Reduced number of circulating endothelial progenitor cells in hypogonadal men
1Department of Histology, Microbiology, and Medical Biotechnologies, Centre for Male Gamete Cryopreservation, University of Padova, Padova, Italy. carlo.foresta@unipd.it
Insights
Low testosterone levels in men with hypogonadotropic hypogonadism are linked to fewer circulating progenitor cells (PCs) and endothelial PCs (EPCs). Testosterone therapy effectively increases these cell counts, suggesting a direct impact on bone marrow.
Area of Science:
- Cardiovascular Research
- Endocrinology
- Cell Biology
Background:
- Endothelial dysfunction is an early indicator of atherosclerosis.
- Circulating progenitor cells (PCs) and endothelial progenitor cells (EPCs) are crucial for repairing damaged endothelium.
- The role of androgens in endothelial repair is less understood compared to estrogens.
Purpose of the Study:
- To investigate circulating PC and EPC levels in men with hypogonadotropic hypogonadism (HH).
- To assess the impact of testosterone (T) replacement therapy on these progenitor cells in HH patients.
Main Methods:
- Prospective study involving young HH patients and age-matched controls.
- HH patients received 6 months of testosterone gel therapy.
- Circulating PC and EPC concentrations were measured, along with androgen receptor expression on cultured EPCs.
Main Results:
- HH patients exhibited significantly lower baseline levels of PCs and EPCs compared to controls.
- Testosterone therapy led to a significant increase in PC and EPC counts.
- Cultured EPCs demonstrated strong androgen receptor expression.
Conclusions:
- Hypotestosteronemia in young men is associated with reduced circulating PCs and EPCs.
- Testosterone treatment can increase PC and EPC levels, potentially via a direct effect on bone marrow and androgen receptors on EPCs.
Context:
Endothelial dysfunction seems to be the first step of the atherosclerotic process. In the past few years, it has been demonstrated that injured endothelial monolayer is restored by a premature pool of circulating progenitor cells (PCs) and a more mature one of circulating endothelial PCs (EPCs). Even though there is increasing evidence that estrogens play a beneficial role on EPCs and, even if debated, on the cardiovascular system, less is known about androgens.
Objective:
Our objective was to evaluate the levels of circulating PCs and EPCs in men with hypogonadotropic hypogonadism (HH) and the effect of prolonged testosterone (T) replacement therapy on these cells.
Design And Setting:
We conducted a prospective study on males with HH at a university andrological center.
Patients:
The study included 10 young HH patients (28.6 +/- 3.1 yr) and 25 age-matched controls.
Interventions:
Idiopathic HH patients were treated with T gel therapy, 50 mg/d for 6 months.
Main Outcome Measures:
We assessed circulating PC and EPC concentrations and immunocytochemistry for androgen receptor expression on cultured EPCs.
Results:
At baseline, HH patients showed a significant reduction of both PCs and EPCs with respect to controls. T replacement therapy induced a significant increase of these cells with respect to baseline. Immunocytochemistry on cultured EPCs showed strong expression of the androgen receptor.
Conclusions:
Hypotestosteronemia is associated with a low number of circulating PCs and EPCs in young HH subjects. T treatment is able to induce an increase in these cells through a possible direct effect on the bone marrow.
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