Sex Hormone Binding Globulin and Estradiol Management - by Dr K. Kullis

Buy Lab Tests Online

Nelson Vergel

Founder, ExcelMale.com
It has been traditionally thought and believed that sex hormone binding globulin (SHBG) is more or less correlated to estradiol (E) levels and the amount of free testosterone (FT). Free - testosterone is the portion of testosterone (T) that is available to enter a cell and bind to the androgen receptor to turn on a variety of anabolic genes to synthesize a variety of T dependent proteins. These tissues include muscle, brain, penis, bone, heart and other tissues.



IMPORTANCE OF BALANCED E LEVELS



It is of great importance to have normally balanced E levels and normal FT levels for male health and wellness.



It is only recently that some doctors are starting to measure estrogen (estradiol) levels when T levels are measured. Balanced E levels are critical to male health and wellness. It is not just a female hormone. Just like women need some T for optimal function, wellness and disease prevention, E is needed for normal male physiology and function. Too low or too high E levels can have major negative effects on male health and fitness.



Over the last 15 years it has been shown that excess E levels in men can contribute and are associated with development of atherosclerosis (heart disease), diabetes, obesity, strokes, enlarged prostate glands, breast tissue growth, breast cancer and other problems. Men with low FT and high E levels have a greater incidence of prostate enlargement and prostate cancer and other problems. Very low or insufficient E levels in men can be associated with weak bones, osteoporosis and bone fractures and may produce lower sex drive etc. That is why non-E converting aromatizing androgens - anabolic hormones are not healthy. Such as the nandrolone family of anabolic meds like stanazolol, oxandrolone, andriol, etc



Most men do not know what their E levels and their sex hormone binding globulin (SHBG) levels are. Also they may not know their FT values. They may only know their total T levels and that is all. Yet E and SHBG levels have profound physiologic effects in men.



A recent article published in the Journal of the American Medical Association (Jakowska, et al “Circulating estradiol and mortality in men with chronic heart failure”, JAMA 2009 May, B, 30; 20 (18): 1892-901).

Those men with lowest or highest quintile (lowest 20 % or highest 20 %) had the highest death rates from congestive heart failure. The ones in the balanced E2 range at about 20-30 pg/mL had the least number of deaths over a 3 year period of time. The lowest quintile of E had 3 times more deaths. The highest quintile had 37 pg/mL of E2 and lowest 20 % had 12 to 13 pg/mL.



Balanced E2 level or desirable E 2 levels are about 20 to 30 pg/mL.

Optimal or balanced E2 are those levels that are not too low or too high also in relation to Total T and Free T levels.



MORTALITY AND E2 LEVELS



A recent paper that followed over 3,000 aging men ages 69—80 for 4.5 years (Tiversen A. et al “Circulating estradiol predicts mortality in elderly men” J Clin Endocrinology Metab 2009 July; 94(7): 2482-8.) Those men with low T had 65 % greater all cause mortality and those men withlow E2 had 55 % more deaths from all causes. Those men who were low both in E2 and T had almost twice the risk to die compared to men in optimal E2 and T ranges.



HOW IS ESTROGEN PRODUCED IN MEN?



Males need to be able to convert (aromatize) T to E to produce E2. Some men have high-aromatase enzyme levels or increased aromatase activity and can spike E2 and the other estrogens also (mainly estrone E1, which is derived from E2). It can lead to low FT and TT also. That is why treatment in some cases with aromatase inhibitor medicines like Anastrazole or Letrazole can lead to higher total T and free T levels.



Those men without aromatase enzyme grow to be very tall and have other problems and need E2 therapy to stop growth to have normal height. More often some men produce too little T so there can be both T and E2 insufficiency. Often you can see E2 levels greater than T and the E2 levels can be higher than those in postmenopausal women. Overall the goal is to have both optimal E2 (free E) and free T (FT) levels.





FREE T MEASURES



Free T is the active form of T that can enter the cell. The main binding of T is to SHBG and albumin. There are different ways to determine FT. Some use free androgen index method, which is done by a calculation formula. Recently the LC/MS-MS (liquid chromatography / mass spectroscopy) has become the most widely and easy to use method.



