Sex Hormone Balance & Your Thyroid

The thyroid gland is, without a doubt, one of the most highly influential glands in the human body. As our Chief Medical Officer, Dr. R.W. “Chip” Watkins, MD, MPH, FAAFP, likes to say: nothing moves in the body without the thyroid.

Table of Contents

Thyroid Hormones and SHBG

Thyroid hormones are important for the catabolism and anabolism of many molecules. Thyroid hormones seem to dictate the production of an important glycoprotein called Sex Hormone Binding Globulin, or SHBG. There is positive correlation between thyroid hormone levels and SHBG levels.

SHBG and Hypothyroidism

One study found that those with hypothyroidism had lower levels of SHBG than subjects with healthy thyroid glands. After the researchers of this study administered thyroid medication to the hypothyroid subjects, they found that their SHBG levels increased in a dose-dependent manner (1).

SHBG and Hyperthyroidism

Another study found high SHBG levels to be associated with hyperthyroidism. This study saw a decrease in SHBG levels after normalizing thyroid hormone levels in hyperthyroid subjects (2).

SHBG’s production occurs in the liver and is regulated by hepatocyte nuclear factor-4-alpha or HNF4A. Thyroid hormones’ ability to raise SHBG levels is proposed to be through increasing HNF4A gene expression, thus indirectly upregulating SHBG levels (3).

High SHBG levels can have some negative implications.

One major negative implication of high SHBG could be a decrease in the level of free, unbound sex hormones circulating in the bloodstream. One study found that male subjects with normal total testosterone levels and low calculated free testosterone had high levels of SHBG (4). Thus, one could possibly draw the connection between high SHBG levels and symptoms of hypogonadism in males, such as low libido and fatigue.

Hypogonadism symptoms and low free estradiol may be present in females with high SHBG, as estradiol also binds to SHBG.

Testing Thyroid Function and SHBG Levels

It is important to assess thyroid hormone and SHBG levels to determine if there is an imbalance. If your SHBG level is elevated, boron supplementation may be helpful in reducing it (5).

In addition to assessing thyroid and sex hormone status, your neurotransmitter and adrenal hormone levels may need to be measured. Thyroid hormones, sex hormones, neurotransmitters, and adrenal hormones all function together to create optimal health and balance throughout the body.

Talk to your health care practitioner today about Sanesco’s testing to gain further insight into your specific biochemistry and hormonal balance.

References

  1. Cavaliere, H., Abelin, N., & Medeiros-Neto, G. (1988). Serum Levels of Total Testosterone and Sex Hormone Binding Globulin in Hypothyroid Patients and Normal Subjects Treated with Incremental Doses of L-T 4 or L-T 3. Journal of Andrology, 9(3), 215-219. doi:10.1002/j.1939-4640.1988.tb01038.x
  2. Ford, H. C., Cooke, R. R., Kelghtley, E. A., & Feek, C. M. (1992). Serum levels of free and bound testosterone in hyperthyroidism. Clin Endocrinol Clinical Endocrinology, 36(2), 187-192. doi:10.1111/j.1365-2265.1992.tb00956.xsex ho
  3. Selva, D. M., & Hammond, G. L. (2009). Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4-alpha. Journal of Molecular Endocrinology, 43(1), 19-27. doi:10.1677/jme-09-0025
  4. Antonio, L., Wu, F. C., O’neill, T. W., Pye, S. R., Ahern, T. B., Laurent, M. R., . . . Vanderschueren, D. (2016). Low Free Testosterone Is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone. The Journal of Clinical Endocrinology & Metabolism, 101(7), 2647-2657. doi:10.1210/jc.2015-4106
  5. Naghii, M. R., Mofid, M., Asgari, A. R., Hedayati, M., & Daneshpour, M. (2011). Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. Journal of Trace Elements in Medicine and Biology, 25(1), 54-58. doi:10.1016/j.jtemb.2010.10.001

Clinical Contributor

Nathan Bridges

Clinical Support Manager at Sanesco International, Inc.

Nathan Bridges is the Clinical Support Manager at Sanesco. He holds a Bachelors of Science in Health and Wellness Promotion with a minor in Psychology. He keeps a healthy mind and body by trail running, playing chess, and regularly reviewing recent research.


