Sex Hormone Binding Globulin (SHBG) Explained: Why It Matters for PCOS, Acne, Thyroid Function, Perimenopause, and More

Sex hormone binding globulin (SHBG) is a protein that binds and transports reproductive hormones like estrogen and testosterone. While it’s not a hormone itself, SHBG determines how much of your hormones are actually active and available to work throughout your body. Together let’s explore the true role of SHBG, factors that impact SHBG levels cells, and how this protein could actually be the critical missing piece for your hormone-related symptoms.

Why SHBG Is a Key Piece in Understanding Hormones and Symptoms

SHBG is made by the liver and acts as a hormone gatekeeper, regulating how much estrogen and testosterone can actually reach your cells. When hormones are bound to SHBG, they are rendered “inactive” and therefore unable to enter cells or exert their effects on tissues throughout the body. 

Only “free hormones” that are not bound to SHBG are active, influencing metabolism, libido, skin health, mood, and more. This is why testing both total and free hormone levels (especially pertaining to testosterone) gives a more accurate picture of hormonal balance alongside SHBG levels. 

Interestingly, SHBG levels fluctuate according to rises and falls in hormone levels as a protective mechanism to prevent symptoms of hormonal surges. For example, it can peak around ovulation, helping buffer high estrogen and testosterone levels to maintain balance. 

That being said, SHBG can be too high or too low because of a variety of factors. This significantly influences hormone-related symptoms, specifically androgenic (driven by testosterone, DHEA, and their metabolites) and estrogen-related symptoms. 

Too little SHBG and your body is flooded with free estrogen and testosterone. This can lead to heavy menstrual periods, irregular cycles, breast tenderness, fatigue, mood swings, weight gain, acne, oily skin, dark course facial or body hair growth (hirsutism), and even hair loss.

Too much SHBG and too many of your hormones become bound and inactivated, leaving you with symptoms of low estrogen and testosterone, even though your total hormone levels may be sufficient. This can lead to irregular periods, fatigue, low mood, low libido, low bone density, vaginal dryness, difficulty building muscle, dry skin, thinning hair and more. 

While lab ranges vary and can be quite a large span (from about 20-120 nmol/L), we consider the ideal SHBG range to be 50-90 nmol/L.

Low SHBG Levels

Low SHBG is common in states of metabolic dysfunction, heightened inflammation, and low estrogen. Metabolic dysfunction, especially insulin resistance, suppress SHBG production in the liver. This aggravates hormone conditions like PCOS (polycystic ovarian syndrome), where insulin resistance drives high androgen availability and therefore common symptoms like acne, oily skin, facial hair growth, and hair thinning. 

Chronic inflammation also suppresses SHBG production thanks to inflammatory cytokines like TNF-α, IL-6, and TGF-β1. Research shows these inflammatory markers are inversely correlated with SHBG levels in both men and women. Some researchers believe SHBG to be a marker of insulin resistance and a predictor of type 2 diabetes, while others have shown a greater connection between high levels of fat in the liver leading to lower SHBG, for example in the case of non-alcoholic fatty liver disease.

Low estrogen levels themselves also reduces SHBG. This is the case among those in perimenopause, as well as those of reproductive age with low estrogen levels. When SHBG lowers, more testosterone becomes available, creating a relative excess of androgens. This shift often drives facial hair growth, hair loss, acne, and central fat storage. This explains many of the hormonal symptoms associated with perimenopause.

High SHBG Levels

At the other end of the spectrum, SHBG can climb too high in response to both acute and chronic rises in estrogen, medications, alcohol, and even energy deficiency. Acute, or short term, rises in estrogen include the time before ovulation. At this time, SHBG rises to as a protective effect to help offset this high hormone environment. 

Two of the most notable medications that increase SHBG are oral contraceptives and spironolactone. Oral contraceptives, particularly those that are estrogen-based, stimulate SHBG production and bind up hormones. While this may temporarily improve acne and heavy periods, these symptoms often rebound after stopping birth control because SHBG drops, flooding your body with available hormones. The rise in SHBG is thought to contribute to the increased risk of blood clots associated with oral contraceptive use.

