Unlocking Hormonal Balance: A Deep Dive into SHBG, PCOS, and DHEA

Abstract

Welcome to this educational journey into the complex world of hormonal health. As Dr. Jimenez, I am excited to share insights gleaned from my clinical practice and the latest evidence-based research from leading experts in functional and integrative medicine. In this post, we will unravel the complexities of key hormonal markers and conditions that often present challenges in clinical practice. We will begin by exploring the crucial role of Sex Hormone-Binding Globulin (SHBG), debunking common misconceptions about lowering SHBG levels, and highlighting its significance as a predictive marker of metabolic health. From there, we will delve into the multifaceted nature of Polycystic Ovary Syndrome (PCOS), discussing its phenotypes, diagnostic criteria, and the foundational roles of insulin resistance and gut health in its pathophysiology. I will share integrative treatment strategies that move beyond symptom management to address root causes. We will also navigate the nuances of interpreting Prostate-Specific Antigen (PSA) levels, explaining how to use free PSA and advanced imaging to make more accurate assessments and avoid unnecessary procedures. Finally, we will shine a light on the often-overlooked but vital hormone, DHEA, discussing its impact on well-being, cognition, and libido, and providing guidance on proper dosing and replacement. Throughout this discussion, I will incorporate how integrative chiropractic care plays a supportive role by addressing the body’s structural and neurological integrity, which is foundational to overall physiological function and hormonal balance.

The Misunderstood Role of Sex Hormone-Binding Globulin (SHBG)

In my years of clinical practice, one of the most frequent questions I encounter concerns Sex Hormone-Binding Globulin (SHBG). Many practitioners and patients see a high SHBG level and immediately ask, “How do I lower it?” This question stems from a basic understanding of hormone transport.

Understanding SHBG’s Function

Think of SHBG as a taxi service for your hormones, particularly androgens like testosterone and estrogens. It’s a protein produced primarily in the liver that binds to these hormones and transports them through the bloodstream.

• SHBG binds to hormones like testosterone and estrogen in the blood.
• It carries these hormones to various cells throughout the body.
• Upon reaching a cell, it drops the hormone off at a receptor site.
• Once a hormone is bound to SHBG, it is considered inactive.
• When the hormone is released from SHBG at the cell’s receptor, it becomes active and can perform its specific function within the cell.

It is important to note that SHBG has a higher affinity for androgens, meaning it binds testosterone more readily than estrogen. This is a critical point. In a patient’s health journey, their lab work showed a relatively high estrogen level and a total testosterone of only 130 ng/dL. They were experiencing significant symptoms of low testosterone, and the reason was their high SHBG. It was binding up most of their available testosterone, leaving very little “free” or bioavailable testosterone to do its job. A high level of SHBG can effectively lower your active testosterone levels.

Why You Shouldn’t Aim to Lower SHBG

Despite this, the goal should not be to artificially lower SHBG. The latest research indicates that a high SHBG is actually associated with positive long-term clinical outcomes. Conversely, low SHBG is a strong predictor of significant health problems.

Studies have consistently shown that low levels of SHBG are linked to:

• Increased risk for cardiovascular disease.
• A higher incidence of metabolic syndrome-related diseases.
• Increased cardiovascular mortality.
• A strong correlation with insulin resistance (Sutton-Tyrrell et al., 2005).

Low SHBG is one of the earliest signs of metabolic dysfunction. We often see shifts in SHBG levels long before a patient’s HbA1c (a marker for long-term blood sugar control) moves out of the normal range. This makes SHBG an invaluable predictive tool. For instance, in women with Polycystic Ovary Syndrome (PCOS), who often present with insulin resistance, we frequently see SHBG levels on the low side of the bell curve.

A study published in Diabetes Care found that women with higher SHBG levels had an 80% lower risk of developing diabetes, while men with higher SHBG levels had a 51% lower risk (Ding et al., 2009). The evidence is clear: forcing SHBG down is counterproductive. The only ways to pharmacologically lower it are by increasing insulin or estrogen, both of which carry their own set of health risks.

The real solution is to overcome the binding effect of a high SHBG by saturating the receptors. This is achieved by carefully raising a patient’s total testosterone to a level where, even after SHBG has bound its share, there is still an adequate amount of free testosterone left over to ensure the patient feels well and is asymptomatic. This is why certain supplements, like Shilajit, can be so effective. They help increase free testosterone, which has allowed me to help my female patients feel their best without pushing their total testosterone to excessively high levels (e.g., 400-450 ng/dL) just to achieve an optimal free testosterone.

It’s also crucial to identify what might be artificially elevating SHBG. Common culprits include oral contraceptives (birth control pills), excessive alcohol consumption, and certain prescription medications. In our practice, as we treat patients for metabolic issues and optimize their hormones, we often see a low SHBG level naturally rise into a healthier range, which is a positive indicator that their metabolic health is improving.