— Update: 05-01-2023 — cohaitungchi.com found an additional article SHBG Lab Test Guide – What to do About High Levels, Low levels & More from the website www.restartmed.com for the keyword low shbg hypothyroidism.

SHBG is short for sex hormone binding globulin and it is a serum blood test that can give you valuable insight into your hormones! 

Low levels of SHBG may be associated with low thyroid function and low estrogen status while high levels may bind up testosterone leading to weight gain, depression, and other symptoms. 

Most physicians don’t put a lot of emphasis on this lab test but it is critical to understanding what is happening with the hormones in your body. 

Learn how to understand your lab results, but more importantly what to do about changes to your SHBG. 

We will discuss high levels, and low levels, and what to do about both: 

Sex Hormone Binding Globulin – Why it is important

So what is SHBG?

SHBG stands for Sex Hormone Binding Globulin. 

And it does exactly what it sounds like it does – binds up sex hormones. 

But why is this important? 

In order to understand we need to talk about some basic physiology. 

First, you need to know that hormones float around in your serum in 2 major forms:

If a hormone is bound to a protein it is NOT available for use. 

Consider this like hormones that your body “stores” for later use, similar to you putting food in a deep freezer. 

Free hormones (such as “free t4” or “free testosterone”) can turn on cellular function and promote genetic changes. 

*Side note: this reasoning is why it’s so important to check your free thyroid hormones if you have hypothyroidism. Checking “total t3” or “total t4” has less clinical utility than the free hormones!

Low shbg hypothyroidism

You can consider the free hormones as the ACTIVE hormones and the more clinically useful measurement of almost all hormones. 

The amount of “free” hormone is usually a VERY small percentage when compared to the “bound” hormone in your blood. 

Your body uses this binding system as a way to regulate certain hormones and keep everything in balance or in check. 

So where does SHBG fit in?

Sex hormone-binding globulin acts as a binding hormone which means that it may be helpful to think of SHBG as a way to inactive hormones floating around in your serum. 

For this reason, you can consider SHBG to be a “Goldilocks” type of protein, meaning you don’t want too much but you also don’t want too little – you need just enough. 

Small changes to SHBG levels can bind up free hormones and result in serious symptoms. 

It also has a strong affinity (meaning it likes to bind) to certain sex hormones. 

It will preferentially bind to hormones in this way:

Preference on dihydrotestosterone or DHT (2) (this is the most potent androgen), then testosterone, then androstenediol, then estradiol, then estrone. 

You will notice that SHBG prefers to bind to and inactivate the various androgens in the body. 

This is very important because of how this impacts androgens and therefore symptoms in both women and men. 

High SHBG will bind up and INACTIVATE both testosterone and DHT meaning that both men and women may start to experience the symptoms of low testosterone (weight gain, depression, loss of muscle mass, irritability, etc.). 

While low levels will leave more testosterone ACTIVE meaning that women may start to experience the symptoms of high testosterone (facial hair growth, weight gain, PCOS, irritability, acne, etc.). 

Read more  10 Essential Oils for Thyroid Support & Roll-On Recipes

What’s worse is that most physicians don’t even test for SHBG even though they understand the difference between “free” and “total” hormone concentration in the blood. 

This makes SHBG a VERY important test to ask for if you are experiencing hormone any hormone imbalance as it may shed light on your current problem. 

What Causes Increased SHBG?

SHBG is influenced by 2 major hormone systems in the body:

#1. Thyroid hormone (3) and…

#2. Estrogen levels (4)

Both of these hormones may stimulate or INCREASE the circulating amount of sex hormone-binding globulin in the serum. 

So what does that mean for you if you have high SHBG?

If you are a woman and you have high SHBG the most likely cause is excessive estrogen use. 

This can be either from a condition known as estrogen dominance – meaning you have too much estrogen in your serum. 

Or because you are taking birth control (5) or some other form of exogenous hormones. 

If you are taking OCP or other hormones and it is causing excessively high levels of SHBG you should take caution! 

Increasing your SHBG will influence the amount of free testosterone in your serum and may be one of the reasons that women on OCP tend to gain weight and experience mood changes (6).

