Testosterone

Dutasteride Effect on Testosterone and Body Mass Index

Nearly every lifter and athlete is familiar with testosterone. Many don't understand it as a chemical or hormone, but as a powerful essence, as when tempers flare and people say "There is too much testosterone in the air." Yet, testosterone is a chemical, a hormone that is one component in the interactive control and feedback systems that maintain one's health through an unimaginably diverse range of conditions.

Testosterone's role in the body is more complex than most appreciate. The advent of prohormone supplements educated the public to the concept of biochemical precursors, promoting the [now-realized as misguided] use of DHEA, androstenedione, and other prohormones for the purpose of elevating androgen levels. Though promoted as being capable of providing the effects of oral anabolic steroids, these products generally failed to deliver; some even elevated estrogen levels.1 A few of the prohormones did provide an anabolic effect, though many (including the FDA) challenged that these products were in fact drugs, rather than a nutrition-based ingredient.

Metabolically, testosterone is both a hormone and a prohormone. Through two separate enzymatic pathways, testosterone can be converted to either estradiol (an estrogen or female sex steroid) or 5 alpha-dihydrotestosterone (a more potent androgen, also called DHT).2 It should be noted that the following discussion relates to adult males only, as the fate and role of these hormones is significantly different in women and adolescents.

Normally, a man's metabolism is balanced, with the 'male' or androgenic factors of testosterone and DHT countering, in fact dominating, the 'female' or estrogenic factors of estradiol and other estrogens. However, this balance is fairly delicate, as excesses either way (androgenic or estrogenic) can cause adverse changes to one's health and appearance. When estrogen levels are elevated, signs of the imbalance become evident through certain feminizing effects, such as the growth of breast tissue under the male's nipple(s). This condition, called gynecomastia, is common in adolescence, as teenaged boys experience tenderness or even swelling of the sub-aureolar (beneath the nipple) tissue.3 Fortunately, most cases go away as the hormonal surges of adolescence calm. Bodybuilders who use high doses of aromatizing anabolic steroids can also experience gynecomastia; to reduce the risk of this, many use aromatase inhibitors (i.e., Arimidex, Femara) to block the conversion of androgens to estrogens.4

Excesses toward the opposing extreme of the range can also occur, though these are rarely diagnosed or even considered in young adult and middle-aged men. Testosterone, and its androgenic metabolite DHT, induce a number of cellular responses in the human body; nearly two thousand genes are known to be responsive to receptor-bound testosterone/DHT.5 It is worth mentioning that most of the effects of androgens (i.e., testosterone, DHT, most anabolic steroids) are due to hormones stimulating genes (DNA) to respond to a growth signal. Other, more immediate, changes are a result of bound testosterone stimulating embedded receptors in cell membranes (non-genomic).6

Only certain tissues generate DHT. Testosterone is produced in the testes and carried throughout the body in the bloodstream. Testosterone enters most tissue (i.e., skeletal muscle, brain, prostate, skin, etc.) and binds to the androgen receptor, generating the changes associated with being a healthy male. However, certain types of tissue contain the enzyme 5 alpha-reductase, which converts testosterone to the more androgenic DHT.7 This conversion involves breaking a double bond in the A-ring of testosterone, adding two hydrogen atoms— hence, Di (two) Hydro(gen) Testosterone. The difference seems minor, but remember that reactions happen at the molecular level, so adding two hydrogens to a molecule at a key point is like attaching two extra arms on a person. It looks different and people (or other molecules in the case of DHT) react to him (it) differently.

DHT levels are generally not measured in blood work. The consequences of an elevated androgenic signal are difficult to differentiate from individual variation and not associated with known consequence during an adult male's young- and mid-adult years. Certainly, some men develop more body hair, go bald, and are more prone to acne; many go on to develop prostate enlargement as they enter their 50s, 60s, and beyond. Yet, none of these differences are considered signs of a disease state. [Hyperandrogenism or precocious puberty are treated as disease states in women and children, respectively.]

Still, many men (and some women) do receive drug treatment to reduce DHT level; the two most common conditions are androgenetic alopecia (male pattern balding) and benign prostatic hyperplasia (an enlarged prostate).8.9 Some bodybuilders and other anabolic steroid users use the same DHT-reducing drugs during a steroid cycle to prevent or reduce hair loss and/or prostate enlargement problems caused by supraphysiologic (above normal) androgen exposure.10

The drugs used to reduce DHT level are called 5 alpha-reductase inhibitors (5aRI), as they act by blocking the enzyme that converts testosterone to DHT. The two drugs in this class that are available in the U.S. are finasteride (brand names: Proscar® and Propecia®) and dutatsteride (Avodart®).

