Still Having Symptoms on HRT? SHBG Could Be Why
Having normal hormone levels doesn't mean your body can access them.
Most female hormone panels measure how much estrogen and testosterone you have. But they don’t tell you how much your body can actually use. That’s what SHBG does — and it’s why you can have normal lab results and still feel exhausted, have no sex drive, and can’t lose weight no matter what you do.
SHBG binds to estrogen and testosterone, regulating how much of each is free to act on your tissues. When SHBG is out of range in women, they can end up with too much or too little active hormone, even when total levels look normal on paper.
About the Experts
Shelly Chvotzkin, D.O., F.A.C.O.O.G., is a board-certified OB-GYN.
Kimberly Hood, M.D., is a board-certified OB/GYN and functional medicine provider specializing in men’s and women’s hormone health, weight management, longevity, thyroid health, and sexual wellness.
What SHBG Does (And Why it Matters)
SHBG is a protein made by the liver that binds to estrogen and testosterone in the bloodstream, determining how much of each hormone is “free” (bioavailable) versus “bound” (inactive).1 Only free hormones can act on your tissues to regulate energy, libido, mood, muscle maintenance, and metabolic stability.
Two women can have identical estrogen or testosterone levels on a lab report but very different amounts available to their tissues based on differences in SHBG.
- Higher SHBG (even within range) reduces how much estrogen and testosterone are available for your body to use, contributing to symptoms like low libido, fatigue, or mood changes.
- Lower SHBG (even within range) increases how much estrogen and testosterone are available for your body to use, which may cause symptoms such as acne, oily skin, hair loss (scalp), and facial/body hair growth as well as irregular or absent periods and fertility problems.
What’s a Normal SHBG Range for Women?
The standard reference range for SHBG levels in adult women is wide — typically 14–144 nmol/L — but levels shift meaningfully across life stages:2
- Reproductive years: In most normally cycling women, SHBG levels fall between 18–86 nmol/L, with an average of 38–40 nmol/L.3
- Perimenopause: Levels can swing unpredictably, ranging from 20–75 nmol/L. Because the liver produces SHBG in response to estrogen, SHBG tracks to estrogen’s erratic rises and falls.
- Postmenopause: The established reference range is 16–115 nmol/L, with average levels around 45–49 nmol/L. Postmenopausal women who don’t take HRT have similar average SHBG levels to premenopausal women, but the drivers change. Rather than estrogen, factors like insulin, waist-to-hip ratio, and testosterone become the dominant forces shaping SHBG after menopause.
- Menopause with HRT: Certain types of HRT — particularly oral estrogen — can significantly raise SHBG, sometimes well above the postmenopausal baseline.
But “normal” SHBG simply reflects what’s common across a broad population, not what’s optimal for your body or to manage your symptoms.
Some clinicians target a narrower range (often around 70–90 nmol/L), but in practice, there’s no single ideal number that applies to everyone.
“I see women who feel great at 30–40, others at 100 or higher, and others who don’t feel better until the dose, route, or timing of their HRT is adjusted,” says board-certified OB-GYN Shelly Chvotzkin, D.O.
SHBG levels don’t exist in isolation — they reflect what’s happening across your metabolic and hormonal systems. Several key factors influence how much SHBG your liver produces:
- Insulin resistance: Elevated insulin levels, as seen in insulin resistance or metabolic syndrome, tend to suppress SHBG production.
- Thyroid function: Higher thyroid hormone levels can increase SHBG, while low thyroid hormone levels are often associated with lower levels.
- Other factors: Higher levels of male hormones (in conditions such as PCOS), excess body fat, and fatty liver disease can all contribute to lower SHBG.
SHBG in Perimenopause and Menopause
During perimenopause, SHBG levels can fluctuate in ways that make symptoms harder to predict.
As estradiol (the most potent form of estrogen) rises and falls, SHBG can temporarily increase in response, binding more estrogen and testosterone and reducing how much reaches your tissues in order to stabilize active hormone levels.
Estrogen fluctuations influence testosterone indirectly through SHBG. When estrogen rises, it signals the liver to produce more SHBG, which binds to testosterone and reduces the amount that’s free and available to your body. When estrogen falls, SHBG may decrease, leaving more testosterone unbound. As a result, even if total testosterone stays the same, shifts in estrogen can cause noticeable changes in how testosterone functions—especially during perimenopause.