Another cause of high SHBG is excessive thyroid hormone replacement therapy. 

This is most often seen in those who are taking T3-containing medications (T3 has a direct influence on hepatic SHBG production) like natural desiccated thyroid hormone or liothyronine/cytomel. 

It can also occur in those taking T4 medication such as Levothyroxine, but this is less common. 

Assessing SHBG accurately in menstruating women can be difficult, though, as women may commonly present with both excess estrogen and hypothyroidism. 

If you are taking thyroid hormone replacement and your SHBG is high you should look at both estrogen levels and your current thyroid dose. 

But how do we “define” a high SHBG?

Like other hormones, we need to look at “optimal ranges” and not just the reference range. 

If you are a woman you want your SHBG to be in the 60-80 nmol/L range. 

Anything higher is considered “too much” and anything lower is considered “insufficient”. 

You can see an example of high SHBG below with relevant laboratory reference ranges: 

Low shbg hypothyroidism

Symptoms of High SHBG

It’s important to realize that high SHBG doesn’t necessarily cause negative symptoms by itself. Instead, symptoms related to your SHBG may be due to an indirect effect that SHBG has on other hormones in your body. 

If you have high SHBG you are more likely to experience negative symptoms related to excess estrogen and/or low testosterone: 

  • Menstrual irregularities
  • Weight gain (pear shape weight gain)
  • Mood changes (depression or anxiety)
  • Breast tenderness, breast fullness
  • Fatigue
  • Bloating and/or water retention
  • Decreased muscle mass (inability to gain muscle mass even while lifting weights)

Rarely, high SHBG may also be caused by excessive thyroid dosing which may lead to the symptoms of hyperthyroidism as well. 

What Causes Low SHBG?

In my experience low SHBG is often ignored (more so than high levels) because it’s more sinister and difficult to spot. 

Low SHBG is most often seen in women who are hypothyroid (meaning they have low thyroid function) and women who are menopausal. 

We know that both thyroid hormone and estrogen stimulate SHBG (7) release, so low levels are often associated with low hormone levels. 

This in turn causes an effect where free testosterone levels rise giving way to the symptoms of PCOS. 

If you are experiencing the symptoms of hypothyroidism then it’s VERY important to evaluate your SHBG. 

This is also true if you are taking thyroid hormone replacement medication. 

SHBG is considered “suboptimal” if it is lower than 60 nmol/L: 

Low shbg hypothyroidism

If you are a menstruating woman (and have a normal cycle) then the most common cause of suboptimal SHBG is low thyroid function. 

It’s also worth pointing out that low SHBG is associated with an increased risk of developing type II diabetes (8) – another important reason why you want to normalize your level if it is low. 

Symptoms of Low SHBG

The symptoms of low SHBG tend to be tied to thyroid function and low estrogen. 

In addition, women with low SHBG may also experience the side effects of excess free testosterone: 

  • Weight gain
  • Fatigue or low energy
  • Menstrual irregularities
  • Facial hair growth
  • Hair loss
  • Acne
  • Depression/anxiety

Please note that the symptoms associated with low SHBG can vary widely from individual to individual. 

For this reason, it’s always best to assess SHBG in the context of other circulating hormones (testosterone, estrogen/progesterone, and thyroid hormone). 

Using SHBG for Assessing Thyroid Function During Thyroid Hormone Replacement Therapy

Another very important clinical utility of SHBG is its ability to assess thyroid function. 

With up to 20% of the population suffering from subclinical hypothyroidism or overt hypothyroidism, this hormone imbalance is incredibly common. 

Furthermore, SHBG is a tool that can help evaluate thyroid function at the cellular level. 

In states of low thyroid function, the SHBG tends to drop. 

When thyroid hormone is replaced, SHBG tends to rise. 

This allows for the SHBG to be used as a marker to assess thyroid hormone absorption and thyroid hormone cellular action. 

If you have low SHBG AND hypothyroidism then testing your SHBG at baseline is very important for assessing if you are taking the right type and dose of thyroid hormone. 

In some cases, taking T4-only thyroid medication such as Levothyroxine or Synthroid may not actually increase the SHBG (9).

