Friday, 29 March 2013

High Sex Hormone Binding Globulin

High Sex Hormone Binding Globulin


The liver does all sorts of wonderful things in our lives; it metabolizes Human Growth Hormone into IGF-1 and IGF-2, it filters toxins from the blood, it helps to regulate the flow of insuline from the pancreas to name a few. Part of it's function is also to release a protien called Sex Hotmone Binding Globulin (SHBG) in an effort to keep sex hormone levels like testosterone from becomming too high. Sometimes, the liver does its job too well, producing more SHBG than is needed. The result is that testosterone gets locked up and carried away before the body has a chance to use it. Testosterone exists in 2 states in the body: free and bound.

Free testosterone is the testosterone that our bodies use to build muscle, produce pheromones, maintain health and libido. Its the stuff that dreams are made of, the holy grail of manliness.

Bound testosterone, on the other hand, has no bioavailability. It simply is attatched to a protien, floating around the bloodstream, unable to interact with any receptors in the body. Basically, its now junk and it will be removed by the liver.

If your blood test showed up with low free testosterone, high bound testosterone, and low estrogen, then you are likely a victim of SHBG. The condition is not likely to get better unless you are willing to be proactive.

Since we cannot live very long without a liver due to its multitude of functions, its best to leave this organ alone and treat the SHBG in the bloodstream instead. Any alteration of liver function can have a domino effect on the rest of the body.

The most effective way of nuetralizing SHBG comes not from the pharmacy, but from the roots of a common weed: urtica dioica, the common stinging nettle. It is interesting that a plant which is so hated by farmers and outdoorsmen offers an inexpensive and safe solution to such a terrible problem.
You could don your work gloves and hiking boots to harvest roots and prepare your own extract. But if you are not a glutten for punishment, you can easily pick some extract up at a health food store and even at some pharmacies.

There are several dietary suppliments geared toward men and men's health that include stinging nettle root and are very reasonably priced when weighed against the benefits that they provide.
Whether you dig your own, or purchase it, whichever option you choose will be preferable to soaking your system with external sources of testosterone and sending your testicles on a crash course with atropy.

I inject sex hormone, says Robbie Williams | The Sun |Showbiz|Bizarre

I inject sex hormone, says Robbie Williams | The Sun |Showbiz|Bizarre

Singer has testosterone
jabs twice a week

0

ROBBIE WILLIAMS has confessed to injecting himself with a sex hormone twice a week, The Sun can reveal.

The TAKE THAT star, 37, said he uses testosterone jabs to fight crippling lethargy. He added: “It has changed my life. I feel I’m getting a second wind.”
The pop superstar has revealed a doctor told him he had the sex drive of a 100-year-old man.
The shock diagnosis came after the heart-throb singer asked a medic for some Human Growth Hormone — popular with wealthy middle-aged men trying to battle the march of time.

He had blood tests in Los Angeles that showed he had extremely low levels of testosterone — a hormone that boosts sex drive.
It is also essential for health and wellbeing. And as a result Robbie — who has battled depression and drug and alcohol addiction — forgot about HGH and began injecting himself with testosterone twice a week.
The chart-topper, who has just rejoined his Take That bandmates for their sold-out Progress tour, revealed all in an incredibly candid interview with Esquire magazine.
He said: “To cut a long story short I went to get some HGH. It’s what all the old fellas are on out there in LA that’s making them look 40 instead of 60.
“It’s improving their health, their memory, their hair, skin.
“Could give you cancer. I weighed that up. Thought I’d have it anyway. Went to see a Hollywood doctor. Had my blood tests. Went back. He said, ‘You don’t need HGH. You’ve got the testosterone of a 100-year-old man.’
“And then everything made sense. It was kind of an epiphany that day.”
Wedded bliss ... Robbie Williams and Ayda Field
Wedded bliss ... Robbie Williams and Ayda Field

Robbie, who wed beautiful American actress AYDA FIELD last year, has now been giving himself the jabs for two years.

The singer also talked about getting back with Take That mates GARY BARLOW, MARK OWEN, HOWARD DONALD and JASON ORANGE after joining them on stage for the first time in 15 years.

And he triggered a guessing game about his old pals after joking he is only the “third weirdest member” of the band.

But he delivered his most controversial views on marriage and monogamy.

Asked if he feared being caught cheating on Ayda by the media, he pledged his love to her but gave mixed messages.

Peppering his comments with the f-word, he said: “The rules aren’t set up right. Because people are f***ing outside of their marriages, outside of their relationships.

“People get caught out every single week in the newspapers. What does that mean?

“I think that means we’re built to f***. And marriage, that whole institution, is made-up bull.”
Robbie said he was such a high-profile personality that he had to be a “good boy”.
 
