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)
ample evidence supports the involvement of DAergic dysfunctions in TS
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
female gender may predict greater tic severity in adulthood
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
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.
Study finds higher Pb levels in young girls is associated with delayed puberty onset. This occurs through an inverse relationship with inhibin B and follicular development. This relationship was also found with Cadmium. Both of these heavy metals are toxic to the ovaries.
New study shows that obese boys/young men pre and post puberty have up to 50% lower testosterone levels than comparative normal BMI counterparts. Also of note, estradiol levels were not associated with the low testosterone levels.
Normal leptin levels are critical to puberty; but in obese men, increased leptin is associated with gonadal decrease in Testosterone. It appears to occur through a decrease in 17-OH progesterone to Testosterone: suggesting an inhibitory activity in the conversion of 17-OH progesterone to Testosterone in obese men.
Elevated insulin levels in men is associated with decreased liver production of SHBG and thus reduced SHBG levels. Obesity is associated with decreased urinary cortisol in this study. The authors found the low cortisol also contributed to the low SHBG as well. Low SHBG is associated with puberty, obesity, IR, hypothyroidism, and during androgen therapy. SHBG is increased as a result of aging, short-term fasting, Estrogen, hyperthyroid, and liver disease.
Around 50% of ageing, obese men presenting to the diabetes clinic have lowered testosterone levels relative to reference ranges
based on healthy young men
The absence of high-level evidence in this
area is illustrated by the Endocrine Society testosterone therapy in men with androgen deficiency clinical practice guidelines
(Bhasin et al. 2010), which are appropriate for, but not specific to men with metabolic disorders. All 32 recommendations made in these guidelines
are based on either very low or low quality evidence.
A key concept relates to making a distinction between replacement and pharmacological testosterone therapy
The presence of symptoms was more closely linked to increasing age than to testosterone levels
Findings similar to type 2 diabetes were reported for men with the metabolic syndrome, which were associated with reductions
in total testosterone of −2.2 nmol/l (95% CI −2.41 to 1.94) and in free testosterone
low testosterone is more predictive of the metabolic syndrome in lean men
Cross-sectional studies uniformly show that 30–50% of men with
type 2 diabetes have lowered circulating testosterone levels, relative to references based on healthy young men
In a recent cross-sectional study of 240 middle-aged men (mean age 54 years) with either type 2 diabetes, type 1 diabetes
or without diabetes (Ng Tang Fui et al. 2013b), increasing BMI and age were dominant drivers of low total and free testosterone respectively.
both diabetes and the metabolic syndrome are associated with a modest reduction in testosterone, in magnitude comparable
with the effect of 10 years of ageing
In a cross-sectional study of 490 men with type 2 diabetes, there was a strong independent association of low testosterone
with anaemia
In men, low testosterone is a marker of poor health, and may improve our ability to predict risk
probably the most important point made in this article
low testosterone identifies men with an adverse metabolic phenotype
Diabetic men with low testosterone are significantly more likely to be obese or insulin resistant
increased inflammation, evidenced by higher CRP levels
Bioavailable
but not free testosterone was independently predictive of mortality
It remains possible that low testosterone is a consequence of insulin resistance, or simply a biomarker,
co-existing because of in-common risk factors.
In prospective studies, reviewed in detail elsewhere (Grossmann et al. 2010) the inverse association of low testosterone with metabolic syndrome or diabetes is less consistent for free testosterone
compared with total testosterone
In a study from the Framingham cohort, SHBG but not testosterone was prospectively and independently associated with incident
metabolic syndrome
low SHBG (Ding et al. 2009) but not testosterone (Haring et al. 2013) with an increased risk of future diabetes
In cross-sectional studies of men with (Grossmann et al. 2008) and without (Bonnet et al. 2013) diabetes, SHBG but not testosterone was inversely associated with worse glycaemic control
SHBG may have biological actions
beyond serving as a carrier protein for and regulator of circulating sex steroids
In men with diabetes, free testosterone, if measured by gold standard equilibrium dialysis (Dhindsa et al. 2004), is reduced
expensive, laborious process filled with variables
Low free testosterone remains inversely associated with insulin resistance, independent of SHBG (Grossmann et al. 2008). This suggests that the low testosterone–dysglycaemia association is not solely a consequence of low SHBG.