Spironolactone is an anti-androgen medication used to treat acne. Similar to oral contraceptives, it raises SHBG to ensure that more androgens are bound up and inactivated. While this is effective at reducing acne while on the medication, it masks the underlying hormonal drivers behind the breakouts. To get to the root of your acne, we need to address the high androgens themselves and any other factors impacting your skin health.

Energy deficiency from disordered eating patterns, underfueling, overexercise, or low-calorie diets, can also raise SHBG. These effects are furthered due to low thyroid activity and thyroid hormones, reduced insulin, and high levels of cortisol, our main stress hormone.

How the Liver Helps Regulate SHBG Levels

Since SHBG is produced in the liver, it makes sense that liver health plays a major role in determining its levels. When the liver is working optimally – metabolizing hormones, filtering out toxins, and processing nutrients – SHBG production tends to stay balanced.

However, if the liver becomes sluggish due to metabolic dysfunction, fatty liver, oxidative stress, poor bile flow, gut dysbiosis, or mold mycotoxin exposure, SHBG synthesis can drop. Not only does SHBG drop, increasing free hormone levels, but this also compromises how efficiently the liver can clear those hormones.

Healthy phase I and phase II detox pathways help maintain proper SHBG levels and overall hormone metabolism. When these systems are overloaded or we don’t have enough nutrients (like amino acids, minerals, and antioxidants) to fuel these chemical reactions, it can lead to SHBG fluctuations as well as hormone imbalances.

There’s also a genetic layer to consider. Certain gene variations influence SHBG levels, liver enzyme activity, and methylation (a biochemical process crucially involved in a variety of body functions related to detoxification, DNA gene expression, and DNA repair). The strongest association is with the MTHFR gene mutations, with the C677T (Ala222Val) variant being linked to lower levels of SHBG.

Exploring the Thyroid-SHBG Connection

The thyroid and liver work closely together to regulate SHBG. Thyroid hormones directly stimulate SHBG synthesis in the liver. Because of this, SHBG is often considered a sensitive marker of thyroid hormone activity in the body, beyond thyroid hormone levels themselves. 

When thyroid function is off, SHBG levels often reflect that imbalance. Hypothyroidism or low thyroid activity reduces SHBG, which can raise free androgens and estrogens, worsening PMS symptoms, acne, fatigue, and irregular cycles. Hyperthyroidism or excess thyroid hormone increases SHBG, lowering available reproductive hormones and sometimes contributing to low libido or menstrual changes. 

Its worth noting that the rise in SHBG from hyperthyroidism can also be seen in the case of overmedication of TSH-lowering drugs, like levothyroxine. The increase in SHBG is proportional to the degree of thyroid hormone excess, with higher T4 and T3 levels associated with greater SHBG elevations. That being said, SHBG has shown to normalize when thyroid hormone levels return to balance.

One key takeaway is that if your SHBG level is low or high, it’s worth looking deeper into your thyroid and liver function. Supporting healthy thyroid activity (through optimal nutrient intake, liver detoxification, and appropriate dosing for those on medication) can help restore SHBG to a healthy range and stabilize sex hormone balance.

Don’t Ignore Your SHBG Levels!

SHBG may not get as much attention as estrogen or testosterone, but it’s one of the most important regulators of hormone balance. When SHBG levels are too low, free androgens can surge, leading to acne, hair growth, and metabolic symptoms. When too high, hormones become overly bound, contributing to fatigue, low libido, or difficulty maintaining muscle and mood.

Because it sits at the intersection of liver function, thyroid health, inflammation, and metabolism, SHBG gives incredible insight into the why behind your hormonal symptoms. Including SHBG into a comprehensive blood lab panel can reveal patterns that standard lab testing alone might miss.

If you’re experiencing hormone-related symptoms that don’t match your lab results, and are seeking answers and a personalized approach, our 1:1 Coaching Program is for you. Leveraging advanced functional medicine testing and functional nutrition and lifestyle support, let’s get to the root of what’s really going on beneath the surface. Book your free discovery call today!

Written by Romana Brennan, MS, RDN