Decoding Polycystic Ovary Syndrome (PCOS)

PCOS is one of the most common endocrine disorders in reproductive-age women, yet it is frequently misunderstood and missed. The classic image of a PCOS patient— higher weight, with acne and hirsutism (male-pattern hair growth)—represents only a fraction of those affected. The condition is far more complex.

The Root Cause: Insulin Resistance

The primary defect in the etiology of PCOS is hyperinsulinemia, or chronically high insulin levels. This metabolic issue often begins in the gut with dysbiosis (an imbalance of gut bacteria). This hyperinsulinemia directly results in the low SHBG levels and, consequently, the high free testosterone that drives many PCOS symptoms.

The elevated insulin leads to testosterone hypersensitivity, causing symptoms such as:

• Cystic acne
• Hirsutism
• Hair loss or male-pattern baldness
• Irregular or absent menstrual cycles

Diagnostic Criteria and Hidden Phenotypes

The diagnostic landscape for PCOS has evolved. We now recognize multiple phenotypes, meaning not all patients look the same. I recently had a 21-year-old patient, a tall, fit collegiate volleyball player. Her labs were classic for PCOS: her Luteinizing Hormone (LH) was nearly triple her Follicle-Stimulating Hormone (FSH), her total testosterone was a modest 40 ng/dL, but her free testosterone was over 8 pg/mL (well above the reference range), and her SHBG was low-normal. Yet she had no hirsutism or acne and was not overweight. Her chief complaint was debilitatingly painful and irregular periods. Without a comprehensive review of her labs and an understanding of PCOS variants, her condition could easily have been missed.

The Rotterdam criteria, the standard for diagnosis, require two of the following three to be present:

1. Oligo-ovulation or anovulation: Infrequent or absent ovulation, presenting as irregular periods.
2. Hyperandrogenism: Clinical signs (acne, hirsutism) or biochemical signs (high free testosterone).
3. Polycystic ovaries on ultrasound: It’s important to note that not all women with PCOS have cysts, and not all ovarian cysts indicate PCOS.

An Integrative Approach to PCOS Treatment

Conventional treatment often focuses on symptom management with medications like birth control pills (to raise SHBG and bind excess androgens) or Spironolactone (to block androgen receptors). While these can be part of a comprehensive plan, they do not address the root cause.

Our approach is to fix the underlying gut dysfunction and insulin resistance.

1. Address Insulin Resistance: Historically, Metformin was the go-to. However, the high doses required (up to 2000mg/day) often cause significant gastrointestinal side effects. Newer options like GLP-1 agonists (e.g., Semaglutide) are game-changers. They effectively lower insulin, which in turn raises SHBG and reduces testosterone sensitivity, helping restore normal menstrual cycles. This process can take time—sometimes up to two or three years to see full restoration of ovulation. I had one patient who, after years of struggling with PCOS-related infertility, finally addressed her insulin resistance and gut health. Three years later, at 37, she conceived her first child. To her surprise, a year after that, she conceived again, a testament to the power of resolving the underlying metabolic issues.
2. Support Gut Health: An anti-inflammatory diet and intermittent fasting are highly beneficial. We also use targeted supplements. A combination product containing Akkermansia muciniphila, a beneficial gut bacterium, has been shown in multiple studies to naturally increase the body’s own GLP-1 production, making it an outstanding tool for these patients.
3. Manage Symptoms: For hirsutism, Spironolactone (100mg daily) can be effective. It blocks androgen receptors, but it can take 6-12 months to see a significant effect. It is a blocker, not a long-term fix for the hormonal imbalance.
4. Hormone Pellet Therapy: For patients who look like they have PCOS or have a history of it, we must be cautious with testosterone pellet therapy. Their low SHBG means that even a standard dose of testosterone can cause their free testosterone to skyrocket, leading to side effects. The rule here is to start low and go slow, using a very conservative dose (e.g., 50-80mg) and monitoring closely.

Chiropractic care is a vital component of this integrative strategy. By performing spinal adjustments, we can help regulate the autonomic nervous system. The nerve supply to the adrenal glands, pancreas, and ovaries originates in the spine. By ensuring proper nerve function through chiropractic adjustments, we can help modulate the body’s stress response (cortisol) and support better organ function, which is foundational for correcting the hyperinsulinemia and hormonal dysregulation seen in PCOS.

Navigating PSA and Prostate Health

Screening for prostate cancer with Prostate-Specific Antigen (PSA) has become confusing, with guidelines changing over the years. Simply looking at a total PSA number is not enough.

Beyond Total PSA: The Importance of Free PSA

PSA is a protein produced by the prostate gland. To get a more accurate picture of a man’s risk, we must look at the percent free PSA.

