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American Journal of Men's Health Nov 2016An increasing number of men are being diagnosed with hypogonadism. While many benefit from testosterone supplementation therapy, others who do not meet the criteria for... (Review)
Review
An increasing number of men are being diagnosed with hypogonadism. While many benefit from testosterone supplementation therapy, others who do not meet the criteria for hormone supplementation have turned to dietary adjuncts as a way or gaining improvements in libido, energy, and physical performance. These oral adjunct medications include controlled substances such as androstenedione, androstenediol as well as other "over-the-counter" options like DHEA (dehydroepiandrosterone) and herbal remedies like Tribulus terrestris This review will focus on the use of these adjunct medications in isolation, or in combination with testosterone supplementation therapy as well as the biochemical nature of the supplements, the results of scientific trials as well as the side effects that limit their use. At the end of this review, physicians will have an improved understanding of the popular testosterone adjuncts being used currently as well as the availability of these substances and how they are used.
Topics: Androstenediol; Androstenedione; Dehydroepiandrosterone; Dietary Supplements; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Quality of Life; Testosterone; Time Factors
PubMed: 26272885
DOI: 10.1177/1557988315598554 -
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 -
Journal of Endocrinological... Aug 2022The aim of this study was to examine the hormonal profile in early-pubertal girls with obesity. We hypothesized that these patients might already present hormonal...
PURPOSE
The aim of this study was to examine the hormonal profile in early-pubertal girls with obesity. We hypothesized that these patients might already present hormonal alterations with POCS-like features.
METHODS
Cross-sectional study in a sample of 283 peri-pubertal girls (prepubertal and early-puberty subgroups), aged 6.1-12.0 years, diagnosed with obesity (BMI-SDS > 2.0, 97th percentile), so-called obesity group. They all underwent clinical examination and blood testing for hormonal measurements (leptin, TSH, FT4, IGF-1, IGFBP3, prolactin, insulin, FSH, LH, estradiol, ACTH, cortisol, 17-OH-P, DHE-S, androstenedione, testosterone and free testosterone). A control group was recruited: 243 healthy girls, aged 6.3-12.1 years, with normal BMI status.
RESULTS
Prepubertal girls with obesity had significantly higher values (p < 0.05) for BMI-SDS, leptin, insulin and HOMA-IR levels than control group. Early-pubertal girls with obesity also had significantly higher values (p < 0.05) for BMI-SDS, leptin, IGF-1, IGFBP3, insulin and HOMA-IR, LH, ratio LH/FSH, ACTH, DHE-S, androstenedione, testosterone and free testosterone levels than control group. In early-pubertal girls with obesity (not prepubertal girls), there was a positive correlation (p < 0.01) between leptin levels with LH, androstenedione and testosterone, and HOMA-IR with LH and testosterone levels. There was also a positive correlation (p < 0.01) between IGF-1 levels with LH, androstenedione, DHE-S and testosterone; and LH levels with testosterone.
CONCLUSION
The results obtained support our hypothesis that an abnormal hormonal profile with POCS-like features can already be detected (insulin resistance and hyperinsulinemia, increased secretion of LH and ACTH, and overproduction of ovarian and adrenal androgens) in early-pubertal girls with obesity.
Topics: Adrenocorticotropic Hormone; Androgens; Androstenedione; Cross-Sectional Studies; Female; Follicle Stimulating Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Obesity; Puberty; Puberty, Precocious; Testosterone
PubMed: 35412268
DOI: 10.1007/s40618-022-01797-4 -
Methods in Molecular Biology (Clifton,... 2023The phytosterol-biotransforming strains can be selected from Mycobacterium sp. using a high concentration of β-sitosterol. The selection is made by culturing the...
The phytosterol-biotransforming strains can be selected from Mycobacterium sp. using a high concentration of β-sitosterol. The selection is made by culturing the strains in a medium enriched with 14 g/L of β-sitosterol as the unique source of carbon. During 2 months, the bacterial cultures are transferred successively. The extraction of the biotransformation products is made with methanol and ethyl acetate. The qualitative and quantitative analyses are made by means of thin-layer chromatography, gas-liquid chromatography (GLC), and GLC-mass spectrometry. Under these conditions, it is observed that after seven transfers, the strains Mycobacterium sp. MB-3683 and Mycobacterium fortuitum B-11045 increase their biotransformation capacity from 20% to 64% and from 34% to 55%, respectively. The products in the highest proportion identified for each trial are androstenedione and androstadienedione. The results suggest that the high substrate concentration could be a selective mechanism to obtain strains more efficient in the biotransformation of β-sitosterol into steroidal bases.
Topics: Phytosterols; Gas Chromatography-Mass Spectrometry; Androstenedione; Carbon; Chromatography, Thin Layer
PubMed: 37642837
DOI: 10.1007/978-1-0716-3385-4_3 -
Frontiers in Endocrinology 2022Although the role of steroid hormones in lipid levels has been partly discussed in the context of separate sexes, the causal relationship between steroid hormones and...
