Psychological Stress [ Hypercortisolism ] 

 

• Enhanced expression and sensitivity of DHT receptors in hair follicle cells

• Increases 5α-reductase, Type 1

 

Chronic psychological stress leads to sustained elevations in cortisol, when cortisol remains elevated over time, it disrupts the normal signaling of the HPG axis, which governs sex hormone production and feedback regulation. This dysregulation has been shown to inadvertently shift metabolism in a way that favors 5α-reductase type 1, and subsequent DHT accumulation. 

 

Concurrently, stress and cortisol signaling also enhances the expression and sensitivity of androgen receptors (ARs) in hair follicle cells,  creating heightened receptor sensitivity and a permissive environment for accelerated follicular miniaturization and hair loss in response to DHT. [23]

 

Elevated Insulin [ Impaired Glucose Tolerance ]

 

• Increases 5α-reductase, Type 1

 

Research shows that insulin spikes associated with high sugar consumption or impaired glucose metabolism significantly increase the activity of 5α-reductase, particularly Type 1 (5αR1), involved in oily skin, hair and acne.  

 

One study demonstrated that between both men and women, higher fasting insulin, increased 5α-reductase activity by approximately 30 - 50%, depending on sex. Another study demonstrated that insulin directly increased the amount of genetic material (mRNA) used to make the 5α-reductase type 1 enzyme within ovarian cells. When insulin was elevated, it doubled 5αR1 within 6 hours, and increased significantly within 12 hours. Whereas no appreciable expression of 5α-reductase type 2 was detected.[18][19]

 

Overweight Status

 

• Increases 5α-reductase, Type 1

 

In circumstances of Increased body fat or obesity, the body processes the hormone cortisol differently. Specifically, cortisol is more favourably broken down via the 5α-reduction pathway, which is carried out by the enzyme 5α-reductase type 1 (5αR1), rather than the normal 5β-reduction pathway.

 

This increase in 5α-reductase appears to be the body's way of protecting itself from the harmful metabolic effects of too much active cortisol, increasing glucose production, fat storage, and insulin resistance in an already compromised position. The byproduct of this is decreased cortisol but elevated DHT.[20]

 

Genetic Disposition 

 

• Increases 5α-reductase, Type 2

 

A genetic polymorphism in the SRD5A2 gene results in a change in the 5α-reductase type 2 enzyme, which increases its activity, allowing it to convert testosterone to dihydrotestosterone (DHT) more efficiently. 

 

This leads to higher local DHT levels in tissues such as the prostate, skin, and hair follicles. Clinically, this gene polymorphism has been linked to increased risk or severity of conditions like benign prostatic hyperplasia (BPH), prostate cancer, and male pattern baldness.[22]

 

Female Hormone Disorders

 

Since DHT is converted from the precursor Testosterone, all hormonal imbalances that correlate to high testosterone production naturally contribute to high DHT, if the enzyme 5α-reductase activity is not limited. For women these imbalances include:

 

• Polycystic Ovaries (PCO)

• Polycystic Ovarian Syndrome (PCOS)

• Increased LH:FSH Ratio

• Progesterone Deficiency

• Elevated Prolactin

• Aromatase Deficiency 

 

Low Sex Hormone Binding Globulin (SHGB) 

 

SHBG is a plasma glycoprotein produced by the liver that binds to DHT, limiting its bioavailability. As a result reduced SHBG levels can significantly increase the proportion of free, unbound DHT, which enhances receptor activation in target tissues such as the scalp, skin, and prostate, potentially exacerbating DHT-mediated conditions including androgenetic alopecia, acne, hirsutism, and benign prostatic hyperplasia.

 

In one clinical study SHBG was measured in 64 men with androgenetic alopecia and in forty males within the same age range without alopecia. The results identified a significant reduction in SHBG levels in bald men, compared with controls. [28] Another study demonstrated for every 24 nmol/L decrease of SHBG found in blood samples, it correlated with a 6.5% reduction in scalp hair density.[29]

 

In relation to a study on women with acne, participants were also found to have much lower levels of SHBG compared to those without acne. In women with acne only, the average SHBG level was 48 nmol/L. In those with acne plus male pattern hair growth, it dropped further to 39 nmol/L. Whereas healthy women without acne had an average SHBG level of 70 nmol/L. [30]
 

Further studies demonstrate the necessary balance between SHBG and DHT levels for maintaining prostate homeostasis. With disruptions of this balance, particularly when SHBG decrease by 20 nmol from standard measure, it increases the risk of benign prostate hyperplasia by approximately 33%  and overall results in greater prostate instability and even increased risk of cancer development and progression.[31][32]

 

Factors attributing to low SHBG factors include: 

 

• Hypothyroidism: cases exhibiting decreased SHGB levels, approx 25% lower compared to individuals with normal thyroid function.

• Elevated Prolactin, also driven by Dopamine Deficiency

• Elevated Insulin, also driven by Impaired Glucose Metabolism  

• Age, with a 2.4% decrease in SHBG every year from beginning of 30’s through to 60

 

[25][26][27][28][33][35]

 

Nutritional deficiencies 

 

Divalent metal ions play a crucial regulatory role in modulating the activity of 5α-reductase. A deficiency in these minerals may lead to unchecked 5α-reductase activity and increased DHT production. Key inhibitory minerals include:

 

• Zinc

• Copper

• Iron [44]