-
Journal of the Endocrine Society Jan 2024Androgen levels are generally measured in serum samples, but urine may be a more feasible option, especially in children, as it is a noninvasive alternative.
CONTEXT
Androgen levels are generally measured in serum samples, but urine may be a more feasible option, especially in children, as it is a noninvasive alternative.
OBJECTIVE
To assess the correlations of 10 urinary androgen metabolites with 4 serum androgens [dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, and total and free testosterone] and assess if their correlations differ by participant characteristics.
METHODS
Our study consisted of 44 girls, ages 6-13, who participated in the New York site of the LEGACY Girls Study and had both serum and urine samples collected at the same visit. We performed Pearson's correlation coefficient tests between 4 serum and 10 individual urinary metabolite measures and their sum. We examined the influence of participant characteristics on the magnitude and direction of the correlations.
RESULTS
The summed urinary metabolite measures had the highest correlation with free testosterone in serum (global sum, r = 0.83) and correlated least with DHEA-S in serum (global sum, r = 0.64). The correlation between individual urinary metabolites and serum androgens ranged from 0.08 to 0.84.Two 11-oxygenated urinary metabolites (5α-androstane-3α-ol-11,17-dione5β-androstane-3α,11β-diol-17-one) were weakly correlated with all serum androgens. Participant age, weight, height, waist:hip ratio, and pubic hair growth stage changed the correlations between urinary and serum androgens measures between 10% and 213%.
CONCLUSION
The sum of urinary androgen metabolites was a good marker of circulating androstenedione, testosterone, and free testosterone. Individual urinary metabolites provide additional information about the metabolic processes of disease development compared to the antecedent serum androgens.
PubMed: 38234314
DOI: 10.1210/jendso/bvad161 -
Neuroscience Mar 2024Aggression is a social behavior that is critical for survival and reproduction. In adults, circulating gonadal hormones, such as androgens, act on neural circuits to...
Aggression is a social behavior that is critical for survival and reproduction. In adults, circulating gonadal hormones, such as androgens, act on neural circuits to modulate aggressive interactions, especially in reproductive contexts. In many species, individuals also demonstrate aggression before reaching gonadal maturation. Adult male song sparrows, Melospiza melodia, breed seasonally but maintain territories year-round. Juvenile (hatch-year) males aggressively compete for territory ownership during their first winter when circulating testosterone is low. Here, we characterized the relationship between the steroid milieu and aggressive behavior in free-living juvenile male song sparrows in winter. We investigated the effect of a 10 min simulated territorial intrusion (STI) on behavior and steroid levels in blood, 10 microdissected brain regions, and four peripheral tissues (liver, pectoral muscle, adrenal glands, and testes). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we quantified 12 steroids: pregnenolone, progesterone, corticosterone, 11-dehydrocorticosterone, dehydroepiandrosterone, androstenedione, testosterone, 5α-dihydrotestosterone, 17β-estradiol 17α-estradiol, estrone, and estriol. We found that juvenile males are robustly aggressive, like adult males. An STI increases progesterone and corticosterone levels in blood and brain and increases 11-dehydrocorticosterone levels in blood only. Pregnenolone, androgens, and estrogens are generally non-detectable and are not affected by an STI. In peripheral tissues, steroid concentrations are very high in the adrenals. These data suggest that adrenal steroids, such as progesterone and corticosterone, might promote juvenile aggression and that juvenile and adult songbirds might rely on distinct neuroendocrine mechanisms to support similar aggressive behaviors.
Topics: Humans; Animals; Male; Songbirds; Corticosterone; Progesterone; Chromatography, Liquid; Tandem Mass Spectrometry; Testosterone; Androgens; Aggression; Estradiol; Pregnenolone
PubMed: 38301739
DOI: 10.1016/j.neuroscience.2024.01.008 -
Endokrynologia Polska Aug 2023The aetiology of gender dysphoria is still unclear. Although prior studies have shown that trans men have higher androgen levels than cisgender women, they all concluded...
INTRODUCTION
The aetiology of gender dysphoria is still unclear. Although prior studies have shown that trans men have higher androgen levels than cisgender women, they all concluded unselected populations. Our reason for performing this study is to evaluate trans men's hormone profile and metabolic status to compare with cisgender women in a more selected population. This is the first case-controlled study to compare anthropometric, metabolic, and endocrinological parameters of drug-naïve trans men with those of cisgender women.
MATERIAL AND METHODS
We designed this study as a single-centre observational cohort study. We included 70 drug naïve trans men, and the control group comprised 34 healthy cisgender women. We measured and compared hormone profiles and metabolic parameters in the 2 groups.