- Perimenopause and menopause: SHBG can amplify the effects of estrogen fluctuations by binding more of the hormone, leaving less available to your tissues and contributing to symptoms like hot flashes, sleep disruption, and mood changes.
- Libido and energy: SHBG helps determine how much testosterone is available to support sex drive, motivation, and muscle maintenance.
- HRT response: SHBG can explain why the same dose of hormone replacement therapy (HRT) works well for one woman and barely moves the needle for another.
Other common features of perimenopause — like stress, poor sleep, and blood sugar swings — can further influence SHBG by driving elevated insulin levels and disrupting thyroid hormone production, both of which affect how much SHBG the liver makes.
High SHBG in Women
High SHBG means the body has less “free,” or unbound estrogen and testosterone available for your tissues to use.
Symptoms of high SHBG often mirror low estrogen and low testosterone symptoms in women:
- Low libido4
- Fatigue
- Depression and mood disorders5
- Vaginal dryness
- Decreased muscle and bone mass
- Irregular or absent periods
- fertility problems
Moderately higher SHBG isn’t automatically a problem. In many cases, levels in the upper half of the reference range (roughly 70–100 nmol/L) reflect a healthy underlying picture — good insulin sensitivity, a well-functioning liver, and balanced estrogen levels. When SHBG is elevated due to an underlying condition—like hyperthyroidism—it’s usually not just the number that raises concern, but the overall pattern. Physicians look at how high the level is, whether it fits your health history and symptoms, and whether other labs (like thyroid markers) point to an underlying issue.
Causes of high SHBG
High levels of SHBG in women tend to occur during specific circumstances or life stages, including:
- Perimenopause. Fluctuating estrogen levels can signal the liver to produce more SHBG as a way to stabilize hormone activity.6
- Hyperthyroidism: Higher levels of thyroid hormones increase the liver’s SHBG production, speeding up overall metabolic activity and hormone turnover.7
- Very low body weight or body fat: Lower fat mass is often associated with lower insulin levels, which remove a key signal that normally suppresses SHBG, allowing levels to rise.
- Pregnancy: Estrogen levels rise significantly during pregnancy, which signals the liver to produce more SHBG as a way to regulate overall hormone activity.
- Smoking: Smoking increases inflammation and chronic stress, which signal the liver to produce more SHBG.8
- Certain medications: Estrogen-based therapies including oral contraceptives and HRT, anti-seizure medications, Tamoxifen for breast cancer treatment, and hyperthyroidism medication can boost liver production of SHBG.9
Treatment for high SHBG
The most effective approach to treating high SHBG is addressing the root cause. “SHBG often reflects what’s happening elsewhere in the body,” explains board-certified OB-GYN Kimberly Hood, M.D. “Addressing underlying issues like thyroid dysfunction or insulin resistance can help bring SHBG back into a more optimal range over time.”
Other treatments for high SHBG in women may include:
Supplements
- Zinc supplementation may support testosterone levels by helping the body produce more of the hormone—particularly in people who are deficient, including postmenopausal women.10
- Stinging nettle supplements may help increase testosterone by preventing it from getting “locked up” by SHBG, keeping more of it available for your body to use.11
Dietary changes
- Some research suggests high-protein diets may improve insulin resistance and fasting insulin levels in women 18–45 with PCOS.12
- While there is some evidence that anti-thyroid drugs such as thiamazole can lower SHBG levels, it’s unclear whether this treatment can push SHBG into a more ideal range.13
Low SHBG in Women
Low SHBG levels mean more free testosterone and estrogen are circulating in the bloodstream. Symptoms tend to resemble higher testosterone levels more than high estrogen levels — because those effects tend to be more noticeable in women. Symptoms of higher testosterone include:14
- Weight gain
- Excessive body and facial hair
- Mood swings
- Acne
In some cases, increased free estrogen may also contribute to symptoms like bloating, breast tenderness, heavier periods, irregular or missed periods, or fertility issues, though these are less specific and can overlap with normal hormonal changes.
Causes of low SHBG
Low SHBG levels may be driven by other health conditions or issues, including:
- Insulin resistance, even when glucose or A1c appear normal.15 16 Elevated insulin levels signal the liver to reduce SHBG production, even before blood sugar markers become abnormal.
