Testosterone is a steroid hormone produced primarily in the testes in men, and in smaller amounts in the ovaries in women and the adrenal glands in both sexes. This hormone plays a role in regulating muscle mass, fat distribution, bone density, and sex drive. Concerns emerged early in the COVID-19 pandemic that the SARS-CoV-2 virus might interfere with the body’s hormone regulation systems. Scientific studies have since confirmed a connection between acute COVID-19 infection and a noticeable decline in circulating testosterone levels. Research now aims to understand the mechanisms behind this endocrine disruption and determine the long-term consequences for those who recover.
COVID-19 Infection and Testosterone Decline
Research has consistently documented a correlation between SARS-CoV-2 infection and lower testosterone levels in male patients upon hospital admission. Men with severe COVID-19 requiring intensive care frequently exhibit significantly lower testosterone levels compared to those with mild or moderate cases.
In one analysis, patients with severe COVID-19 averaged serum testosterone levels of 0.75 ng/ml, substantially lower than the 2.19 ng/ml observed in those with mild disease. Many hospitalized male patients present with testosterone levels that meet the clinical definition of hypogonadism. This pattern suggests that low testosterone is a consequence or a marker of the body’s severe reaction to the viral infection, not merely a pre-existing condition.
Even following recovery, a percentage of male survivors continue to experience persistently low testosterone levels, which may contribute to Long COVID symptoms. While some men see their levels spontaneously return to baseline, up to 50% of those with low levels at three months still had persistently low testosterone at a 12-month follow-up.
Biological Mechanisms of Endocrine Disruption
The decline in testosterone levels during COVID-19 infection is caused by direct viral damage and systemic inflammatory response. The SARS-CoV-2 virus gains entry into human cells by binding to the Angiotensin-Converting Enzyme 2 (ACE2) receptor, which is widely present across endocrine tissues. The testes express high levels of ACE2, particularly on the Leydig cells, the main producers of testosterone.
Direct Viral Damage (Primary Hypogonadism)
The high ACE2 expression allows the virus to infiltrate and cause direct injury to testosterone-producing cells, sometimes resulting in orchitis. This direct damage represents primary hypogonadism, where the source organ is compromised. Autopsy studies have confirmed viral particles within testicular tissue, supporting the idea of a direct viral attack.
Systemic Inflammation (Secondary Hypogonadism)
Severe systemic inflammation characteristic of moderate to severe COVID-19 suppresses the entire hormone regulatory network, known as the hypothalamic-pituitary-gonadal (HPG) axis. The massive release of pro-inflammatory signaling molecules, such as interleukin-6 (IL-6), during a “cytokine storm” inhibits the signals sent from the brain that stimulate the testes. This suppression of the central regulatory system leads to secondary hypogonadism. Additionally, the vascular effects of COVID-19, including microclotting, may impair blood flow to the testes, indirectly compromising Leydig cell function.
Addressing the Vaccine Question
A common public concern centers on whether the COVID-19 vaccines might similarly affect testosterone levels or male reproductive health. Current scientific consensus indicates that vaccination does not cause a significant or lasting negative impact on male hormone levels or fertility parameters. The available data suggests that the vaccines are safe, with some studies even reporting a slight, non-significant increase in testosterone levels post-vaccination.
The biological reason for this difference lies in the mechanism of action. The vaccines introduce genetic material or a harmless vector to teach the immune system to recognize the spike protein. They do not replicate the full live virus, nor do they target the ACE2 receptor pathway or reproductive organs in the same manner as an acute infection. The short-lived nature of the vaccine components means they do not establish the persistent inflammation or direct organ invasion that the live SARS-CoV-2 virus causes.
Research examining semen parameters, including sperm count and motility, has consistently shown no adverse effects. By preventing or mitigating a severe COVID-19 infection, vaccination acts as an indirect protective measure against the known risks the actual virus poses to male fertility and testosterone production.
Recovery and Clinical Management
For men who develop low testosterone following a COVID-19 infection, the prognosis for recovery is variable, depending on the severity of the initial illness and the underlying mechanism of the hormone disruption. In many cases, particularly after mild or moderate infections, the low testosterone levels resulting from transient inflammation often resolve spontaneously as the body recovers. This recovery typically occurs as the systemic inflammatory markers return to normal and the HPG axis resumes its normal function.
However, if the hypogonadism persists for several months or is accompanied by distinct symptoms such as fatigue, reduced libido, or erectile dysfunction, clinical intervention may be necessary. Physicians will first conduct follow-up testing to determine if the hypogonadism is primary (testes-related) or secondary (brain-related) and to rule out other possible causes. Management is primarily focused on addressing the underlying inflammation and supporting general health through lifestyle adjustments, including optimizing sleep, nutrition, and exercise.
If the low levels are sustained and symptomatic, particularly in the context of Long COVID, a doctor may consider the initiation of Testosterone Replacement Therapy (TRT). TRT can effectively alleviate the specific symptoms of hypogonadism, such as improving sexual function and energy levels. While TRT improves hormone-related symptoms, it may not significantly affect the broader, non-hormonal symptoms associated with the overall Long COVID syndrome.