5a-DHT

5a-Dihydrotestosterone

5-alpha-dihydrotestosterone (5-alpha-DHT), also known as Dihydrotestosterone or DHT, is a potent androgen derived from testosterone that plays a crucial role in various physiological processes, including the development of male secondary sexual characteristics and the maintenance of reproductive function.

It has various clinical implications for health and disease primarily in men but also in women.

Testosterone, classically considered a male hormone, plays a multifaceted role beyond its association with masculinity. As a pivotal biomarker of health and wellness, testosterone influences various physiological processes in both men and women.

5-alpha-DHT serves multiple essential functions in men and women, including regulating libido, building muscle mass and bone density, enhancing red blood cell production, stabilizing mood and promoting an overall sense of well-being.

It also directs the development and maintenance of masculine secondary sexual characteristics including deepening of the voice, growth of facial and body hair, changes in fat distribution, leading to a more "masculine" body shape, and others.

Understanding the level of 5-alpha-DHT in the body is essential in assessing hormone balance and activity in men and women.

What is 5-alpha-Dihydrotestosterone (5-alpha-DHT?)

5-alpha-DHT is the active form of testosterone. The conversion of testosterone to 5-alpha-Dihydrotestosterone (5-alpha-DHT) occurs through the action of the enzyme 5-alpha reductase.

There are two isoenzymes of 5-alpha reductase: type 1 and type 2. Type 1 is present in most tissues, while type 2 is primarily found in the prostate and genital tissues. [17.]

This process primarily takes place in target tissues such as the prostate gland, hair follicles, and skin. 5-alpha-DHT is synthesized locally within these tissues and exerts its biological effects by binding to androgen receptors with greater affinity than testosterone.

This conversion is essential for the development and maintenance of male reproductive tissues and secondary sexual characteristics. However, excessive 5-alpha-DHT production has been implicated in conditions like androgenic alopecia and benign prostatic hyperplasia (BPH).

5-alpha-Dihydrotestosterone (5-alpha-DHT) is also produced in women through the conversion of testosterone by the enzyme 5-alpha reductase. While women have lower levels of testosterone compared to men, they still possess the necessary enzymes and tissues—such as the skin, hair follicles, and adrenal glands—that can convert testosterone into 5-alpha-DHT.

Although 5-alpha-DHT is present in smaller quantities in women, it still plays a role in maintaining libido, bone density, and overall sense of well-being. However, excessive 5-alpha-DHT production in women can lead to conditions like hirsutism (excessive body hair growth), acne, and female pattern hair loss.

Understanding 5-alpha-DHT production in women is important for managing hormonal imbalances and associated health issues.

What is Free 5-alpha-DHT?

Free 5-alpha-Dihydrotestosterone (5-alpha-DHT) refers to the unbound, bioavailable form of the hormone circulating in the bloodstream, readily available to exert its physiological effects on target tissues.

Unlike bound 5-alpha-DHT, which is attached to proteins like sex hormone-binding globulin (SHBG) and albumin and may be less active, free 5-alpha-DHT can interact with androgen receptors in various tissues, influencing processes such as hair growth, prostate function, and sexual development.

Monitoring free 5-alpha-DHT levels can provide valuable insights into androgen status and potential health implications, particularly in conditions like androgenic alopecia and benign prostatic hyperplasia (BPH).

What Does 5-alpha-DHT Do?

As the active metabolite of testosterone, 5-alpha-DHT is responsible for the effects of testosterone in men and women:

Primary sexual development in males: testicular descent, spermatogenesis, enlargement of the penis and testes, and increasing libido are all due to rising testosterone levels in males

Secondary sex characteristics: it plays a crucial role in the development and maintenance of male secondary sexual characteristics in males including muscle mass, enlargement of the Adam’s apple, voice deepening, and body hair growth

Libido and sexual function: testosterone promotes healthy sexual function by regulating libido and contributing to sexual desire and arousal in both men and women

Spermatogenesis: testosterone is responsible for sperm production in men

Increases in muscle mass: testosterone stimulates protein synthesis in muscles

Red blood cell production: through a process called erythropoiesis, testosterone stimulates red blood cell production, contributing to the oxygen-carrying capacity of the blood and overall cardiovascular health. This is also why men have a higher hematocrit than women. [1.]

Mood: Testosterone may play a role in mood stability by enhancing the effects affecting emotions and mental well-being and reducing depressed symptoms. [19.]

Bone Health in Females: In females, testosterone contributes to bone strength, helping to maintain skeletal health and reduce the risk of osteoporosis. [23.]

