few and weak associations between androgen levels and sexual function were observed.
WHAT IS KNOWN ALREADY
The literature shows that women with PCOS report lower levels of sexual function and sexual satisfactionand more sexual distress. Contributing factors seem to be obesity, alopecia, hirsutism, acne, infertility, anxiety, depression, and low self-esteem. In women with PCOS clinical and/or biochemical hyperandrogenism is common; its relationship with sexualfunction is, however, inconclusive.
STUDY DESIGN, SIZE, DURATION
This observational prospective case control study with 135 women (68 PCOS, 67 control) was conductedfrom March 2017 until March 2020.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Heterosexual women with and without PCOS, aged 18-40 years, in a steady relationshipand without any comorbidities, underwent an extensive medical and endocrine screening using liquid chromatography-tandem mass spectrometry and validated sexual function questionnaires.
MAIN RESULTS AND THE ROLE OF CHANCE
Women with PCOS reported significantly lower sexual function (Female Sexual Function Index (FSFI) P < 0.001, partial η2 = 0.104), higher levels of sexual distress (Female Sexual Distress Scale-Revised P < 0.001, partial η2 = 0.090), and they more often complied with the definition of sexual dysfunction (41.2% vs 11.9%, P < 0.001, Phi V = 0.331) and clinical sexual distress (51.5% vs 19.4%, P < 0.001, Phi V = 0.335). Regression analysis adjusted for confounders showed only few and weak associations between androgen levels and sexual function, with each model explaining a maximum of 15% sexual function. Following significant Group × Hormone interactions, analyses for both groups separately showed no significant associations in the PCOS group. The control group showed only weak negative associations between testosterone and FSFI pain (β = -6.022, P = 0.044, Adj R2 = 0.050), between FAI and FSFI orgasm (β = -3.360, P = 0.023, Adj R2 = 0.049) and between androstenedione and clinical sexual distress (β = -7.293, P = 0.036, exp(β) = 0.001).
LIMITATIONS, REASONS FOR CAUTION
The focus of the study on sexual functioning potentially creates selection bias. Possibly women with more severe sexual disturbances did or did not choose to participate. Differences between women with PCOS and controls in relationship duration and hormonal contraceptive use might have skewed the sexual function outcomes.
WIDER IMPLICATIONS OF THE FINDINGS
Sexual function is impaired in women with PCOS. However, endocrine perturbations seem to have minimal direct impact on sexual function. Addressing sexuality and offering psychosexual counseling is important in the clinical care for women with PCOS.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the departments of the participating centers: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Psychosomatic OBGYN and Sexology, Leiden University Medical Center, Leiden, the Netherlands; and Department of Sexology and Psychosomatic OBGYN, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands. J.S.E.L. received unrestricted research grants from the following companies (in alphabetical order): Ansh Labs, Ferring, Merck Serono and Roche Diagnostics. He also received consultancy fees from Ansh Labs, Ferring, Titus Healthcare and Roche Diagnostics. The other authors have no conflicts of interest.
TRIAL REGISTRATION NUMBER
CCMO register, registration number: NL55484.078.16, 10 March 2016. https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm.
Topics: Female; Humans; Male; Pregnancy; Androgens; Case-Control Studies; Hyperandrogenism; Infertility, Female; Polycystic Ovary Syndrome; Sexual Dysfunction, Physiological; Prospective Studies
PubMed: 37776157
DOI: 10.1093/humrep/dead193 -
The Journal of Clinical Endocrinology... Nov 2023Epidemiological and preclinical data support cardiovascular, mainly protective, effects of sex steroids in men, but the mechanisms underlying the cardiovascular actions...
CONTEXT
Epidemiological and preclinical data support cardiovascular, mainly protective, effects of sex steroids in men, but the mechanisms underlying the cardiovascular actions of sex steroids are poorly understood. Vascular calcification parallels the development of atherosclerosis, but is increasingly recognized as a diversified, highly regulated process, which itself may have pathophysiological importance for clinical cardiovascular events.
OBJECTIVE
To investigate the association between serum sex steroids and coronary artery calcification (CAC) in elderly men.
METHODS
We used gas chromatography tandem mass spectrometry to analyze a comprehensive sex steroid profile, including levels of dehydroepiandrosterone (DHEA), androstenedione, estrone, testosterone, estradiol, and dihydrotestosterone, in men from the population-based AGES-Reykjavik study (n = 1287, mean 76 years). Further, sex hormone-binding globulin (SHBG) was assayed and bioavailable hormone levels calculated. CAC score was determined by computed tomography. The main outcome measures were cross-sectional associations between dehydroepiandrosterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and quintiles of CAC.
