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Nathan Goodyear

Longitudinal relationships of circul... [J Clin Endocrinol Metab. 2014] - PubMed - NCBI - 0 views

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    Declining Testosterone, calculated free Testosterone, Estradiol, and Estrone levels appear to be associated with muscle mass/strength decline in elderly men.  This points to a global decrease in HPA function rather than an individual, specific hormone deficiency.
Nathan Goodyear

Obesity and testicular function. [Mol Cell Endocrinol. 2010] - PubMed - NCBI - 0 views

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    This article, here only abstract available, points to low Testosterone as the effect and not the cause.  The cause being obesity.  An interesting association between leptin and low T is found.  Leptin is a hormone produced from adipocytes, this study found leptin receptors in the leydig cells of testes.  Thus, increased leptin production from increased abdominal adiposity can result in a decrease in 17,20 lyase activity and thus a direct inhibition of leydig cell Testosterone production.
Nathan Goodyear

Testosterone and metabolic syndrome Cunningham GR - Asian J Androl - 0 views

  • The relationship of low testosterone to MetS often is considered to be bidirectional; however, the relationships probably are not direct
  • Many of the components of the MetS are recognized risk factors for the development of cardiovascular disease (CVD)
  • Multiple cross-sectional studies have found low TT and low sex hormone binding globulin (SHBG) levels in Caucasian and African-American men with the MetS, irrespective of age
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  • Low TT and SHBG levels also are prevalent in Chinese [7],[8] and Korean [9] men with the MetS
  • Normally 40%-50% of TT is bound to SHBG, so reducing SHBG levels will decrease TT.
  • Hyperinsulinism suppresses SHBG synthesis and secretion by the liver
  • significant increase in SHBG levels occurred after acutely lowering insulin levels in obese men
  • Estradiol levels are increased in men with the MetS, and they are positively correlated with the number of abnormal components of the MetS.
  • Although it is known that estrogen will increase SHBG levels, apparently the hyperinsulinism associated with obesity has a greater effect on SHBG levels
  • Estradiol also can inhibit luteinizing hormone (LH) secretion
  • Inflammatory cytokines are thought to have a direct effect on the pituitary to reduce LH secretion [15] and also a direct effect on Leydig cell secretion of testosterone
  • Low TT Levels have been shown to predict development of the MetS in men with normal BMI
  • Men in the lowest quartiles of serum TT, calculated free testosterone (cFT) and SHBG at baseline had the highest odds ratios for developing the MetS or DM during the 11 years follow-up
  • More recently, investigators conducting population-based studies have reported that only SHBG is associated with future development of the MetS
  • Additional evidence that low TT increases the risk of MetS comes from androgen deprivation treatment of prostate cancer
  • Low TT and low bioavailable testosterone (bT) were each significantly associated with elevated 20 years risk of CVD mortality in an older population in which cause-specific mortality was age, adiposity, and lifestyle-adjusted.
  • combination of low bT and ATP III-defined MetS is associated with increased cardiovascular mortality in men aged 40 years and above
  • in elderly men, testosterone may weakly protect against CVD. Alternatively, low TT may indicate poor general health
  • Muraleedharan and Jones [27] concluded that there is convincing evidence that low T is a biomarker for disease severity and mortality.
  • The evidence that TRT improves insulin sensitivity and glucose control is conflicted
  • It is widely recognized that testosterone treatment can reduce fat mass and increase lean body mass; however, until recently most reports have not been associated with much weight loss
  • Changes in body composition and weight loss are considered potential mechanisms by which testosterone treatment improves insulin sensitivity and glucose control in patients with diabetes. Effects on inflammatory cytokines [38] and changes in oxidative metabolism [39] also have been reported to improve glucose metabolism.
  • Testosterone replacement therapy has been reported to improve some or all of the components of the MetS.
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    To be read article on Testosterone and Metabolic Syndrome.
Nathan Goodyear

Predictors of skeletal muscle mass in elderly men and women - 0 views

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    Study of men and women finds that low free Testosterone, physical activity, and IGF1 is associated with muscle mass in men; no such relationship between sex hormone and muscle mass in women was found.
Nathan Goodyear

Growth hormone responses to 3 differ... [Appl Physiol Nutr Metab. 2008] - PubMed - NCBI - 0 views

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    Endurance training increases GH more than resistance and sprints/short interval training.  This increase in GH, though seen in all age groups, decreased in older aged men.
Nathan Goodyear

