Dihydrotestosterone – DHT

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What is Dihydrotestosterone?

Testosterone to DHT 1

Dihydrotestosterone, or DHT, is a sex hormone, like testosterone. It plays a significant role in both the development and maintenance of certain male physical and sexual characteristics. It also plays an important role in certain men’s health problems, like benign prostatic hyperplasia (prostate enlargement aka BPH) and male pattern baldness. For these reasons, dihydrotestosterone has long been a source of scientific study for the potential benefits of both supplementation and blocking.

 


 

How is DHT Formed?

DHT

Dihydrotestosterone is formed when testosterone comes into contact with the enzyme 5-alpha reductase. 5-alpha reductase then reduces testosterone into dihydrotestosterone. Once this conversion has occurred, the DHT molecule can no longer be converted into another familiar sex hormone, estradiol (a form of estrogen), by the enzyme aromatase. 5-alpha reductase is only located in specific areas of the body, including the prostate gland, testes, hair follicles, and adrenal glands. As a result, these areas are where it mainly produces its effects.

Dihydrotestosterone is actually a more potent sex hormone than testosterone. In fact, it is the strongest male androgen. It binds to the same receptor as testosterone but does so with two to three times more affinity. It also remains bound to the receptor five times longer than testosterone. This high potency has led some to theorize that supplementation with dihydrotestosterone would be a good therapy for decreased levels of testosterone in older and younger men. However, very little evidence exists that suggests DHT supplementation is beneficial.

 

Effects of Dihydrotestosterone on the Body

As previously mentioned, dihydrotestosterone is important throughout a male’s life. During puberty, it aids in the development of certain sexual characteristics, including the testes and pubic hair. It is also the major contributor to prostate growth and development. DHT also seems to play a role in sexual function, libido, and mood, as studies show that men taking the 5-alpha reductase DHT blocker may experience diminished libido, erectile dysfunction, prolonged time to ejaculation, and depression.1-2 However, the exact mechanism by which it effects sexual function, libido, and mood is unknown. Unfortunately, DHT may also induce the following two health problems in men:

  • 1) Benign prostatic hyperplasia. DHT plays a very important role in the development and progression of prostate enlargement (BPH).
  • 2) Male pattern baldness. DHT is the primary cause of male pattern baldness (MPB). It shrinks the hair follicles causing an eventual loss of hair in a specific pattern.

Interestingly, a small population of men living in the village of Salinas in the Dominican Republic cannot convert testosterone to dihydrotestosterone. They are capable of all the testosterone dependent functions, but without dihydrotestosterone their prostates remain completely underdeveloped and they retain their hairlines.3

 


 

Blocking Dihydrotestosterone: DHT Blockers

As dihydrotestosterone is a primary cause of prostatic enlargement and male pattern baldness, blocking the binding of the hormone to its receptors at these sites produces obvious benefits.4-8 The FDA approved medications in the United States for these purposes include the following drugs. Both DHT blockers are known as 5-alpha reductase inhibitors.

  • Finasteride (brand names include Proscar (5mg dose for BPH) and Propecia (1mg dose for MPB))
  • Dutasteride (brand name Avodart)

Benefits of DHT Blockers

Dutasteride is approved to treat benign prostatic hyperplasia and is frequently used off-label for male pattern baldness. Finasteride is approved to treat both conditions.9-10 A lower dose of the medications is used to treat MPB than is used to treat BPH. It should also be noted that two large randomized control trials (the Prostate Cancer Prevention Trial (PCPT)4 and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial)8 showed that men treated with either dutasteride or finasteride were less likely to develop prostate cancer.

Side Effects of DHT Blockers

Although use of 5-alpha reductase inhibitors decreased the incidence of prostate cancer in its users overall, 5-alpha reductase users had an increased incidence of high-grade prostate cancer when compared with placebo. An explanation for this phenomenon has not yet been elucidated. However, men beginning therapy with 5-alpha reductase inhibitors should have a thorough examination to rule out conditions such as prostate cancer that can mimic BPH.4,8

Other possible side effects of 5-alpha reductase inhibitors that should be noted and monitored include diminished libido, erectile dysfunction, prolonged time to ejaculation, depression, brain fog, and memory loss. Obviously, these potential side effects are clearly unwanted by any man. Therefore, it is important to weigh both the severity of the problem along with the possibility for potential side effects with your physician.

 

On a side note, another very popular and effective medication to treat male pattern baldness is minoxidil (brand name Rogaine). Minoxidil is primarily used as a blood pressure lowering medication, but it is also used topically for MPB and can decrease or stop the rate of hair loss and in some cases even regrow lost hair. Minoxidil is not a 5-alpha reductase inhibitor. The exact mechanism by which minoxidil assuages MPB is not known. Researchers speculate that by dilating blood vessels around hair follicles, it increases their supply of oxygen and nutrients consequently prolonging life.

 


 

Supplementing DHT: DHT Supplements

As mentioned above, dihydrotestosterone is a more potent sex hormone than testosterone. Since DHT is more potent than testosterone and cannot be converted into estradiol (a form of estrogen), it has been theorized that supplementation with DHT would be a good therapy for men with low testosterone. Nevertheless, very little evidence exists that suggests such supplementation is beneficial.