But he added: “I am pleased there is a media waiting for me to f*** up because it keeps me on the straight and narrow. But if it wasn’t for jealousy and social constraints, I think the rules would be different.”

Esquire editor ALEX BILMES pushed him by asking if he would be unfaithful if he could guarantee it would remain a secret.

He replied: “Actually, no, because I don’t want to break Ayda’s heart. That’s the last thing I want to do. I met Ayda, I fell in love, that’s what happened.

“But I would be way more tempted because at the end of the day I am a man, with the stuff that makes you a man — go forth and multiply. And multiply with absolutely everyone.”

Thoughtful ... Robbie Williams clasps a coffee in a café in magazine pic
Thoughtful ... Robbie Williams clasps a coffee in a café in magazine pic
Benni Valsson courtesy of Esquire
 
Referring to previous conquests and clasping an apple, he added: “I feel more emotionally connected to this apple than I do to a person I’ve just slept with.

“Women reading that will think that’s awful. But that’s what men are made of.”

Interview ... Esquire
Interview ... Esquire
 
Robbie had a string of relationships earlier in his career with girls including GERI HALLIWELL, RACHEL HUNTER and NICOLE APPLETON.

But he has finally discovered domestic bliss with Ayda, 32, who sat beside him throughout the interview.

Talking about last year’s wedding in detail for the first time, Robbie said: “It was a very simple affair. Just about 40 people, a good group of friends. Just people that dig me and Ayda. No best man, no bridesmaids, no rehearsal, no going round to her dad to ask if it was OK. She got to dress up in a princess dress and look amazing. And I got to tell her I was going to look after her.

“She loves me because I’m me. I’m quite charming, easy going, good company, loveable. We’re a team. And you think differently as a team.”

It’s a commitment Robbie has struggled to find before.
 
He said of past lovers: “I was always looking for an excuse to leave. So many people have easily given me that excuse. Controlling? Bye bye. The minute you don’t want me to put that cigarette in my mouth, you’re gone. Any funny games? Bye bye.”

Triumphant return ... Take That on stage in Sunderland on the opening leg of the Progress tour
Triumphant return ... Take That on stage in Sunderland on the opening leg of the Progress tour
Getty
Robbie is still wary of the prospect of parenthood. He said it made him “petrified” even though Ayda chipped in: “I can’t wait to have our little monkeys.”

The singer explained he would have to prioritise kids over himself, which he would find difficult as he can often be selfish.

He said: “I get a lot of time off and I love fannying about.

“Play Football Manager, write songs, look on the internet for conspiracy theories, hang out, live in the sun. It’s a wonderful life of getting up when I want, going to sleep when I want. A kid will f*** that.”

Full interview and more pictures are in July issue of Esquire, on sale Monday.




comment

TESTOSTERONE jabs are great for treating very low libido — otherwise they just make you too aggressive.
And the injections can be pretty dangerous.

True, they boost muscles. But they can shrink the testicles so you end up with small balls and huge biceps.

They can also lead to prostate problems and have been linked with heart disease.

Males generally produce ten times more testosterone than females.

That’s why men have more heart attacks than women.

Robbie Williams Reveals He Uses a Sex Hormone by splashnews

HGH, Thyroid impact - What Is a Sex Hormone Binding Globulin?

HGH, Thyroid impact - What Is a Sex Hormone Binding Globulin?

 "Amounts of the binding proteins increase with high levels of growth hormone, estrogen, and thyroxine, which is one of the primary hormones produced by the thyroid gland."
A sex hormone binding globulin (SHBG) is what is known as a glycoprotein, a group of carbohydrate chains attached to polypeptide chains, which binds to human sex hormones. These binding proteins are most often found bound to the primary male sex hormone, testosterone, and the primary female sex hormone, estradiol, which is a type of estrogen. Major production of sex hormone binding globulin occurs in the liver, but it may also be produced in the brain, uterus, testes, and in the placenta during pregnancy. The function of this protein is to limit the levels of active unbound sex hormones in the body. Very high or very low levels of the protein in the body can indicate a variety of health conditions in both women and men.

Most sex hormones within the bloodstream are biochemically bound to sex hormone binding globulins. Only a tiny portion of sex hormones are "free" and able to enter cells where they bind to hormone receptors. Therefore, the availability of sex hormones in the human body is directly linked to the amount of SHBG the body produces.

When produced by the testes, SHBG is instead known as an androgen-binding protein, a protein that specifically binds to androgens, or male sex hormones. This protein is produced in the Sertoli cells, which are cells found in the seminiferous tubules that are responsible for nurturing developing sperm. High levels of androgen-binding protein in the testes allow sperm cells to mature in a process called spermatogenesis.