Androgen therapy and atherosclerotic cardiovascular disease - 0 views

  • In women, it is much clearer that androgen excess is linked to the burden of CVD risk factors
  • insulin resistance is a consequence of androgen effects
  • Women with PCOS have a sustained exposure to high physiologic androgen levels. This condition is associated with endothelial dysfunction, obesity and metabolic abnormalities such as insulin resistance and dyslipidaemia
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  • Further evidence of a link between high androgen levels and CVD or CVD risk factors is observed in women with polycystic ovary syndrome (PCOS)
  • For T treatment in aging women, the current data would suggest androgen excess has adverse effects on CVD risk factors, especially in women with diabetes
  • androgen use and abuse is increasing in our society, either for therapeutic or recreational reasons
  • For men, exogenous T treatment appears largely beneficial
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    I love these review articles that highlight the metabolic differences of hormones in women versus men.  The medical community as a whole doesn't seem to get this at all.  The marketing-based medical community doesn't either.
Nathan Goodyear

Ibuprofen alters human testicular physiology to produce a state of compensated hypogona... - 0 views

  • The levels of LH in the ibuprofen group had increased by 23% after 14 d of administration
  • This increase was even more pronounced at 44 d, at 33%
  • We found an 18% decrease (P = 0.056) in the ibuprofen group compared with the placebo group after 14 d (Fig. 1A) and a 23% decrease (P = 0.02) after 44 d (Fig. 1C). Taken together, these in vivo data suggest that ibuprofen induced a state of compensated hypogonadism during the trial, which occurred as early as 14 d and was maintained until the end of the trial at 44 d
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  • We first investigated testosterone production after 24 and 48 h of ibuprofen exposure to assess its effects on Leydig cell steroidogenesis. Inhibition of testosterone levels was significant and dose-dependent (β = −0.405, P = 0.01 at 24 h and β = −0.664, P < 0.0001 at 48 h) (Fig. 2A) and was augmented over time
  • The AMH data show that the hypogonadism affected not only Leydig cells but also Sertoli cells and also occurred as early as 14 d of administration
  • Sertoli cell activity showed that AMH levels decreased significantly with ibuprofen administration, by 9% (P = 0.02) after 14 d (Fig. 1B) and by 7% (P = 0.05) after 44 d compared with the placebo group
  • Examination of the effect of ibuprofen exposure on both the ∆4 and ∆5 steroid pathways (Fig. 2B) showed that it generally inhibited all steroids from pregnenolone down to testosterone and 17β-estradiol; the production of each steroid measured decreased at doses of 10−5–10−4 M. Under control conditions, production of androstenediol and dehydroepiandrosterone (DHEA) was below the limit of detection except in one experiment with DHEA
  • Measuring the mRNA expression of genes involved in steroidogenesis in vitro showed that ibuprofen had a profound inhibitory effect on the expression of these genes (Fig. 3 B–D), consistent with that seen above in our ex vivo organ model. Taken together, these data examining effects on the endocrine cells confirm that ibuprofen-induced changes in the transcriptional machinery were the likely reason for the inhibition of steroidogenesis.
  • Suppression of gene expression concerned the initial conversion of cholesterol to the final testosterone synthesis. Hence, expression of genes involved in cholesterol transport to the Leydig cell mitochondria was impaired