Experimental evidence reviewed below suggests that visceral adipose tissue is an important intermediate (rather than a
confounder) in the inverse association of testosterone with insulin resistance and metabolic disorders.
testosterone promotes the commitment of
pluripotent stem cells into the myogenic lineage and inhibits their differentiation into adipocytes
testosterone regulates the metabolic functions
of mature adipocytes (Xu et al. 1991, Marin et al. 1995) and myocytes (Pitteloud et al. 2005) in ways that reduce insulin resistance.
Pre-clinical evidence (reviewed in Rao et al. (2013)) suggests that at the cellular level, testosterone may improve glucose metabolism by modulating the expression of the glucose-transported
Glut4 and the insulin receptor, as well as by regulating key enzymes involved in glycolysis.
More recently testosterone has
been shown to protect murine pancreatic β cells against glucotoxicity-induced apoptosis
Interestingly, a reciprocal feedback also appears to exist, given that not only chronic (Cameron et al. 1990, Allan 2013) but also, as shown more recently (Iranmanesh et al. 2012, Caronia et al. 2013), acute hyperglycaemia can lower testosterone levels.
There is
also evidence that testosterone regulates insulin sensitivity directly and acutely
In men with prostate cancer commencing androgen deprivation therapy, both total as well as, although not in all studies (Smith 2004), visceral fat mass increases (Hamilton et al. 2011) within 3 months
More prolonged (>12 months) androgen deprivation therapy has been associated with increased risk of diabetes in several
large observational registry studies
Testosterone has also been shown to reduce the concentration of pro-inflammatory cytokines in some, but not all studies, reviewed
recently in Kelly & Jones (2013). It is not know whether this effect is independent of testosterone-induced changes in body composition.
the observations discussed in this section suggest that it is the decrease in testosterone that causes insulin
resistance and diabetes. One important caveat remains: the strongest evidence that low testosterone is the cause rather than
consequence of insulin resistance comes from men with prostate cancer (Grossmann & Zajac 2011a) or biochemical castration, and from mice lacking the androgen receptor.
Several large prospective studies have shown that weight gain or development of type 2 diabetes is major drivers of the
age-related decline in testosterone levels
there is increasing evidence that healthy ageing by itself is generally not associated with marked reductions in
testosterone
Circulating testosterone, on an average 30%, is lower in obese compared with lean men
increased visceral fat is an important component in the association of low testosterone and insulin resistance
The vast majority of men with metabolic disorders have functional gonadal axis suppression with modest reductions in testosterone
levels
obesity is a dominant
risk factor
men with Klinefelter syndrome have an increased risk of metabolic disorders. Interestingly, greater body fat
mass is already present before puberty
Only 5% of men with type 2 diabetes have elevated LH levels
inhibition of the gonadal axis predominantly takes place in the hypothalamus,
especially with more severe obesity
Metabolic factors, such as leptin, insulin (via deficiency or resistance) and ghrelin
are believed to act at the ventromedial and arcuate nuclei of the hypothalamus to inhibit gonadotropin-releasing hormone (GNRH)
secretion from GNRH neurons situated in the preoptic area
kisspeptin has emerged as one of the
most potent secretagogues of GNRH release
hypothesis that obesity-mediated inhibition of kisspeptin signalling contributes to the suppression
of the HPT axis, infusion of a bioactive kisspeptin fragment has been recently shown to robustly increase LH pulsatility,
LH levels and circulating testosterone in hypotestosteronaemic men with type 2 diabetes
A smaller study with a similar experimental design found that acute testosterone withdrawal reduced insulin sensitivity
independent of body weight, whereas oestradiol withdrawal had no effects
suppression of the diabesity-associated HPT axis is functional, and may hence be
reversible
Obesity and dysglycaemia and associated comorbidities such as obstructive sleep apnoea (Hoyos et al. 2012b) are important contributors to the suppression of the HPT axis
weight gain and development
of diabetes accelerate the age-related decline in testosterone
Modifiable risk factors such as obesity and co-morbidities are more strongly associated with a decline in circulating testosterone
levels than age alone
55% of symptomatic androgen deficiency reverted to a normal testosterone or an asymptomatic state after 8-year follow-up,
suggesting that androgen deficiency is not a stable state
Weight loss can reactivate the hypothalamic–pituitary–testicular axis
Leptin treatment resolves hypogonadism in leptin-deficient men
The hypothalamic–pituitary–testicular axis remains responsive to treatment with aromatase inhibitors or selective oestrogen
receptor modulators in obese men
Kisspeptin treatment increases LH secretion, pulse frequency and circulating testosterone levels in hypotestosteronaemic men
with type 2 diabetes
change in BMI was associated with the change in testosterone (Corona et al. 2013a,b).