There is an epidemic around the world of men with insufficient FT levels of less than 15-20 pg/mL and excess E2 levels greater than 35 to 40 pg/ml. When there is excess E2 it may indicate excess aromataze enzyme activity.



The cause of excess aromatase activity can be related to obesity, type 2 diabetes, certain disease states, genetics etc. The ideal FT should be about 20-35 pg/mL. The aromatase enzyme, SHBG and E2 are big determinants how much FT a male will have and should be measured in all men.



WHAT IS SEX HORMONE BINDING GLOBULIN (SHBG) AND WHY IT IS CRITICAL?



SHBG is a plasma protein synthesized and secreted by the liver. It was believed to serve to act as both a transporter and reservoir for the sex steroids. It binds estrogens and androgens. The binding of the sex steroids to SHBG determines the amount of free or bio-available sex hormones for cell use. It regulates the access of androgens and estrogens to their target tissues.



Recently it has been established that there is a cell membrane receptor for SHBG called SHBG –R , receptor. SHBG has various genetic variants, which can influence their levels, which contribute to expression of various disease states.



Androgen and estrogen levels and other factors influence SHBG synthesis by the liver.

SHBG binds up to 98 % of the steroid hormones in the blood including: dihydrotestosterone (DHT), T and androstenediol with high affinity. SHBG binds estradiol (E2) and estrone (E1) with slightly lower affinity than the androgens.



There are number of disease states that can increase blood levels of SHBG and therefore lower free T levels.



Increased SHBG conditions include:



1.Testicular cancer,

2.Breast cancer, fibrocystic breast disease,

3.Elevated estradiol levels,

4.Elevated thyroid levels,

5.Aging,

6.Extreme weight loss as in anorexia nervosa.

7.Pregnancy,

8.Estrogen containing birth control pills,

9.Diets low in protein. In elderly men ages 40 to 70 years. Increased SHBG leads to lower FT and increased risk for fragility, low bone density, fractures, anemia, decreased sexual function etc. [J Clin Endocrinol Metab. 2000 Jan; 85 (1) 293-6]

10.Certain meds such as the Dilantin (a phentyoin) drug class, which can produce increased activity of the enzyme for SHBG synthesis.

11.Liver chirrosis (fibrosis) occurs from scar tissue in the liver , usually formed from excess alcohol abuse or maybe other drugs or chemicals over time. Liver chirrosis is associated with increased SHBG,

12.Cigarettes smoking leads to increased SHBG,

13.Any compromise of liver detoxification such as alcohol abuse, certain meds, heavy metals etc can decrease liver capacity to excrete excess estrogens from the body,

14.Any estrogen use, maybe even the plant estrogens (phytoetrogens) can increase SHBG,

15.Increased conversion T to E (aromatization).





Even the selective estrogen receptor modulating (SERM’S) meds like Clomophine (Clomid), Tamoxifen (Nolvadex), Raloxifene (Evista) may increase SHBG.



These SERM’S have estrogen receptor blocking actions and also have some intrinsic estrogenic effects also. That is why you can see decreased FT levels with their usage. Clomid has the greatest estrogenic effects biochemically and can have negative mood effects. Raloxifen likely has the lowest adverse mood effects (depression, low mood, emotionality, “funk” etc).





Women normally have higher levels of SHBG than men if men are producing adequate androgens and women produce adequate estrogens.



HOW TO TREAT ELEVATED SHBG


1.Remove any of the agents or treat the condition, which lead to elevated SHBG. In some cases it may be difficult to identify the cause of elevated SHBG.

2.Use anti-aromatase meds such as Anastrazole, Letrazol, if E2 is elevated,

3.Stop smoking and/or abusing alcohol,

4.Increase protein intake, if low. Avoid soy, which is an incomplete protein,

5.Avoid plant estrogenic herbs and foods,

6.Use androgens like natural T if medically indicated,

7.Increase intake of Omega-3 fish oils (EPA/DHA) consumption to about EPA=1.2 to 1.4 gram and DHA= 1.0 to 2 gram

8.Nettle root (Ulrica urens) in highly concentrated extracts can be effective in binding to SHBG and thereby displacing T and DHT from SHBG and into the free form for cell use. Potent Nettle root concentrates also can act as a 5-alpha reluctance inhibitor, which can partially inhibit the conversion of T to DHT and overall decrease SHBG levels.

