Nelson Vergel
Founder, ExcelMale.com
Published in Olympian News Magazine - 2010
PART I
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.
Go to part II:
How to lower your sex hormone binding globulin