Testing and Monitoring 5-alpha-DHT Levels

Overview of 5-alpha-DHT Testing Methods

Testing for free 5-alpha-Dihydrotestosterone (5-alpha-DHT) levels typically involves assessing the amount of unbound 5-alpha-DHT circulating in the bloodstream. This can be achieved through laboratory assays that measure the concentration of free 5-alpha-DHT in serum or plasma samples.

Various techniques may be employed, including immunoassays and liquid chromatography-mass spectrometry (LC-MS), which provide accurate quantification of free 5-alpha-DHT levels.

Urine testing for 5-alpha-DHT can also be used as part of a comprehensive assessment of androgen metabolism. [12.]

Additionally, some specialized testing methods may assess free 5-alpha-DHT directly in specific target tissues, such as the scalp for individuals experiencing hair loss. Monitoring free 5-alpha-DHT levels can offer valuable insights into androgen status and help diagnose and manage conditions related to 5-alpha-DHT imbalance, such as androgenic alopecia and benign prostatic hyperplasia (BPH).

When to Test 5-alpha-DHT Levels

Clinical indications for testing 5-alpha-DHT in men and women include:

Androgen-related conditions: Assessment of 5-alpha-DHT levels may be warranted in individuals presenting with symptoms of androgen excess or deficiency, such as hirsutism (excessive hair growth), androgenic alopecia (male-pattern baldness), acne, virilization in women, or symptoms of hypogonadism in men.

Evaluation of androgenetic alopecia: 5-alpha-DHT is implicated in the pathogenesis of androgenetic alopecia, commonly known as male-pattern baldness. Testing 5-alpha-DHT levels can aid in diagnosing and monitoring this condition, particularly in men.

Monitoring androgen replacement therapy: In individuals undergoing androgen replacement therapy for conditions such as hypogonadism or transgender hormone therapy, assessing 5-alpha-DHT levels can help ensure therapeutic efficacy and safety, as excessive 5-alpha-DHT levels may lead to adverse effects such as prostate enlargement or acne.

Evaluation of hyperandrogenism: Testing 5-alpha-DHT levels can be useful in assessing hyperandrogenic disorders in women, including polycystic ovary syndrome (PCOS), congenital adrenal hyperplasia (CAH), and androgen-secreting tumors, which may present with symptoms such as irregular menstruation, acne, and hirsutism.

Monitoring response to treatment: Measuring 5-alpha-DHT levels before and after initiating treatment for androgen-related conditions allows healthcare providers to assess treatment effectiveness and adjust therapy as needed. This may include interventions such as anti-androgen medications, oral contraceptives, or lifestyle modifications.

Common Testing Methods for 5-alpha-DHT

Free 5-alpha-DHT Blood Test:

Blood testing for free 5-alpha-Dihydrotestosterone (5-alpha-DHT) serves as a valuable diagnostic tool in assessing androgen status, particularly in individuals presenting with symptoms of androgen excess or deficiency.

Benefits: considered the gold standard for testosterone assessment, blood testing offers convenience and widespread availability, providing healthcare providers with quantitative data on circulating free 5-alpha-DHT levels.

Drawbacks: like testosterone 5-alpha-DHT may have diurnal fluctuations. Additionally, it may not fully capture tissue-specific 5-alpha-DHT activity, as 5-alpha-DHT exerts its effects primarily at the cellular level.

Despite these drawbacks, blood testing for free 5-alpha-DHT remains an essential component of endocrine evaluation, aiding in the diagnosis and management of various androgen-related conditions.

Requires venipuncture, which may be uncomfortable for some individuals.

5-alpha-DHT Urine Test:

Urine testing offers insights into androgen metabolism pathways, particularly through assessing alpha vs. beta androgen metabolites including 5-alpha-DHT. It aids in monitoring testosterone therapy as it relates to testosterone metabolism, including transdermal, intramuscular injection, and pellet administration, as urine levels typically correlate with serum levels. [5., 7.]

Benefits: ease of sample collection and the ability to measure both free and conjugated forms of 5-alpha-DHT, offering a comprehensive view of androgen status. Urine testing for 5-alpha-DHT also allows for multiple samples to be collected over a specified time period, enabling evaluation of diurnal variations in 5-alpha-DHT levels. `

Drawbacks: Less commonly used. 5-alpha-DHT levels in urine may be influenced by factors such as hydration status and kidney function.

5-alpha-DHT Scalp Testing

5-alpha-DHT testing at the scalp involves assessing the concentration of 5-alpha-Dihydrotestosterone (5-alpha-DHT) directly on the scalp tissue or in the hair follicles. This method aims to determine the local levels of 5-alpha-DHT, which are implicated in conditions such as androgenic alopecia (male-pattern baldness).

