Q. What are the possible causes for fatigue that did not improve with TRT?

Hello doctor,

I am a 42-year-old male. I had undescended testes from childhood which went untreated (hence I had always been and am on single testis only). The undescended testis still lies in the groin. I used to feel fatigued most of the times over the years, due to which I had difficulty in concentrating, focussing and managing day-to-day tasks. About a year ago, I started on TRT (testosterone replacement therapy). I used injectables (Nebido) for seven months. TRT worked very well for six months and I experienced positive results in various aspects (better focus, better memory, energetic, improved libido, was able to manage my tasks very well). After six months my hemoglobin increased from 16.6 to 18.5 and hematocrit went up from 46 to 54, and my doctor advised to donate blood. At this point, I started feeling fatigued and headache (typical high hemoglobin symptoms).

I donated blood for the first time three months ago. However, after donation, I felt less energy and benefits of TRT also started fading away. Within a month, hemoglobin again went up from 16 to 17.6 and hematocrit was at 51. I went through venesection two months ago to bring it down. From then onwards, on the advice of my doctor, I switched from injectables to gel (Testogel). Hemoglobin and hematocrit again went up and I had to undergo another venesection last month. I was also low on Iron (ferritin - 46). So, I started taking a lot of oral iron supplements (ferrous sulfate - 65 mg elemental iron). I took up to eight tablets per day for three to four days. Iron levels improved (ferritin 118 ng/ml), but hemoglobin also shot up to 17.5 (as per recent report).Questions:

1. What do you think could be the possible reasons for fatigue that I have been facing since last few months?
2. When I started TRT it took six to seven months for hemoglobin to rise from 16.6 to 18.5 while after I gave blood in the first blood donation, hemoglobin rises by similar points in 30 to 45 days only.
3. MCV results confirm that the size of RBC’s is increasing since I am on TRT, it means that the new RBC’s have more iron. However, I have been continuously feeling fatigued before first blood donation till now.
4. My iron stores (ferritin) is still towards low (74) as per latest blood test and I am currently taking iron oral supplements. Do you think that the fatigue symptoms will improve once ferritin comes in the midrange (150)?

Thank you doctor,

The decision of going on TRT was taken carefully in consultation with doctors, and I am absolutely satisfied with that decision. I was hoping for a response to the questions I have raised. Can you please be precise and answer the questions that I raised in my query?