We sought to evaluate the response of serum testosterone to hCG monotherapy as evidence of its efficacy at various doses and therapeutic durations, as well as its safety. Despite its promise, scant literature exists on use of hCG as a monotherapy for patients with suspicion of late-onset hypogonadism, whose primary indication for therapy is not fertility. As LH would do, hCG acts on Leydig cells, stimulating them to produce and release intratesticular testosterone (1). However, per the recent American Urological Association (AUA) guidelines, it should be reserved for patients with testosterone deficiency, as defined as less than 300 ng/dL (8). Most often, testosterone replacement therapy (TRT) is offered to these men (3). Even when a testosterone value looks appealing on paper, treatment is not successful if symptoms have not improved, hematocrit has risen too far, fertility plans were ignored, or side effects are emerging. If testosterone rises above the female physiologic range, the risk of androgenic adverse effects increases and the treatment logic starts to break down (Parish et al., Climacteric, 2021; Parish and Kling, Menopause, 2023). Future studies should evaluate changes in hematocrit levels in these patients, as well as the effect that baseline luteinizing hormone may play on response to hCG monotherapy. Testosterone, the primary hormone involved in TRT, stimulates the production of erythropoietin (EPO), a molecule that signals the bone marrow to generate more red blood cells. To ensure your health and safety while on TRT, it's essential to monitor your hematocrit levels regularly. It represents the proportion of red blood cells compared to the liquid component of blood, which is primarily composed of water. Hematocrit refers to the percentage of red blood cells present in a given volume of blood. Testosterone Replacement Therapy (TRT) has proven to be a highly effective treatment for men dealing with low testosterone levels, offering improvements in symptoms such as fatigue, libido, erectile function, and even mood. However, on TRT, this stimulation can sometimes lead to an overproduction of red blood cells, a condition known as erythrocytosis. Hematocrit is the percentage of your blood volume that is composed of red blood cells. Sometimes polycythemia overlaps with hemochromatosis and excess blood levels of iron, so iron supplements could exacerbate testosterone-induced polycythemia. For example, your doctor might recommend low-dose aspirin to reduce your risk of blood clots from elevated hematocrit. The higher the altitude, the less oxygen in the environment—meaning you might require extra red blood cells to oxygenate your tissues, says Shatzel. New research suggests that men with higher-than-average hematocrit at baseline have more than double the risk of developing hematocrit levels 50 percent or higher when using TRT. When your blood gets oversaturated with red blood cells relative to white blood cells, platelets, and plasma, it blood gets too thick. Symptoms mainly occur in polycythemia vera (PV), a rare bone marrow condition. Certain kidney-related issues can increase this signal even when oxygen levels are normal. Some therapies or hormonal conditions can raise hemoglobin and hematocrit. These are among the most common causes of true polycythemia. Pellets are implanted under the skin every 3 to 6 months and deliver a steady hormone release. Side effects include injection site pain, swelling, or nodules. The American Urological Association recommends PSA screening and digital rectal exams before and during therapy, particularly for men over 40. Modern injectable, topical, and pellet forms carry minimal hepatic risk, but liver function should still be monitored periodically. Exogenous testosterone signals the brain to reduce its own production via the hypothalamic-pituitary-gonadal (HPG) axis. A 2018 study in the British Journal of Clinical Pharmacology found men on TRT had a nearly 4% higher risk of sleep apnea. Some men experience mood swings, irritability, or emotional sensitivity during the initial weeks of therapy.