RESULTS
Of the 70 trans men individuals, 16 (22.85%) met the Rotterdam criteria and were diagnosed with polycystic ovary syndrome (PCOS); 4 individuals in the control group met the criteria (11.7%). Although we matched body mass index in the groups, total testosterone, free androgen index, androstenedione, 17 hydroxyprogesterone, muscle strength, triglyceride, and homeostatic model assessment of insulin resistance levels were significantly higher in the trans men than in the cisgender women (p < 0.05). Even after were excluded PCOS patients, hyperandrogenaemia was apparent in the trans men.
CONCLUSION
Our study showed that trans men have clearly higher androgen levels, which may have been the reason for metabolic changes compared to cisgender women. However, the main reason for hyperandrogenism in drug-naïve trans men is still not known, and more comprehensive studies are needed.
PubMed: 37577993
DOI: 10.5603/EP.a2023.0052 -
Problemy Endokrinologii Jan 2024Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders requiring lifelong glucocorticoid replacement (GC) therapy. Lack of GC therapy leads to... (Review)
Review
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders requiring lifelong glucocorticoid replacement (GC) therapy. Lack of GC therapy leads to precocious puberty in boys, heterosexual development in girls, accelerated bone maturation and short final height in both sexes. In adolescence, the lack of GC therapy is the cause of menstrual disorders in girls and the development of TART in boys, as a result reducing the reproductive potential in both sexes. On the other hand, an overdose of GC leads to drug-induced Itsenko-Cushing's syndrome. In order to select adequate doses of GC in childhood and adolescence, multiple determinations of 17-hydroxyprogesterone, androstenedione, and testosterone in blood plasma, and thus multiple venous blood sampling are required. The blood sampling requires specially trained medical staff and can effect on the results due to stress reaction especially in young patients. Hence, the development and implementation of a non-invasive method for determining the steroid profile is extremely important in monitoring GC therapy in children. In addition, the currently used immunofluorescence assay cannot determine other adrenal steroids, has a high variation due to the «cross-reaction» of steroids that are similar in structure, which inflates the results. Unlike immunofluorescence assay, liquid chromatography and tandem mass spectrometry is more preferable method, since it is more specific and accurate. In this literature review, saliva presented as an alternative substrate and the non-invasive method for determining the steroid profile. This method can solve the above disadvantages, simplify and make more accurate the selection of GC therapy in patients with CAH, which is especially important in childhood.
Topics: Adolescent; Child; Female; Humans; Male; 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Glucocorticoids; Puberty, Precocious; Steroids
PubMed: 38311999
DOI: 10.14341/probl13328 -
World Journal of Clinical Cases Mar 2024Ovarian cancer is one of the most common malignant tumors in female reproductive system in the world, and the choice of its treatment is very important for the survival...
BACKGROUND
Ovarian cancer is one of the most common malignant tumors in female reproductive system in the world, and the choice of its treatment is very important for the survival rate and prognosis of patients. Traditional open surgery is the main treatment for ovarian cancer, but it has the disadvantages of big trauma and slow recovery. With the continuous development of minimally invasive technology, minimally invasive laparoscopic surgery under general anesthesia has been gradually applied to the treatment of ovarian cancer because of its advantages of less trauma and quick recovery. However, the efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia in the treatment of ovarian cancer are still controversial.
AIM
To explore the efficacy and safety of general anesthesia minimally invasive surgery in the treatment of ovarian cancer.
METHODS
The clinical data of 90 patients with early ovarian cancer in our hospital were analyzed retrospectively. According to the different surgical treatment methods, patients were divided into study group and control group (45 cases in each group). The study group received minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer, while the control group received traditional open surgery for ovarian cancer. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), clinical efficacy and safety of the two groups were compared.
RESULTS
The intraoperative blood loss, length of hospital stay, postoperative gas evacuation time, and postoperative EORTC QLQ-C30 score of the study group were significantly better than those of the control group ( < 0.05). The incidence of postoperative complications in the study group was significantly lower than in the control group ( < 0.05). The two groups had no significant differences in the preoperative adrenocorticotropic hormone (ACTH), androstenedione (AD), cortisol (Cor), cluster of differentiation 3 positive (CD3+), and cluster of differentiation 4 positive (CD4+) indexes ( > 0.05). In contrast, postoperatively, the study group's ACTH, AD, and Cor indexes were lower, and the CD3+ and CD4+ indexes were higher than those in the control group ( < 0.05).
