Transcript Testosterone and 5-Alpha Reductase Inhibitors

Testosterone and 5-Alpha
Reductase Inhibitors
Stephen Chromi, PharmD
PGY-1 Pharmacy Practice Resident
St. Joseph’s/Candler Health System
TESTOSTERONE
Testosterone Enanthate
Testim 1% Gel
Other Testosterone Products
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Cream:
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Implant, SubQ:
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Testopel, 75mg
Injection, Oil, as Cypionate:
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First-Testosterone MC, 2%
Depo-Testosterone, 100mg/ml, 200mg/ml
Mucoadhesive, Buccal:
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Striant, 30mg
Other Testosterone Products
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Ointment:
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Patch, transdermal:
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First-Testosterone, 2%
Androderm, 2.5mg/24hr, 5mg/24hr
Powder for compounding, USP and Propionate
Solution, topical:
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Axiron, 30mg/actuation
Androgel 1%, 1.62%
Dihydrotestosterone
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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 alphareductase convert testosterone into DHT,
although alternative pathways exist.
5-Alpha-Reductase
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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.
Avodart
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Avodart (Dutasteride)
comes in 0.5mg soft
capsules.
Unlike Finasteride, it
inhibits both 5-alphareductase isoforms 1
and 2
Dutasteride
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.
5-Alpha-Reductase Inhibitors
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Side effects:
Mostly sexual side effects
 Impotence
 Decreased ejaculate volume
 Decreased libido
 Gynecomastia
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Article Review
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“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
Study Purpose
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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
Trial Design
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Healthy men age 18-50 years
8 treatment groups, 20 weeks total:
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all patient received testosterone, either…
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50mg, 125mg, 300mg, or 600mg/wk
Placebo vs. Dutasteride 2.5mg/day
Outcomes
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Primary outcome:
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Change in fat-free mass from baseline measured by
dual-energy x-ray absorptiometry
Secondary outcomes:
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Fat mass, Leg-press and Chest-press strength, sexual
function, sebum production, and prostate volumes
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All outcomes measured at baseline and after 20
weeks
Results
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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.
Results
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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.
Results
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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.
Discussion
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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.
DHT’s role better understood?
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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.
Future Research
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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.
QUESTIONS?