  • A previous study reported androsterone levels decreased by 63% among men receiving 400 mg of ibuprofen every 6 h for 4 wk
  • We next examined the gene expression involved in testicular steroidogenesis ex vivo and found that levels of expression of every gene that we studied except CYP19A1 decreased after exposure for 48 h compared with controls
  • the changes in gene expression indicate that the transcriptional machinery behind the endocrine action of Leydig cells was most likely impaired by ibuprofen exposure.
  • Together, these data show that ibuprofen also directly impairs Sertoli cell function ex vivo by inhibiting transcription
  • ibuprofen use in men led to (i) elevation of LH; (ii) a decreased testosterone/LH ratio and, to a lesser degree, a decreased inhibin B/FSH ratio; and (iii) a reduction in the levels of the Sertoli cell hormone AMH
  • The decrease in the free testosterone/LH ratio resulted primarily from the increased LH levels, revealing that testicular responsiveness to gonadotropins likely declined during the ibuprofen exposure. Our data from the ex vivo experiments support this notion, indicating that the observed elevation in LH resulted from ibuprofen’s direct antiandrogenic action
  • AMH levels were consistently suppressed by ibuprofen both in vivo and ex vivo, indicating that this hormone is uncoupled from gonadotropins in adult men. The ibuprofen suppression of AMH further demonstrated that the analgesic targeted not only the Leydig cells but also the Sertoli cells, a feature encountered not only in the human adult testis but also in the fetal testis
  • ibuprofen displayed broad transcription-repression abilities involving steroidogenesis, peptide hormones, and prostaglandin synthesis
  • a chemical compound, through its effects on the signaling compounds, can result in changes in the testis at gene level, resulting in perturbations at higher physiological levels in the adult human
  • The analgesics acetaminophen/paracetamol and ibuprofen have previously been shown to inhibit the postexercise response in muscles by repressing transcription
  • Previous ex vivo studies on adult testis have indeed pointed to an antiandrogenicity, only on Leydig cells, of phthalates (41), aspirin, indomethacin (42), and bisphenol A (BPA) and its analogs
  • ibuprofen’s effects were not restricted to Leydig and Sertoli cells, as data showed that the expression of genes in peritubular cells was also affected
  • short-term exposure
  • In the clinical setting, compromised Leydig cell function resulting in increased insensitivity to LH is defined as compensated hypogonadism (4), an entity associated with all-cause mortality
  • compensated hypogonadic men present with an increased likelihood of reproductive, cognitive, and physical symptoms
  • an inverse relationship was recently reported between endurance exercise training and male sexual libido
  • AMH concentrations are lower in seminal plasma from patients with azoospermia than from men with normal sperm levels
  • inhibin B is a key clinical marker of reproductive health (32). The function of AMH, also secreted by Sertoli cells, and its regulation through FSH remain unclear in men
  • the striking dual effect of ibuprofen observed here on both Leydig and Sertoli cells makes this NSAID the chemical compound, of all the chemical classes considered, with the broadest endocrine-disturbing properties identified so far in men.
  • after administration of 600 mg of ibuprofen to healthy volunteers
  • 14 d or at the last day of administration at 44 d
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    ibuprofen alters genetic expression that results in decreased Testosterone production.
Nathan Goodyear