9.Artificial progesterones like Norgestrol, Noresthisterone can reduce SHBG. That is bad idea since these androgenic like progestin’s can lower the good HDL cholesterol and produce negative mood effects in men.





PART II


Some of the conditions that can lead to increased SHBG, include:



1.Testicular cancer is the most common cancer of young men. This is the cancer cyclist Lance Armstrong had.



2.Breast cancer. Even men can get it, if they have gynecomastia (gyno) – male breast growth. It is estimated that maybe 3 % of men with gyno develop breast cancer. A male with gyno and elevated SHBG should have mammographic and other evaluation for possible breast cancer. Mild gyno can often be treated with meds such as Tamoxifen and Aromatase Inhibitors. If gyno persists and gets larger then surgical removal is my suggestion. I have seen too many men suffer mentally and physically for too long from gyno.



3.Elevated Estradiol levels from various causes such as increased body fat, excess alcohol usage, liver damage, exposure to Estrogen, medications and other agents.



4.Extremely elevated thyroid levels such as in Grave’s disease. This can be treated medically usually and occasionally surgically.



5.Aging. It is not clear why aging causes elevation of SHBG and lower free Testosterone, but likely causes can be inflammatory signals along with age associated disregulated physiological events. Aging is associated with lower androgens (Testosterone) in men even with normal physiologic aging, which can lead to increased SHBG. Administration of Testosterone decreases SHBG levels.



6.Extreme weight loss such as seen in anorexia nervosa.



7.Low protein diets. SHBG is increased in vegans usually from a plant based low whole protein diets. Not many pure vegans are very muscular.



CAUSES AND FACTORS FOR LOW SHBG



SHBG binds up to 98 % of the sex steroid hormones in the blood including Dihydrotestosterone (DHT), Testosterone, Androstenediol, and Estrogen and Estrone (but with lower affinity) than the Androgens.



Conditions with low SHBG:


1.High Testosterone (Androgen) levels. Women who are “hirsuite” (exhibit male characteristics) often have excessive body hair, balding, facial hair, acne, and obesity. This is commonly seen in a metabolic disorder of women called the polycystic ovarian syndrome (PCOS). These women have high risk for many diseases such as diabetes, cardio-vascular disease and other conditions. Men on Testosterone therapy have low SHBG.



2.Low Estrogen levels can lead to low SHBG. Estrogens have the effect to stimulate liver synthesis of SHBG and raise SHBG. Women in menopause with low Estrogen will have low SHBG.



3.Hypothyroidism can lower SHBG. Having low thyroid is not a good idea since it leads to low metabolism and fat gain can be a consequence. Classic Hypothyroidism is easily diagnosed and treated. However there are many who have subclinical hypothyroidism. They may have low morning body temperatures, lethargy and sometimes a fat gain despite normal thyroid lab numbers. A number of thyroid studies have shown that if the TSH value climbs to above 2 to 2.5 it may be an indication of the early start of onset hypothyroidism. Some endocrinologist feel the TSH should be kept around 2.0 for best health. TSH is the brain’s (pituitary) output of this hormone in greater amounts than usual when the hypothalamus – the brain sensor-reads low thyroid levels in the circulation. TSH is often the first clue of a thyroid and/or sometimes a pituitary disorder.



Some suffer from the controversial Wilson’s Syndrome when hypothyroidism may occur because T4 is not converted properly to T3. Since T3 is “engine for cell metabolism” in the same way that Free Testosterone is the “engine portion” for the effects of Total Testosterone. Occasionally some have a syndrome called “Reverse T3 dominance”. An inert form of T3 called Reverse T3 is made from T4 in greater amounts than usually made for a variety reasons. In this scenario the Reverse T3 ties up the T3 receptors in cells and normal T3 can’t activate cell metabolism and the person may suffers from a number of low thyroid symptoms. One treatment is to use slow release T3 (a sustained release of the medicine called Cytomel) to displace the bad Reverse T3 molecule. There is a whole treatment protocol for this process, which is to long to discuss.