BACKGROUND
Although the role of steroid hormones in lipid levels has been partly discussed in the context of separate sexes, the causal relationship between steroid hormones and lipid metabolism according to sex has not been elucidated because of the limitations of observational studies. We assessed the relationship between steroid hormones and lipid metabolism in separate sexes using a two-sample Mendelian randomization (MR) study.
METHODS
Instrumental variables for dehydroepiandrosterone sulfate (DHEAS), progesterone, estradiol, and androstenedione were selected. MR analysis was performed using inverse-variance weighted, MR-Egger, weighted median, and MR pleiotropy residual sum and outlier tests. Cochran's Q test, the MR-Egger intercept test, and leave-one-out analysis were used for sensitivity analyses.
RESULTS
The results showed that the three steroid hormones affected lipid metabolism and exhibited sex differences. In males, DHEAS was negatively correlated with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B ( = 0.007; = 0.006; = 0.041, respectively), and progesterone was negatively correlated with TC and LDL-C ( = 0.019; = 0.038, respectively). In females, DHEAS was negatively correlated with TC ( = 0.026) and androstenedione was negatively correlated with triglycerides and apolipoprotein A ( = 0.022; = 0.009, respectively). No statistically significant association was observed between the estradiol levels and lipid metabolism in male or female participants.
CONCLUSIONS
Our findings identified sex-specific causal networks between steroid hormones and lipid metabolism. Steroid hormones, including DHEAS, progesterone, and androstenedione, exhibited beneficial effects on lipid metabolism in both sexes; however, the specific lipid profiles affected by steroid hormones differed between the sexes.
Topics: Humans; Male; Female; Lipid Metabolism; Sex Characteristics; Cholesterol, LDL; Progesterone; Mendelian Randomization Analysis; Androstenedione; Cholesterol, HDL; Steroids; Estradiol; Apolipoproteins
PubMed: 36726474
DOI: 10.3389/fendo.2022.1119154 -
Clinical Chemistry Dec 2023Androgens are synthesized from cholesterol through sequential conversions by enzymes in the adrenal glands and gonads. Serum levels of androgens change during the... (Review)
Review
BACKGROUND
Androgens are synthesized from cholesterol through sequential conversions by enzymes in the adrenal glands and gonads. Serum levels of androgens change during the different phases of life and regulate important developmental and maturational processes. Androgen excess or deficiency can therefore present at various ages in various ways.
CONTENT
The diagnostic approach for atypical genitalia, premature pubarche, delayed pubertal onset or progression, and hirsutism or virilization, including measurement of androgens (testosterone, androstenedione, 17-OHprogesterone, dehydroepiandrosterone, and dihydrotestosterone) is discussed in the current review. Androgens can be measured in serum, saliva, urine, or dried blood spots. Techniques to measure androgens, including immunoassays and LC-MS, have their own advantages and pitfalls. In addition, pre- and postanalytical issues are important when measuring androgens.
SUMMARY
During clinical interpretation of androgen measurements, it is important to take preanalytical circumstances, such as time of blood withdrawal, into account. As immunoassays have major drawbacks, especially in samples from women and neonates, concentrations measured using these assays should be interpreted with care. Reference intervals can only be used in relation to the measurement technique and the standardization of the assay. In the near future, new androgens will probably be added to the current repertoire to further improve the diagnosis and follow-up of androgen excess or deficiency.
Topics: Infant, Newborn; Female; Humans; Androgens; Testosterone; Androstenedione; Virilism; Hirsutism; Dehydroepiandrosterone
PubMed: 37794651
DOI: 10.1093/clinchem/hvad146 -
Steroids Mar 2022Although DHEA sulfate (DS) is the most abundant steroid in the circulation, breast fluid contains an approximately 80-fold greater concentration than serum. Transport of... (Review)
Review
Although DHEA sulfate (DS) is the most abundant steroid in the circulation, breast fluid contains an approximately 80-fold greater concentration than serum. Transport of DS into cells requires organic anion transporting polypeptides (OATPs), which are specific for cell type, cell location, and substrate, but may have a broader specificity for housekeeping functions. Specific classes, which may be modified by soluble factors including neutral steroids, have been identified in the breast. After transport, DS may be cleaved to DHEA by ubiquitous sulfatases, which may be modified by the cell milieu, or DHEA may enter by diffusion. Synthesis from cholesterol does not occur because CYP17B12 and cytochrome b5 are lacking in breast tissues. Case-control studies reveal a positive association of serum DS with risk of breast cancer. The association is even greater with DHEA, particularly in postmenopausal women with HR + invasive tumors. Metabolites of DHEA, androstenedione and testosterone, are associated with breast cancer but DHEA is likely to have an independent role as well. Mechanisms by which DHEA may promote breast cancer relate to its effect in increasing circulating IGF-I, by inhibiting the suppressive effect of glucocorticoids, and by promoting retention of pre-adipocytes with aromatase activity. In addition, DHEA may interact with the G-protein coupled receptor GPER for stimulation of miR-21 and subsequent activation of the MAPK pathway. DHEA also has antitumor properties that relate to stimulation of immunity, suppression of inflammation, and elevation of adipose tissue adiponectin synthesis. The net effect may depend on the which factors predominate.
Topics: Androstenedione; Breast Neoplasms; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Testosterone
PubMed: 35122788
DOI: 10.1016/j.steroids.2022.108970 -
Methods in Molecular Biology (Clifton,... 2023The chapter describes the bioconversion of phytosterols into androstenedione (AD) by Mycolicibacterium spp. in shake flasks and fermenters, as well as LC-MS-based...
The chapter describes the bioconversion of phytosterols into androstenedione (AD) by Mycolicibacterium spp. in shake flasks and fermenters, as well as LC-MS-based methods for analysis of phytosterols and steroid products. Phytosterols are derived as by-products of vegetable oil refining and manufacture of wood pulp. They contain the same four-ring nucleus as steroids and may be converted to high-value steroids by removing the sidechain at C17 and minor changes at other sites in the ring structure. Many bacteria, including Mycolicibacterium spp., can degrade phytosterols. Mutants of Mycolicibacterium spp. unable of ring cleavage can, when growing on phytosterols, accumulate the steroid intermediates androstenedione (AD) and androstadienedione (ADD). The practical challenge with microbial conversion of phytosterols to steroids is that both the substrate and the product are virtually insoluble in water. In addition, some steroids, notably ADD, may be toxic for the cells. Two main strategies have been employed to overcome this challenge: the use of two-phase systems and the addition of chemically modified cyclodextrins. The latter method is used here. Defined cultivation and bioconversion media for both shake flask and fermenter are given, as well as hints how to minimize the practical problems due to the water-insoluble phytosterol. Sampling, sample extraction, and quantification of substrates and products using LC-MS analysis are described.
Topics: Humans; Androstenedione; Bioreactors; Cell Nucleus; Phytosterols; Tremor; Water
PubMed: 37642849
DOI: 10.1007/978-1-0716-3385-4_15 -
Molecules (Basel, Switzerland) Jul 2019As a result of the findings of scientists working on the biosynthesis and metabolism of steroids in the plant and animal kingdoms over the past five decades, it has... (Review)
Review
As a result of the findings of scientists working on the biosynthesis and metabolism of steroids in the plant and animal kingdoms over the past five decades, it has become apparent that those compounds that naturally occur in animals can also be found as natural constituents of plants and vice versa, i.e., they have essentially the same fate in the majority of living organisms. This review summarizes the current state of knowledge on the occurrence of animal steroid hormones in the plant kingdom, particularly focusing on progesterone, testosterone, androstadienedione (boldione), androstenedione, and estrogens.
Topics: Androstadienes; Androstenedione; Animals; Biosynthetic Pathways; Estrogens; Phytosterols; Plants; Progesterone; Steroids; Testosterone
PubMed: 31315257
DOI: 10.3390/molecules24142585 -
European Journal of Preventive... Jul 2022The contribution of sex hormones to micro- and macrovascular damage might differ among women and men. In particular, little is known about the association between sex...
AIMS
The contribution of sex hormones to micro- and macrovascular damage might differ among women and men. In particular, little is known about the association between sex hormones and small vessel disease. Therefore, we examined the association of total oestradiol, total testosterone, free-androgen index (FAI), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione levels with micro- and macrovascular diseases.
METHODS AND RESULTS
This cross-sectional study included 2950 women and 2495 men from the population-based Rotterdam Study. As proxy of microvascular damage, we measured diameters of retinal arterioles and venules. Markers of macrovascular damage included carotid intima-media thickness and carotid plaque, coronary artery calcification (CAC), and peripheral artery disease. Linear and logistic regression models were used and adjusted for age, cardiovascular risk factors, and years since menopause. Associations with microvasculature: In women, total testosterone [mean difference per 1-unit increase in natural-log transformed total testosterone (95% confidence interval, CI): 2.59 (0.08-5.09)] and androstenedione [4.88 (1.82-7.95)] and in men DHEAS [2.80 (0.23-5.37)] and androstenedione [5.83 (2.19-9.46)] were associated with larger venular caliber. Associations with markers of large vessel disease: In women, higher total testosterone [-0.29 (-0.56 to -0.03)], FAI [-0.33 (-0.56 to -0.10)], and androstenedione levels [-0.33 (-0.64 to -0.02)] were associated with lower CAC burden and FAI [odds ratio (95% CI): 0.82 (0.71-0.94)] was associated with lower prevalence of plaque.
CONCLUSION
A more androgenic profile was associated with more microvascular damage in both women and men. Among women, however, higher androgen levels were also associated with less macrovascular damage. Our findings suggest that androgens might have distinct effects on the vasculature, depending on the vascular bed and stages of the atherosclerosis process.
Topics: Androgens; Androstenedione; Biomarkers; Carotid Intima-Media Thickness; Cross-Sectional Studies; Dehydroepiandrosterone Sulfate; Female; Gonadal Steroid Hormones; Humans; Male; Sex Hormone-Binding Globulin; Testosterone
PubMed: 33580786
DOI: 10.1093/eurjpc/zwaa031