In PBMCs stimulated with mTB, sex-divergent NK cells responses were also found. We found monocyte-derived IL-6, TNF and IL-15 were upregulated by testosterone, and monocyte-released IL-12B as candidate genes to best explain several upregulated transcripts measured in NK and CD8+ T cells during GAHT (Fig. 4a). As testosterone modulated monocyte function strongly during masculinizing GAHT, we performed NicheNet analyses to infer downstream consequences on other immune cell populations. Treg cells are more abundant in postpubertal male participants than in age-matched female participants26 but, during GAHT, frequencies were stable over 12 months (Extended Data Fig. 5d). CD4/CD8 T cell ratios were higher in female in than male participants20,21 but no decrease occurred during testosterone treatment (Extended Data Fig. 5a), indicating that genetic factors rather than steroids are responsible for this.
While a high red blood cell count can indicate a disease or disorder, it doesn’t always mean you have a health condition. Often, people with polycythemia vera also undergo routine blood withdrawals (therapeutic phlebotomy) to keep their red blood cell count under control. If a health condition is causing a high red blood cell count, your provider may recommend a procedure or medication to lower it. Stress can lead to an increase in red blood cells, neutrophils (a type of white blood cell) and platelets. Many cancers actually cause your red blood cells to drop. Sometimes, people with a high red blood cell count don’t develop any symptoms at all.
Women mount a stronger response to viruses yet are more prone to autoimmune diseases, such as lupus. The most optimised natural testosterone booster ever developed. Nutrient deficiencies can also affect your hormonal status resulting in low testosterone.
But when levels rise too high, the blood becomes thicker. With proper evaluation, most patients can continue therapy successfully while keeping hemoglobin in a safe range. When someone on TRT has high hemoglobin, it is important to look beyond testosterone alone. If a patient has extremely high hemoglobin levels that do not improve with TRT adjustment, doctors may test for PV or other bone marrow disorders. Patients living at high altitude may have naturally higher baseline hemoglobin. In all these situations, the body increases hemoglobin to help deliver more oxygen.
These findings indicate that SLAMF7 upregulation could contribute to testosterone-mediated potentiation of TNF responses in monocytes. SLAMF7 is induced by IFNγ19 and we found one of its receptor genes, IFNGR2, upregulated in monocytes after testosterone treatment (Fig. 3f). H–k, z-score transformed mRNA counts of LPS-induced NFKB1 (h), SLAMF7 (i), R848-induced SOCS1 (j) and SOCS3 (k). TNF family proteins such as TNF, RANKL, TNFSFR9 and TRAIL were elevated in plasma during testosterone therapy (Fig. 3d and Extended Data Fig. 4a). Top genes involved in the Hallmark TNF response include IL-1, IL-6 and TNF but also NFκB pathway member NFKB1 were all induced more strongly by LPS stimulation after 3 months of testosterone in vivo (Fig. 3c). These results offer further insights to testosterone-mediated attenuation of IFN-I responses in pDCs.
The guidelines of many professional societies for testosterone treatment of hypogonadism in men recommend monitoring of hemoglobin and hematocrit during testosterone treatment7,26,27. Estimated changes from baseline in circulating counts of erythrocytes, platelets and leukocytes for treatment groups in the OPTIMEN trial. No testosterone-treated subject had total leukocyte count greater than 10,500 cells/μL or platelet count greater than 450,000 cells/μL. Estimated changes from baseline in the circulating numbers of total leukocytes, platelets, and erythrocytes as well as the absolute and relative counts of the leukocyte subtypes for testosterone dose groups in the 5aR trial.
Purified antibodies were obtained in carrier/protein-free buffer and coupled to lanthanide metals using the MaxPar X8 or MCP9 antibody conjugation kits (Standard BioTools Inc.) as per the manufacturer’s recommendations. Cells were then stained using a cocktail of metal-conjugated antibodies targeting intracellular antigens (Supplementary Table 3) and incubated for 1 h at ambient temperature. Samples were then thawed, fixed and lysed using Lysis and Wash buffers (Whole blood processing kit; Cytodelics AB). Blood samples were mixed with a stabilizer63 (Whole blood processing kit component; Cytodelics AB) within the first hour post blood-draw and cryopreserved according to the manufacturer’s recommendations. Five main immune clusters were identified and used for further analyses.
Genetics and individual responseEvery person’s body reacts to testosterone differently. When breathing stops during sleep, the body gets lower oxygen levels. Testosterone pelletsPellets are implanted under the skin and release testosterone slowly over several months. Some people switch to gels if they develop high hemoglobin while using injections. They may still raise hemoglobin, but the risk is a bit lower. Right after an injection, the blood level of testosterone can be well above the normal range. This happens because injections create higher peaks in testosterone levels.

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