Sex hormone binding globulin levels in the body are influenced by a number of different factors, with the protein decreasing or increasing in the presence of a variety of hormones. Insulin is a hormone that controls the body's metabolism and also decreases the amount of sex hormone binding globulins in the body. High levels of androgenic hormones also decrease sex hormone binding globulin levels. Amounts of the binding proteins increase with high levels of growth hormone, estrogen, and thyroxine, which is one of the primary hormones produced by the thyroid gland.

Many health conditions are indicated by increased or decreased levels of sex hormone binding globulin. For instance, since pregnancy usually leads to the production of more female sex hormones, such as estrogen, it also leads to higher SHBG levels. Low levels of this binding protein are linked to diabetes, hypothyroidism, or a decreased production of thyroid hormones, and polycystic ovary syndrome, a condition in which women produce too many male sex hormones, which is one of the leading causes of female infertility.

Levels of sex hormone binding globulin may be tested to assess levels of male sex hormones in the body. The test is usually performed on men who have a male sex hormone deficiency and on women who have an overabundance of male sex hormones. Testing for levels of SHBG is not a common test; usually, medical professionals will test for testosterone levels first. However, in cases where these tests are inconclusive, such as instances where testosterone levels appear normal in a woman who presents with a number of secondary male sex characteristics, SHBG levels will be tested as well. Higher levels of the binding protein mean that the body has less "free" testosterone available, while lower levels indicate elevated "free" testosterone.

Related wiseGEEK Articles

SHBG - Clinical: Sex Hormone-Binding Globulin (SHBG), Serum

SHBG - Clinical: Sex Hormone-Binding Globulin (SHBG), Serum

Useful For

Diagnosis and follow-up of women with symptoms or signs of androgen excess (eg, polycystic ovarian syndrome and idiopathic hirsutism)

An adjunct in monitoring sex-steroid and anti-androgen therapy

An adjunct in the diagnosis of disorders of puberty

An adjunct in the diagnosis and follow-up of anorexia nervosa

An adjunct in the diagnosis of thyrotoxicosis (tissue marker of thyroid hormone excess)

A possible adjunct in diagnosis and follow-up of insulin resistance and cardiovascular and type 2 diabetes risk assessment, particularly in women

In laboratories without access to bioavailable testosterone or equilibrium dialysis-based "true" free testosterone assays, sex hormone-binding globulin measurement is crucial in cases when assessment of the free testosterone fraction (aka free androgen index or calculated free testosterone) is required. At Mayo Medical Laboratories, both bioavailable testosterone (TTBS/80065 Testosterone, Total and Bioavailable, Serum) and free testosterone (TGRP/8508 Testosterone, Total and Free, Serum) measurements are available. Free testosterone (TGRP/8508) is measured by equilibrium dialysis, obviating the need for sex hormone-binding globulin measurements to calculate free androgen fractions.

Clinical Information

Sex hormone-binding globulin (SHBG), a homodimeric 90,000 to 100,000 molecular weight glycoprotein, is synthesized in the liver. Metabolic clearance of SHBG is biphasic, with a fast initial distribution from vascular compartment into extracellular space (half-life of a few hours), followed by a slower degradation phase (half-life of several days).

SHBG binds sex steroids with high affinity (KD approximately 10[-10]M), dihydrotestosterone (DHT) ->testosterone (T) ->estrone/estradiol (E). Although each monomeric subunit contains 1 steroid binding site, the dimer tends to bind only a single sex-steroid molecule. The main function of SHBG is sex-steroid transport within the blood stream and to extravascular target tissues. SHBG also plays a key role in regulating bioavailable sex-steroid concentrations through competition of sex steroids for available binding sites and fluctuations in SHBG concentrations. Because of the higher affinity of SHBG for DHT and T, compared to E, SHBG also has profound effects on the balance between bioavailable androgens and estrogens. Increased SHBG levels may be associated with symptoms and signs of hypogonadism in men, while decreased levels can result in androgenization in women.

SHBG levels in prepubertal children are higher than in adults. With the increase in fat mass during early puberty they begin to fall, a process that accelerates as androgen levels rise. Men have lower levels compared with women and nutritional status is inversely correlated with SHBG levels throughout life, possibly mediated by insulin resistance. Insulin resistance, even without obesity, results in lower SHBG levels. This is associated with increased intra-abdominal fat deposition and an unfavorable cardiovascular risk profile. In postmenopausal women, it may also predict the future development of type 2 diabetes mellitus. Androgens and norethisterone-related synthetic progesterones also decrease SHBG in women.