RESULTS
Serum levels of DHEA, androstenedione, testosterone, dihydrotestosterone, and bioavailable testosterone showed significant inverse associations with CAC, while estrone, estradiol, bioavailable estradiol, and SHBG did not. DHEA, testosterone, and bioavailable testosterone remained associated with CAC after adjustment for traditional cardiovascular risk factors. In addition, our results support partially independent associations between adrenal-derived DHEA and testes-derived testosterone and CAC.
CONCLUSION
Serum levels of DHEA and testosterone are inversely associated with CAC in elderly men, partially independently from each other. These results raise the question whether androgens from both the adrenals and the testes may contribute to male cardiovascular health.
Topics: Aged; Humans; Male; Androstenedione; Coronary Artery Disease; Dehydroepiandrosterone; Dihydrotestosterone; Estradiol; Estrone; Sex Hormone-Binding Globulin; Testosterone; Vascular Calcification
PubMed: 37391895
DOI: 10.1210/clinem/dgad351 -
Gynecological Endocrinology : the... Dec 2023To establish a cutoff level of AMH which could help for the diagnosis of PCOS, to investigate the predictive value of AMH combined with androgens in Chinese women to...
OBJECTIVE
To establish a cutoff level of AMH which could help for the diagnosis of PCOS, to investigate the predictive value of AMH combined with androgens in Chinese women to diagnose PCOS.
MATERIALS AND METHODS
This is a prospective case control study, 550 women recruited (aged 20-40 years), in which 450 PCOS women recruited according to the Rotterdam criteria and 100 non-PCOS women in the control group were from the women for the pregnancy preparation examination. AMH were measured by the Elecsys AMH Plus immunoassay. Androgens and other sex hormone were measured. The validity of AMH toward the diagnosis of PCOS, or AMH combined with total testosterone, free testosterone, bioavailable testosterone and androstenedione was estimated by receiver operating characteristic (ROC)curves, and correlations between paired variables was estimated by Spearman's rank correlation coefficient.
RESULTS
The cutoff value of AMH in Chinese reproductive-age women with PCOS is 4.64 ng/mL, AUC under the curve is 0.938, with 81.6% sensitivity, and 92.0% specificity. Total testosterone, free testosterone, bioactive testosterone, and androstenedione are significantly higher in women with PCOS of reproductive age than in controls. The combination of AMH and free testosterone resulted in a higher AUC of 94.8%, with higher sensitivity (86.1%) and excellent specificity (90.3%) for the prediction of PCOS.
CONCLUSION
The Elecsys AMH Plus immunoassay, with a cutoff of 4.64 ng/mL, is a robust method for identifying PCOM to aid in PCOS diagnosis. The combination of AMH and free testosterone resulted in a higher AUC of 94.8% for the diagnose of PCOS.
Topics: Humans; Female; Polycystic Ovary Syndrome; Androgens; Anti-Mullerian Hormone; Androstenedione; Case-Control Studies; East Asian People; Testosterone; Peptide Hormones
PubMed: 37141919
DOI: 10.1080/09513590.2023.2206927 -
Journal of Endocrinological... Feb 2024The aim of our study was to compare the incidence of idiopathic central precocious puberty (CPP) in our highly specialized Endocrinological Center before and after the...
PURPOSE
The aim of our study was to compare the incidence of idiopathic central precocious puberty (CPP) in our highly specialized Endocrinological Center before and after the onset of COVID-19 lockdown; we also aimed to identify any potential difference between girls with CPP from the two different time periods.
METHODS
We retrospectively analyzed the auxological profile of 49 girls with idiopathic CPP: 30 with pre-lockdown onset and 19 with post-lockdown onset of the disease. We collected patients' characteristics (medical history, physical examination, baseline and dynamic hormonal assessment, bone age, pelvic ultrasound) and compared them between the two groups.
RESULTS
We registered an almost threefold increase in CPP incidence in the 2020-2021 period compared to the previous six years. In post-lockdown patients we found a trend for an earlier diagnosis in terms of both chronological age (p 0.0866) and days between the onset of first pubertal signs and diagnosis (p 0.0618). We also found that post-lockdown patients had a significantly lower hypothalamus-pituitary-gonadal axis activation (lower ∆LH% after GnRH test, p 0.0497), a significantly lower increase in bone age calculated at RUS with TW3 method (p 0.0438) and a significantly reduced ovarian activation in females (lower delta-4-androstenedione levels, p 0.0115). Interestingly, post-lockdown patients were born from mothers with an older age at menarche (p 0.0039).
CONCLUSIONS
Besides confirming a significant increase in new diagnoses of CPP in the post-lockdown period, our findings among Post-lockdown girls also suggest a less progressive form of CPP and a stronger environmental influence compared to genetic background in determining the timing of pubertal onset.
Topics: Female; Humans; Infant, Newborn; Puberty, Precocious; COVID-19; Retrospective Studies; Communicable Disease Control; Menarche; Gonadotropin-Releasing Hormone
PubMed: 37566202
DOI: 10.1007/s40618-023-02146-9