First, dihydrotestosterone levels in the blood do not change substantially in aging men, unlike testosterone and free testosterone which both significantly decline.11-17 Thus, it is not necessary to replace DHT. Second, dihydrotestosterone does not convert back into testosterone, so supplementing with DHT will not increase testosterone levels in men with low testosterone. Third, while DHT is more potent than testosterone, it possesses far less anabolic (muscle-building) action. Therefore, it fails to produce many of the positive effects testosterone supplementation might otherwise produce. Lastly, as mentioned above, DHT plays an important role in certain men’s health problems, like benign prostatic hyperplasia (prostate enlargement aka BPH) and male pattern baldness.

Advanced Discussion

The available data on DHT supplementation is sparse and there are few studies available on the matter, none of them large scale. One small placebo controlled trial evaluated the effect of transdermal dihydrotestosterone gel in older men with partial androgen deficiency showed that, although DHT supplementation was safe and had expected effects on blood levels of certain steroid hormones, it had little effect on physical or cognitive functioning.18 Another small study showed that transdermal dihydrotestosterone administration in healthy older men had a mild but statistically significant decrease in overall sexual desire that abated after discontinuation of therapy. The same study showed that dihydrotestosterone gel had no effect on other measures of sexual function or mood.19 DHT may also be beneficial in increasing exercise ability in patients with chronic heart disease. Larger studies will be necessary to elucidate the true effects of DHT supplementation on hormone levels, exercise ability, and sexual function.

External Resources: Wikipedia: Dihydrotestosterone

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2. Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML. “Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients”. J Sex Med. 2011 8 (3): 872–84.

3. Imperato-McGinley J, Guerrero L, Gautler T et al. Steroid 5-alpha reductase in man: An inherited form of pseudohermaphroditism. Science. 1974; 186: 1213-15.

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5. Unger JM, Thompson IM, LeBlanc M, Crowler JJ, Goodman PJ, Ford LG, Coltman CA. Estimated impact of the Prostate Cancer Prevention Trial on population mortality. Cancer. 2005; 103 (7): 1375-1380.

6. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA Jr. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med. 2004; 350(22): 2239-46.

7. Thompson IM, Ankerst DP, Chi C, Lucia MS, Goodman PJ, Crowley JJ, Parnes HL, Coltman CA Jr. Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. JAMA. 2005; 294(1): 66-70.

8. Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, Pettaway CA, Tammela TL, Teloken C, Tindall DJ, Somerville MC, Wilson TH, Fowler IL, Rittmaster RS. Effect of Dutasteride on the Risk of Prostate Cancer. N Engl J Med 2010; 362: 1192-1202.

9. Feinstein RP. Androgenic Alopecia. http://emedicine.medscape.com/article/1070167-overview#a0104: Medscape Reference; 2012.

10. Rossi A, Cantisani C, Scarno M, Trucchia A, Fortuna MC, Calvieri S. Finasteride, 1 mg daily administration on male androgenetic alopecia in different age groups: 10-year follow-up. Dermatol Ther. 2011; Vol 24: 455-461.

11. Kaufman JM, Vermeulen A. The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications. Endocr Rev. 2005 Oct; 26(6): 833-76.

12. Toorians AWFT, Kelleher S, Gooren LJ, Jimenez M, Handelsman DJ. Estimating the contribution of the prostate to blood dihydrotestosterone. J Clin Endocrinol Metab. 2003; 88: 5207–5211.

13. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ, McKinlay JB. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2002; 87: 589–598.

14. Vermeulen A, Kaufman JM, Giagulli VA. Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. J Clin Endocrinol Metab. 1996 81: 1821–1826.

15. Gray A, Feldman HA, McKinlay JB, Longcope C. Age, disease, and changing sex hormone levels in middle-aged men. Results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 1991; 73: 1016–1025.

16. Couillard C, Gagnon J, Bergeron J, Leon AS, Rao DC, Skinner JS, Wilmore JH, Despres JP, Bouchard C. Contribution of body fatness and adipose tissue distribution to the age variation in plasma steroid hormone concentrations in men: The HERITAGE family study. J Clin Endocrinol Metab. 2000; 85: 1026–1031.

17. Sparrow D, Bosse R, Rowe JW. The influence of age, alcohol consumption, and body build on gonadal function in men. J Clin Endocrinol Metab. 1980; 51: 508–512.

18. Ly LP, Jimenez M, Zhuang TN, Celermajer DS, Conway AJ, Handelsman DJ. 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. The Journal of Clinical Endocrinology & Metabolism. September 2001; 86 (9): 4078–4088.

19. Sartorius GA,  Ly LP, Handelsman DJ. Male Sexual Function Can Be Maintained Without Aromatization: Randomized Placebo-Controlled Trial of Dihydrotestosterone in Healthy, Older Men for 24 Months. The Journal of Sexual Medicine. October 2014; 11 (10): 2562–2570.