Endogenous or exogenous thyroid hormones or estrogens increase SHBG levels. In men, there is also an age-related gradual rise, possibly secondary to the mild age-related fall in testosterone production. This process can result in bioavailable testosterone levels that are much lower than would be expected based on total testosterone measurements alone.

Reference Values

CHILDREN
Males
Tanner Stages*
Mean Age
Reference Range (nmol/L)
Stage I
7.1
31-167
Stage II
11.5
49-179
Stage III
13.6
5.8-182
Stage IV
15.1
14-98
Stage V
18.0
10-57
*Puberty onset (transition from Tanner stage I to Tanner stage II) occurs for boys at a median age of 11.5 (+/-2) years. For boys, there is no definite proven relationship between puberty onset and body weight or ethnic origin. Progression through Tanner stages is variable. Tanner stage V (young adult) should be reached by age 18.

Females
Tanner Stages*
Mean Age
Reference Range (nmol/L)
Stage I
7.1
43-197
Stage II
10.5
7.7-119
Stage III
11.6
31-191
Stage IV
12.3
31-166
Stage V
14.5
18-144
*Puberty onset (transition from Tanner stage I to Tanner stage II) occurs for girls at a median age of 10.5 (+/-2) years. There is evidence that it may occur up to 1 year earlier in obese girls and in African American girls. Progression through Tanner stages is variable. Tanner stage V (young adult) should be reached by age 18.

ADULTS          
Males: 10-57 nmol/L
Females (non-pregnant): 18-144 nmol/L

Interpretation

Many conditions of mild-to-moderate androgen excess in women, particularly polycystic ovarian syndrome, are associated with low sex hormone-binding globulin (SHBG) levels. Most of these women are also insulin resistant and many are obese. A defect in SHBG production could lead to bioavailable androgen excess, in turn causing insulin resistance that depresses SHBG levels further. There are rare cases of SHBG mutations that clearly follow this pattern. SHBG levels are typically very low in these individuals. However, in most patients, SHBG levels are mildly depressed or even within the lower part of the normal range. In these patients, the primary problem may be androgen overproduction, insulin resistance, or both. A definitive cause cannot be usually established. Any therapy that either increases SHBG levels (eg, estrogens or weight loss), reduces bioactivity of androgens (eg, androgen receptor antagonists, alpha-reductase inhibitors), or reduces insulin resistance (eg, weight loss, metformin, peroxisome proliferator-activated receptor [PPAR] gamma agonists), can be effective. Improvement is usually associated with a rise in SHBG levels, but bioavailable or free testosterone levels should also be monitored.

The primary method of monitoring sex-steroid or antiandrogen therapy is direct measurement of the relevant sex-steroids and gonadotropins. However, for many synthetic androgens and estrogens (eg, ethinyl-estradiol) clinical assays are not available. In those instances, rises in SHBG levels indicate successful anti-androgen or estrogen therapy, while falls indicate successful androgen treatment.

Adult SHBG levels in boys with signs of precocious puberty support that the condition is testosterone driven, rather than representing premature adrenarche.

Patients with anorexia nervosa have high SHBG levels. With successful treatment, levels start to fall as nutritional status improves. Normalization of SHBG precedes, and may be predictive of, future normalization of reproductive function.

Thyrotoxicosis increases SHBG levels. In situations when assessment of true functional thyroid status may be difficult (eg, patients receiving amiodarone treatment, individuals with thyroid hormone transport-protein abnormalities, patients with suspected thyroid hormone resistance or suspected inappropriate thyroid-stimulating hormone (TSH) secretion such as a TSH-secreting pituitary adenoma), an elevated SHBG level suggests tissue thyrotoxicosis, while a normal level indicates euthyroidism or near-euthyroidism. In patients with gradual worsening of thyrotoxicosis (eg, toxic nodular goiter), serial SHBG measurement, in addition to clinical assessment, thyroid hormone, and TSH measurement, may assist in the timing of treatment decisions. Similarly, SHBG measurement may be of value in fine-tuning suppressive TSH therapy for patients with nodular thyroid disease or treated thyroid cancer. Results are not definitive in the short-term in patients receiving drugs that displace total thyroxine (T4) from albumin.

SHBG is also produced by placental tissue and therefore values will be elevated during pregnancy. Reference ranges for pregnant females have not been established in our institution.

In patients with known insulin resistance, "metabolic syndrome," or high risk of type 2 diabetes (eg, women with a history of gestational diabetes), low SHBG levels may predict progressive insulin resistance, cardiovascular complications, and progression to type 2 diabetes. An increase in SHBG levels may indicate successful therapeutic intervention.

