Dihydrotestosterone, or DHT, refers to an endogenous sex hormone that is formed from testosterone, the primary male sex hormone and a potent anabolic steroid. DHT acts from within the epididymis, a duct located behind the testes in the male reproductive system. It is associated with the development of typically male secondary sex characteristics, including body hair growth and voice deepening. DHT is vital in the healthy development of the male reproductive system, including the genitalia and the prostate.
Dihydrosestosterone is associated with muscle growth, and appears to be more potent than testosterone alone in that regard. A study published by the Journal of Molecular Endocrinology explored the effects of dihydrotestosterone and gonadectomy (or castration) on skeletal muscle in a laboratory mouse model. Upon examining seventy-nine genetic transcripts expressed as a result of intravenous DHT injection, researchers observed that dihydrotestosterone promoted protein synthesis, cell proliferation, and ATP production in vivo. It also appeared to mediate contraction and relaxation in the skeletal muscle.
A 2011 study published by the Journal of Physiology yielded similar results. Researchers explored the acute/non-genomic effects of dihydrotestosterone in skeletal muscles. This study was conducted in vitro, and analysis was conducted by observing amino acid uptake and cellular signal transduction events in fast and slow-twitch skeletal muscle fibers. Results indicated that DHT increased muscle force production in fast contracting muscles and decreased force in slow acting muscle. These data indicated to the researchers that dihydrotestosterone may be a superior muscle-building hormone to testosterone. Further, results confirmed that DHT increases protein synthesis and the transport of essential amino acids into muscle fibers when testosterone cannot.
While the previous two studies were conducted via laboratory mouse models in vitro and in vivo, the following study (conducted in 2006) observed the effects of dihydrotestosterone replacement therapy in health men aged sixty-five and older. The meta-study, published by the Journal of the American Geriatrics Society, analyzed thirty-eight statistical comparisons and found that both testosterone and DHT therapy produced a moderate increase in muscle strength among healthy elderly men.
DHT may also promote muscle growth and improve motor function in patients afflicted with progressive degenerative diseases such as amyotrophic lateral sclerosis (ALS). A study examining DHT administration in mice with amyotrophic lateral sclerosis assessed the hormone’s potential anabolic and neuroprotective effects on axons and motoneurons. Results indicated that DHT-treated mice demonstrated decreased muscle atrophy, elevated body weight, and stronger grip-strength. The researchers recommended further examination of dihydrotestosterone and its ability to ameliorate clinical symptoms in muscular diseases such as ALS.
Suppression of dihydrotestosterone concentrations has been clinically associated with decreased libido, erectile dysfunction (in a small proportion of men), and a minor decrease in sperm concentration. A 2002 study published by The Journal of Clinical Endocrinology and Metabolism assessed the effects of transdermal dihydrotestosterone in 114 men ages 50 to 70 years old. After three months of transdermal administration, men in the dihydrotestosterone group improved in terms of early morning erectile function and erectile maintenance in comparison to the placebo group. Researchers concluded that transdermal administration of DHT may improve sexual function in aging men.
However, placebo-controlled studies of this sort are relatively limited. DHT is known to play a role in sexual function, but its exact mechanism and the risks associated with too much dihydrotestosterone are still being elucidated.
In a 2016 study published by Experimental and Therapeutic Medicine, researchers explored how dihydrotestosterone modulates synaptic plasticity in laboratory mice with mild cognitive impairments. By using qPCR (qualitative polymerase chain reaction) and western blot analysis, researchers were able to determine DHT expression in synaptic marker proteins in the hippocampus of treated rats. Results indicted that DHT promoted the expression of CREB (cellular transcription factor), PSD95 (postsynaptic density protein 95), and drebrin (a family of developmental proteins) in the hippocampus of the castrated-DHT group. It was surmised that dihydrotestosterone depletion inhibited synaptic plasticity and increased memory-related neuropathology.
Similar results were observed among aged female ovariectomized mice in a 2009 study published by Learning & Memory. Researchers observed behavioral performance in twenty-two to twenty-four-month old female mice treated with either testosterone or dihydrotestosterone (or placebo capsules). While DHT improved passive avoidance retention in female rats significantly, testosterone only increased this factor marginally. In turn, while testosterone enhanced spatial memory retention in aged female rats, dihydrotestosterone did not. Researchers concluded that these hormones have the capacity to improve cognition in aged subjects, though the benefits were dependent on the type of treatment.