- PCOS, even in women who are lean or do not meet all diagnostic criteria.17 18
- Hypothyroidism, because an underactive thyroid directly reduces the liver’s production of SHBG.
- Obesity or increased visceral fat drives insulin resistance and inflammation, both of which suppress SHBG.
- High testosterone and other male hormones, whether produced by the body or from medications, can signal the liver to reduce SHBG output.
- Metabolic syndrome, a condition that combines several SHBG-lowering factors at once, making the suppressive effect more significant than any single cause alone.
- Chronic inflammation interferes with the liver’s ability to produce SHBG at healthy levels.
Treatments for low SHBG
- Weight loss: Losing just 5–10% of body weight significantly increases SHBG.19
- Thyroid treatment: Thyroid hormones prompt the liver to produce more SHBG, so an effective treatment for hypothyroidism would raise low SHBG levels.20
- Change of hormone regimen: Raising estrogen levels through birth control or by adjusting HRT dosage, or switching from oral to transdermal estrogen often increases SHBG.
- Dietary changes: Diets with low sugar and high fiber content (e.g., fruits, vegetables, lean protein, and whole grains) may increase SHBG levels.21
SHBG and Estrogen Therapy
The type of estrogen therapy and the dosage you use can significantly influence your SHBG levels and by extension, how well the treatment controls your symptoms.
Oral vs transdermal estrogen
- Oral estrogen: Whether taken as HRT or in birth control pills, oral estrogen passes through the liver before entering your circulation. This stimulates the liver to produce more SHBG, which can increase total estradiol levels but blunt the amount that’s free and available.22 This may explain why some women taking oral estrogen still experience symptoms like hot flashes, low libido, or mood changes.
- Transdermal estrogen: Patches, gels, and creams bypass the liver and have a minimal impact on SHBG, often resulting in more stable and predictable levels of free estradiol.23
Dosage
Estrogen dosage can directly influence SHBG levels, particularly if it’s taken orally.
“Generally, the higher the oral dose of estrogen, the higher the SHBG,” Chvotzkin says. As SHBG rises, less estrogen is available to the body for use. In practical terms, this means that increasing your dose might not lead to better symptom control because SHBG often rises with additional estrogen.
Adjusting the dose or switching from oral to transdermal estrogen is a better lever to help improve how much hormone is available. “Women feel best based on free hormone availability, not the total hormone level,” Chvotzkin says.
SHBG and Testosterone Therapy for Women
Two women with similar symptoms — low libido, fatigue, poor body composition — may need very different testosterone doses depending on their SHBG levels.24 25
- If SHBG is high, you’ll need more total testosterone to get adequate free testosterone
- If SHBG is low, you’ll need a lower dose of testosterone therapy
Checking SHBG alongside total testosterone helps avoid both under-treatment and symptoms of excess testosterone, such as acne, oily skin, unwanted hair growth, or irritability.26
The Bottom Line
SHBG regulates how much testosterone and estrogen can be used in the female body and can reveal early signs of insulin resistance, thyroid dysfunction, perimenopause changes, and whether your HRT is working as intended. Getting your SHBG tested regularly starting in midlife gives your doctor the insight needed to fine-tune your treatment and address underlying conditions before they progress.
FAQs
How does thyroid affect SHBG?
Thyroid hormones help regulate SHBG production. Higher levels of thyroid hormone can raise SHBG, while lower thyroid function can lower it.
Does SHBG increase with weight loss?
Yes, as you lose weight, SHBG levels may rise. As weight decreases—particularly visceral fat—insulin levels tend to drop and inflammation improves, and this shift reduces signals that suppress SHBG, allowing the liver to produce more of it.
Is it better to have higher or lower SHBG?
Generally, SHBG levels should remain in a mid-range between 14–144 nmol/L, which is 18–86 nmol/L for women with regular menstrual cycles. SHBG levels are generally higher in women than men and may increase with age.
Does stress increase SHBG?
Yes, high stress levels can lead to elevated SHBG levels. The body reacts to stress by elevating hormones like cortisol, estrogen, and testosterone, as well as SHBG, the protein that regulates them.
