-
Australian Journal of General Practice Jul 2019Older men, especially those who are overweight or obese and have comorbidities, not uncommonly present with non-specific androgen deficiency-like symptoms, such as low...
BACKGROUND
Older men, especially those who are overweight or obese and have comorbidities, not uncommonly present with non-specific androgen deficiency-like symptoms, such as low energy and sexual dysfunction, and modestly lowered serum testosterone relative to reference ranges based on healthy young men.
OBJECTIVE
The aim of this paper is to describe the clinical approach to men who present with non-specific androgen deficiency-like symptoms.
DISCUSSION
Most men who present with non-specific androgen deficiency-like symptoms do not have organic hypogonadism due to pituitary or testicular disease, but instead have functional gonadal axis suppression due to ill health. Lifestyle measures - especially weight loss, optimisation of comorbidities and cessation of offending medications - can improve symptoms and increase serum testosterone; this should be the first-line approach. Recent randomised controlled trials (RCTs) have reported modest benefits of testosterone treatment in stringently selected older men. However, the true long-term risks and benefits of testosterone treatment in such men are not known. Further study is required before testosterone treatment can be routinely recommended for indications other than organic hypogonadism.
Topics: Aged; Aged, 80 and over; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Obesity; Testosterone
PubMed: 31256511
DOI: 10.31128/AJGP-01-19-4831 -
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 -
Investigative and Clinical Urology Nov 2016Although testosterone therapy in men with testosterone deficiency was introduced in the early 1940s, utilization of this effective treatment approach in hypogonadal men... (Review)
Review
Although testosterone therapy in men with testosterone deficiency was introduced in the early 1940s, utilization of this effective treatment approach in hypogonadal men is met with considerable skepticism and resistance. Indeed, for decades, the fear that testosterone may cause prostate cancer has hampered clinical progress in this field. Nevertheless, even after considerable knowledge was acquired that this fear is unsubstantiated, many in the medical community remain hesitant to utilize this therapeutic approach to treat men with hypogonadism. As the fears concerning prostate cancer have subsided, a new controversy regarding use of testosterone therapy and increase in cardiovascular disease was introduced. Although the new controversy was based on one ill-fated clinical trial, one meta-analysis with studies that utilized unapproved formulation in men with liver cirrhosis, and two retrospective studies with suspect or nonvalidated statistical methodologies and database contaminations, the flames of such controversy were fanned by the lay press and academics alike. In this review we discuss the adverse effect of testosterone deficiency and highlight the numerous proven benefits of testosterone therapy on men's health and debunk the myth that testosterone therapy increases cardiovascular risk. Ultimately, we believe that there is considerable scientific and clinical evidence to suggest that testosterone therapy is safe and effective with restoration of physiological levels in men with testosterone deficiency, irrespective of its etiology.
Topics: Cardiovascular Diseases; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Prostatic Neoplasms; Testosterone
PubMed: 27847912
DOI: 10.4111/icu.2016.57.6.384 -
Archives of Endocrinology and Metabolism Jul 2019
Topics: Brazil; Endocrinology; Female; Humans; Libido; Testosterone
PubMed: 31340239
DOI: 10.20945/2359-3997000000153 -
The Journal of Sexual Medicine Dec 2017Testosterone deficiency (TD) is an increasingly common problem with significant health implications, but its diagnosis and management can be challenging. (Review)
Review
BACKGROUND
Testosterone deficiency (TD) is an increasingly common problem with significant health implications, but its diagnosis and management can be challenging.
AIM
To review the available literature on TD and provide evidence-based statements for UK clinical practice.
METHODS
Evidence was derived from Medline, EMBASE, and Cochrane searches on hypogonadism, testosterone (T) therapy, and cardiovascular safety from May 2005 to May 2015. Further searches continued until May 2017.
OUTCOMES
To provide a guideline on diagnosing and managing TD, with levels of evidence and grades of recommendation, based on a critical review of the literature and consensus of the British Society of Sexual Medicine panel.
RESULTS
25 statements are provided, relating to 5 key areas: screening, diagnosis, initiating T therapy, benefits and risks of T therapy, and follow-up. 7 statements are supported by level 1, 8 by level 2, 5 by level 3, and 5 by level 4 evidence.
CLINICAL IMPLICATIONS
To help guide UK practitioners on effectively diagnosing and managing primary and age-related TD.
STRENGTHS AND LIMITATIONS
A large amount of literature was carefully sourced and reviewed, presenting the best evidence available at the time. However, some statements provided are based on poor-quality evidence. This is a rapidly evolving area of research and recommendations are subject to change. Guidelines can never replace clinical expertise when making treatment decisions for individual patients, but rather help to focus decisions and take personal values and preferences and individual circumstances into account. Many issues remain controversial, but in the meantime, clinicians need to manage patient needs and clinical expectations armed with the best clinical evidence and the multidisciplinary expert opinion available.