CONCLUSION
Minimally invasive laparoscopic surgery under general anesthesia in patients with early ovarian cancer can significantly improve the efficacy and safety, improve the short-term prognosis and quality of life of patients, and is worth popularizing.
PubMed: 38576746
DOI: 10.12998/wjcc.v12.i9.1569 -
Clinical Chemistry and Laboratory... May 2024Current liquid chromatography-tandem mass spectrometry (LC-MS/MS) applications for circulating androgen measurements are technically diverse. Previously, variable... (Comparative Study)
Comparative Study
OBJECTIVES
Current liquid chromatography-tandem mass spectrometry (LC-MS/MS) applications for circulating androgen measurements are technically diverse. Previously, variable results have been reported for testosterone. Data are scarce for androstenedione and absent for dehydroepiandrosterone sulfate (DHEAS). We assessed the agreement of androstenedione, DHEAS and testosterone LC-MS/MS measurements among nine European centers and explored benefits of calibration system unification.
METHODS
Androgens were measured twice by laboratory-specific procedures in 78 patient samples and in EQA materials. Results were obtained by and external calibration. Intra- and inter-laboratory performances were valued.
RESULTS
Intra-laboratory CVs ranged between 4.2-13.2 % for androstenedione, 1.6-10.8 % for DHEAS, and 4.3-8.7 % and 2.6-7.1 % for female and male testosterone, respectively. Bias and trueness in EQA materials were within ±20 %. Median inter-laboratory CV with vs. external calibration were 12.0 vs. 9.6 % for androstenedione (p<0.001), 7.2 vs. 4.9 % for DHEAS (p<0.001), 6.4 vs. 7.6 % for female testosterone (p<0.001) and 6.8 and 7.4 % for male testosterone (p=0.111). Median bias vs. all laboratory median with and external calibration were -13.3 to 20.5 % and -4.9 to 18.7 % for androstenedione, -10.9 to 4.8 % and -3.4 to 3.5 % for DHEAS, -2.7 to 6.5 % and -11.3 to 6.6 % for testosterone in females, and -7.0 to 8.5 % and -7.5 to 11.8 % for testosterone in males, respectively.
CONCLUSIONS
Methods showed high intra-laboratory precision but variable bias and trueness. Inter-laboratory agreement was remarkably good. Calibration system unification improved agreement in androstenedione and DHEAS, but not in testosterone measurements. Multiple components, such as commutability of calibrators and EQA materials and internal standard choices, likely contribute to inter-laboratory variability.
Topics: Androstenedione; Testosterone; Humans; Tandem Mass Spectrometry; Calibration; Male; Female; Chromatography, Liquid; Dehydroepiandrosterone Sulfate; Middle Aged; Liquid Chromatography-Mass Spectrometry
PubMed: 38205643
DOI: 10.1515/cclm-2023-1138 -
International Journal of Molecular... Jan 2024Estrogens play critical roles in embryonic development, gonadal sex differentiation, behavior, and reproduction in vertebrates and in several human cancers. Estrogens...
Estrogens play critical roles in embryonic development, gonadal sex differentiation, behavior, and reproduction in vertebrates and in several human cancers. Estrogens are synthesized from testosterone and androstenedione by the endoplasmic reticulum membrane-bound P450 aromatase/cytochrome P450 oxidoreductase complex (CYP19/CPR). Here, we report the characterization of novel mammalian CYP19 isoforms encoded by CYP19 gene copies. These CYP19 isoforms are all defined by a combination of mutations in the N-terminal transmembrane helix (E42K, D43N) and in helix C of the catalytic domain (P146T, F147Y). The mutant CYP19 isoforms show increased androgen conversion due to the KN transmembrane helix. In addition, the TY substitutions in helix C result in a substrate preference for androstenedione. Our structural models suggest that CYP19 mutants may interact differently with the membrane (affecting substrate uptake) and with CPR (affecting electron transfer), providing structural clues for the catalytic differences.
Topics: Animals; Female; Humans; Pregnancy; Amino Acids; Androstenedione; Aromatase; Estrogens; Mammals; Protein Isoforms; Protein Structure, Tertiary; Protein Structure, Secondary
PubMed: 38338720
DOI: 10.3390/ijms25031440 -
Endocrine May 2024To investigate the incidence of nephrolithiasis in a cohort of children with congenital adrenal hyperplasia (CAH), and to study if there is an association with the...
PURPOSE
To investigate the incidence of nephrolithiasis in a cohort of children with congenital adrenal hyperplasia (CAH), and to study if there is an association with the metabolic control of the disease.