4.Hyperprolactinemia: Prolactin is produced in the pituitary gland. Elevated blood levels of prolactin can decrease SHBG. However increased blood levels of prolactin also usually produces low Testosterone levels and you would expect elevated SHBG. In all men prolactin elevations need to be investigated since pituitary gland tumors can produce elevated prolactin leading to low Testosterone. Pituitary gland tumors need to be treated medically and sometimes surgically.



5.Elevated cortisol levels. Sometimes persistent elevations of cortisol levels as seen with Cushing’s syndrome and other disorders, can keep SHBG low. Cushing’s often is a result of pituitary gland tumors causing adrenal gland cortisol overproduction. Sometimes the adrenal becomes overactive resulting in chronically elevated cortisol (a secondary form of Cushing’s).



6.Obesity and elevated insulin levels. Extremely obese people often can have low SHBG. There is an inverse relation of SHBG to abdominal fat and subcutaneous fat. The causation mechanisms are multifactorial such as high insulin levels, insulin resistance, Type 2 diabetes, and others. Low SHBG levels contribute or can be a result of low Testosterone levels.





7.Drug side effects such as a result of using cortisone preparations like Prednisone can lower SHBG.





TREATMENTS TO KEEP SHBG AT NORMAL PHYSIOLOGICAL LEVELS.


1.Treat the female PCOS with variety of agents. You should consult an endocrinologist for proper therapy.



2.Lower Estrogen levels. Treat by balancing E/T ratios. Add Estrogen if you are a female and have medical indications for it’s use.



3.Low thyroid. Treat with thyroid medications and the underlying causes of it.



4.Elevated prolactin. Treatment discussed already.



5.Elevated cortisol. Treat the medical causes and remove drugs like Prednisone, if indicated.



6.Obesity and high insulin levels. Treat by loosing weight. Gluten free and vegan diets can help with weight loss. I recommend “partial vegan diets” since for muscle mass you need whole animal proteins. Diets high in vegetables can decrease certain cancer risks.



7.Drug side effects. Consult your doctor.





SUMMARY


It has been traditionally thought by many those in the world of the muscle building and body building, that low SHBG is always good thing. It has also been believed that SHBG has only one role and function – to transport and regulate in the blood the amount of bound and free or cell-bio-available Testosterone and other Androgens that can be incorporated into the cell and turn the cells anabolic machinery to promote new muscle and other tissue growth (the anabolic effect).



The new science of Testosterone and SHBG reveals that the traditional thinking about SHBG is that SHBG is more than sex hormone transport. It has its own “independent actions” such as related to development of Type 2 diabetes mellitus, cardio-vascular disease and other conditions. There are sexual differences how SHBG affects men and women in its androgen / sex hormone: independent role.



It has been recently shown that low SHBG independently predicts the onset of and risk for Type 2 diabetes. Free Testosterone levels were not associated with Type 2 diabetes. Decreased total Testosterone was associated with increased risk for Type 2 diabetes [Araujo, A et al J Gerontol A Biol Med Sci 2010; 65A: 503-509]
 
Defy Medical TRT clinic doctor

JanSz

New Member
Excellent article.
It is missing one important variable, HGH or IGF-1.

Dr Hertoghe in his The Hormone Handbook, page 69 warns about excessive GH use because it reduces SHBG.

But it is very comon for men to suffer from high SHBG and low GH and IGF-1.

...
 
Buy Lab Tests Online
Defy Medical TRT clinic

Sponsors

enclomiphene
nelson vergel coaching for men
Discounted Labs
TRT in UK Balance my hormones
Testosterone books nelson vergel
Register on ExcelMale.com
Trimix HCG Offer Excelmale
Thumos USA men's mentoring and coaching
Testosterone TRT HRT Doctor Near Me

Online statistics

Members online
5
Guests online
6
Total visitors
11

Latest posts

bodybuilder test discounted labs
Top