Testosterone and Erythrocyte Lifespan

Abstract Context Endogenous and exogenous androgens increase circulating erythrocytes and hemoglobin but their effects on erythrocyte lifespan is not known. Objective To investigate androgen effects on immature and mature erythrocyte lifespan in humans and mice using novel non-radioactive minimally invasive methods. Design Human erythrocyte lifespan was estimated using alveolar carbon monoxide concentration and blood hemoglobin in Levitt’s formula in hypogonadal or transgender men before and up to 18 weeks after commencing testosterone (T) treatment. Erythrocyte lifespan was estimated in androgen receptor (AR) knockout and wild-type mice after T or dihydrotestosterone (DHT) treatment of intact females or orchidectomized males using in vivo biotin labelling of erythrocyte surface epitopes for reticulocytes (Ter119+CD71+) and two markers of erythrocytes (CD45-, Ter119+CD71-) monitoring their blood disappearance rate by flow cytometry. Results Before treatment, hypogonadal and transgender men had marked reduction in erythrocyte lifespan compared with controls. T treatment increased erythrocyte lifespan at 6 weeks but returned to pre-treatment levels at 18 weeks while serum T and blood hemoglobin were increased by T treatment remaining elevated at 18-weeks. In mice T and DHT treatment had higher erythrocyte (but not reticulocyte) lifespan but neither orchidectomy nor AR inactivation significantly influenced erythrocyte or reticulocyte lifespan. Conclusions We conclude that hypogonadal men have reduced erythrocyte lifespan and acute androgen-induced increase in circulating erythrocyte lifespan may contribute to the well-known erythropoietic effects of androgens, but longer-term effects require further investigation to determine how much they contribute to androgen-induced increases in circulating hemoglobin.