METHODS
This study was designed as a multicenter 1 year-prospective study involving 52 subjects (35 males) with confirmed molecular diagnosis of CAH due to 21-hydroxylase deficiency (21-OHD). Each patient was evaluated at three different time-points: T0, T1 (+6 months of follow-up), T2 (+12 months of follow up). At each follow up visit, auxological data were collected, and adrenocorticotrophic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), Δ4-androstenedione, dehydroepiandrosterone sulfate (DHEAS) serum levels, and urinary excretion of creatinine, calcium, oxalate and citrate were assayed. Moreover, a renal ultrasound was performed.
RESULTS
The incidence of nephrolithiasis, assessed by ultrasound was 17.3% at T0, 13.5% at T1 and 11.5% at T2. At T0, one subject showed nephrocalcinosis. In the study population, a statistically significant difference was found for 17-OHP [T0: 11.1 (3.0-25.1) ng/mL; T1: 7.1 (1.8-19.9) ng/mL; T2: 5.9 (2.0-20.0) ng/mL, p < 0.005], and Δ4-androstenedione [T0: 0.9 (0.3-2.5) ng/mL; T1: 0.3 (0.3-1.1) ng/mL; T2: 0.5 (0.3-1.5) ng/mL, p < 0.005] which both decreased over the follow up time. No statistically significant difference among metabolic markers was found in the group of the subjects with nephrolithiasis, even if 17-OHP, DHEAS and Δ4-androstenedione levels showed a tendency towards a reduction from T0 to T2. Principal component analysis (PCA) was performed to study possible hidden patterns of associations/correlations between variables, and to assess the trend of them during the time. PCA revealed a decrease in the amount of the variables 17-OHP, Δ4-androstenedione, and ACTH that occurred during follow-up, which was also observed in subjects showing nephrolithiasis.
CONCLUSIONS
our data demonstrated that children affected with 21-OHD can be at risk of developing nephrolithiasis. Additional studies are needed to clarify the pathogenesis and other possible risk factors for this condition, and to establish if regular screening of kidney ultrasound in these patients can be indicated.
Topics: Humans; Adrenal Hyperplasia, Congenital; Male; Female; Child; Nephrolithiasis; Prospective Studies; Child, Preschool; 17-alpha-Hydroxyprogesterone; Incidence; Adolescent; Adrenocorticotropic Hormone; Dehydroepiandrosterone Sulfate; Infant; Androstenedione; Ultrasonography; Risk Factors
PubMed: 38536547
DOI: 10.1007/s12020-024-03792-6 -
The Journal of Reproduction and... Dec 2023Insulin-like growth factor-1 (IGF-1) plays a crucial role in follicular growth and stimulates steroid hormone production in bovine follicles. Steroid hormones are...
Insulin-like growth factor-1 (IGF-1) plays a crucial role in follicular growth and stimulates steroid hormone production in bovine follicles. Steroid hormones are synthesized through the actions of steroidogenic enzymes, specifically STAR, CYP11A1, HSD3B, and CYP19A1 in both theca cells (TCs) and granulosa cells (GCs), under the influence of gonadotropins. Particularly, estradiol 17β (E2) assumes a central role in follicular development and selection by activating estrogen receptors β (ESR2) in GCs. We assessed ESR2 mRNA expression in GCs of developing follicles and investigated the impact of IGF-1 on the mRNA expression of ESR2, CYP19A1, FSHR, and LHCGR, STAR, CYP11A1, and HSD17B in cultured GCs and TCs, respectively. Additionally, we assessed the influence of IGF-1 on androstenedione (A4), progesterone (P4), and testosterone (T) production in TCs. Small-sized follicles (< 6 mm) exhibited the highest levels of ESR2 mRNA expression, whereas medium-sized follicles (7-8 mm) displayed higher levels than large-sized follicles (≥ 9 mm) (P < 0.05). IGF-1 increased the mRNA expression of ESR2, CYP19A1, and FSHR in GCs of follicles of both sizes, except for FSHR mRNA in medium-sized follicles (P < 0.05). IGF-1 significantly elevated mRNA expression of LHCGR, STAR, CYP11A1, and CYP17B in TCs of small- and medium-sized follicles (P < 0.05). Moreover, IGF-1 augmented the production of A4 and P4 but had no impact on T production in TCs of small- and medium-sized follicles. Taken together, our findings indicate that IGF-1 upregulates steroidogenic enzymes and steroid hormone production, underscoring the crucial role of IGF-1 in follicle development and selection.
