3-Alpha Androstanediol-G

3-Alpha Diol-G, also known as 5α-androstane-3α,17β-diol glucuronide, is a C19 steroid metabolite derived from testosterone and dihydrotestosterone (DHT).  

It is produced mainly in peripheral tissues like the skin, particularly around hair follicles, where it plays a crucial role in androgen activity. 

Due to its significant role, 3-Alpha Diol-G is used as a biomarker for peripheral androgen activity and is associated with conditions such as idiopathic hirsutism, acne, polycystic ovarian syndrome (PCOS), and potentially prostate cancer.

In clinical settings, elevated levels of 3-Alpha Diol-G are linked to several health issues.  For instance, women with hirsutism and PCOS often exhibit increased 3-Alpha Diol-G levels, which decrease with effective treatment. 

Elevated levels have also been seen in prostate cancer, while decreased levels can be seen in benign prostatic hyperplasia and androgen deficiency.  

Monitoring 3-Alpha Diol-G levels helps in managing these conditions and tailoring appropriate therapeutic strategies.

What is 3-Alpha Diol-G?  [1.]

3-Alpha Diol-G, also known as 5α-androstane-3α,17β-diol glucuronide, is a C19 steroid and a metabolite of testosterone and dihydrotestosterone (DHT).  It is commonly abbreviated as 3α Diol G, 5α Diol G, or simply α Diol G. 

This compound is produced mainly in peripheral tissues such as the skin, particularly around hair follicles, where it plays a role in androgen activity.  [4.] 

Clinical Significance of 3-Alpha Diol-G

3-Alpha Diol-G is used as a biomarker for peripheral androgen activity.  

Elevated levels of 3α Diol G are associated with conditions such as idiopathic hirsutism,  acne, polycystic ovarian syndrome (PCOS), and may be associated with prostate cancer, while decreased levels may be associated with benign prostatic hyperplasia and androgen deficiency.  [2., 5., 7.]

It is particularly useful in monitoring the progress of treatment for these conditions.  For instance, increased levels of 3α Diol G have been observed in women with hirsutism and PCOS, and these levels tend to decrease with effective treatment.  

3-Alpha Diol-G Associations with Health Conditions

3-Alpha Diol-G is associated with various health conditions.  

Idiopathic Hirsutism

Elevated 3α Diol G levels are a marker for excessive hair growth in women, particularly in areas where hair is not normally present.  [11.]

Polycystic Ovarian Syndrome (PCOS)

3α Diol G levels are used to monitor androgen activity and the effectiveness of treatments in women with PCOS.  [10.] 

Acne  [3.] 

One study showed that in adult women with acne, 60% presented with increased androgen levels, and among those with normal androgen levels and no menstrual dysfunctions, 50% had elevated 3α-diol G levels. 

This suggests that high 3α-diol G is a significant factor in acne pathogenesis, indicating that anti-androgenic drugs may be beneficial for treating acne in these patients.

Cyclosporine A Therapy

Diabetic patients undergoing cyclosporine A therapy have shown increased levels of 3α Diol G, which can result in the appearance of hair in previously hairless areas.  [1.] 

Prostate Cancer  [5., 6.]

While not all research validates the relationship between 3-alpha diol-G levels, 3α-diol G is recognized as a significant precursor for dihydrotestosterone (DHT) synthesis in prostate cancer cells. 

Elevated 3α-diol G levels, facilitated by the enzyme HSD17B6, correlate with increased intratumoral DHT synthesis, contributing to prostate cancer progression and resistance to androgen deprivation therapy.

Benign Prostatic Hyperplasia  [2., 12.]

One study found that 3α-diol G (androstanediol glucuronide) levels were higher in controls compared to BPH patients. This indicates that higher levels of 3α-diol G may be associated with a lower risk of developing BPH. 

The findings imply that androgens, along with estrogens and androstanediols, play a role in the development of BPH, with the presence of testosterone potentially contributing to this condition.

Androgen Deficiency and Related Conditions

3-Alpha Diol-G levels can provide insights into androgen deficiency states, such as hypogonadism or androgen insensitivity syndromes. Low levels of 3-Alpha Diol-G may indicate a deficiency in androgen production or action, which can contribute to various clinical manifestations and guide hormone replacement therapy decisions.

Lab Testing for 3-Alpha Diol-G

Test Information, Sample Collection and Preparation

3-Alpha Diol-G can be measured in various biological samples, including blood and urine.  [8.]  Blood samples are typically collected through venipuncture, while urine samples are collected over a 24-hour period or as a spot sample.

Overnight fasting is preferred.  

Blood vs. Urine Testing of 3-Alpha Diol-G  [4., 8.] 

3-alpha diol-G (3α-diol G) is formed from the peripheral metabolism of androgens, primarily in tissues such as the skin. 

Serum 3α-diol G is produced peripherally, as confirmed by the production of 3α-diol G from skin.

In contrast, urinary 3α-diol G might include contributions from other sources, such as the kidneys, beyond just peripheral tissues. 

Therefore, while both serum and urinary 3α-diol G reflect androgen metabolism, their sources might differ, with serum 3α-diol G being more closely linked to peripheral androgen activity.

Interpretation of 3-Alpha Diol-G Test Results

Optimal Levels of 3-Alpha Diol-G

It is important to assess individual hormone levels within the context of an individual’s broader hormone profile, taking into account the metabolites of various sex hormones.  

Additionally, a comprehensive assessment of hormonal health, signs and symptoms, diet and lifestyle, and time of life must be considered.  

For reference, one company reports optimal levels of 3-alpha Diol-G in serum as: [9.] 

Adult Males: 425-3230 ng/dL

Adult Females: 77-940 ng/dL

Clinical Significance of Elevated Levels of 3-Alpha Diol-G

Elevated levels of 3-alpha diol-G may indicate conditions such as hirsutism, acne, polycystic ovary syndrome (PCOS), hirsutism, or prostate cancer.   

Clinical Significance of Decreased Levels of 3-Alpha Diol-G

Decreased levels may be associated with benign prostatic hyperplasia (BPH) or androgen deficiency.

3-Alpha Diol-G Related Biomarkers

In addition to 3-Alpha Diol-G, several other biomarkers are closely related and can provide valuable insights into androgen activity and associated medical conditions.

Testosterone (total and free)

Testosterone, the primary male sex hormone, plays a crucial role in various physiological processes. Both total testosterone and free (unbound) testosterone levels are important biomarkers for assessing androgen status. 

Elevated levels may indicate conditions like polycystic ovary syndrome (PCOS) or androgen excess disorders, while low levels can be associated with hypogonadism or androgen deficiency.

Androsterone Glucuronide

Androsterone glucuronide is another metabolite of dihydrotestosterone (DHT) and a biomarker for androgen activity.  It is formed through the metabolism of DHT by the enzyme 3α-hydroxysteroid dehydrogenase (3α-HSD) and subsequent glucuronidation, similar to the formation of 3-Alpha Diol-G. 

Elevated levels of androsterone glucuronide may be observed in conditions like PCOS and hirsutism.

Other Steroid Hormones and Metabolites

Various other steroid hormones and their metabolites can provide valuable information about androgen activity and related conditions. These include dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and estrogens. 

Measuring these biomarkers in combination with 3-Alpha Diol-G and other androgen metabolites can aid in the comprehensive evaluation of hormonal imbalances and related disorders.

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