A 2003 study published by the Journal of Andrology examined cognitive changes associated with supplementation of testosterone or dihydrotestosterone in men exhibiting mild hypogonadism. A series of cognitive tests were administered to subjects prior to supplementation and then again at days 30 and 90 of treatment. Researchers observed significant improvements in spatial memory with DHT supplementation. Verbal memory scores improved with testosterone administration.
A 2009 study published by the Journal of Neurochemistry yielded similar results. Researchers observed the effects of androgens in intact and castrated male mice. Results indicated that castration impaired spatial working memory, but had no effect on recognition memory, motor coordination, or passive avoidance memory. Researchers also examined the effects of dihydrotestosterone androgen replacement on the same parameters. Following a twenty-four hour interval of administration, dihydrotestosterone appeared to recover spatial memory performance in vivo.
Dihydrotestosterone has been implicated as a causal factor in androgenetic alopecia, more commonly known as male pattern hair loss. The degree to which dihydrotestosterone affects individuals depends on a variety of factors; for example, men with higher androgen receptor sensitivity or higher levels of DHT receptors at the hair follicles may be more likely to experience androgenetic alopecia with age. Currently, the reasons for fluctuating DHT levels in the epididymis are poorly understood. However, some contemporary data suggest that dihydrotestosterone (as well as type 2 5α-reductase, the enzyme that catalyzes the transformation of testosterone into DHT) is chiefly responsible for androgenetic alopecia, and thus managing DHT levels may help combat male pattern hair loss.
A 1999 study published by the Journal of the American Academy of Dermatology explored the ability of a type 2 5α-reductase inhibitor to ameliorate or slow androgenetic alopecia. For 42 days, researchers administered 0.01, 0.05, 0.2, 1, or 5 mg daily of finasteride to men with age-related pattern hair loss and conducted scalp biopsies before and after treatment. Results indicated that finasteride dosages as low as 0.2 mg daily significantly decreased scalp skin and serum DHT levels. Researchers suggested further exploration into the effects of finasteride at dosages between 0.2 and 5 mg.
However, more recent research indicates that finasteride may result in significant and unwanted side effects, including persistent sexual dysfunction as a result of modulating DHT levels in the epididymis. A 2011 study published by the Journal of Sexual Medicine addressed the types and duration of sexual side effects in healthy men aged twenty-one to forty-six years old taking finasteride for androgenetic alopecia. After one month of finasteride use, 92% of users developed erectile dysfunction, 92% developed decreased arousal, and 69% reported difficulty with achieving orgasm. Researchers reported that the total sexual dysfunction score increased with long-term use, the mean duration of side effects being 40 months from the time of finasteride cessation.
Though dihydrotestosterone is a primary sexual hormone and anabolic steroid in men, it is also present in women to a lesser degree. Elevated levels of the hormone are significantly implicated in the development of adult acne, particularly in women. In a study published by the Journal of Investigative Dermatology, researchers examined a total of 62 skin biopsies from 32 subjects (both male and female) with and without acne. Results of the biopsies revealed that acne-affected skin produced 2 to 20 times more dihydrotestosterone than unaffected skin.
Further research has indicated that androstenedione is the major pre-hormone for dihydrotestosterone formation in women. As such, several androgen receptor blockers have been elucidated as possibly effective adult acne treatment in women with hormonal imbalances. Among them are spironolactone, a synthetic steroidal androgen receptor blocker that works against acne vulgaris and hirsutism, and flutamide, a nonsteroidal androgen receptor blocker that treats acne, androgenetic alopecia, and hirsutism. Oral contraceptices are also commonly used toward the suppression of ovarian androgen production.
Decreased Cancer Risk
Since the mid-twentieth century, researchers have hypothesized that human prostatic adenocarcinoma is dependent on dihydrotestosterone for growth, as opposed to testosterone. Androgen deprivation therapy has been the standard for advanced prostate cancer since Nobel Prize winner Charles B. Huggins innovated castration and estrogen administration in the treatment of this type of carcinoma. More recent findings have sought to elucidate the relationship between dihydrotestosterone and prostate cancer, in order to refine treatment possibilities.
Unfortunately, there is some lack of clarity surrounding DHT and its role in the progression of prostate cancer. The first large-scale, placebo-controlled trial to examine this link was the Prostate Cancer Prevention Trial (PCPT) trial, involving healthy men 55 years of age and older. The study began in 1993 and was conducted at 221 sites across the United States. Data from this clinical trial revealed that 30% fewer men taking the drug finasteride developed prostate cancer than men not taking the drug. This would suggest that a decrease in DHT might offer some protective capabilities against prostatic cancer. However, 6.4% of the tumors in the finasteride group exhibited High Gleason scores, as opposed to the low scores observed in those administered placebo. These contradictory results have sparked some controversy in the cancer research sphere.
