1. Testosterone and 5-Alpha Reductase Inhibitors Stephen Chromi, PharmD PGY-1 Pharmacy Practice Resident St. Joseph’s/Candler Health System

2. TESTOSTERONE

6. Testosterone Enanthate

8. Testim 1% Gel

9. Other Testosterone Products Cream: Cream: First-Testosterone MC, 2% First-Testosterone MC, 2% Implant, SubQ: Implant, SubQ: Testopel, 75mg Testopel, 75mg Injection, Oil, as Cypionate: Injection, Oil, as Cypionate: Depo-Testosterone, 100mg/ml, 200mg/ml Depo-Testosterone, 100mg/ml, 200mg/ml Mucoadhesive, Buccal: Mucoadhesive, Buccal: Striant, 30mg Striant, 30mg

10. Other Testosterone Products Ointment: Ointment: First-Testosterone, 2% First-Testosterone, 2% Patch, transdermal: Patch, transdermal: Androderm, 2.5mg/24hr, 5mg/24hr Androderm, 2.5mg/24hr, 5mg/24hr Powder for compounding, USP and Propionate Powder for compounding, USP and Propionate Solution, topical: Solution, topical: Axiron, 30mg/actuation Axiron, 30mg/actuation

11. Androgel 1%, 1.62%

12. 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. 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. 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. At least 2 isoenzymes of steroid 5 alpha- reductase convert testosterone into DHT, although alternative pathways exist.

13. 5-Alpha-Reductase The isoenzymes of 5-Alpha-Reductase are concentrated in certain tissues, particularly the prostate and skin. 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. 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.

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

16. Dutasteride

17. 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.

18. 5-Alpha-Reductase Inhibitors Side effects: Side effects: Mostly sexual side effects Mostly sexual side effects Impotence Impotence Decreased ejaculate volume Decreased ejaculate volume Decreased libido Decreased libido Gynecomastia Gynecomastia

19. 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” “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 Published in JAMA; March 7, 2012 Bhasin S, Travison TG, Storer TW et al Bhasin S, Travison TG, Storer TW et al

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

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

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

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

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

25. Results Prostate volumes and PSA levels: Did not differ significantly among or between any groups 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. 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.

26. Discussion The placebo vs dutasteride groups did not differ significantly in any way. 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. 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. Unfortunately, the study ended up being very small, which calls into question the legitimacy of the results.

27. DHT’s 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 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. It may be that DHT is the primary hormone in these areas, or that it amplifies testosterones effects on these tissues.

28. Future Research I think a larger study of testosterone therapy with 5-alpha-reductase therapy is warranted. 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. 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. I think we should also use the practical dose of Avodart, 0.5mg daily.

29. QUESTIONS?