High Sex Hormone Binding Globulin?

April 1, 2018

Many patients come to me after being turned down by their doctor for testosterone replacement. They feel the symptoms of low testosterone only to be told  their labs look great. How can this be? Sometimes it can be related to high sex hormone binding globulin (SHBG). Even in the presence of normal to optimal total testosterone this can play out as untreated low testosterone.

Did you Know...

Free testosterone, the fraction of total testosterone not locked onto SHBG, is the testosterone that has by far the most significant effect on your body. The following article highlights the importance of this topic.


SHBG – A Modulator to be Modulated

by Allison Smith, ND (Doctor of Naturopathy)

SHBG, or Sex Hormone Binding Globulin, controls testosterone effect in both men and women by modulating changes in sex steroid levels. When SHBG goes up, free testosterone goes down.

I like to think of SHBG as a sponge that soaks up androgens and to some degree estrogens as well.

Since it binds so specifically and tightly to testosterone, it makes up part of the equation that equals androgen excess or androgen deficiency. Knowing how to manipulate SHBG can be a useful tool in a number of scenarios.

Role: Bind to and carry testosterone (and less strongly E2 and DHT) through the blood stream to target tissues and to the liver for modification and removal from the body. This bond is very strong. The bound testosterone is not easily removed from the SHBG and is therefore considered inactive.

Production Sites: Liver mostly, testes, brain

Production Signals: Estradiol, triiodothyronine (T3)

Down-Regulated by: Insulin

Aliases: ABP (androgen binding protein), SSBG (sex steroid binding globulin), TEBG (testosterone binding beta globulin), GBG (gonadal steroid binding globulin)

Action: Controls clearance and bioavailability of testosterone



Prescription Drugs & SHBG Levels

Some drugs such as Spironolactone alter binding of androgens to the receptor sites on SHBG, therefore leading to increased clearance of testosterone and to the rise of estrogen and SHBG. Other medications can cause a sustained increase in prolactin levels that suppress testosterone and raise SHBG. Safe to say, most if not all oral drugs have some effect on the liver and SHBG levels. Listed are some of the ones that make the most impact.


Drugs that Raise SHBG via Increasing Prolactin:

  • Antipsychotics (both typical and atypical)

  • Antidepressants (SSRIs, Tricyclics, MAO-Is)

  • Xanax and Buspar

  • H2 Antagonists (Cimetidine, Ranitidine)

  • Morphine

  • Some Antihypertensives

Drugs that Raise SHBG:

  • Raloxifene (Evista)

  • Tamoxifen

  • Spironolactone

  • Anticonvulsants (Phenytoin)

  • Oral (but not transdermal) estradiol

  • Ethinyl estradiol (oral contraceptives)

  • Metformin

  • Exogenous insulin in Type 2 DM

  • Coffee!

Drugs that Suppress SHBG:

  • Progestins

  • Glucocorticoids

  • Exogenous insulin in Type I DM


  • Some people have a genetic variation in their SHBG structure that slows or speeds its degradation leading to high or low levels. Current research projects are studying specific SHBG SNPs with regard to risk of Type 2 diabetes

Areas of Application:

How to Influence SHBG:
Pinpoint the cause of the imbalance whenever possible and instead of trying to lower a high SHBG and raise a low SHBG, zoom out to support balance in the system. If SHBG is high or low, look deeper. Always consider the main endocrine inputs: INSULIN, ESTRADIOL, THYROID.


Accompanying Tests:

  • Fasting Insulin

  • HgbA1c

  • Sex Steroids (E2, T, DHEA-S)

  • Thyroid Panel (TSH, fT3, fT4)

  • LH and FSH

  • IGF-1

  • Prolactin

  • Liver function tests

Some Treatment Examples:


*this article may be found at: http://blog.zrtlab.com/shbg-modulator-01

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