The Reduction by Dustasteride of Prostate Cancer Events (REDUCE) trial produced similarly murky results in 2010. This trial tested the effects of dutasteride, a selective inhibitor of both type 1 and type 2 isoforms of 5α-reductase, in men 50-75 years of age with a prostate-specific antigen level of 2.4 to 10.0 ng per mililiter. This trial indicated an overall reduction in cancerous proliferation the number of patients with a Low Gleason score upon receiving dutasteride in comparison to placebo. However, researchers also observed that patients with a High Gleason score maintained this score more consistently throughout the course of the four-year trial.
Based on these inconsistencies and a limited amount of research, it is difficult to confirm how exactly DHT acts in the progression of human prostatic adenocarcinoma.
There have been several safety and efficacy reviews conducted with respect to the promotion and inhibition of dihydrotestosterone development in treated patients. In 1994, the Merck Research Laboratories in New Jersey, USA conducted a three-year safety and efficacy trial, utilizing two large multicenters and assigning finasteride to men with benign prostatic hyperplasia for twelve months. After twelve months, patients had the option to participate in an extension to the study, in which all subjects received 5 mg of finasteride (including the placebo group). After thirty-six months, researchers determined a strong safety profile and sustained clinical efficacy, ultimately deeming finasteride to be a low-risk medical option for patients afflicted with benign prostatic hyperplasia.
However, 5α-reductase inhibitors are associated with adverse side effects in a subset of men. A literature review conducted by The Journal of Sexual Medicine observed that finasteride and similar treatments were associated with erectile dysfunction, diminished libido, gynecomastia, and depression, indicating a possible causal relationship between these symptoms and a decrease in dihydrotestosterone levels.
Too much DHT is also associated with negative side effects, particularly in women. Dihydrotestosterone in excess may cause hair loss in both men and women, an overall increase in acne, and increased potential for the development of prostate cancer. Further, in men, an excess of dihydrotestosterone can result in benign prostate hypertrophy, or an enlarged prostate. Present investigations are being conducted in order to determine dihydrotestosterone’s relationship to metabolic syndrome and diabetes.
Toxicity associated with dihydrotestosterone supplementation is similar to that seen with excessive dosages of vitamin D. Symptoms include abdominal distress and discomfort, vertigo, tinnitus, lethargy, depression, amnesia, and syncope. Dihydrotestosterone supplementation is contraindicated in patients with hypercalcemia, and/or abnormal sensitivity to vitamin D.
5α-reductase inhibitors are contraindicated in patients who are pregnant or nursing, and who have liver function abnormalities.
Research regarding nutraceutical supplements that support dihydrotestosterone is relatively limited. However, there is some clinical evidence to support the following as androgen boosters.
A 2009 study published by the Clinical Journal of Sports Medicine investigated resting concentrations of dihydrotestosterone and other androgens after three weeks of creatine supplementation in male rugby players with a median age of twenty. Results indicated that, after seven days of creatine supplementation, serum testosterone levels remained unchanged. However, dihydrotestosterone levels increased by 56% ad remained at levels between 20% – 40% above baseline during the six-week washout period. Researchers determined that creatine supplementation may act through an increased rate of conversion of testosterone to dihydrotestosterone. This is a list of the best Creatine on the market.
Extracted from a vine shrub native to Thailand, Butea superba has been demonstrated to yield antiestrogenic and androgenic activity in male and female rats (both intact and overiectomized females). However, the only published study regarding Butea superba’s androgenic capabilities in human patients observed an instance of hyperandrogenemia (excessive dihydrotestosterone) in a single Thai male, aged thirty-five years. His DHT levels decreased to normal upon cessation of Butea superba supplementation. Based on existing research, low levels of Butea superba appear to be safe for human consumption. Doses at 48 mg/kg and above are inadvisable. This is a list of the best Butea superba on the market.
A 1981 study published by Archives of Andrology examined the effects of zinc therapy on plasma testosterone, dihydrotestosterone, and sperm count in thirty-seven patients with idiopathic infertility. Researchers observed that, while testosterone and sperm count were unaffected by zinc, dihydrotestosterone levels increased significantly. More recent research is very limited and further investigation is required to validate zinc’s effects in the human androgenic system. This is a list of the best Zinc on the market.
Popular natural dihydrotestosterone blockers include: