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Gynecologie, Obstetrique, Fertilite &... Oct 2022Postmenopausal hyperandrogenism is an androgen excess originating from either the adrenals and/or the ovaries. Clinically, symptoms can be moderate (increase in terminal... (Review)
Review
Postmenopausal hyperandrogenism is an androgen excess originating from either the adrenals and/or the ovaries. Clinically, symptoms can be moderate (increase in terminal hair growth, acnea) or severe with signs of virilization (alopecia, clitoridomegaly). In either setting, physicians need to exclude relatively rare but potentially life-threatening underlying tumorous causes, such as adrenal androgen-secreting tumors. The objectives of this review are to evaluate which hormonal measurements (T, delta 4 androstenedione, 17 OH progesterone, SDHEA, FSH, LH) and/or imaging (pelvic ultrasound, MRI or adrenal CT-scan) could be useful identifying the origin of the androgen excess. Our review illustrates that the rate of progression of hirsutism and/or alopecia, and serum testosterone levels are in favor of tumors. Pelvic MRI and adrenal CT-scan are useful tools for identifying the different causes of androgen excess.
Topics: Adrenal Gland Neoplasms; Alopecia; Androgens; Androstenedione; Female; Follicle Stimulating Hormone; Humans; Hyperandrogenism; Menopause; Ovary; Progesterone; Testosterone
PubMed: 35609786
DOI: 10.1016/j.gofs.2022.05.002 -
Molecules (Basel, Switzerland) May 2022Androstenedione (AD) is a key intermediate in the body's steroid metabolism, used as a precursor for several steroid substances, such as testosterone, estradiol, ethinyl... (Review)
Review
Androstenedione (AD) is a key intermediate in the body's steroid metabolism, used as a precursor for several steroid substances, such as testosterone, estradiol, ethinyl estradiol, testolactone, progesterone, cortisone, cortisol, prednisone, and prednisolone. The world market for AD and ADD (androstadienedione) exceeds 1000 tons per year, which stimulates the pharmaceutical industry's search for newer and cheaper raw materials to produce steroidal compounds. In light of this interest, we aimed to investigate the progress of AD biosynthesis from phytosterols by prospecting scientific articles (Scopus, Web of Science, and Google Scholar databases) and patents (USPTO database). A wide variety of articles and patents involving AD and phytosterol were found in the last few decades, resulting in 108 relevant articles (from January 2000 to December 2021) and 23 patents of interest (from January 1976 to December 2021). The separation of these documents into macro, meso, and micro categories revealed that most studies (articles) are performed in China (54.8%) and in universities (76%), while patents are mostly granted to United States companies. It also highlights the fact that AD production studies are focused on "process improvement" techniques and on possible modifications of the "microorganism" involved in biosynthesis (64 and 62 documents, respectively). The most-reported "process improvement" technique is "chemical addition" (40%), which means that the addition of solvents, surfactants, cofactors, inducers, ionic liquids, etc., can significantly increase AD production. Microbial genetic modifications stand out in the "microorganism" category because this strategy improves AD yield considerably. These documents also revealed the main aspects of AD and ADD biosynthesis: sp. (basonym: sp.) (40%) and (known previously as ) (32%) are the most recurrent species studied. Microbial incubation temperatures can vary from 29 °C to 37 °C; incubation can last from 72 h to 14 days; the mixture is agitated at 140 to 220 rpm; vegetable oils, mainly soybean, can be used as the source of a mixture of phytosterols. In general, the results obtained in the present technological prospecting study are fundamental to mapping the possibilities of AD biosynthesis process optimization, as well as to identifying emerging technologies and methodologies in this scenario.
Topics: Androgens; Androstenedione; Biotransformation; Mycobacteriaceae; Phytosterols; Steroids
PubMed: 35630641
DOI: 10.3390/molecules27103164 -
Methods in Molecular Biology (Clifton,... 2023Phytosterols, coming as a by-product of vegetable oils or wood pulp, contain the cyclopentanoperhydrophenanthrene nucleus and can be bioconverted into steroid...