Topics: Animals; Cattle; Female; Cholesterol Side-Chain Cleavage Enzyme; Estradiol; Granulosa Cells; Insulin-Like Growth Factor I; Ovarian Follicle; Progesterone; Receptors, Estradiol; RNA, Messenger; Gonadal Steroid Hormones
PubMed: 37940556
DOI: 10.1262/jrd.2023-047 -
Human Reproduction (Oxford, England) May 2024Is resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity associated with differential changes in endocrine and metabolic... (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY QUESTION
Is resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity associated with differential changes in endocrine and metabolic parameters (weight, insulin resistance, anti-Müllerian hormone (AMH), and androgens) compared to women with PCOS who remained anovulatory?
SUMMARY ANSWER
Resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity is associated with changes in serum 11β-hydroxyandrostenedione (11OHA4) concentrations.
WHAT IS KNOWN ALREADY
Lifestyle interventions have been shown to reduce clinical and biochemical hyperandrogenism in women with PCOS. Weight loss of 5-10% may reverse anovulatory status, thereby increasing natural conception rates. However, the mechanisms underlying why some women with PCOS remain anovulatory and others resume ovulation after weight loss are unclear. Reproductive characteristics at baseline and a greater degree of change in endocrine and metabolic features with lifestyle intervention may be crucial for ovulatory response.
STUDY DESIGN, SIZE, DURATION
We used data and samples originating from an earlier randomized controlled trial (RCT), which examined the efficacy of a 6-month lifestyle intervention prior to infertility treatment compared to prompt infertility treatment on live birth rate in women with obesity. A total of 577 women with obesity (BMI > 29 kg/m2) were randomized between 2009 and 2012. Anovulatory women with PCOS who were allocated to the intervention arm of the original RCT (n = 95) were included in the current analysis.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We defined women as having resumed ovulation (RO+) based on the following criteria: spontaneous pregnancy; or assignment to expectant management; or IUI in natural cycles as the treatment strategy after lifestyle intervention. Steroid hormones were measured using liquid chromatography tandem mass spectrometry. Generalized estimating equations with adjustment for baseline measures and interaction between group and time was used to examine differences in changes of endocrine and metabolic parameters between RO+ (n = 34) and persistently anovulatory women (RO-, n = 61) at 3 and 6 months after intervention.
MAIN RESULTS AND THE ROLE OF CHANCE
At baseline, the mean ± SD age was 27.5 ± 3.6 years in the RO+ group and 27.9 ± 4.1 years in the RO- group (P = 0.65), and the mean ± SD weights were 101.2 ± 9.5 kg and 105.0 ± 14.6 kg, respectively (P = 0.13). Baseline AMH concentrations showed significant differences between RO+ and RO- women (median and interquartile range [IQR] 4.7 [3.2; 8.3] versus 7.2 [5.3; 10.8] ng/ml, respectively). Baseline androgen concentrations did not differ between the two groups. During and after lifestyle intervention, both groups showed weight loss; changes in 11OHA4 were significantly different between the RO+ and RO groups (P-value for interaction = 0.03). There was a similar trend for SHBG (interaction P-value = 0.07), and DHEA-S (interaction P-value = 0.06), with the most pronounced differences observed in the first 3 months. Other parameters, such as AMH and FAI, decreased over time but with no difference between the groups.
LIMITATIONS, REASONS FOR CAUTION
No high-resolution transvaginal ultrasonography was used to confirm ovulatory status at the end of the lifestyle program. The small sample size may limit the robustness of the results.
WIDER IMPLICATIONS OF THE FINDINGS
Reduction of androgen concentrations during and after lifestyle intervention is associated with recovery of ovulatory cycles. If our results are confirmed in other studies, androgen concentrations could be monitored during lifestyle intervention to provide individualized recommendations on the timing of resumption of ovulation in anovulatory women with PCOS and obesity.
STUDY FUNDING/COMPETING INTEREST(S)
The study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). The Department of Obstetrics and Gynecology of the UMCG received an unrestricted educational grant from Ferring Pharmaceuticals BV, The Netherlands. A.H. reports consultancy for the development and implementation of a lifestyle App MyFertiCoach developed by Ferring Pharmaceutical Company. All other authors have no conflicts to declare.
TRIAL REGISTRATION NUMBER
The LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530).
Topics: Humans; Female; Obesity; Ovulation; Adult; Polycystic Ovary Syndrome; Anovulation; Androstenedione; Insulin Resistance; Pregnancy; Anti-Mullerian Hormone; Weight Loss
PubMed: 38503490
DOI: 10.1093/humrep/deae058