CONCLUSION
Improving the diagnosis and management of TD in adult men should provide somatic, sexual, and psychological benefits and subsequent improvements in quality of life. Hackett G, Kirby M, Edwards D, et al. British Society for Sexual Medicine Guidelines on Adult Testosterone Deficiency, With Statements for UK Practice. J Sex Med 2017;14:1504-1523.
Topics: Adult; Consensus; Humans; Hypogonadism; Male; Medicine; Practice Guidelines as Topic; Testosterone; United Kingdom
PubMed: 29198507
DOI: 10.1016/j.jsxm.2017.10.067 -
BMC Women's Health May 2023Associations of luteinizing hormone (LH) with androgens during the menopausal transition and associations between follicle-stimulating hormone (FSH) levels and various...
INTRODUCTION
Associations of luteinizing hormone (LH) with androgens during the menopausal transition and associations between follicle-stimulating hormone (FSH) levels and various diseases related to reproductive hormones in postmenopause have received much attention. LH and FSH are also known to be associated with activities of enzymes related to reproductive hormones. We examined the associations of LH and FSH with androgens and estrogens in each stage of the menopausal transition according to a classification from menopausal transition to postmenopause.
METHODS
This study was a cross-sectional design. We basically used the Stage of Reproductive Aging Workshop (STRAW) + 10. We divided the 173 subjects into 6 groups according to menstrual regularity and follicle-stimulating hormone level: mid reproductive stage (Group A), late reproductive stage (Group B), early menopausal transition (Group C), late menopausal transition (Group D), very early postmenopause (Group E) and early postmenopause (Group F). Levels of LH, FSH, dehydroepiandrosterone sulfate (DHEAS), estradiol, estrone, testosterone (T), free T, androstenedione and androstenediol were measured.
RESULTS
In Group A, LH showed significant positive correlations with androstenedione and estrone. In Group D, LH was positively associated with T and free T and was negatively associated with estradiol. In Groups B, C, D and F, LH showed significant positive correlations with FSH, and there was a tendency for an association between LH and FSH in Group E. FSH was associated with estradiol but not with estrone in Groups C and D.
CONCLUSION
The associations of LH and FSH with reproductive hormones are different depending on the stage of the menopausal transition.
TRIAL REGISTRATION
Trial registration number 2356-1; Date of registration: 18/02/2018, retrospectively registered.
Topics: Female; Humans; Androstenedione; Estrone; Follicle Stimulating Hormone; Cross-Sectional Studies; Luteinizing Hormone; Menopause; Estradiol; Androgens; Testosterone
PubMed: 37231423
DOI: 10.1186/s12905-023-02438-5 -
Frontiers in Endocrinology 2023Clinical studies have shown that low levels of endogenous testosterone are associated with cardiovascular diseases. Considering the intimate connection between oxidative...
INTRODUCTION
Clinical studies have shown that low levels of endogenous testosterone are associated with cardiovascular diseases. Considering the intimate connection between oxidative metabolism and myocardial contractility, we determined the effects of testosterone deficiency on the two spatially distinct subpopulations of cardiac mitochondria, subsarcolemmal (SSM) and interfibrillar (IFM).
METHODS
We assessed cardiac function and cardiac mitochondria structure of SSM and IFM after 12 weeks of testosterone deficiency in male Wistar rats.
RESULTS AND DISCUSSION
Results show that low testosterone reduced myocardial contractility. Orchidectomy increased total left ventricular mitochondrial protein in the SSM, but not in IFM. The membrane potential, size and internal complexity in the IFM after orchidectomy were higher compared to the SHAM group. However, the rate of oxidative phosphorylation with all substrates in the IFM after orchidectomy was lower compared to the SHAM group. Testosterone replacement restored these changes. In the testosterone-deficient SSM group, oxidative phosphorylation was decreased with palmitoyl-L-carnitine as substrate; however, the mitochondrial calcium retention capacity in IFM was increased. There was no difference in swelling of the mitochondria in either group. These changes in IFM were followed by a reduction in phosphorylated form of AMP-activated protein kinase (p-AMPK-α), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) translocation to mitochondria and decreased mitochondrial transcription factor A (TFAM). Testosterone deficiency increased NADPH oxidase (NOX), angiotensin converting enzyme (ACE) protein expression and reduced mitochondrial antioxidant proteins such as manganese superoxide dismutase (Mn-SOD) and catalase in the IFM. Treatment with apocynin (1.5 mM in drinking water) normalized myocardial contractility and interfibrillar mitochondrial function in the testosterone depleted animals. In conclusion, our findings demonstrate that testosterone deficiency leads to reduced myocardial contractility and impaired cardiac interfibrillar mitochondrial function. Our data suggest the involvement of reactive oxygen species, with a possibility of NOX as an enzymatic source.