Phytosterols, coming as a by-product of vegetable oils or wood pulp, contain the cyclopentanoperhydrophenanthrene nucleus and can be bioconverted into steroid intermediates by removing the C17 side chain. This chapter shows the scale-up, from flask to bioreactor, of phytosterols bioconversion into 4-androstene-3,17-dione (androstenedione; AD) using Mycolicibacterium neoaurum B-3805. Due to the fact that phytosterols and AD are nearly insoluble in water, two-phase systems and the use of chemically modified cyclodextrins have been described as methods to solve it. Here, we use a water-oil two-phase system that allows the bioconversion of up to 20 g/L of phytosterols into AD in 5 L and 20 L bioreactors.
Topics: Androstenedione; Androstenes; Bioreactors; Phytosterols; Water
PubMed: 37642848
DOI: 10.1007/978-1-0716-3385-4_14 -
Clinical Endocrinology Nov 2021To document associations between anti-Müllerian hormone (AMH) and circulating androgens in nonhealthcare-seeking premenopausal women.
OBJECTIVE
To document associations between anti-Müllerian hormone (AMH) and circulating androgens in nonhealthcare-seeking premenopausal women.
DESIGN
Community-based, cross-sectional study.
SETTING
Eastern states of Australia.
PARTICIPANTS
Women aged 18-39 years not using systemic hormones, not pregnant or breastfeeding within 3 months, and not postmenopausal.
MEASUREMENTS
AMH, measured by the Beckman Access 2, 2 site immunometric assay from fresh samples, and testosterone, androstenedione, dehydroepiandrosterone (DHEA) and 11-oxygenated C19 steroids, measured by liquid chromatography-tandem mass spectrometry.
RESULTS
Data were available for 794 women, median age of 33 years (range: 18-39). 76.1% were of European ancestry and 48.2% were parous. Serum AMH was positively associated with testosterone (rho = .29, p < .001) androstenedione (rho = .39, p < .001) and DHEA (rho = .10, p = .005) but not 11-ketoandrostenedione or 11-ketotestosterone. When adjusted for age, body mass index and smoking, using quantile regression, independent positive associations remained between AMH and testosterone (β coefficient: 20.90, 95% confidence interval [CI]: 13.79-28.03; p < .001) and androstenedione (β coefficient: 5.90, 95% CI: 3.76-8.03; p < .001). The serum concentration of testosterone was greater at the top AMH quintile than other quintiles (0.56 nmol/L [range: 0.21-1.90] vs. 0.36 nmol/L [range: 0.13-0.87]; p = .001) in women with self-reported polycystic ovary syndrome.
CONCLUSIONS
The positive associations between serum testosterone and androstenedione and AMH in premenopausal women is consistent with androgens directly or indirectly influencing AMH production during follicular development. As the highest AMH concentrations are most likely to be seen in women with multifollicular ovaries, it would be expected that women with multifollicular ovaries would have higher serum testosterone. Therefore, whether hyperandrogenemia and multifollicular ovaries should be considered independent characteristics of polycystic ovary syndrome warrants review.
Topics: Adolescent; Adult; Androgens; Androstenedione; Anti-Mullerian Hormone; Cross-Sectional Studies; Female; Humans; Pregnancy; Testosterone; Young Adult
PubMed: 34524701
DOI: 10.1111/cen.14592 -
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 -
Clinical Endocrinology Sep 2022We examined if measurement of adrenal androgens adds to subtype diagnostics of primary aldosteronism (PA) under cosyntropin-stimulated adrenal venous sampling (AVS).
OBJECTIVE
We examined if measurement of adrenal androgens adds to subtype diagnostics of primary aldosteronism (PA) under cosyntropin-stimulated adrenal venous sampling (AVS).
DESIGN
A prospective pre-specified secondary endpoint analysis of 49 patients with confirmed PA, of whom 29 underwent unilateral adrenalectomy with long-term follow-up.
METHODS
Concentrations of androstenedione, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were measured during AVS in addition to aldosterone and cortisol. Subjects with lateralisation index (LI) of ≥4 were treated with unilateral adrenalectomy, and the immunohistochemical subtype was determined with CYP11B2 and CYP11B1 stains. The performance of adrenal androgens was evaluated by receiver operating characteristics (ROC) curve analyses in adrenalectomy and medical therapy groups.