Evidence of male hypogonadism at an early age as a familial risk of type 2 diabetes. - ... - 0 views

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    male children of parents with diabetes found to have significantly lower serum total Testosterone, free Testosterone, and bioavailable Testosterone compared to male children of parents without diabetes.
Nathan Goodyear

Sex hormones in male patients with systemic lupus erythematosus: a comparison with othe... - 0 views

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    low Testosterone found in men with Lupus; the authors conclude is is more associative with chronic disease.
Nathan Goodyear

Systemic lupus erythematosus: sex hormones in male patients. - PubMed - NCBI - 0 views

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    more men with lupus have low Testosterone compared to controls in small study.
Nathan Goodyear

Age Trends in the Level of Serum Testosterone and Other Hormones in Middle-Aged Men: Lo... - 0 views

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    MMAS study finds an age associated decline in Total Testosterone and free Testosterone levels. This study focus on the % decline based on other variables i.e. age, BMI...IN contrast, a 3.5% rise in DHT levels were observed. There is debate about the correlation of serum DHT and intra-tissue DHT. In fact, studies suggest there is little correlation.
Nathan Goodyear

The implication of neuroactive steroids in Tourette syndrome pathogenesis: a ... - 0 views

  • The typical onset of TS occurs at 6–7 years of age and is characterized by the appearance of simple, recurrent motor tics, followed by the manifestation of phonic tics after several months [12]. In most children, TS symptoms undergo a progressive exacerbation, which reaches its zenith at the beginning of puberty (11–12 years of age), and is then followed by a gradual remission in the majority of patients
  • 30–40% of TS-affected children retain their symptoms in adulthood
  • Multiple neurotransmitters have been implicated in TS, including dopamine (DA), serotonin, norepinephrine, acetylcholine, glutamate and γ-amino-butyric acid (GABA)
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  • female gender may predict greater tic severity in adulthood
  • male gender is a major risk factor for TS (with a male:female prevalence ratio estimated at ~4:1)
  • the typical age of onset coincides with adrenarche (6–7 years old); symptoms increase in severity until the beginning of puberty (12 years old) and then undergo a spontaneous amelioration, which becomes apparent with the end of puberty (at 18–19 years of age)
  • TS is diagnosed later in females than males
  • ample evidence supports the involvement of DAergic dysfunctions in TS
  • a number of clinical observations showed that tics in TS patients could be exacerbated by anabolic androgens
  • steroidogenic enzymes and androgen receptors may serve as putative therapeutic targets for this disorder
  • Unlike males, tic severity is typically increased after puberty in females
  • 26% of females were found to experience exacerbation of tics in the estrogenic phase of the menstrual cycle, and this phenomenon was found to be correlated with increased tic severity at menarche
  • biochemical hallmark of adrenarche is the acquisition of 17,20 lyase activity by cytochrome P450 C17 (CYP17A1)
  • increased synthesis of dehydroepiandrosterone (DHEA) and androstenedione, which leads to the growth of axillary and pubic hair as well as enhancement in the oiliness of the skin
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    interesting read on hormones and tourette's.. Proposed that 5 alpha reductase activity is involved in worsening of tics.  This makes sense as Testosterone in men with low T is known to increase dopamine and dopaminergic dysfunction is known to play a role in tourette's;  the clinical presentation of girls vs boys is very different.  The authors of this article propose that 5 alpha reductase activity controls a back door method where by progesterone is converted to androgens.
Nathan Goodyear

Testosterone and benign prostatic hyperplasia Jarvis TR, Chughtai B, Kaplan SA, - Asian... - 0 views

  • The prevalence of hypogonadism (often defined as serum testosterone < 300 ng dl−1 ) ranges from 6% [10] to as high as 38%
  • The process of BPH, however, continues as men age and despite the fact their serum testosterone decreases
  • Liu et al. [12] demonstrated that in a group of older males (mean age 59.8 years) that there was not a significant correlation of serum testosterone levels (total, free or bioavailable) with either prostate volume or International Prostate Symptom Score (IPSS)
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  • in eugonadal men, studies have demonstrated that the prostate can increase in volume by approximately 12%
  • There seems to be little doubt that the treatment with testosterone of a young hypogonadal male leads to significant growth of the prostate
  • Behre et al. [22] demonstrated increased prostate volume and prostate-specific antigen (PSA) levels in hypogonadal men
  • Most studies, however, have shown no effect of exogenous androgens on PSA or prostate volume for older hypogonadal males
  • They argue that the prostate is relatively insensitive to changes in androgen concentration at normal levels or in mild hypogonadism because the AR is saturated by androgens and therefore maximal androgen-AR binding is achieved. Conversely, the prostate is very sensitive to changes in androgen levels when testosterone is low
  • saturation model
  • visceral obesity (one of the most significant components of metabolic syndrome) is associated with prostate volume and influences prostate growth during TRT.
  • This hypothesis of inflammation induced LUTS is also argued to be a mechanism for improvement of LUTS with PDE5I
  • The concept, therefore, that treatment with TRT of hypogonadal males with metabolic syndrome might lead to improvement/stabilization of their LUTS, appears to be confirmed in recent work by Francomano et al.
  • There was also an improvement in components of the patient's metabolic syndrome (such as BMI, waist circumference, hemoglobin A1c [HbA1c], insulin sensitivity, and lipid profile) as well as inflammatory markers and C-reactive protein.
  • They concluded that TRT was safe in this group of men, and hypothesize that TRT mitigates the pro-inflammatory factors associated with metabolic syndrome.
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    Authors review the literature behind Testosterone and BPH.  The authors highlight the 4 proposed theories behind BPH: Testosterone, Estrogen, inflammation, and metabolic.   The conclusion is mixed: pointing out that no high level of evidence exists on either side of the debate of Testosterone and BPH.
Nathan Goodyear

Age Trends in the Level of Serum Testosterone and Other Hormones in Middle-Aged Men: Lo... - 0 views

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    This study found that in longitudinal studies, testosterone decline accelerated compared to cross sectional studies.  They concluded that decreasing health could be the explanation.  But, what if the decline in testosterone explained the decreasing health?
Nathan Goodyear

Beyond the male sex hormone: deciphering the metabolic and vascular actions of testoste... - 0 views