A genetic variant of SHBG (Asp327->Asn) introduces an additional glycosylation site in 10% to 20% of the population, resulting in significantly slower degradation. These individuals tend to have higher SHBG levels for any given level of other factors influencing SHBG.

Cautions

Human antimouse antibodies may be present in specimens from patients who have received immunotherapy utilizing monoclonal antibodies. Other heterophile antibodies may also be present in patient specimens. This assay has been specifically formulated to minimize the effects of these antibodies on the assay. However, results from patients known to have such antibodies must be carefully evaluated.

Clinical Reference

1. Pugeat M, Crave JC, Tourniare J, Forest MG: Clinical utility of sex hormone-binding globulin measurement. Horm Res 1996;45:148-155
2. Tehernof A, Despres JP: Sex steroid hormone, sex hormone-binding globulin, and obesity in men and women. Horm Metab Res 2000;32:526-536
3. Kahn SM, Hryb DJ, Nakhle AM, Romas NA: Sex hormone-binding globulin is synthesized in target cells. J Endocrinol 2002;175:113-120
4. Hammond GL: Access of reproductive steroids to target issues. Obstet Gynecol Clin North Am 2002;29:411-423
5. Elmlinger MW, Kuhnel W, Ranke MB: Reference ranges for serum concentrations of lutropin (LH), follitropin (FSH), estradiol (E2), prolactin, progesterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S), cortisol and ferritin in neonates, children, and young adults. Clin Chem Lab Med 2002;40(11):1151-1160


sex hormone binding globulin and testosterone levels - General Practice Notebook

sex hormone binding globulin and testosterone levels - General Practice Notebook



  • approximately 60-70% of testosterone is bound to sex hormone binding globulin (SHBG)
  • SHBG levels are lowered via exogenous androgens, obesity and abnormally high growth hormone levels. This reduction in SHBG levels also leads to a reduction in total testosterone concentrations
  • SHBG may be increased via thyrotoxicosis, oestrogens and liver failure. This increase in SHBG levels leads to an increase in total testerone concentrations
Despite changes in the SHBG, free testosterone levels generally remain within the normal range because of feedback adjustment of gonadotrophin secretion. There is an increase in SHBG capacity with age.
  • concentrations of sex hormone-binding globulin (SHBG) increase with age
    • age-related decline in serum free or bioavailable (non-SHBG-bound) testosterone is greater than that of total testosterone
      • this change in SHBG concentration with age means that a larger proportion of older men have levels of free or bioavailable testosterone below the normal range for younger men (1)
Reference:
Links:

SEX HORMONE-BINDING GLOBULIN IN NON-CIRRHOTIC ALCOHOLIC PATIENTS DURING EARLY WITHDRAWAL AND AFTER LONGER ABSTINENCE

SEX HORMONE-BINDING GLOBULIN IN NON-CIRRHOTIC ALCOHOLIC PATIENTS DURING EARLY WITHDRAWAL AND AFTER LONGER ABSTINENCE
"We conclude that excessive alcohol ingestion is associated with marked increases of SHBG which slowly revert during abstinence. High SHBG does not fully explain the low Tf values or the presence of clinical hypo-androgenism in alcoholics. This SHBG response to ethanol makes it a potential marker of excessive alcohol intake.  "

Abstract

In recently intoxicated non-cirrhotic male alcohol-misusing and -dependent patients, we studied, during early withdrawal and more prolonged abstinence, the rate of changes of sex hormones and their binding globulin (SHBG), the prevalence of hypo-androgenism and possible determinant factors of SHBG increase. 

 Twenty-one alcoholics and 21 controls were studied. SHBG plasma levels, sex hormones (SH), cortisol, insulin and thyroid hormones were measured at admission and discharge. SHBG and SH were also determined on days 2, 4 and 7 after admission and on weeks 2, 6 and 12 after discharge. SHBG showed a 3-fold increase, decreasing slowly during the first 10 days, but remaining above control values. Luteinizing hormone was also increased. Free testosterone (Tf) was low at admission and correlated negatively with SHBG during the first 10 days. By day 10, Tf reached normal values, despite SHBG remaining elevated. 

The other sex hormones were normal. Neither insulin nor thyroid hormones correlated with SHBG. Cortisol was high at admission and then normalized. Clinical hypo-androgenism was found in 33–50% of patients, but did not correlate with SHBG or SH. During follow-up, nine patients relapsed. In those remaining abstinent, SHBG continued decreasing, reaching normal levels in the 12th week. In those who relapsed, SHBG remained high or even increased further. Gamma-glutamyltransferase showed similar but faster changes. 