This may be a sign that the body is having difficulty with the conversion of T4 to T3 in peripheral tissues. 

Remember:

T3 tends to increase SHBG more so than T4 levels. 

SHBG can also be used to assess if your thyroid dosing is too high. 

If your SHBG is elevated AFTER you take thyroid hormone then this may indicate that your thyroid dosing is excessive and should be reduced. 

It’s very important to keep SHBG in the “Goldilocks” range of 60-80 nmol/L. 

How to Treat High SHBG (how to lower it when it’s high)

Treating high SHBG has more to do with finding out the CAUSE of high SHBG in your body, rather than treating the SHBG level itself. 

With that in mind if you have high SHBG you will want to take the following steps to find the root cause:

#1. Check serum estrogen levels

The first step is to assess both estrogen and progesterone levels. 

This means assessing estradiol (the most potent estrogen in your serum) as well as progesterone. 

Estradiol levels vary from woman to woman so the absolute value is not as important as the difference in the ratio between progesterone and estradiol. 

It’s best to assess the estradiol/progesterone ratio mid-luteal phase of the menstrual cycle (if menstruating). 

Look for a ratio that is 10:1 (estrogen:progesterone). 

Low shbg hypothyroidism

If you have high levels of estrogens in your body (or low progesterone) you can find more information about treating both here. 

#2. Check free thyroid hormones (consider altering your thyroid hormone dose)

If your estrogen:progesterone ratio is not an issue then your high levels may be related to thyroid function. 

At a minimum, make sure to assess both free T3 and free T4 levels (but really you should check a complete thyroid panel). 

Excessively high free T3 and/or free T4 may be the cause of high SHBG in individuals taking thyroid hormone replacement medication (especially if it contains T3). 

#3. Consider alternatives to OCP if you are taking birth control medication

One of the most common causes of high SHBG is the use of oral contraceptives or birth control medications. 

The only way to lower SHBG if it’s related to these medications is to discontinue their use. 

You should discuss this option with your physician and talk about other options (depending on why you are using them in the first place). 

If you are using OCP medications for birth control then you may find better results switching to a form of birth control that does not include hormones such as the copper IUD. 

How to Treat Low SHBG (how to increase it when it’s low)

Low SHBG tends to be more difficult to treat than high SHBG. 

If you know that you have “suboptimal” SHBG then you will need to look at the following areas: 

#1. Get a complete thyroid lab panel

If you are a menstruating woman with low SHBG then this is the most important first step to take. 

To get a full thyroid panel you will need the following tests: 

  • Thyroid stimulating hormone or TSH
  • Free T3
  • Free T4
  • Reverse T3
  • Thyroid antibodies

Once you get all of these tests you can compare your set of labs to optimal thyroid lab tests and determine if your thyroid is contributing to your SHBG level. 

If it is, then you will need to take steps to increase thyroid function in your body either by taking thyroid hormone replacement therapy or by increasing thyroid function naturally. 

#2. Assess your estrogen/progesterone ratio (especially if menopausal)

This is really only important if you are menopausal. 

After menopause estrogen levels fall which can cause SHBG to drop. 

Read more  Hypothyroidism and low blood pressure health risks

Some menopausal women are sensitive to this small drop and therefore may benefit from bio-identical hormone replacement therapy. 

#3. Check free testosterone levels

Low SHBG may indirectly leave more testosterone in the free and active state. 

You can determine if this is happening in your body by assessing the free testosterone in the serum. 

The combination of low thyroid function and low SHBG causes many of the symptoms seen in PCOS. 

If you think this might be happening to you, then the best treatment is to get on the right thyroid hormone replacement medication which is often enough to normalize SHBG and help alleviate many of the symptoms of PCOS. 

There are many other causes of PCOS, however, so this may not work for everyone. 

Back to you

The bottom line?

This binding protein gives you important information about what is happening with various hormones in your body. 

High SHBG is often caused by excessive estrogen levels while low SHBG is often the result of hypothyroidism (or low thyroid function). 

The key to treating SHBG is to identify what is causing the abnormality and fix that problem. 