It typically involves collecting samples of scalp tissue or hair follicles for analysis, often through biopsy or other specialized techniques.

By measuring 5-alpha-DHT levels at the scalp, healthcare providers can better understand the role of this androgen hormone in hair loss and tailor treatment approaches accordingly. However, this method is invasive and may not always be feasible for routine clinical use, limiting its widespread applicability.

Normal Reference Ranges

Reference ranges are set by labs and may vary among companies. Common reference ranges include:

Men:

Serum, >19 years: 112-955 pg/mL

Urine: 5-25 ng/mg over 24 hours

Women:

Serum, 20-55 years: ≤300 pg/mL

Serum, >55 years: ≤128 pg/mL

Urine: 0-6.6 mg/mg over 24 hours

Causes of High 5-alpha-DHT

Causes of high 5-alpha-Dihydrotestosterone (5-alpha-DHT) levels in both men and women can include:

Excessive androgen production: Conditions such as polycystic ovary syndrome (PCOS) or congenital adrenal hyperplasia (CAH) can lead to increased production of androgens, including 5-alpha-DHT.

Increased activity of 5-alpha reductase enzyme: Elevated activity of the enzyme 5-alpha reductase, responsible for converting testosterone to 5-alpha-DHT, can result in higher 5-alpha-DHT levels.

Medications: Certain medications, such as testosterone replacement therapy or anabolic steroids, can raise 5-alpha-DHT levels.

‍Hormonal imbalances: Conditions associated with hormonal imbalances, such as adrenal tumors or other conditions causes excessive testosterone production, may lead to increased 5-alpha-DHT production.

Genetic factors: Inherited genetic variations or mutations affecting enzymes involved in 5-alpha-DHT metabolism or receptor sensitivity can contribute to elevated 5-alpha-DHT levels.

Insulin resistance: Conditions like metabolic syndrome or type 2 diabetes, characterized by insulin resistance, may be associated with elevated 5-alpha-DHT levels. [4.]

How to Lower 5-alpha-DHT

Dietary modifications: Reduce consumption of foods high in saturated fats and processed sugars, as they may contribute to increased 5-alpha-DHT levels. Incorporate more fruits, vegetables, and whole grains into your diet to support hormonal balance.

Anti-androgenic herbs: Consider incorporating herbs like saw palmetto, pumpkin seed oil, and spearmint tea into your routine, as they are believed to have anti-androgenic properties that may help lower 5-alpha-DHT levels. [3.]

Topical treatments: Explore the use of topical treatments containing ingredients like ketoconazole or green tea extract, which have been shown to inhibit 5-alpha-DHT production when applied to the scalp. [14., 16.]

Prescription medications: Consult with a healthcare provider about prescription medications like finasteride or dutasteride, which are FDA-approved for reducing 5-alpha-DHT levels and are commonly used to treat conditions like benign prostatic hyperplasia (BPH) and male pattern baldness.

Hormonal therapy: In some cases, hormonal therapy may be recommended to regulate hormone levels and reduce 5-alpha-DHT production. This approach should be overseen by a qualified healthcare provider to ensure safety and effectiveness.

Lifestyle modifications: Adopt healthy lifestyle habits such as regular exercise, adequate sleep, and limiting alcohol intake, as these can help maintain overall hormonal balance and support optimal 5-alpha-DHT levels.

Avoidance of androgens: Minimize exposure to androgens in the environment, such as anabolic steroids or testosterone-promoting supplements, as these can increase 5-alpha-DHT levels and lead to adverse health effects.

‍

Causes of Low 5-alpha-DHT

Age-related Decline

One of the primary factors contributing to low 5-alpha-DHT levels is the natural decline in testosterone production that occurs with age.

As men and women age, their testosterone levels gradually decrease, with levels declining per year after about the age of 30. This decline in testosterone production may lead to symptoms such as decreased libido, fatigue, decreased muscle mass, and in men, erectile dysfunction.

Medical Conditions and Diseases

Various medical conditions and diseases can also contribute to low 5-alpha-DHT levels in men. These may include conditions affecting the testes, such as hypogonadism, testicular cancer, or injury to the testes.

Additionally, conditions affecting the hypothalamus or pituitary gland, such as pituitary tumors or head trauma, can disrupt the production of hormones that stimulate testosterone production.

Other medical conditions, such as obesity, diabetes, chronic illness, or HIV/AIDS, are also associated with lower testosterone levels. [9.]

Medications and Lifestyle Factors

Various medications and lifestyle factors that decrease testosterone will also decrease free and total 5-alpha-DHT levels.