RESULTS
During AVS, the correlations between cortisol and androstenedione, DHEA and DHEAS for LI and selectivity index (SI) were highly significant. The right and left side SIs for androstenedione and DHEA were higher (p < .001) than for cortisol. In ROC analysis, the optimal LI cut-off values for androstenedione, DHEA and DHEAS were 4.2, 4.5 and 4.6, respectively. The performance of these LIs for adrenal androgens did not differ from that of cortisol.
CONCLUSIONS
Under cosyntropin-stimulated AVS, the measurement of androstenedione and DHEA did not improve the cannulation selectivity. The performance of cortisol and adrenal androgens are confirmatory but not superior to cortisol-based results in lateralisation diagnostics of PA.
Topics: Adrenal Glands; Aldosterone; Androgens; Androstenedione; Cosyntropin; Dehydroepiandrosterone; Humans; Hydrocortisone; Hyperaldosteronism; Prospective Studies; Retrospective Studies
PubMed: 35167715
DOI: 10.1111/cen.14691 -
Steroids Oct 2018Recently, measurements of steroids like testosterone, androstenedione, cortisol and cortisone in saliva are more and more applied in diagnostics and scientific studies....
BACKGROUND
Recently, measurements of steroids like testosterone, androstenedione, cortisol and cortisone in saliva are more and more applied in diagnostics and scientific studies. This is mainly due to the simple and non-invasive collection of saliva. We aimed to evaluate the optimal way to collect saliva for steroid hormone measurement.
METHODS
We investigated in twenty volunteers whether there is a difference between steroid hormone concentrations in unstimulated and stimulated saliva collected while chewing, using cotton and synthetic Salivettes®, citric acid or chewing gum. Furthermore, total unstimulated saliva was compared to parotid gland saliva. Testosterone, androstenedione, cortisol and cortisone were measured using Liquid-Chromatography Tandem Mass Spectrometry (LC-MS/MS).
RESULTS
Salivary testosterone, androstenedione and cortisol concentrations were unaffected by stimulation upon mouth and tongue movements, cortisone levels were on average 16% lower. Concentrations of all hormones were lower in parotid gland saliva compared to total unstimulated saliva (on average 51%, 26%, 66% and 49% lower, for testosterone, androstenedione, cortisol and cortisone, respectively). Concentrations of testosterone as well as androstenedione were lower when using synthetic Salivettes® (58% and 41%, respectively) and were higher when using cotton Salivettes® (217% and 46%, respectively). Cortisol levels in saliva were unaffected by using Salivettes®. However, cortisol and testosterone levels were higher in with chewing gum stimulated saliva (16% and 55%, respectively). Cortisone concentrations were lower in all types of stimulations (on average 25%-35%).
CONCLUSION
The way saliva is collected should be considered when analysing and interpreting salivary hormone concentrations. We advocate unstimulated saliva collection in simple polypropylene tubes for all steroid measurements.
Topics: Adult; Androstenedione; Cortisone; Female; Humans; Hydrocortisone; Male; Middle Aged; Saliva; Steroids; Testosterone; Young Adult
PubMed: 29864449
DOI: 10.1016/j.steroids.2018.05.013 -
Endocrinology Nov 2023Serum sex steroid levels fluctuate throughout the reproductive cycle. However, the degree to which sex steroid tissue content mimics circulating content is unknown....
Serum sex steroid levels fluctuate throughout the reproductive cycle. However, the degree to which sex steroid tissue content mimics circulating content is unknown. Understanding the flux and physiological quantity of tissue steroid content is imperative for targeted hormonal therapy development. Utilizing a gold-standard ultrasensitive liquid chromatography-mass spectrometry (LC/MS) method we determined sex steroid (17β-estradiol [E2], testosterone, androstenedione, and progesterone) fluctuations in serum and in 15 tissues throughout the murine estrous cycle (proestrus, estrus, and diestrus I) and in ovariectomized (OVX) mice. We observed dynamic fluctuations in serum and tissue steroid content throughout the estrous cycle with proestrus generally presenting the highest content of E2, testosterone, and androstenedione, and lowest content of progesterone. In general, the trend in circulating steroid content between the stages of the estrous cycle was mimicked in tissue. However, the absolute amounts of steroid levels when normalized to tissue weight were found to be significantly different between the tissues with the serum steroid quantity often being significantly lower than the tissue quantity. Additionally, we found that OVX mice generally displayed a depletion of all steroids in the various tissues assessed, except in the adrenal glands which were determined to be the main site of peripheral E2 production after ovary removal. This investigation provides a comprehensive analysis of steroid content throughout the estrous cycle in a multitude of tissues and serum. We believe this information will help serve as the basis for the development of physiologically relevant, tissue-specific hormonal therapies.