Topics: Rats; Animals; Male; Rats, Wistar; Myocardium; Mitochondria, Heart; Oxidative Stress; Testosterone
PubMed: 37780627
DOI: 10.3389/fendo.2023.1206387 -
Hormones (Athens, Greece) Dec 2021The aim of the present literature review is to describe the influence of sex hormones on the human voice in physiological conditions. As a secondary sexual organ, the... (Review)
Review
The aim of the present literature review is to describe the influence of sex hormones on the human voice in physiological conditions. As a secondary sexual organ, the larynx is affected by sex hormones and may change considerably over the lifespan. In the current review, sex hormone-related voice modifications occurring during childhood, puberty, the menstrual cycle, pregnancy and senescence are described. The roles of sex hormones (including gonadotropins, testosterone, estrogen, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone-sulfate) underlying physiological voice changes are discussed, the main differences between males and females are explained and clinical implications are taken into account.
Topics: Androgens; Androstenedione; Dehydroepiandrosterone; Estrogens; Female; Gonadal Steroid Hormones; Gonadotropins; Humans; Male; Pregnancy; Testosterone; Voice
PubMed: 34046877
DOI: 10.1007/s42000-021-00298-y -
The Journal of Clinical Endocrinology... Aug 2020The gonads are the major source of sex steroids during reproductive ages. The gonadal function declines abruptly in women and gradually in men. The adrenals produce... (Comparative Study)
Comparative Study
CONTEXT
The gonads are the major source of sex steroids during reproductive ages. The gonadal function declines abruptly in women and gradually in men. The adrenals produce 11-oxygenated androgens (11-oxyandrogens), which start rising during adrenarche. Following menopause, 11-oxyandrogens levels remain similar to reproductive ages.
OBJECTIVE
To compare the circulating 11-oxyandrogen concentrations in men and women across adult ages.
METHODS
We used mass spectrometry to measure testosterone (T), androstenedione (A4), 11β-hydroxytestosterone (11OHT), 11-ketotestosterone (11KT), 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), cortisol, and cortisone in morning sera obtained from adults in outpatient setting. We performed double immunofluorescence of 3β-hydroxysteroid dehydrogenase type 2 and cytochrome b5 in adrenal tissue from 19 men, age 23-78 years.
RESULTS
We included 590 patients (319 men), aged 18 to 97 years, and 84% white. 11KT and 11KA4 were stable across ages in women, but they declined in men (0.21 and 0.06 ng/dL/year, respectively; P < 0.05). 11OHA4 and 11OHT increased modestly with age in women (0.6 and 0.09 ng/dL/year, respectively; P < 0.01), and both remained stable across ages in men. As body mass index (BMI) increased, 11KA4 decreased in women, and 11KT increased in men, both suggesting higher 17β-hydroxysteroid dehydrogenase activity in obese individuals. A4 and T declined with age and A4 with BMI in both sexes; T declined with BMI in men. Adrenal androgenic enzyme expressions in aging men were similar to those observed in women.
CONCLUSIONS
In contrast with traditional androgens, the production of 11OHA4 and 11OHT is sustained with aging in both sexes. The bioactive androgen 11KT declines in aging men but not in women.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Androgens; Androstenedione; Cohort Studies; Female; Humans; Hydroxytestosterones; Male; Middle Aged; Sex Factors; Testosterone; Young Adult
PubMed: 32498089
DOI: 10.1210/clinem/dgaa343 -
Psychoneuroendocrinology Aug 2021Hypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or...
BACKGROUND
Hypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or additionally to core emotional symptoms such as sadness and anhedonia. We examined whether androgen levels 1) differ between men with and without MDD cross-sectionally, 2) are associated with an elevated risk for onset of MDD prospectively, and 3) associate with all individual MDD symptoms, or only with hypogonadism overlapping symptoms.
METHODS
In 823 men (mean age 43.5 years), baseline plasma levels of total testosterone, 5α-dihydrotestosterone (5α-DHT), and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulphate (DHEAS) and sex hormone binding globulin with radioimmunoassay, whereas free testosterone was calculated. MDD status was assessed at baseline and after two years using structured interviews and individual MDD symptoms were self-rated at baseline, and after one and two years.
RESULTS
None of the androgen levels were associated with current or onset (incidence or recurrence) of MDD. Free testosterone was only inversely associated with interest in sex. Also, androstenedione and DHEAS were positively associated with some individual MDD symptoms, and 5α-DHT levels showed non-linear associations (both with low and high levels) with MDD symptom severity and several individual MDD symptoms.
CONCLUSIONS
These results support the idea that circulating androgens synthesised by the testes are of limited clinical relevance to MDD in adult men, but levels of androstenedione, DHEAS and 5α-DHT may be associated with some individual MDD symptoms.
Topics: Adult; Androgens; Androstenedione; Dehydroepiandrosterone Sulfate; Depression; Depressive Disorder, Major; Dihydrotestosterone; Humans; Male; Sex Hormone-Binding Globulin; Testosterone
PubMed: 34049017
DOI: 10.1016/j.psyneuen.2021.105278