  • androgen deprivation therapy results in unfavorable changes in body composition, insulin resistance, and dyslipidemia and predisposes men to develop atherosclerosis and an increased risk of cardiovascular mortality
  • The hypogonadal–obesity cycle hypothesis was originally proposed by Cohen in 1999 to explain the relationship between low testosterone levels and metabolic disease. It was based on the finding that obesity impairs testosterone levels by increasing the aromatization of testosterone to estradiol, while low testosterone levels promote increased fat deposition
  • adipocytokines contribute to low testosterone levels as well as to the processes underlying metabolic syndromes and type 2 diabetes
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  • hypogonadal–obesity–adipocytokine hypothesis
  • The presence of estradiol and the adipocytokines TNF-α, IL6, and leptin (as a result of leptin resistance in obesity) inhibits the hypothalamic–pituitary–testicular axis response to decreasing androgen levels
  • An increasing number of studies have illustrated the potential for applying metabolomics to the field of androgen research
  • As early as the 1940s, the therapeutic use of testosterone was reported to improve angina pectoris in men with coronary artery disease
  • most of the epidemiological studies reported increased cardiovascular risk and mortality in men with low testosterone levels
  • long-term testosterone replacement appears to be a safe and effective means of treating hypogonadal elderly men
  • a recent interventional trial showed that testosterone treatment was associated with decreased mortality when compared with no testosterone treatment in an observational cohort of men with low testosterone levels
  • a number of short-term studies conducted support the notion that testosterone therapy reduces the cardiovascular risk
  • The majority of animal studies support the hypothesis that the actions of testosterone on vascular relaxation are both endothelium-dependent and -independent vasodilatory effects
  • Endothelial-dependent actions of testosterone increase the expression or activity of endothelial nitric oxide synthase and enhance nitric oxide production, which in turn activates cyclic guanosine monophosphate to induce vasorelaxation in smooth muscle cells
  • Endothelial-independent mechanisms of testosterone are believed to occur primarily via inhibition of voltage-operated Ca2+ channels and/or activation of K+ channels in smooth muscle cells
  • Testosterone may also inhibit intracellular Ca2+ influx via store-operated Ca2+ channels by blocking the response to prostaglandin F2α
  • testosterone has demonstrated anti-inflammatory effects to protect against atherogenesis in animal studies
  • both genomic AR activation to modulate gene transcription and non-genomic activation to modulate the rapid intracellular signaling pathways of ion channels may mediate testosterone effects on vascular function and inflammation.
  • Butenandt & Ruzicka first showed how testosterone is synthesized and responsible for masculine characteristics in the early 1930s
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    Awesome review on the current understanding of Testosterone and Diabetes, metabolic syndrome, and CVD.  This article even goes into the literature on androgen receptors.
Nathan Goodyear

Influence of increasing body mass index on semen and reproductive hormonal parameters i... - 0 views

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    retrospective cohort finds mild but significant relationships b/t BMI and total Testosterone, Testosterone:Estradiol and Estradiol alone.  BMI was inversely correlated with Testosterone and the T:E2 ratio; but directly correlated with E2 alone. There was also a negative correlation with sperm concentration, motility and morphology.
Nathan Goodyear

Effect of exposure to p,p'-DDE on male hormone profile in Mexican flower grow... - 0 views

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    DDE in hispanic farm workers found to be inversely associated with testosterone.  Again, DDE and other persistent organohalogen pollutants, work to lower testosterone in men.
Nathan Goodyear

Thieme E-Journals - Hormone and Metabolic Research / Abstract - 0 views

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    small study, but males with pancreatic cancer were found to have higher levels of FSH (p < 0.01), LH and oestradiol (p < 0.001) and lower levels of progesterone (p < 0.01) and testosterone (p < 0.05) than the controls. Female patients with pancreatic cancer were found to have higher levels of oestradiol (p < 0.001) and lower levels of LH, FSH and progesterone.  Though cause and effect is not known, the expression of ER alpha in pancreatic cancer is known and the inflammatory and pro-growth signal of ER alpha is known, thus heavy stimulation would be unwise.
Nathan Goodyear

Exposure to DEHP and MEHP from hatching to adu... [Aquat Toxicol. 2013] - PubMed - NCBI - 0 views

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    endocrine disrupting pthalates disrupt marine animal hormones.  This effect was more prevalent in males than females.
Nathan Goodyear

Serum levels of sex hormone-binding globulin (SHBG) are not associated with lower level... - 0 views

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    Age increases SHBG.  This study doesn't find a correlation with non-SHBG Testosterone in "health" men.  The term health is probably key.
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