Certain medications and lifestyle factors can impact testosterone levels. Medications such as corticosteroids, opioid pain medications, and chemotherapy drugs can suppress testosterone production. Excessive alcohol consumption, smoking, and drug use can also negatively affect testosterone levels.

Additionally, chronic stress, poor sleep quality, and a sedentary lifestyle may contribute to lower testosterone levels. Addressing these factors through lifestyle modifications and medication adjustments may help improve testosterone levels and overall health. [9.]

Certain medications, such as 5-alpha reductase inhibitors used to treat benign prostatic hyperplasia (BPH) or hair loss, can lower 5-alpha-DHT levels.

How to Increase 5-alpha-DHT

Optimize diet: Consume foods rich in healthy fats, such as avocados, nuts, seeds, and fatty fish, to support hormone production.

Manage stress: Implement stress-reduction techniques like meditation, yoga, or deep breathing exercises to lower cortisol levels, which can inhibit testosterone and therefore 5-alpha-DHT production. [21.]

Regular exercise: Engage in resistance training and high-intensity interval training (HIIT) to stimulate testosterone production, which can subsequently increase 5-alpha-DHT levels. [22.]

Get adequate sleep: Prioritize quality sleep to optimize hormone regulation and promote 5-alpha-DHT synthesis during nighttime.

Maintain optimal weight: Achieve and maintain a healthy weight to prevent excess body fat, which can lead to hormonal imbalances and inhibit 5-alpha-DHT production.

Consider supplements: Certain supplements like zinc, DHEA and vitamin D may support 5-alpha-DHT production and metabolism when taken as directed by a healthcare provider. [13.]

Limit alcohol consumption: Excessive alcohol intake can impair liver function, affecting hormone metabolism and potentially reducing 5-alpha-DHT levels.

Discuss testosterone replacement therapy (TRT) with your doctor to see if you may be a candidate.

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What's

5a-DHT

5a-Dihydrotestosterone (5a-DHT) is a powerful hormone that plays a significant role in both males and females. It's a derivative of testosterone, one of the most well-known hormones, and is actually considered to be its more potent form. In males, 5a-DHT is responsible for the development of male characteristics during puberty, such as the deepening of the voice, growth of facial and body hair, and the development of the male reproductive system. It also plays a role in maintaining prostate health. In females, 5a-DHT is present in smaller amounts but is equally important. It contributes to the growth of body hair and plays a role in the health and function of the reproductive system. 5a-DHT is produced in various parts of the body, including the adrenal glands, hair follicles, and the prostate or ovaries. It's a key player in the complex symphony of hormones that keep our bodies functioning properly.

If Your Levels Are High

High levels of 5a-Dihydrotestosterone (5a-DHT), a potent form of testosterone, could indicate a variety of conditions or factors. In men, it could suggest an overactive adrenal gland or prostate, as these are areas where the hormone is produced. It could also be a sign of certain genetic conditions that cause the body to produce more 5a-DHT. In women, high levels might be linked to conditions like polycystic ovary syndrome (PCOS), which can cause the ovaries to produce more of this hormone. Certain medications, such as those used to treat prostate issues in men or hormonal imbalances in women, can also increase 5a-DHT levels. Additionally, external factors like stress or intense physical activity can temporarily boost 5a-DHT production. It's important to note that while 5a-DHT plays crucial roles in the body, too much of it can lead to issues like hair loss in both men and women.

Symptoms of High Levels

Symptoms of high levels of 5a-Dihydrotestosterone could include excessive hair growth or hair loss, changes in skin condition such as acne, changes in mood or behavior, and in men, enlargement of the prostate or increased urination. In women, symptoms might also include irregular menstrual cycles or signs of masculinization, such as a deepening voice.

If Your Levels are Low

Low levels of 5a-Dihydrotestosterone (5a-DHT), a strong hormone derived from testosterone, could mean a few things. In men, it might suggest issues with puberty development, like voice deepening, body hair growth, and the formation of the male reproductive system. It could also hint at problems with prostate health. For women, who naturally have less 5a-DHT, low levels might affect body hair growth and the reproductive system's health and function. This hormone is made in different parts of the body, like the adrenal glands, hair follicles, and the prostate or ovaries. Certain medications, like 5-alpha reductase inhibitors used for conditions like enlarged prostate or hair loss, can also lower 5a-DHT levels. So, low levels could be due to these medications or conditions like 5-alpha reductase deficiency, which affects how the body makes 5a-DHT.

Symptoms of Low Levels

Symptoms of low levels of 5a-Dihydrotestosterone could include delayed or incomplete puberty in males, such as lack of deepening of the voice or body hair growth. In adults, symptoms might include decreased libido, erectile dysfunction, or changes in body composition. In females, symptoms could include changes in body hair growth or menstrual irregularities.

