Effects of various modes of androgen substitution therapy on erythropoiesis.
Level 2 - randomized trial
Individual randomized controlled trial
What was done
Fifty-five men with confirmed hypogonadism (after a minimum 3-month washout of prior testosterone) were randomized to four androgen replacement regimens: oral mesterolone (100 mg/day), oral testosterone undecanoate (160 mg/day), intramuscular testosterone enanthate (250 mg every 21 days), or subcutaneous crystalline testosterone implants (1200 mg). Serum testosterone, dihydrotestosterone (DHT), hemoglobin, and hematocrit were assessed before, during, and after therapy.
What was found
Mesterolone did not increase serum testosterone. Mean testosterone reached 5.7 ± 0.3 nmol/l with testosterone undecanoate (2-fold baseline increase), 13.5 ± 0.7 nmol/l with testosterone enanthate (6-fold increase), and 23.2 ± 1.1 nmol/l with testosterone implants (8.5-fold increase). DHT levels during treatment were 4.3 ± 0.2 nmol/l (mesterolone), 3.3 ± 0.2 nmol/l (undecanoate), 4.0 ± 0.4 nmol/l (enanthate), and 5.5 ± 0.4 nmol/l (implants). Hemoglobin and hematocrit rose significantly with undecanoate (+12.7 ± 2.8 g/l and +3.9 ± 1.1%), enanthate (+21.1 ± 2.6 g/l and +6.4 ± 0.9%), and implants (+21.7 ± 4.0 g/l and +6.5 ± 1.6%), but changes were not statistically significant with mesterolone (+5.6 ± 1.8 g/l and +1.8 ± 0.4%). Except for one subject in the implant group, hemoglobin and hematocrit stayed within normal limits.
Why it matters
The study indicates that erythropoietic stimulation is driven by testosterone rather than DHT in a dose-dependent fashion, with maximal stimulation occurring once testosterone reaches low-normal physiological ranges.
Limits
The sample size is small (55 men across four treatment arms). The abstract does not specify follow-up duration, blinding, or long-term clinical safety outcomes.
Cited by
- supports Testosterone stimulates erythropoiesis in a dose-dependent manner.