weight loss can lead to genuine reactivation
of the gonadal axis by reversal of obesity-associated hypothalamic suppression
There is pre-clinical and observational evidence that chronic hyperglycaemia can inhibit the HPT axis
in men who improved their glycaemic control over time, testosterone levels increased. By
contrast, in those men in whom glycaemic control worsened, testosterone decreased
testosterone levels should be measured after successful weight loss to identify men with an insufficient rise
in their testosterone levels. Such men may have HPT axis pathology unrelated to their obesity, which will require appropriate
evaluation and management.
Energy storage occurs mainly at the level of white adipose tissue, where adipocytes secrete the anorexigenic adipokine leptin
humans and laboratory animals with leptin or insulin deficiency or resistance and/or increased ghrelin levels exhibit delayed or absent puberty and frequently display hypogonadotropic hypogonadism, which prevents fertility
Ghrelin suppresses pulsatile gonadotropin-releasing hormone (GnRH) release [14,15], thus serving as a signal to suppress reproduction in times of famine
Good, although brief, discussion of the interaction between metabolism and hormones. Kisspeptin is a GNRH secreatagogue "upstream". Insulin, Leptin, and Gherlin can inhibit GNRH through resistance and low levels. Probably a U shaped graph of optimal activity.
Animal study finds that Cadmium is estrogenic. This study found that not only was Cadmium an endocrine disruptor for the pregnant animals, but was also estrogenic in the mammary glands of the offspring.
strongly supports an association between levels of androgens and leptin in both men and women
The association between androgen levels and leptin seems to be dependent of fat distribution in men
There is a growing bulk of evidence suggesting that testosterone may influence leptin levels. Testosterone administration reduces leptin levels in hypogonadal27,28 and eugonadal men
testosterone suppression by GnRH agonist treatment of central precocious puberty in boys increases leptin levels
Testosterone levels decreased with increasing central obesity in healthy men, while they increase with increasing obesity in healthy women, the latter irrespective of menstrual status
this could be due to obesity-related hyperleptinemia that inhibits testosterone secretion at the testicular level.46,47 These changes, which are proposed to be components of the insulin resistance syndrome,48 are associated with increased risk for cardiovascular disease in both men and women
in the more obese subjects, the higher leptin levels due to increased adiposity might reduce secretion of testosterone
loss of regulation of leptin by testosterone in obese men and women could be an important feature of the insulin resistance syndrome
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Stretch marks are formed deep within the dermis layer and happen due to rapid stretching, this causes damage to the skin's connecting tissues. To get rid of these stretch marks we are introducing to you our latest laser treatment i.e. PIXIGENUS. It is a unique technology to eliminate stretchmarks from various parts of the body. Watch the full video to know more.
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Pharma Sust 250mg injections treat hypogonadism disorders in men, after the illness, impotence due to lack of hormones, menstrual symptoms in men such as reducing sexual pleasure and physiological activities.
Side effects:
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In pre-puberty boys: develop sex early, increase the frequency of erectile dysfunction, enlargement of the penis, and early growth of bone heads.
The body of the white pimples is a common feature of boys entering puberty. Understanding their nature will help you no longer worry.
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