This will help normalize SHBG levels in your serum and should help to reduce your symptoms. 

Now I want to hear from you:

Do you have abnormalities in your SHBG level?

Have you been able to identify what is causing the problem?

Why or why not?

Leave your comment below! 

Low shbg hypothyroidism

— Update: 06-01-2023 — cohaitungchi.com found an additional article What is SHBG? + Symptoms of Low Levels & How to Raise from the website labs.selfdecode.com for the keyword low shbg hypothyroidism.

Low shbg hypothyroidism

Sex Hormone-Binding Globulin (SHBG) is an important protein that decreases the effects of sex hormones (especially testosterone) by binding to them. Unusually low blood SHBG levels can be indicative of several hormone disorders. Read on to learn more about this protein, the conditions associated with low levels, and what factors may raise them.

What is SHBG?

What Does SHBG Do?

Sex hormone-binding globulin (SHBG), also known as testosterone-binding globulin, is a protein that binds to sex hormones and carries them through the blood [1, 2].

SHBG binds to the following sex hormones, listed in order of affinity [3]:

  • Dihydrotestosterone/DHT (male)
  • Testosterone (male)
  • Androstenediol (male)
  • Estradiol (female)
  • Estrone (female)

SHBG has a greater affinity for male sex hormones (androgens) than female sex hormones (estrogens).

The main functions of SHBG include:

  • Controlling the availability of sex hormones [4]
  • Transporting sex hormones through blood [5]

SHBG Production

Sex hormone binding globulin is mainly made in the liver, where its production is stimulated by female sex hormones and thyroid hormones [6, 7].

SHBG can also be made in these organs:

  • Brain [8]
  • Kidneys [9]
  • Breasts [10]
  • Uterus [11]
  • Placenta [12]
  • Ovaries [13]
  • Prostate [14]
  • Testicles [15]

SHBG is also produced by some types of tumors, such as breast, ovarian, and uterine [16, 17, 18].

SHBG production is blocked by:

SHBG levels are very low in babies of both sexes (10x lower than in their mothers) and increase gradually during childhood until puberty, when they decrease 2x in girls and 4x in boys. The lower SHBG levels in boys allow for higher concentrations of available male sex hormones, which are necessary for their growth in height and the development of their sex organs [22, 23, 1].

In adult men, SHBG levels are stable for many years but progressively rise as they age, which causes a reduction in free but not in total male sex hormone levels [24, 25].

In adult women, SHBG progressively decreases from 20 – 60 years and starts increasing after that [26].

Roles of Sex Hormone-Binding Globulin

1) Reduces the Availability and Activity of Sex Hormones

Only unbound (free) hormones can cross cell membranes and reach their targets. By binding to sex hormones, sex hormone binding globulin can reduce their availability and thus, their activity. However, unbound hormones also disappear more quickly from blood [27, 4, 5].

Because SHBG has more affinity for male hormones, it mainly reduces the activity and elimination rate of male sex hormones. SHBG levels are lower in men than in women, implying that both the activity and elimination rate of male sex hormones are higher in men. Conditions that cause increased SHBG production (e.g., hyperthyroidism) reduce the activity and elimination rate of sex hormones. Conditions that result in decreased SHBG levels (e.g., polycystic ovarian syndrome) increase both activity and elimination rate [3, 28, 29].

2) Transports Sex Hormones Through Blood

Since sex hormones are fatty molecules and can’t dissolve in water, they are transported through the body by binding to a protein like SHBG or albumin. While female sex hormones can undergo modifications that allow them to dissolve in water, male sex hormones need to be bound to transport proteins [5, 30, 31].

Other

SHBG can bind to receptors on cell membranes and stimulate the production of a messenger molecule (cAMP), implying that it may not only transport sex hormones to their target tissues but also trigger biological effects [32, 33].