We conclude that excessive alcohol ingestion is associated with marked increases of SHBG which slowly revert during abstinence. High SHBG does not fully explain the low Tf values or the presence of clinical hypo-androgenism in alcoholics. This SHBG response to ethanol makes it a potential marker of excessive alcohol intake.

  1. Luis Valladares3
+ Author Affiliations
  1. 1Department of Internal Medicine, Central Division, Faculty of Medicine, University of Chile,
  2. 2Chilean–Japanese Institute of Digestive Diseases, San Borja–Arriaran Clinical Hospital, Santiago, and
  3. 3Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile
  • Received May 26, 1998.
  • Revision received March 15, 1999.
  • Accepted May 20, 1999.

What Testosterone Decline in Aging Men Is Normal?

What Testosterone Decline in Aging Men Is Normal?

  • Written by 
  • Tuesday, 06 November 2012 
low-t











Today there is a lot of talk of Low T in middle age men. With aging babyboomers there is a huge finacial market to market testosterone replacement in middle age to aging men.

However, the clinical importance of declining testosterone levels in older men is unclear. So what testosterone decline in aging men should be considered normal?

Low T and Aging

Serum testosterone levels gradually decline as men age, but the degree to which serum testosterone levels decline, as well as the extent of associated clinical changes (reduced libido, low bone mineral density and height loss, and decreased energy), is variable.

This age-related decline in serum testosterone levels has been confirmed in several cross-sectional and longitudinal studies and results from dysfunction in the hypothalamic-pituitary-testicular axis.2-4 The clinical importance of this decline is controversial, however. Recognizing this variability and understanding what may be considered changes in body function due to "normal aging" versus potentially treatable age-related testosterone (or androgen) deficiency is crucial in the care of older men. The role of evaluating testosterone levels and their clinical significance is reviewed here.

Aging is associated with declines in total serum testosterone concentration, increases in sex hormone-binding globulin (SHBG) concentration, and decreases in free testosterone. In one large cross-sectional study of more than 3000 men ages 40 to 79, serum testosterone concentration fell 0.4% per year, free testosterone concentration 1.3%.3 In another study, of 890 men, total testosterone levels were <325 ng/dL (considered androgen deficient) in 20%, 30%, and 50% of men in their 60s, 70s, and 80s, respectively.4

Free testosterone is considered the biologically active form of the sex hormone-binding globulin (SHBG). As men age, SHBG level rises, binding more testosterone and leaving less free testosterone available to act on target tissues. There is no uniformity in how aging men respond to this changing hormonal milieu, however. As a result, a controversy exists about whether this is a disease state. When it comes to low testosterone, what is normal senescence? What is illness?

Symptoms and signs suggestive of androgen deficiency in older men include reduced libido, low bone mineral density and height loss, and, less specifically, decreased energy, anemia, depressed mood, reduced muscle strength and bulk, and increased body fat.5 When these signs and symptoms accompany significantly lower levels of both types of testosterone, the patient may be diagnosed with late-onset hypogonadism. Cutoffs for the definition of low testosterone vary, although generally accepted values are =200 or =300 ng/dL of total testosterone.6

Unlike younger men with hypogonadism who present prominently with specific gonadal dysfunction (for example, infertility, incomplete or delayed sexual development), older men have nonspecific symptoms that can frequently be caused by other common disorders. For example, in the largest longitudinal study of testosterone deficiency, researchers found that up to 25% of elderly men who complained of sexual dysfunction, including low libido and erectile dysfunction, had normal-range testosterone levels for their age.7 In light of these findings, what is the best approach to patients who may—or may not—need treatment?

The Endocrine Society updated its clinical guidelines on androgen deficiency evaluation and treatment in 2010.6 It proposed a practical approach to evaluating testosterone deficiency in older men who present with low libido, decreased energy, depressed mood, osteoporosis, or recent fracture. If a clinician suspects testosterone deficiency, the first step should include an early morning total testosterone measurement. If the level is <300 ng/dL, the test should be repeated twice to account for fluctuations. If free testosterone levels remain below this threshold, the patient should be evaluated for pituitary or testicular disease. If these are ruled out, primary late-onset hypogonadism may be diagnosed and androgen treatment (testosterone replacement) may be considered.

To date, there are relatively few well-designed, large studies on hypogonadism in aging men. To better understand if this is a distinct clinical syndrome, future trials should be powered to assess whether testosterone deficiency in older men independently predicts important outcomes such as osteoporosis, muscle strength, mood disorders, and sexual dysfunction. This will best inform us as we try to move forward with treatment.

