4. AUA guideline on TRT / polycythemia
• Prior to testosterone therapy, patients should
undergo baseline assessment of Hb/Hct
• If Hct >50% -> with-hold testosterone therapy until
the etiology of the high Hct is explained
– polycthemia vera, living at altitude, obstructive sleep
apnea, tobacco use
5. Why does TRT Erythrocytosis?
Jones S, et al. J Sex Med. 2015
Increased erythropoietinDecreased hepcidin
Exacerbation of OSA
6. Comparison of the incidence of polycythemia among
TT preparation
1. Wheeler KM, Smith RP, Kumar RA, Setia S, Costabile RA, Kavoussi PK, J Urol. 2017
2. Rotker KL, Alavian M, Nelson B, Baird G, Miner M, Sigman M, Hwang K Asian J Androl 2018
% Polycythemia
(HCt > 52%)
Intramuscular T injections 19%
Subcutaneous T pellets 12 – 17%
Transdermal T 5%
7. Different Testosterone Therapy Formulations have different Durations of Action
1. Behre, H & Wang, Chuen-Ching & Handelsman, D & Nieschlag, Ebo. (2004). Pharmacology of testosterone preparations. Testosterone: Action, Deficiency, Substitution.
2. Pastuszak, A.W., Mittakanti, H., Liu, J.S., Gomez, L., Lipshultz, L.I. and Khera, M. (2012), Pharmacokinetic Evaluation and Dosing of Subcutaneous Testosterone Pellets. Journal of Andrology
Subcutaneous Pellets Topical GelIM Testosterone
LONG-ACTING SHORT-ACTING
8. • Participants received one of the following
Testosterone cypionate regimens for 6 months:
• 100mg IM once weekly
• 200mg IM every other week
• Results demonstrated a lower risk of
erythrocytosis with adherence to a lower
dosage, higher frequency TRT regimen
1. El-Khatib FM, Patel P, Angulo, L, Yafi F et al..,Unpublished data 2020
Does Frequency and dosage play a role?
Larger area under the curve (longer duration of high T levels)
could predict risk of polycythemia
Premal Patel Laura Angulo
9. Comparison of polycythemia between Testosterone cypionate vs.
Intranasal Testosterone Gel
1. Best J, Gonzalez D, Masterson T et al., 2020. CUAJ (In Press)
2. Ramasamy R, Masterson T, Best J et al, 2020 J Urol. (In Press)
231
658
616
652
231
658
616
652
Baseline 1 3 6
Visit (Months)
200
300
400
600
800
1500
Meanand95%CI
Testosterone
45.9
40.8
33.9
Baseline 3 6
Visit (Months)
30
40
50
60
Meanand95%CI
Total Motile Sperm Count
Jordan Best Thomas
Masterson
10. RCT @ UM : Testosterone Cypionate vs Natesto
• 200 men
• 1:1 randomization (Natesto TID vs
Testosterone cypionate)
• 200mg every 2 weeks
• 6 month follow-up
• Primary Endpoint: HCt
• Secondary Endpoints: PSA, Estradiol, DHT
Daniel Gonzalez Jesse Ory
11. How to manage polycythemia in TRT?
1. Lundy, Scott D. et al. Obstructive Sleep Apnea Is Associated With Polycythemia in Hypogonadal Men on Testosterone Replacement Therapy The Journal of Sexual Medicine, (In press)
• While on testosterone therapy, a Hct ≥54%
warrants intervention consider
phlebotomy
• In men with high on-treatment total or free
testosterone levels, dose adjustment should
be attempted as first-line management.
• Men with on-treatment low/normal total and
free testosterone levels should be referred to
a hematologist for further evaluation.
12. Take Home Points
• Erythrocytosis is a potential side effect of Testosterone
therapy
• Longer-acting formulations appear to have higher
incidence of polycythemia compared to shorter-acting
T
• Screen for Obstructive sleep apnea in men who
develop polycythemia on TRT
Editor's Notes
When we look back at our 3 models for erythrocytosis, there are many moving parts, which may depend on the type, strength and timing of testosterone.
Even this model is too simplified. We can see other nuance in this model when looking at polycythemia secondary to obstructive sleep apnea.
The lack of peaks leading to polycythemia is also supported with this paper comparing clomiphene and T (of several modalities). SERM polycythemia rate 1.7% while T is 11.2 %. Because the increase in T with SERMs is secondary to increased LH and FSH, it is unlikely that there are as high peaks of T as there are with direct T therapy.
Different modalities of T have different pharmacokinetics.
The differing pharmacokinetics can play a role in how the body responds and how the hematocrit changes. These differing peaks and troughs change hct level. For example…
The testosterone modality with the shortest half life and the shortest duration of a peak is intranasal testosterone.