Genetics of SHBG

There are several variations in the SHBG gene, that are associated with increased or decreased blood levels of this protein and are linked to different conditions [34]:

  • The rs6257 variant reduces blood SHBG levels and is associated with breast cancer in women and type 2 diabetes in both men and women [35, 36].
  • The presence of the rs6258 variant reduces the affinity of SHBG for testosterone, and is associated with higher levels of free testosterone [37].
  • The rs6259 variant increases SHBG levels by reducing its elimination and has been associated with a lower frequency of breast and uterine cancer in women, low sperm movement in men, and lower incidence of type 2 diabetes in both men and women [38, 39, 40, 36].
  • rs1799941 increases blood SHBG levels and has been associated with a higher bone density and lower sperm quality in men, and a lower incidence of type 2 diabetes in both men and women [41, 42, 43].
  • The SHBG gene can be longer or shorter depending on the number of repeats of a certain sequence. More than 6 repeats (rs35785886 variant) decreases SHBG production. This variant is associated with conditions such as polycystic ovarian syndrome (PCOS), excessive body hair, delayed onset of the first period, and coronary artery disease in women, and low sperm concentration and increased bone density in men [44, 45, 46, 47, 41].

All About Low SHBG Levels

The conditions we discuss here are commonly associated with low SHBG levels, but this single symptom is not enough for a diagnosis. Work with your doctor to discover what underlying conditions might be causing your low levels of this protein and to develop an appropriate plan to improve your health.

Symptoms of Low SHBG Levels

Symptoms of low sex hormone binding globulin levels are similar to those of excessive male sex hormone levels.

In females, they include [48, 49, 50, 51, 52]:

  • Excessive body hair/male-pattern hair growth (hirsutism)
  • Acne
  • Dandruff
  • Baldness
  • Voice deepening
  • Increased muscle mass
  • Reduced breast size
  • Irregular or absent periods
  • Enlargement of the clitoris
  • Weight gain

Though rare, low SHBG in males may cause:

  • Early puberty (in children) [53]
  • Acne [54]
  • Baldness [54]
  • Increased body hair [54]
  • Aggression [55]
  • Erectile dysfunction [56]
  • Gynecomastia (breast growth) [57]
  • Infertility [58]

Causes of Low SHBG Levels

Causes shown here are commonly associated with low SHBG. Work with your doctor or other health care professional for an accurate diagnosis.

1) High Insulin Levels

In a study on 47 women with polycystic ovarian syndrome (PCOS), high blood insulin levels were linked to low SHBG concentration [59].

Similarly, Mexican-Americans (a population with a high risk of type 2 diabetes) had higher insulin and lower SHBG levels than non-Hispanic whites in a study on 96 people [60].

Diazoxide (a medication for low blood sugar) increased SHBG levels in a small study on 6 women with polycystic ovarian syndrome [61].

Three studies found reduced SHBG production in human liver cells treated with insulin [62, 63].

A clinical trial on 20 men found that insulin (0.1 – 0.4 UI/kg dosages) increased SHBG production in those with type 2 diabetes [63].

However, a study in cells suggested that the effect of insulin on SHBG levels is non-specific and reflects a reduced production of proteins [64].

2) High Growth Hormone Levels

Acromegaly is a disorder in which the pituitary gland produces too much growth hormone in adults. Several observational studies on over 100 people have measured lower SHBG levels in patients with acromegaly [52, 65, 66].

In overweight healthy men, injection of low growth hormone doses (0.02 U/kg/day for 14 days) decreased blood SHBG levels in a small clinical trial on 8 men [67].

3) High Prolactin Levels

A prolactinoma is a tumor in the pituitary gland that causes the excessive production of the hormone prolactin (PRL). Prolactinomas reduced blood SHBG levels in a study on 20 people. In another study on 28 women with excessive prolactin production, the drug bromocriptine restored prolactin and SHBG levels [68, 69].

In a cell study, prolactin reduced SHBG production [19].

Read more  Do you have Hashimoto’s hypothyroidism and Chronic Fatigue Syndrome?

4) High Testosterone Levels

High testosterone levels are normally considered to reduce SHBG production. The addition of testosterone blocked SHBG production in two cell studies [70, 71].

However, testosterone had no effect on SHBG production in two cell studies and stimulated SHBG production in two other ones [7, 72, 73, 74].

5) Thyroid Hormone Levels

The relationship between low thyroid hormone levels (hypothyroidism) and SHBG concentration is unclear. While three studies found decreased SHBG levels in hypothyroid patients, three other studies measured normal SHBG levels in people with low thyroid hormone levels [75, 76, 77, 78, 79, 80].