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See References

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[2.] Bachmann G, Bancroft J, Braunstein G, Burger H, Davis S, Dennerstein L, Goldstein I, Guay A, Leiblum S, Lobo R, Notelovitz M, Rosen R, Sarrel P, Sherwin B, Simon J, Simpson E, Shifren J, Spark R, Traish A; Princeton. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. Fertil Steril. 2002 Apr;77(4):660-5. doi: 10.1016/s0015-0282(02)02969-2. PMID: 11937111.

[3.] Cho YH, Lee SY, Jeong DW, Choi EJ, Kim YJ, Lee JG, Yi YH, Cha HS. Effect of pumpkin seed oil on hair growth in men with androgenetic alopecia: a randomized, double-blind, placebo-controlled trial. Evid Based Complement Alternat Med. 2014;2014:549721. doi: 10.1155/2014/549721. Epub 2014 Apr 23. PMID: 24864154; PMCID: PMC4017725.

[4.] Cui P, Hu W, Ma T, et al. Long-term androgen excess induces insulin resistance and non-alcoholic fatty liver disease in PCOS-like rats. The Journal of Steroid Biochemistry and Molecular Biology. 2021;208:105829. doi:https://doi.org/10.1016/j.jsbmb.2021.105829

[5.] Dehennin L, Matsumoto AM. Long-term administration of testosterone enanthate to normal men: Alterations of the urinary profile of androgen metabolites potentially useful for detection of testosterone misuse in sport. The Journal of Steroid Biochemistry and Molecular Biology. 1993;44(2):179-189. doi:https://doi.org/10.1016/0960-0760(93)90026-s‌

[6.] 5-alpha-Dihydrotestosterone, Serum - Mayo Clinic Laboratories | Pediatric Catalog. Testcatalog.org. Published 2019. Accessed February 28, 2024. https://pediatric.testcatalog.org/show/5-alpha-DHTS

[7.] Eklund E, Andersson A, Ekström L, Hirschberg AL. Urinary Steroid Profile in Elite Female Athletes in Relation to Serum Androgens and in Comparison With Untrained Controls. Frontiers in Physiology. 2021;12. doi:https://doi.org/10.3389/fphys.2021.702305

[8.] Keevil B, MacDonald P, Macdowall W, Lee D, Wu F. Salivary testosterone measurement by liquid chromatography tandem mass spectrometry in adult males and females. Annals of Clinical Biochemistry: International Journal of Laboratory Medicine. 2013;51(3):368-378. doi:https://doi.org/10.1177/0004563213506412

[9.] Ko DH, Kim SE, Lee JY. Prevalence of Low Testosterone According to Health Behavior in Older Adults Men. Healthcare (Basel). 2020 Dec 24;9(1):15. doi: 10.3390/healthcare9010015. PMID: 33374470; PMCID: PMC7824172.

[10.] Lood Y, Aardal-Eriksson E, Webe C, Ahlner J, Ekman B, Wahlberg J. Relationship between testosterone in serum, saliva and urine during treatment with intramuscular testosterone undecanoate in gender dysphoria and male hypogonadism. Andrology. 2017;6(1):86-93. doi:https://doi.org/10.1111/andr.12435

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[12.] Newman M, Curran DA. Reliability of a dried urine test for comprehensive assessment of urine hormones and metabolites. BMC Chem. 2021 Mar 15;15(1):18. doi: 10.1186/s13065-021-00744-3. PMID: 33722278; PMCID: PMC7962249.

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Test for

5a-Dihydrotestosterone

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The DUTCH Sex Hormone Metabolites test measures estrogen, progesterone, and androgen hormones and metabolites. It is perfect to use for a baseline hormone reading or to monitor hormone replacement therapy. This test cannot be ordered for patients under 12 years of age.

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The Hormone and Urinary Metabolites Assessment Profile (HuMap™) provides a comprehensive overview of steroid hormones, their metabolites, and the efficiency of the enzymes that metabolize these hormones.

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This bundle combines the DUTCH Cycle Mapping™ and the DUTCH Complete™ tests. It offers a comprehensive hormonal analysis throughout the entire menstrual cycle. This bundle cannot be ordered for patients under 12 years of age.

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The DUTCH Cycle Mapping™ PLUS provides a comprehensive analysis of a woman's monthly cycle, including hormone metabolites and the Cortisol Awakening Response (CAR). This helps to identify issues with infertility, PCOS, and other month-long symptoms. This test includes the insomnia cortisol sample. This test cannot be ordered for patients under 12 years of age.

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