Sex Hormone-Binding Globulin (SHBG) Levels Do Fluctuate
Yes, SHBG levels can fluctuate significantly based on various physiological and lifestyle factors. According to clinical evidence, SHBG concentrations show remarkable variability among individuals, with nearly 20-fold differences observed between the lowest and highest values in clinical populations 1.
Factors That Cause SHBG Fluctuations
Physiological Factors:
- Age: SHBG levels tend to increase with age. Research shows significantly higher mean SHBG levels in men ≥55 years (36.6±15.8 nmol/l) compared to men ≤54 years (27.7±13.3 nmol/l) 1.
- Weight changes: Rapid weight loss can dramatically increase SHBG levels. In one study, abdominally obese men experienced an increase from 27.6±11.9 to 48.1±23.5 nmol/l during a very low-calorie diet period 2.
- Thyroid function: Thyroid hormones significantly affect SHBG production, with thyroid disorders causing notable fluctuations 3, 4.
Metabolic Conditions:
- Obesity: A major confounder that decreases SHBG levels 3.
- Insulin resistance: Associated with lower SHBG levels 5.
- Liver disease/cirrhosis: Can significantly alter SHBG production since it's primarily synthesized in the liver 3, 4.
Medications and Substances:
- Oral contraceptives: Can increase SHBG levels substantially 3.
- Hormone replacement therapy: Different administration routes have varying impacts (transdermal has less effect than oral) 3.
- Alcohol consumption: Can influence SHBG concentrations 4.
- Certain foods: Licorice and grapefruit juice can affect hormone metabolism and potentially SHBG levels 3.
Monitoring SHBG Levels
The Endocrine Society recommends:
- Measuring SHBG and free testosterone levels every 3-6 months when monitoring hormone status 3.
- Using calculated free testosterone rather than free androgen index, as the latter correlates poorly with actual free testosterone levels 3.
Clinical Implications of SHBG Fluctuations
SHBG binds sex steroids with high affinity, regulating their availability in blood and accessibility to target tissues 5. Since SHBG tightly binds testosterone, making it biologically unavailable, fluctuations in SHBG directly impact free hormone levels 1.
In the context of metabolic health, the EASL-EASD-EASO clinical practice guidelines note that circulating SHBG levels can serve as a surrogate marker for target engagement in certain treatments, such as resmetirom for metabolic dysfunction-associated steatotic liver disease 6.
Important Considerations
- Normal variability: A single measurement may not reflect your typical levels due to natural fluctuations.
- Clinical context: Interpretation of SHBG levels should always consider clinical symptoms and other hormone measurements.
- Testing conditions: For the most accurate results, SHBG should be measured under standardized conditions, preferably in the morning.
For your specific case with a previous measurement of 99 nmol/L, this would be considered on the higher end of the normal range. Follow-up testing may be warranted, especially if you're experiencing symptoms that could be related to hormone imbalances.