Topics: Female; Mice; Animals; Progesterone; Androstenedione; Gonadal Steroid Hormones; Estradiol; Estrous Cycle; Testosterone
PubMed: 37967240
DOI: 10.1210/endocr/bqad175 -
Methods in Enzymology 2023The "rediscovery" 11β-hydroxyandrostenedione (11OHA4) placed the spotlight on this unique adrenal-derived hormone with researchers and clinicians once again focusing on...
The "rediscovery" 11β-hydroxyandrostenedione (11OHA4) placed the spotlight on this unique adrenal-derived hormone with researchers and clinicians once again focusing on the steroid's presence in endocrine pathology. Little was known about the steroid other than its chemical characterisation and that a mitochondrial cytochrome P450 enzyme catalysed the 11β-hydroxylation of 11OHA4. The fact that neither the biosynthesis nor metabolism of 11OHA4 had been fully characterised presented an ideal opportunity to investigate the metabolic pathways. In addition, methodologies and analytical tools have improved vastly since 11OHA4 was first identified in the 1950s. Cell models, recombinant DNA technology and steroid quantification using liquid chromatography mass spectrometry have greatly facilitated investigations in the field of steroidogenesis. Evident from the structure is that 11OHA4 can be metabolised by hydroxysteroid dehydrogenases and reductases acting on the C4/C5 double bond and on functional moieties at specific carbons on the cyclopentane-perhydro-phenanthrene backbone of the steroid. In this chapter, the biosynthesis and metabolism of 11OHA4 is followed using two strategies that complement each another; (i) human cell models either transiently transfected with recombinant DNA or expressing endogenous steroidogenic enzymes and (ii) steroid identification and quantification using high resolution mass spectrometry. These methodologies have proven invaluable in the determination of 11OHA4's metabolic route. Both strategies are presented with the focus on the accurate identification and quantification of steroids using UHPLC-MS/MS and UPC-MS/MS. The protocols described in this chapter lay a sound foundation which can aid the researcher and be adapted and implement in future studies.
Topics: Humans; Androstenedione; Tandem Mass Spectrometry; DNA, Recombinant; Steroids; Metabolic Networks and Pathways
PubMed: 37802580
DOI: 10.1016/bs.mie.2023.05.002 -
Molecules (Basel, Switzerland) Oct 2021Androstenedione is a steroidal hormone produced in male and female gonads, as well as in the adrenal glands, and it is known for its key role in the production of... (Review)
Review
Androstenedione is a steroidal hormone produced in male and female gonads, as well as in the adrenal glands, and it is known for its key role in the production of estrogen and testosterone. Androstenedione is also sold as an oral supplement, that is being utilized to increase testosterone levels. Simply known as "andro" by athletes, it is commonly touted as a natural alternative to anabolic steroids. By boosting testosterone levels, it is thought to be an enhancer for athletic performance, build body muscles, reduce fats, increase energy, maintain healthy RBCs, and increase sexual performance. Nevertheless, several of these effects are not yet scientifically proven. Though commonly used as a supplement for body building, it is listed among performance-enhancing drugs (PEDs) which is banned by the World Anti-Doping Agency, as well as the International Olympic Committee. This review focuses on the action mechanism behind androstenedione's health effects, and further side effects including clinical features, populations at risk, pharmacokinetics, metabolism, and toxicokinetics. A review of androstenedione regulation in drug doping is also presented.
Topics: Anabolic Agents; Androstenedione; Animals; Athletes; Athletic Performance; Dietary Supplements; Doping in Sports; Female; Humans; Male; Sex Factors; Testosterone
PubMed: 34684800
DOI: 10.3390/molecules26206210