Everyone has heard of testosterone. But few are familiar with dihydrotestosterone.
Dihydrotestosterone (DHT) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT
from testosterone in certain tissues including the prostate gland, seminal vesicles, epididymides, skin, hair follicles, liver, and brain.
Testosterone is attributed with all the masculine traits it delivers from muscle mass, sexual function, recovery, antiaging and neuroprotective properties.
During puberty, it is responsible for facial and body hair and the deepening of the voice and growth. However, DHT also plays a large role in these things too. In fact, it is more powerful than testosterone in many respects and thus may play a larger role in at least some of these functions.
This is the first of a three-part article series on DHT. This first article covers the basics, the benefits, and what to look out for in high or low DHT.
The second part will dive into the confusing subject of DHT’s role in prostate issues, hair loss, as well as acne. And in part three, we’ll look at various lifestyle, diet, supplements and herbal options for either increasing or decreasing DHT.
The Basics of DHT
DHT is created inside the human body by enzymatic conversion using 5-alpha-reductase (5AR) of testosterone into DHT.
However, that is not the only way DHT can be created. Androstenedione is also converted by 5AR into androstanedione which is then converted by the enzyme 17-oxoreductase into DHT.[1] According to this study, this pathway created more DHT than through the first more well-known path.
DHT has a higher affinity (roughly double) for binding to androgen receptors in cells and furthermore, it appears to stay bound to these receptors longer (testosterone dissociating five-times faster).[2]
From that study, I found this quote interesting,
“Our results suggest that the weaker androgenic potency of testosterone compared to that of dihydrotestosterone resides in its weaker interaction with the androgen receptor, most clearly demonstrable as an increase in the dissociation rate of testosterone from the receptor. When present in relatively high concentrations, however, testosterone overcomes this defect by mass action.”
In other words, although DHT is stronger and longer-lasting, most people have one-tenth to one-twentieth the amount of DHT as total testosterone available.
Lastly, and perhaps more importantly, DHT upregulates androgen receptor synthesis and reduces turnover. [3]
I’m convinced that so much of hormone health has to do with the receptors, possibly more so than the hormones themselves. But as these are not easily measured like that of circulating amounts in the blood, we don’t have a good picture of the workings inside living human cells.
DHT also gets bound up to SHBG at a higher rate than testosterone. (As covered in this article, that doesn’t mean it’s inert, but may change in how it functions.)
Unlike testosterone, DHT cannot be converted into estrogen via the aromatase enzyme. In fact, there is limited research showing that DHT may limit aromatase activity[4] and even competes with estradiol for binding into estrogen receptors,[5] therefore having some antiestrogenic activity.
Like many other hormones, the liver is responsible for creating most DHT; however, it is also synthesized in smaller amounts locally in the genitals, prostate, skin, hair, kidneys, brain and elsewhere.
DHT Reference Ranges
1. Normal range for an adult male is 30-85 ng/dL.
2. Normal range for an adult female is 5-30 ng/dL.
As with all reference ranges, there will be some variance between labs and doctors.
Again, while looking at serum or blood levels is useful, it does not give a full picture. “Circulating levels of DHT in response to testosterone replacement therapy (TRT) do not correlate with those found in androgen-sensitive tissue (e.g., prostate, adipose, muscle) due to local regulatory mechanisms that tightly control intracellular androgen homeostasis.”[6]
This becomes particularly important when we discuss the androgen-sensitive prostate and hair follicles later on.
Ideal DHT Reference Range?
One other thing worth mentioning is something t I found in another article, it stated, “My experience on the Peak Testosterone Forum is that often men experience libido problems when one gets into the low 30’s (or below) ng/dl range.”[7]
If libido is an issue for you then you may need to consider having your DHT measured.
An ideal range for most men is probably going to be above 50 ng/dL.
Symptoms of Low DHT
• Low Sex Drive
• Impaired Sexual Function
• Decreased Muscle Mass
• Mood Swings
• Irritability
• Depression
• Lack of Motivation
• Lethargy
• Low Bone Strength
• Decreased Insulin Sensitivity
Symptoms of High DHT
• Excessive Libido
• Increased Sweating
• Increased Body or Facial Hair
• Hair Loss
• Acne
The complicated details of prostate issues and hair loss with DHT will be covered in the next article. High DHT is generally not seen as an issue, except where it may be localized in certain tissues, but this is where it starts getting into confusing topics.
Benefits from DHT as found in Human Trials
To understand some of the effects of DHT we can look at a number of studies that have been done supplementing directly with DHT.
