Part 1

Causes and Solutions for Elevated SHBG and TBG Levels

Sex hormone binding globulin, SHBG for short, is a critical protein that transports hormones through the blood. It regulates sex hormone levels, primarily estrogen and testosterone. 

If your hormones are out of balance, or if you have PCOS, insulin resistance, or liver disease, ask your doctor to check your SHBG levels. When SHBG levels are too high or too low, it impacts your hormones and health. 

“If your hormones are out of balance, or if you have PCOS, insulin resistance, or liver disease, ask your doctor to check your SHBG levels. When SHBG levels are too high or too low, it impacts your hormones and health.”

Keep reading to learn more about:

• What is SHBG? 
• High and low SHBG and related symptoms
• The role of mitochondria
• How to lower SHBG when needed
• How to raise SHBG when needed

Let’s take a look! 

What is SHBG (Sex Hormone Binding Globulin)?

SHBG is an essential protein made by the liver.  Its primary role is to transport steroid hormones, including: 

• Estradiol – the most abundant form of estrogen in a woman who is cycling 

• Testosterone – the primary androgen found in men and women

• DHT (dihydrotestosterone) – a more potent form of testosterone, found in both men and women. It’s linked to male pattern baldness. 

When these hormones are bound to SHBG, they can’t bind to cells and have an effect. Sex hormones need to be unbound and free in the blood to exert their effects. In this way, SHBG helps regulate hormone levels. 

High SHBG Level Symptoms and Related Diseases

When SHBG is high, there are lower levels of circulating estrogen and testosterone available. 

High SHBG symptoms in women may include both symptoms of low estradiol levels and low testosterone, including:

• Decreased libido
• Lack of motivation 
• Irregular periods
• Vaginal dryness
• Decreased bone mass
• Memory loss
• Fatigue
• Mood changes and depression 

Elevated levels over time may contribute to diseases, including breast cancer and osteoporosis. 

On the other hand, low SHBG is more likely to be related to metabolic disorders like insulin resistance, diabetes, and PCOS.

Liver Disease
Since SHBG is made in the liver, liver health is critical for balancing SHBG levels. When the liver is damaged or overloaded it is unable to produce as much SHBG, and levels may be lower. In other cases, such as cirrhosis, SHBG may be elevated. In addition, normal SHBG levels seem protective against non-alcoholic fatty liver disease in women. 

Hyperthyroidism

When thyroid hormone levels are high, everything in the body speeds up, including the production of SHBG. High SHBG is associated with hyperthyroidism and Graves’ disease, autoimmune hyperthyroidism. 

‍

With higher SHBG, less estrogen and testosterone is available for use, which may be associated with irregular or absent periods in women. 

‍Importance of Cellular Health and Mitochondria Function 

Mitochondria function is essential for liver health and function, including the production of SHBG. 

‍

Mitochondria are found in every cell and transform sugar (or fat or protein) and oxygen into energy (as ATP). Cellular health requires efficient mitochondria. Furthermore, mitochondria require robust nutrition, including antioxidants and B vitamins, to work efficiently without damaging cells. 

A Functional Medicine Approach to Lowering SHBG Levels 

I always order an SHBG blood test when there are signs of hormone imbalance. When estrogen and testosterone are high or low, I always want to understand why to create an effective treatment plan for each patient. 

When my patient is experiencing symptoms of low hormones and SHBG is high, here are some strategies to consider: 

• Test for factors driving elevated SHBG, like hyperthyroidism and liver function.

• Evaluate medication use that might influence SHBG. 

• Work to maintain healthy body weight and eat enough food, including protein. Being underweight and having a low protein intake may be associated with higher SHBG and lower sex hormone levels. 

• Use natural remedies, such as nettle leaf, to help decrease SHBG levels. 

• Support hormone levels with herbal medicine, supplements, bioidentical hormone replacement, or other strategies. 

When my patient is experiencing elevated hormone symptoms, such as high testosterone in PCOS, along with low SHBG levels, here are some strategies to consider: 

• Test for factors driving SHBG levels lower like thyroid hormones (hypothyroidism), liver markers, and insulin resistance.
• Evaluate steroid and other medication use that may affect SHBG levels. 

• Use diet and lifestyle strategies to manage blood sugar, reverse insulin resistance, and obtain a healthy weight. 

• Increase exercise. Exercise promotes SHBG production. 

• Support liver detoxification pathways to support the clearing of excess hormones and support liver health. 

• Use supplements to help balance hormones and lower SHBG. Consider inositol, spearmint, licorice, white peony, and others. Working with a functional medicine practitioner is vital to choosing the right formula for you. 

Sex hormone binding globulin is critical in regulating estrogen and testosterone levels in women. It’s an important blood test when working to understand the root of hormone imbalance. Luckily, we can use many supportive functional medicine tools to bring levels back into balance. 

In Part 2 of this series, learn more about thyroxine binding globulin and what this protein means for thyroid health. 

‍

References

1. Goldštajn, M. Š., Toljan, K., Grgić, F., Jurković, I., & Baldani, D. P. (2016). Sex Hormone Binding Globulin (SHBG) as a Marker of Clinical Disorders. Collegium antropologicum, 40(3), 211–218.
2. Qu, X., & Donnelly, R. (2020). Sex Hormone-Binding Globulin (SHBG) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome. International journal of molecular sciences, 21(21), 8191. 
3. Wang, X., Xie, J., Pang, J., Zhang, H., Chen, X., Lin, J., Li, Q., Chen, Q., Ma, J., Xu, X., Yang, Y., Ling, W., & Chen, Y. (2020). Serum SHBG Is Associated With the Development and Regression of Nonalcoholic Fatty Liver Disease: A Prospective Study. The Journal of clinical endocrinology and metabolism, 105(3), dgz244. 
4. Jaruvongvanich, V., Sanguankeo, A., Riangwiwat, T., & Upala, S. (2017). Testosterone, Sex Hormone-Binding Globulin and Nonalcoholic Fatty Liver Disease: a Systematic Review and Meta-Analysis. Annals of hepatology, 16(3), 382–394. 
5. Chopra I. J. (1975). Gonadal steroids and gonadotropins in hyperthyroidism. The Medical clinics of North America, 59(5), 1109–1121. 
6. Round, P., Das, S., Wu, T. S., Wähälä, K., Van Petegem, F., & Hammond, G. L. (2020). Molecular interactions between sex hormone-binding globulin and nonsteroidal ligands that enhance androgen activity. The Journal of biological chemistry, 295(5), 1202–1211. 
7. Friedenreich, C. M., Woolcott, C. G., McTiernan, A., Ballard-Barbash, R., Brant, R. F., Stanczyk, F. Z., Terry, T., Boyd, N. F., Yaffe, M. J., Irwin, M. L., Jones, C. A., Yasui, Y., Campbell, K. L., McNeely, M. L., Karvinen, K. H., Wang, Q., & Courneya, K. S. (2010). Alberta physical activity and breast cancer prevention trial: sex hormone changes in a year-long exercise intervention among postmenopausal women. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 28(9), 1458–1466. 

‍