Testosterone and 5-Alpha Reductase Inhibitors

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Testosterone and 5-Alpha Reductase Inhibitors

• Stephen Chromi, PharmD
• PGY-1 Pharmacy Practice Resident
• St. Josephs/Candler Health System

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TESTOSTERONE
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Testosterone Enanthate
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Testim 1 Gel
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Other Testosterone Products

• Cream
• First-Testosterone MC, 2
• Implant, SubQ
• Testopel, 75mg
• Injection, Oil, as Cypionate
• Depo-Testosterone, 100mg/ml, 200mg/ml
• Mucoadhesive, Buccal
• Striant, 30mg

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Other Testosterone Products

• Ointment
• First-Testosterone, 2
• Patch, transdermal
• Androderm, 2.5mg/24hr, 5mg/24hr
• Powder for compounding, USP and Propionate
• Solution, topical
• Axiron, 30mg/actuation

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Androgel 1, 1.62
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Dihydrotestosterone

• Dihydrotestosterone or DHT is a potent metabolite
  of testosterone. It is known to be involved in
  BPH and hair loss. It also has potent anabolic
  effects, like testosterone itself.
• The role of DHT in post-embryonic life remains
  poorly understood.
• At least 2 isoenzymes of steroid 5
  alpha-reductase convert testosterone into DHT,
  although alternative pathways exist.

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5-Alpha-Reductase

• The isoenzymes of 5-Alpha-Reductase are
  concentrated in certain tissues, particularly the
  prostate and skin.
• There is a question as to whether DHT is the only
  form of testosterone that acts on those tissues
  or if the presence of DHT simply magnifies the
  effects of testosterone.

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Avodart

• Avodart (Dutasteride) comes in 0.5mg soft
  capsules.
• Unlike Finasteride, it inhibits both
  5-alpha-reductase isoforms 1 and 2

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Dutasteride
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Dutasteride efficacy

• In a 4 year study involving over 2000 patients,
  Dutasteride (compared to placebo) was found to
  decrease prostate volume by 20.7 and increase
  peak urinary flow by 1.8ml/sec.

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5-Alpha-Reductase Inhibitors

• Side effects
• Mostly sexual side effects
• Impotence
• Decreased ejaculate volume
• Decreased libido
• Gynecomastia

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Article Review

• Effect of Testosterone Supplementation With and
  Without a Dual 5-Alpha Reductase Inhibitor on
  Fat-Free Mass in Men With Suppressed Testosterone
  Production A Randomized Controlled Trial
• Published in JAMA March 7, 2012
• Bhasin S, Travison TG, Storer TW et al

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Study Purpose

• To determine if testosterone supplementation is
  still effective for anabolic purposes when a dual
  5-alpha-reductase inhibitor is also used.
• Secondary goals were to also look at the
  effectiveness of the 5-alpha-reductase inhibitor
  when testosterone is supplemented

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Trial Design

• Healthy men age 18-50 years
• 8 treatment groups, 20 weeks total
• all patient received testosterone, either
• 50mg, 125mg, 300mg, or 600mg/wk
• Placebo vs. Dutasteride 2.5mg/day

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Outcomes

• Primary outcome
• Change in fat-free mass from baseline measured by
  dual-energy x-ray absorptiometry
• Secondary outcomes
• Fat mass, Leg-press and Chest-press strength,
  sexual function, sebum production, and prostate
  volumes
• All outcomes measured at baseline and after 20
  weeks

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Results

• Of the 3792 men screened, 102 patients completed
  the 20-week trial
• Participants displayed similar baseline
  characteristics
• Total and free testosterone levels increased with
  testosterone dose in all groups and did not
  differ significantly between groups.

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Results

• Fat-free mass Increased with increasing
  testosterone doses but did not differ between
  groups.
• Muscle strength Increased with increasing
  testosterone doses but did not differ between
  groups.
• Sexual function Did not differ significantly
  among or between any groups.

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Results

• Prostate volumes and PSA levels Did not differ
  significantly among or between any groups
• Sebum production and acne Sebum production on
  the forehead was related to testosterone dose and
  did not differ between the placebo and
  dutasteride groups. The acne scores did not
  differ between groups.

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Discussion

• The placebo vs dutasteride groups did not differ
  significantly in any way.
• It seems obvious that the anabolic effects of
  testosterone on muscle can still be accomplished
  while on a 5-alpha-reductase inhibitor.
• Unfortunately, the study ended up being very
  small, which calls into question the legitimacy
  of the results.

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DHTs role better understood?

• It may be theorized that some effects of
  testosterone do not require the conversion to
  DHT, such as muscle and bone anabolism. The
  effects of DHT may be more related to the tissues
  of the prostate and skin (hair).
• It may be that DHT is the primary hormone in
  these areas, or that it amplifies testosterones
  effects on these tissues.

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Future Research

• I think a larger study of testosterone therapy
  with 5-alpha-reductase therapy is warranted.
• We need to know if testosterone therapy mitigates
  the effectiveness of 5-alpha-reductase inhibitors
  in BPH and hair loss.
• I think we should also use the practical dose of
  Avodart, 0.5mg daily.

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QUESTIONS?