Finasteride and dutasteride are both in the same class of drug, but there is a distinct difference between the two. The enzyme 5 alpha-reductase exists in two forms, type 1 and type 2.7,11 Finasteride, the original 5aRI, inhibits only type 2. Finasteride has been shown to aid in slowing hair loss in certain conditions (not all hair loss is due to high levels of DHT), as well as reducing symptoms of prostate enlargement (e.g., difficulty with urinating).11

However, many cases in which finasteride was prescribed demonstrated only partial success. It was discovered that while finasteride was preventing the conversion of testosterone to DHT by the enzyme 5aRI type 2, other steroid molecules are reduced by 5aRI type 1 in other tissues. These type 1 reduced steroids enter the prostate and are converted into DHT through the actions of other hormones.12

This opened the market for a drug that can block both types of 5aRI, namely dutasteride. Clinically, dutasteride has shown itself to be more effective than finasteride.11 At this point, most readers are likely wondering how this relates to building muscle.

Natural testosterone production is regulated by slowing hormone production as concentrations rise in the blood. The region of the brain that controls production monitors testosterone by measuring the metabolites, estradiol and DHT. Prior studies have shown that the use of aromatase inhibitors do increase circulating (blood) testosterone, presumably by reducing negative feedback by inhibiting estradiol production.13

Early studies of the effect of 5aRI inhibition on circulating testosterone have been mixed, but many used finasteride which is only partially effective at reducing DHT formation.11 Thus, it was interesting to read the findings of a study using dutasteride on serum (blood) testosterone. This study, conducted at Seoul National University in Korea, looked at the effect of dutasteride compared to another form of therapy or the combination on testosterone level.14 The men were being treated for an enlarged prostate.

Prior to receiving treatment, serum testosterone (total) was measured, as well as body mass index (BMI). The men were followed every three months and then reevaluated after one year. As might be expected, blocking one of the 'turn-off' signals allowed the body to maintain a higher concentration of testosterone. However, it was not as simple as saying that taking dutasteride raises a man's testosterone. It is important to realize that the subjects in this study were older Asian males. Generally, Eastern Asians have androgen receptors that are less potent in terms of prolonging the androgen signal to the relevant genes (DNA).15 Further, the effect was pronounced for men who had lower testosterone (35-40 percent increase), and dutasteride was less effective at elevating testosterone for men with normal (10-15 percent increase) to high-normal testosterone (unchanged to slightly decreased). It would be inappropriate to apply this study to a population of young adult males of other races.

Fortunately, earlier studies did examine dutasteride use in young men. The drug reduced DHT by 80 percent, and increased both free and total testosterone.16 Interestingly, it was not the peak or pulsatile testosterone that was most significantly affected, but the baseline concentration. This suggests that the brain raised the threshold concentration for testosterone (DHT/estradiol) before it would shut down production. It is interesting that dutasteride is rarely mentioned during post-cycle therapy, as this might be a potential application. Another study published in 2008 following men aged 18-55 showed no change in bone density, lipoproteins (cholesterol), and hemoglobin. PSA, a lab measure of prostate health, lowered; reduced sexual activity was reported by a number of subjects.17

The subjects in the Seoul National University study also experienced a number of adverse side effects, most being sexual-related. Approximately one in 12 men experienced erectile difficulty (less powerful hard-ons); the same number complained of problems with ejaculating (male orgasm); slightly fewer noted a reduced libido (sex drive). These complaints, along with others such as gynecomastia, are commonly reported with 5aRI use at the dose used to protect against prostate enlargement.18

Interestingly, a study of female-to-male transsexuals treated with a long-acting testosterone and dutasteride observed an effect suggesting the addition of dutasteride resulted in a failure to gain lean mass (muscle).19 Conversely, a rat study demonstrated that the anabolic effect of supraphysiologic testosterone is maintained during 5aRI use.20

Independent studies have been discussed in closed circles, looking at the potential for the combined use of 5aRI and aromatase inhibitors together in elevating testosterone. The results were alleged to be dramatic and there is some support for investigating the use of 5aRI, along with aromatase inhibitors during post-cycle therapy. However, aside from the adverse sexual effects noted with 5aRI use and reduced ability to put on muscle, there is another risk that is significant— particularly if the use is proposed to occur during the post-cycle period in an anabolic steroid user.

It is not uncommon for an anabolic steroid user to experience some changes in mood; some even experience symptoms of depression, and suicidality has been associated with the discontinuation of anabolic steroids.21 Finasteride and dutasteride work by blocking the enzyme 5 alpha-reductase. Unfortunately, the activity of 5 alpha-reductase is not restricted to the production of DHT, but also is involved in the production of other steroids. Among these are steroids that affect brain function.22 Depression is a side effect reported among 5aRI users; this may be a result in changes in neurosteroids that alter emotions and mood.23 Using a drug that may exacerbate depression during a period that is already prone to depressed mood could be dangerous and should not be pursued until the matter is more closely studied.

5 alpha-reductase inhibition has been explored in supplements using certain botanical extracts with little real-world success. While it is probable that 5aRI use would promote elevations in serum testosterone, the net effect appears to be negative to quality of life and performance enhancement. As always, this drug, like all others, should not be used outside of the direction of a licensed health professional.

References:

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