6) High Growth Factor Levels

In a cell study, the growth factors IGF-1 (insulin-like growth factor), EGF (epidermal growth factor), and TGF-alpha (transforming growth factor alpha) reduced SHBG production [81].

However, a study on over 1,000 men did not find an association between IGF-1 and SHBG levels [82].

7) Non-Alcoholic Fatty Liver Disease

Since SHBG is made in the liver, non-alcoholic fatty liver disease may affect its levels in the body.

Low SHBG levels have been associated with non-alcoholic fatty liver disease in studies on type 2 diabetics and PCOS. However, it’s difficult to prove causality based on these studies [83, 84, 85, 86].

8) Inflammation

Inflammatory markers, which indicate a pro-inflammatory state, were associated with lower SHBG levels in a study on over 400 women [87].

In another study on almost 700 people, a marker of inflammation (hs-CRP) was associated with lower SHBG levels [88].

9) Genetic Mutations

Genetic mutations can result in low SHBG levels. For instance, a mutation in the SHBG gene resulted in undetectable levels of SHBG in two siblings [89].

10) High Sugar Levels

In genetically modified mice that produce human SHBG, a high-sugar diet reduced SHBG production by 50% after 1 week [90].

Conditions Associated With Low SHBG Levels

While these conditions have been associated with low SHBG in clinical research, this is not necessarily an exhaustive list. Your doctor is best positioned to diagnose any conditions you may have and to determine whether SHBG is a relevant marker.

1) Type 2 Diabetes

A meta-analysis of 43 observational studies and over 13,000 people found a protective role of high SHBG from developing type 2 diabetes, especially in women [91].

Another meta-analysis of 15 studies found a reduced incidence of type 2 diabetes among men and women with mutations causing increased SHBG production [92].

Similarly, two studies on 2,500 people found a link between low SHBG levels and increased type 2 diabetes risks [93, 36].

In two studies on 690 people, this correlation was only seen in women [94, 95].

2) Gestational Diabetes

Low pre-pregnancy SHBG was identified as a risk factor for developing diabetes during pregnancy in an observational study on over 250 women [96].

3) Obesity and Obesity-Related Conditions

Metabolic syndrome is a condition characterized by the following symptoms [97]:

  • Obesity
  • High blood pressure
  • High blood sugar levels
  • High blood triglyceride levels
  • Low blood levels of HDL cholesterol

In a meta-analysis of 52 studies, metabolic syndrome was associated with low SHBG levels in both men and women [98].

Having low SHBG levels is a significant risk factor (several fold increased likelihood) for developing metabolic syndrome based on a study on almost 2,500 people [99, 100, 101].

Insulin sensitivity, the opposite of insulin resistance seen with diabetes, was associated with high SHBG levels in three studies on over 300 people [102, 103, 104].

4) Breast Cancer

A meta-analysis of 9 studies found a link between low SHBG levels and increased risk of developing breast cancer [105].

Two observational studies on almost 3,000 people found the same association [106, 107].

5) Heart Disease

In two studies on almost 4,000 women, low SHBG levels were associated with an increased risk of developing heart disease [108, 109].

6) High Blood Pressure

In an observational study on almost 3,000 people, low SHBG was a risk factor for high blood pressure, but only in men [110].

7) Polycystic Ovarian Syndrome

SHBG levels were lower in 23 women with PCOS [61, 111].

Although two studies on over 800 women found a link between a variation causing reduced SHBG production and polycystic ovarian syndrome, two other studies on almost 600 women failed to find the same association [112, 113, 114, 115].

Another study examining all four SHBG SNPs (rs1779941, rs6297, rs6259, and rs727428) did not find any associations with PCOS [116].

8) High Cortisol

Cushing’s syndrome is a condition with abnormally high cortisol levels [117].

Cushing’s syndrome was linked to reduced SHBG levels in multiple studies on 135 people [118, 119, 120, 121].

9) Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia is a genetic disorder in which the body produces insufficient cortisol and excessive male sex hormone levels [122].

In a study on 240 people, congenital adrenal hyperplasia was associated with higher SHBG levels in women but not in men [123].

Factors That May Raise SHBG

Individuals wishing to increase their SHBG levels will be most likely women with symptoms of male sex hormone excess. If your SHBG levels are too low, discuss with your doctor what strategies may help you raise them. Never implement them in place of what your doctor recommends or prescribes.

Some lifestyle changes that may help increase SHBG levels include:

1) Physical Exercise

Moderately intense aerobic exercise for a year increased SHBG levels in a clinical trial on over 100 people [124].

Similarly, moderate to intense exercise for a year increased SHBG and reduced estradiol and free estradiol levels in a trial on over 300 women [125].

A study on over 13,000 women found that exercise was associated with higher SHBG levels. Higher BMI was associated with lower SHBG levels [126].

2) Weight Loss

In multiple trials on over 300 people, SHBG levels increased after weight loss [127, 128, 129, 130].

Weight loss from either a higher-protein/low-fat diet or a higher-carbohydrate/low-fat diet increased SHBG levels in a clincal trial on over 100 overweight and obese men [131].

3) Caffeine Intake

Regular coffee intake was linked to increased blood SHBG in multiple studies on 19,000 people [126, 132, 133, 134, 135].

Different types of caffeinated drinks (coffee, green tea, black tea, oolong tea, and cola) were linked to increased SHBG levels in 50 women [136].

However, a clinical trial on 42 people had mixed results and did not find significant effects of coffee consumption (regular or decaf) on SHBG levels [137].

4) Dietary Changes: Mediterranean Diet

A study on 27 obese men found that a low-fat, high-fiber diet, with exercise, effectively increased SHBG levels [138].

Additionally, the following foods and beverages increased SHBG production. However, additional clinical studies need to be done before these findings are considered conclusive:

Drugs That Increase SHBG Levels

Note: By writing this section, we are not recommending these drugs. We are simply providing information that is available in the scientific literature. Many drugs have side effects and should not be taken unless prescribed by a physician. Please discuss your medications with your doctor.

Oral Contraceptives

Because they include synthetic female sex hormones, birth control pills can increase SHBG levels.

Different combinations of birth control pills caused an increase in SHBG levels to different degrees in a clinical trial on 91 people, with 30 mg ethinylestradiol plus 2 mg dienogest having the strongest effect [144].

Both a triphasic birth control (containing ethinylestradiol and gestodene) and a monophasic version (containing 35 mg ethinylestradiol and 250 mg norgestimate) increased SHBG levels 200 – 240% on days 11 and 21 in a clinical trial on 46 women. Even on pill-free days, SHBG levels were elevated compared to pre-treatment [145].

SHBG levels in women currently taking birth control pills were 4x higher compared to those who have never taken it in a study on over 100 women. Discontinuing the pill decreased SHBG levels slightly, but they were still higher than those who had never taken it [146].

Aromatase Blockers

Treatment with the aromatase blockers risedronate (35 mg/week) or letrozole (2.5 mg/day) increased SHBG levels in two clinical trials on over 100 men and women [147, 148].

Anti-Seizure Medication

SHBG levels increased in epileptic patients treated with anti-seizure medication in several studies:

Selective Estrogen Receptor Modulators

The following selective estrogen receptor modulators increased SHBG levels in clinical trials:

  • Tamoxifen (breast cancer medication) [153]
  • Raloxifene (osteoporosis and breast cancer medication) [154]
  • Bazedoxifene (osteoporosis medication) [155]
  • Clomiphene (women infertility medication) [156]
  • Ospemifene (medication for painful sexual intercourse in women) [157]
  • Toremifene (breast cancer medication) [158]

Metformin

Several clinical trials have found that metformin (type 2 diabetes medication) increased SHBG levels [159, 160, 161].

Certain Antipsychotics

SHBG levels raised after treatment with conventional antipsychotic medications (haloperidol, haloperidol with chlorpromazine, or chlorpromazine) in a clinical trial on 68 people but not with olanzapine, a second-generation antipsychotic, even when olanzapine was taken with conventional antipsychotics [162].

Further Reading

References

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About the Author: Tung Chi