One study used a transdermal DHT gel and looked at many different effects. This study was done with men 60 years or older for three months. 33 men completed the study, with 17 in the DHT group and 16 in the placebo control group.[8]
What Changed:
• Increased DHT (obviously)
• Decreased Total and Free Testosterone
• Decreased LH and FSH
• Decreased LDL and Total Cholesterol
• Increased Hemoglobin, Hematocrit, and Red Blood Cell Counts
• Decreased Skin Thickness
• Decreased Fat Mass
• Increased Strength (in one of the three tests used)
What did Not Change:
• SHBG
• Estradiol
• HDL
• Triglycerides
• Lean Mass
• Waist to Hip Ratio
• Strength (in two of the three tests used)
• Gait, Balance and Mobility Tests
• Cognitive Function
• Quality of Life Scales
In another study with a ten-day test of injected DHT, similar hormonal results were observed except for the lowering of estradiol (E2). [9]
Still another DHT gel study featured 120 men (60 in the DHT group and 60 with placebo) over six months. The median age was 58 years old. These men had low testosterone, high SHBG, lack of morning wood and various other symptoms associated with such before they began. [10]
These findings include:
- Morning wood increased as did the ability to maintain erections.
- LH, FSH, E2, T, and SHBG all decreased
- No changes in well-being were found.
- No changes in liver function or lipid profiles.
- Hemoglobin and hematocrit levels increased.
- Prostate weight and PSA levels did not change.
A two year daily DHT gel study looked at similar effects. Here they did find the increased lean mass and decreased fat mass though by small amounts.11]
It’s also pretty amazing to see on these charts, how supplementing with DHT radically increased DHT while also, radically decreased testosterone. These returned towards normal after the gel was stopped.
DHT and Sexual Function
DHT’s function in sex was first made clear by patients being treated for prostate disease or hair loss with drugs such as Finasteride or related 5AR-inhibiting compounds. Unfortunately, these drugs also have some devastating and sometimes permanent side effects. Placebo-controlled studies of Finasteride show this is a consistent side effect. [12]
These drugs are associated with a 5% to 9% new onset of erectile dysfunction, decreased libido, and a decreased ability to orgasm. [13] This appears to show that DHT plays a strong role in these areas, though it is not the only thing that these drugs affect.
One other interesting study looked at 92 healthy men between the ages of 18-22 years old. DHT, and only DHT out of many other hormones measured include testosterone, DHEA, estradiol, estrone, androstenedione, and SHBG, was a predictor of the number of orgasms per week. [14]
Levels of increase of DHT by 39 ng/dL in blood corresponded to an average of one more orgasm per week.
Whether these men were having more orgasms because DHT was high or they had higher DHT because they were having more orgasms, it isn’t clear. My guess is that both are true since hormones operate on feedback loops. Actions can reinforce levels which can reinforce actions and so on.
Thus, more orgasms may be important to help raise DHT and higher DHT seems to increase sexual function.
Cognitive Effects of DHT
When reviewing the data, this paper said that “likely that there are local, tissue-specific effects of DHT on cognition and/or mood that may be difficult to discern in the context of systemic hormonal alterations, despite the fact that lipophilic steroid hormones like T and DHT can cross the blood-brain barrier” [6]
Unfortunately, the specifics of such cognitive or memory effects are not known. There are some possibilities pointed out in animal studies where DHT modified the synaptic structure, but it’s too early yet to say for sure. There’s also possible action on the GABA neurotransmitter and receptors.[15]
Anti-aging, Telomere and Auto-Immune Effects of DHT
In that same review of DHT, I found this line stating that testosterone and DHT could possibly affect telomere length,
“It is intriguing to speculate that the increase in all-cause and cancer-specific mortality observed in men with low T and DHT may, in part, reflect reduced actions of DHT and estradiol to preserve telomere length.” [6]
There is also some evidence which shows that DHT plays a role in the reason that men overall, have less auto-immunity than women. [16]
DHT’s Role in Muscle Growth and Fat Loss
Some of the earlier studies noted some changes in fat and muscle mass, though not huge amounts and yet, other studies did not have the same results.
Still, there are some other studies with mice, that show some interesting interactions may occur. These include DHT promoting the uptake of amino acids into fast-twitch muscles. [17] Also, DHT increasing ATP production, cell signaling, cell proliferation, and increased protein synthesis. [18]
Clearly, DHT plays a role in a wide range of areas in the body. As you can see there is a lot of potentially important roles for DHT that we’re just now beginning to find and understand with science.
Next week, I’ll dive into DHT’s role in hair and the prostate, two of the most significant areas in which it has been implicated for decades.