References:
  • Medpage Today, Sanjai Sinha, MD. Testosterone Decline With Aging: What Is Normal? .
  • Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2002;87:589-598.
  • Wu FC, Tajar A, Pye SR, et al. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab. 2008;93:2737-2745.
  • Harman SM, Metter EJ, Tobin JD, et al; Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86:724-731.
  • Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010; 95:2536–2559
  • Araujo AB, Esche GR, Kupelian V, et al. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007;92:4241-4247
  • Wu FC, Tajar A, Beynon JM, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363:123-135

SHBG: The Test | Sex Hormone Binding Globulin

SHBG: The Test | Sex Hormone Binding Globulin

Also known as: Testosterone-estrogen Binding Globulin; TeBG
Formal name: Sex Hormone Binding Globulin
Related tests: Testosterone, Free Testosterone, Bioavailable Testosterone, LH, Albumin, Estradiol, Prolactin

The Test

This article was last reviewed on February 7, 2012.  |  This article was last modified on February 13, 2012

Concerns - Testosterone treatment in aging men | Endocrine Today

Testosterone treatment in aging men | Endocrine Today

Concerns arise
Concern about prostate cancer is the major reason why more older men are not treated with testosterone replacement therapy. We know that prostate growth occurs at puberty as testosterone levels increase, and that men with 5-alpha-reductase type 1 develop only rudimentary or no prostate. We also know that medical or surgical castration causes metastatic prostate cancer to regress until it becomes androgen-independent. Prostate cancer is a disease of older men. It is estimated that there will be 186,320 new cases of prostate cancer diagnosed in the United States this year, and that there will be 28,660 deaths caused by prostate cancer. Prostate cancer is the most common non-skin malignancy in men, accounting for 25% of malignancies. It is second only to lung and bronchial cancers as a cause of death, accounting for 10% of cancer deaths in men. Moreover, at least 50% of men aged 65 years and older will have occult prostate cancer at autopsy. Most of these cancers do not become clinical cancers. A recent meta-analysis of 18 prospective studies concluded that higher serum testosterone and free testosterone levels do not predict increased risk of prostate cancer. Most authorities do not think that testosterone causes prostate cancer, but it may facilitate its growth.

It is not known if raising the serum testosterone level into the eugonadal range will increase the risk for these small occult cancers to become clinical prostate cancers. We estimated that it will require a five-year study involving 6000 men to detect a 30% increase in clinical prostate cancers. A study of this magnitude would be very expensive. Marks randomly assigned 40 men with testosterone levels lower than 300 ng/dL to testosterone enanthate (150 mg by intramuscular injection every two weeks) or placebo injections for six months. He performed prostate biopsies at baseline and six months. Although serum levels of testosterone and dihydrotestosterone increased, prostatic levels of these hormones were not altered significantly. Furthermore, expression of multiple cancer-related genes in the prostate was not affected by testosterone treatment.

The study proposed by Snyder et al is not powered to provide a definitive answer regarding prostate cancer, but it would add greatly to our knowledge of potential side effects of testosterone replacement therapy in this age group. Rosen et al have proposed a registry of men with low testosterone levels who are being treated with testosterone therapy. A registry also could provide valuable information even though it would not be as definitive as a large clinical trial.

There are many older men with low serum testosterone levels and symptoms similar to those of younger hypogonadal men. Most of these men are not being treated for valid concerns. Although many clinical investigators are attempting to contribute to a better understanding of the benefit–risk ratio, realistically it will be at least six to eight years before definitive information is available.

In the interim, clinicians and patients will need to weigh the potential benefits and risks of treatment when serum levels of testosterone are low on multiple determinations. When a decision is made to treat with replacement doses of testosterone, the symptoms and signs associated with testosterone deficiency, the hematocrit, lower urinary tract symptoms, digital rectal examination of the prostate and the prostate specific antigen must be monitored periodically.
For more information:
  • Amory JK, Watts NB, Easley KA, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab. 2004;89:503-510.
  • Araujo AB, Esche GR, Kupelian V, et al. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007;92:4241-4247.
  • Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006;91:1995-2010.
  • Endogenous Hormones, Prostate Cancer Collaborative Group, Roddam AW, Allen NE, et al. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst. 2008;100:170-183.
  • Harman SM, Metter EJ, Tobin JD, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86:724-731.
  • Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71-96.
  • Kenny AM, Prestwood KM, Gruman CA, et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci. 2001;56:M266-M272.
  • Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93:68-75.
  • Marks LS, Mazer NA, Mostaghel E, et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA. 2006;296:2351-2361.
  • Snyder PJ, Peachey H, Hannoush P, et al. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab. 1999;84:2647-2653.
Glenn R. Cunningham, MD, is Professor of Medicine and Professor of Molecular and Cellular Biology at Baylor College of Medicine, Houston, Medical Director of St. Luke’s Episcopal Hospital Diabetes Program, and is a member of the Endocrine Today Editorial Board.