• Total PSA: The overall amount of PSA in the blood.
• Free PSA: The amount of PSA that is not bound to other proteins.

There is an inverse relationship: the lower the percent free PSA, the higher the risk for prostate cancer. A low free PSA percentage is a more sensitive and accurate indicator than total PSA alone.

Another critical factor is PSA velocity, or the rate of change over time. A PSA that jumps by more than two points in a single year is a major red flag for aggressive cancer, even if the total number is still within the “normal” range of less than 4.0 ng/mL. I have seen cases where a urologist dismissed a PSA of 3.9 as technically normal, failing to recognize that it had been 0.9 just one year prior. This rapid change demanded further investigation.

Modern Guidelines for Prostate Cancer Screening

Here is the protocol we use in our practice to help us decide when to refer to urology versus when to pursue watchful waiting.

• Total PSA > 4.0 ng/mL: We automatically reflex to run a percent free PSA.
• Free PSA < 10%: This indicates a >50% likelihood of prostate cancer. This patient needs an immediate workup.
• Free PSA 10-20%: This is an intermediate-risk zone. We can treat for potential prostatitis (inflammation of the prostate), a common cause of elevated PSA, and recheck in three months.
• Free PSA > 20%: This indicates a very low likelihood of cancer. We can recheck in three months.

Instead of immediately sending a high-risk patient for an invasive biopsy, our gold standard is a 3-Tesla multi-parametric prostate MRI. This advanced imaging can accurately identify and characterize lesions. It’s non-invasive, preferred by nearly all patients, and can also diagnose chronic prostatitis, giving us confidence that a PSA bump is inflammatory rather than malignant. We do not initiate testosterone therapy in any man with a suspicious or unevaluated PSA elevation.

It’s also important to counsel patients that activities like sexual intercourse can temporarily elevate total PSA. However, these activities do not impact the percent free PSA, making it a more stable and reliable marker.

DHEA: The Overlooked Neurosteroid

Dehydroepiandrosterone (DHEA) is a hormone produced by the adrenal glands that is often overlooked but plays a massive role in our overall health, well-being, and quality of life. I have seen countless patients, particularly women, who have good testosterone levels but still complain of low libido, depression, and fatigue. More often than not, a quick check of their DHEA level reveals the problem.

The Critical Functions of DHEA

DHEA is classified as a neurosteroid because it is also synthesized directly in the central nervous system. It has independent receptors in the brain, which explains why low levels can cause cognitive and mood symptoms even when other hormones are balanced.

Like other hormones, DHEA levels peak in our 20s and decline steadily with age. This decline is associated with:

• Poor immune function
• Inflammation
• Depression
• Reduced bone density
• Cognitive decline (the decline is even more pronounced in Alzheimer’s patients).

In women, DHEA is a significant precursor to androgens, converting readily to DHT (dihydrotestosterone), which is crucial for libido and sexual function. Simply optimizing DHEA can dramatically improve a woman’s sex drive and ability to orgasm, even if her testosterone levels are already in a good range.

Dosing and Supplementation

We aim for DHEA-S (the sulfated, more stable form) levels to be in the upper quartile of the lab’s reference range—the right side of the bell curve.

• If a patient’s DHEA is low but still in the low triple digits, simply optimizing their thyroid and other hormones can often raise it naturally.
• If DHEA is in the double digits, I treat it from day one.

In my practice, I use compounded, bioidentical DHEA. In the United States, DHEA is sold as an over-the-counter supplement, but the supplement industry is notoriously unregulated. In most other countries, it is a prescription hormone, which I believe is appropriate. For compounded DHEA, we typically start with 5-10 mg for females and 20 mg for males. If a patient prefers an over-the-counter option, I suggest starting with 25 mg and retesting levels in six weeks. We avoid DHEA in PCOS patients, as their levels are typically already elevated.

By integrating these advanced diagnostic and treatment principles—from understanding the metabolic significance of SHBG to addressing the root causes of PCOS and properly using markers such as free PSA and DHEA—we can provide a truly comprehensive and effective path to hormonal health and wellness for our patients.

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References

Ding, E. L., Song, Y., Malik, V. S., & Liu, S. (2009). Sex hormone-binding globulin and risk of type 2 diabetes in women and men. The New England Journal of Medicine, 361(12), 1152–1163. https://doi.org/10.1056/NEJMoa0806407

Sutton-Tyrrell, K., Wildman, R. P., Matthews, K. A., Chae, C., Lasley, B. L., Brockwell, S., Pasternak, R. C., & Lloyd-Jones, D. (2005). Sex-hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women: the Study of Women’s Health Across the Nation (SWAN). Circulation, 111(10), 1242–1249. https://doi.org/10.1161/01.CIR.0000157685.32134.CE