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Starting TRT without a baseline makes it hard to know whether future increases are from testosterone or from something else. Most high hemoglobin levels can be managed with simple adjustments if found in time. Thick blood does not flow as easily and may increase the risk of complications. Because of this, doctors use regular blood tests to make sure your levels stay safe. It quickly lowers hematocrit and may be recommended if levels are very high or if the person has symptoms.
Before assessing differential gene expression, genes with fewer than 100 reads across samples were filtered out, as well as genes that did not have a normalized count of ten in at least one-fourth of the samples. We performed Bulk RNA-seq on a NovaSeq 6000 instrument using one flow cell SP-200 (Illumina) with paired-end reads and a read length 2 × 100. To analyse changes in gene expression, we performed RNA-seq using RNA extracted from PAXgene blood samples. Cells were washed, counted and cryopreserved in a solution of 90% FBS (Sigma-Aldrich) mixed with 10% dimethylsulfoxide (DMSO; Sigma-Aldrich), initially stored at −80 °C overnight and then transferred to −150 °C for future use. The leftover blood after plasma removal was mixed equally with PBS and layered over Lymphoprep (STEMCELL Technologies) for PBMC isolation by density gradient centrifugation following the manufacturer’s protocol. The remaining blood was centrifuged at 4 °C and 1,200g for 10 min, after which plasma was collected and stored at −80 °C.
Understanding your bloodwork is the most important skill any research compound user can develop. Elizabeth Millard is a freelance writer focusing on health, wellness, fitness, and food. Call your healthcare provider for medical advice about side effects. Talk to your healthcare provider if you have concerns about fertility. Keep a list of them with you to show to your healthcare provider and pharmacist when you get a new medicine.
If hematocrit is 54% or higher, stopping TRT temporarily allows levels to return to a safe range. Still, action is taken based on lab results—even if no symptoms exist—because thickened blood can be risky even without warning signs. Some people feel normal even with elevated levels, while others develop headaches, dizziness, flushing, or vision changes. Not everyone with high hematocrit will develop complications, but the risk becomes higher as the level rises, especially above the 54% threshold. At this level, the blood is much thicker, and the risk of clot-related problems rises. A hematocrit level in the 52–54% range is more concerning and often requires a change in treatment. Many people on TRT fall into this range occasionally, especially early in treatment or after a dose adjustment.
Cryopreserved PBMCs obtained from individuals undergoing gender-affirming testosterone treatment were collected at baseline and after 3 months of testosterone treatment. A total of 12,377,068 cells from the 60 samples of participants undergoing testosterone treatment were further analysed. TF motif analysis was conducted by identifying overrepresented motifs in a set of differentially accessible peaks between pre- and post-testosterone therapy (3 or 12 months) for all the five immune subsets using hypergeometric tests and P values corrected for several hypotheses (Benjamini–Hochberg).
It is conceivable that loss of oestradiol-mediated signals can also contribute to attenuated IFN-I responses through other mechanisms not investigated herein. Inhibitors of IFN-I responses—SOCS1 and SOCS3—were also induced by DHT alone, indicating direct effects of androgens in suppressing IFN-I responses. Results showed that NFκB-mediated responses to LPS stimulation were potentiated by DHT alone through AR and not by loss of ESR-mediated signals. To test this question, we designed an in vitro system in which blood from 11 cis female donors was pretreated with either DHT (in the presence or absence of the AR inhibitor enzalutamide) or the ESR inhibitor fulvestrant only. We find that testosterone increase and the resulting oestradiol suppression, alters a cross-regulation axis involving IFN-I and TNF.
If hemoglobin falls too slowly, therapeutic phlebotomy may be used to bring levels down faster. The goal is to make sure levels return to a healthy range without dropping too low. Before stopping treatment, many doctors try other methods to bring hemoglobin back down. If symptoms are severe or appear suddenly, a doctor may recommend stopping TRT right away, even if blood levels are below the 54% threshold. Even before reaching the cutoff numbers, some people develop symptoms related to very thick blood.

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