Weronika Szybiak-Skora, et al. (2025). New Insights in the Diagnostic Potential of Sex Hormone-Binding Globulin (SHBG)—Clinical Approach
↑Xianqin Qu, et al. (2020). Sex Hormone-Binding Globulin (SHBG) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome
↑Pasquali R, et al. (1997). Determinants of sex hormone-binding globulin blood concentrations in premenopausal and postmenopausal women with different estrogen status
↑Ahmed AlAwlaqi, et al. (2017). Role of Hormones in Hypoactive Sexual Desire Disorder and Current Treatment
↑Laura A Colangelo, et al. (2012). Association of Sex Hormones and SHBG with Depressive Symptoms in Post-menopausal Women: the Multi-Ethnic Study of Atherosclerosis
↑Zhao Qian, et al. (2025). The Effect of 17β-Estradiol Plus Norethisterone Acetate on Estradiol, Testosterone, IGF-1 and SHBG in Postmenopausal Women: A Meta-Analysis of Randomized Controlled Trials
↑Markus A. Thaler, et al. (2015). The Biomarker Sex Hormone-Binding Globulin – From Established Applications to Emerging Trends in Clinical Medicine
↑Fan B, et al. (2024). Associations between smoking, sex steroid hormones, trouble sleeping, and depression among U.S. adults: a cross-sectional study from NHANES (2013–2016)
↑Thijssen JH. (1988).Hormonal and nonhormonal factors affecting sex hormone-binding globulin levels in blood
↑Leila Mazaheri Nia, et al. (2021). Effect of Zinc on Testosterone Levels and Sexual Function of Postmenopausal Women: A Randomized Controlled Trial
↑Phillip Round, et al. (2019). Molecular Interactions Between Sex Hormone–Binding Globulin and Nonsteroidal Ligands that Enhance Androgen Activity
↑Fang Wang, et al. (2024). Effects of High-Protein Diets on the Cardiometabolic Factors and Reproductive Hormones of Women with Polycystic Ovary Syndrome: A Systematic review and meta-analysis
↑Weronika Szybiak-Skora, et al. (2025). New Insights in the Diagnostic Potential of Sex Hormone-Binding Globulin (SHBG)—Clinical Approach
↑SHBG Blood Test. What Is an SHBG Blood Test? (n.d.).
↑Kristin Ottarsdottir, et al. (2020). Longitudinal Associations Between Sex Hormone-Binding Globulin and Insulin Resistance
↑Adrian H. Heald, et al. (2021). Low Sex Hormone Binding Globulin: A Potential Predictor of Future Glucose Dysregulation in Women
↑Xi Luo, et al. (2020). Decreased Sex Hormone-Binding Globulin Indicated Worse Biometric, Lipid, Liver, and Renal Function Parameters in Women with Polycystic Ovary Syndrome
↑Samantha Cassar, et al. (2016). Insulin Resistance in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Euglycaemic–Hyperinsulinaemic Clamp Studies
↑Catherine Duggan, et al. (2019 ). Long-Term Weight Loss Maintenance, Sex Steroid Hormones, and Sex Hormone-Binding Globulin
↑Benjamin Fenske, et al. (2015). Endogenous Androgens and Sex Hormone–Binding Globulin in Women and Risk of Metabolic Syndrome and Type 2 Diabetes
↑Menga Huang, et al. (2017). Relationship Between Dietary Carbohydrates Intake and Circulating Sex Hormone‐Binding Globulin Levels in Postmenopausal Women
↑Zhao Qian, et al. (2025). The Effect of 17β-Estradiol Plus Norethisterone Acetate on Estradiol, Testosterone, IGF-1 and SHBG in Postmenopausal Women: A Meta-Analysis of Randomized Controlled Trials
↑D.-H. Lu, et al. (2023). Association Between Hormone Replacement Therapy and Sex Hormones in Postmenopausal Women: A Systematic Review and Meta-Analysis
↑Ahmed AlAwlaqi, et al. (2017). Role of Hormones in Hypoactive Sexual Desire Disorder and Current Treatment
↑Laura A Colangelo, et al. (2012 ). Association of Sex Hormones and SHBG with Depressive Symptoms in Post-menopausal Women: the Multi-Ethnic Study of Atherosclerosis
↑SHBG Blood Test. What Is an SHBG Blood Test? (n.d.).
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