References:
1. Fouad Mansour M, Pelletier M, Tchernof A. Characterization of 5α-reductase activity and isoenzymes in human abdominal adipose tissues. J Steroid Biochem Mol Biol. 2016 Jul;161:45-53. https://www.ncbi.nlm.nih.gov/pubmed/26855069
2. Grino PB, Griffin JE, Wilson JD. Testosterone at high concentrations interacts with the human androgen receptor similarly to dihydrotestosterone. Endocrinology. 1990 Feb;126(2):1165-72. https://www.ncbi.nlm.nih.gov/pubmed/2298157
3. Syms AJ , Norris JS, Panko WB, Smith RG. Mechanism of androgen-receptor augmentation. Analysis of receptor synthesis and degradation by the density-shift technique. J Biol Chem. 1985;260(1):455–461. https://www.ncbi.nlm.nih.gov/pubmed/3871197
4. Schumacher M, Hutchison RE, Hutchison JB. Inhibition of hypothalamic aromatase activity by 5 Beta-dihydrotestosterone. J Neuroendocrinol. 1991 Apr 1;3(2):221-6. https://www.ncbi.nlm.nih.gov/pubmed/19215525
5. Casey RW, Wilson JD. Antiestrogenic action of dihydrotestosterone in mouse breast. Competition with estradiol for binding to the estrogen receptor. J Clin Invest. 1984 Dec;74(6):2272-8. https://www.ncbi.nlm.nih.gov/pubmed/6542571
6. Ronald S. Swerdloff, Robert E. Dudley, Stephanie T. Page, Christina Wang, Wael A. Salameh, Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels, Endocrine Reviews, Volume 38, Issue 3, 1 June 2017, Pages 220–254, https://doi.org/10.1210/er.2016-1067
7. DHT (Dihydrotestosterone) Levels. (n.d.). Retrieved August 8, 2019, from https://www.peaktestosterone.com/DHT_Levels.aspx
8. Ly LP, Jimenez M, Zhuang TN, et al. A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. J Clin Endocrinol Metab. 2001 Sep;86(9):4078-88. https://www.ncbi.nlm.nih.gov/pubmed/11549629
9. Kuhn JM, Rieu M, Laudat MH, et al. Effects of 10 days administration of percutaneous dihydrotestosterone on the pituitary-testicular axis in normal men. J Clin Endocrinol Metab. 1984 Feb;58(2):231-5. https://www.ncbi.nlm.nih.gov/pubmed/6363434
10. Kunelius P, Lukkarinen O, Hannuksela ML, Itkonen O, Tapanainen JS. The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study. J Clin Endocrinol Metab. 2002 Apr;87(4):1467-72. https://www.ncbi.nlm.nih.gov/pubmed/11932266
11. Idan A, Griffiths KA, Harwood DT, Seibel MJ, Turner L, Conway AJ, Handelsman DJ. Long-term effects of dihydrotestosterone treatment on prostate growth in healthy, middle-aged men without prostate disease: a randomized, placebo-controlled trial. Ann Intern Med . 2010;153(10):621–632. https://www.ncbi.nlm.nih.gov/pubmed/21079217
12. Gormley GJ , Stoner E, Bruskewitz RC, et al. The Finasteride Study Group. The effect of finasteride in men with benign prostatic hyperplasia. N Engl J Med . 1992;327(17):1185–1191. https://www.ncbi.nlm.nih.gov/pubmed/1383816
13. Gur S , Kadowitz PJ, Hellstrom WJ. Effects of 5-α reductase inhibitors on erectile function, sexual desire and ejaculation. Expert Opin Drug Saf . 2013;12(1):81–90. https://www.ncbi.nlm.nih.gov/pubmed/23173718
14. Mantzoros CS , Georgiadis EI, Trichopoulos D. Contribution of dihydrotestosterone to male sexual behaviour. BMJ . 1995;310(6990):1289–1291. https://www.ncbi.nlm.nih.gov/pubmed/7773040
15. Frye CA, Park D, Tanaka M, Rosellini R, Svare B. The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference. Psychoneuroendocrinology. 2001 Oct;26(7):731-50. https://www.ncbi.nlm.nih.gov/pubmed/11500254
16. Meng-Lei Zhu, Pearl Bakhru, et al. Sex bias in CNS autoimmune disease mediated by androgen control of autoimmune regulator. Nat Commun. 2016; 7: 11350. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512610/
17. Hamdi MM, Mutungi G. Dihydrotestosterone stimulates amino acid uptake and the expression of LAT2 in mouse skeletal muscle fibres through an ERK1/2-dependent mechanism. J Physiol. 2011 Jul 15;589(Pt 14):3623-40. https://www.ncbi.nlm.nih.gov/pubmed/21606113
18. Yoshioka M, Boivin A, Ye P, Labrie F, St-Amand J. Effects of dihydrotestosterone on skeletal muscle transcriptome in mice measured by serial analysis of gene expression. J Mol Endocrinol. 2006 Apr;36(2):247-59. https://www.ncbi.nlm.nih.gov/pubmed/16595697
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Lost Empire Herbs
Could I use DHT gel be used to improv my mood?
I don’t know if DHT is used specifically for that, whereas testosterone does, but it may help.
Thanks Logan!
I love the informative science articles. However, I expected you to tell us the most important herb and dosage for regulating a positive amount of DHT. Maybe that is coming later, but I am really interested because I am sure you already have the answer.
Thanks
Again.
SL
That is covered in Part 3.
Great article Logan! I’ve been bio hacking my DHT (for increases) for about a year now with only positive results. Looking forward to the rest of this article.
Thanks, M.
Nice!! Glad to hear you have seen success!