Sex hormone-binding globulin - Wikipedia

Sex hormone-binding globulin - Wikipedia

Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to sex hormones, to be specific, androgens and estrogens. Other steroid hormones such as progesterone, cortisol, and other corticosteroids are bound by transcortin.

Contents

Transport of sex hormones

Testosterone and estradiol circulate in the bloodstream, bound mostly to SHBG and to a lesser extent serum albumin and corticosteroid-binding globulin (CBG) (AKA transcortin). Only a very small fraction of about 1-2% is unbound, or "free," and thus biologically active and able to enter a cell and activate its receptor. SHBG inhibits the function of these hormones. Thus, bioavailability of sex hormones is influenced by the level of SHBG. The binding affinity of sex steroids for SHBG is dihydrotestosterone (DHT) > testosterone > androstenediol > estradiol > estrone.[1] DHEA is weakly bound to SHBG as well, but DHEA-S is not.[1] Androstenedione is not bound to SHBG either, and is instead bound solely to albumin.[2]

SHBG production

SHBG is produced mostly by the liver and is released into the bloodstream. Other sites that produce SHBG include the brain, uterus, testes, and placenta. Testes-produced SHBG is called androgen-binding protein. The gene for SHBG is located on chromosome 17.

Control

SHBG has both enhancing and inhibiting hormonal influences. It decreases with high levels of insulin, growth hormone, insulin-like growth factor 1 (IGF-1), androgens, prolactin and transcortin. High estrogen, and thyroxine cause it to increase.
Recent evidence suggests hepatic lipogenesis reduces SHBG, not insulin. Genetic corollaries to this mechanism have been identified.[3][4]

Blood values

Reference ranges for blood tests for SHBG have been estimated to be:[5]
Patient type Range
Adult female, premenopausal 40 - 120 nmol/L
Adult female, postmenopausal 28 - 112 nmol/L
Adult male 20 - 60 nmol/L
Age 1 - 23 months 60 - 252 nmol/L
Prepubertal (24m - 8y) 72 - 220 nmol/L
Pubertal female 36 - 125 nmol/L
Pubertal male 16 - 100 nmol/L

Conditions associated with high or low levels

SHBG levels are decreased by androgens, anabolic steroids,[6] polycystic ovary syndrome, hypothyroidism, diabetes, obesity, Cushing's syndrome, and acromegaly. SHBG levels increase with estrogenic states (oral contraceptives), pregnancy, hyperthyroidism, cirrhosis, anorexia nervosa, and certain drugs. Long-term calorie restriction of more than 50 percent increases SHBG, while lowering free and total testosterone and estradiol. DHEA-S, which lacks affinity for SHBG, is not affected by calorie restriction.[7]

Measurement of sex hormones

When checking serum estradiol or testosterone, a total level that includes free and bound fractions can be assayed, or the free portion may be measured alone. A free androgen index expresses the ratio of testosterone to SHBG and can be used to summarize the activity of free testosterone. The total testosterone is likely the most accurate measurement of testosterone levels.[citation needed] Sex hormone-binding globulin can be measured separate from the total fraction of testosterone.

See also

References

  1. ^ a b Somboonporn W, Davis SR (June 2004). "Testosterone effects on the breast: implications for testosterone therapy for women". Endocrine Reviews 25 (3): 374–88. doi:10.1210/er.2003-0016. PMID 15180949.
  2. ^ Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. 24 April 2001. ISBN 978-0-7817-1750-2. Retrieved 4 August 2012.
  3. ^ "Too much sugar turns off gene that controls the effects of sex steroids". PhysOrg.com. 2007-11-07. Retrieved 2008-02-10.
  4. ^ Selva DM, Hogeveen KN, Innis SM, Hammond GL (2007). "Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone–binding globulin gene". J. Clin. Invest. 117 (12): 3979–87. doi:10.1172/JCI32249. PMC 2066187. PMID 17992261.
  5. ^ Unit Code 91215 at Mayo Clinic Medical Laboratories. Retrieved April 2011
  6. ^ Ruokonen A, Alén M, Bolton N, Vihko R (July 1985). "Response of serum testosterone and its precursor steroids, SHBG and CBG to anabolic steroid and testosterone self-administration in man". Journal of Steroid Biochemistry 23 (1): 33–8. PMID 3160892.
  7. ^ Cangemi R, Friedmann AJ, Holloszy JO, Fontana L (April 2010). "Long-term effects of calorie restriction on serum sex-hormone concentrations in men". Aging Cell 9 (2): 236–42. doi:10.1111/j.1474-9726.2010.00553.x. PMID 20096034.

Further reading