Low testosterone

We've seen some suggestions of low testosterone in men with ME/CFS and Long covid. Not in all men of course, but some reports of a trend in that direction.

I've heard it suggested that the drop in testosterone was essentially part of the sickness response, the idea being that, if a man is sick, he should be resting in the cave, rather than running off after a woolly mammoth, or some other sort of demanding venture such as embarking on parenthood. Which made me think that perhaps it's yet another brick in the wall for the hypothesis of a persistent but cryptic infection, or at least the body thinking there is a persistent infection.

There is discussion in papers about alternative hypotheses including that men with low testosterone might be more vulnerable to getting infections and/or post-infection syndromes. The former is probably true, in that men who are older and with other comorbidities might have lower testosterone and a higher chance of getting an infection, especially a symptomatic infection. But, I don't think we've seen any prospective study showing that men with lower testosterone are more likely to end up with ME/CFS or LC? So, perhaps it is a consequence, rather than a pre-disposing factor?

I thought it might be interesting to collect up the evidence we have on this.

 

Detection of Male Hypogonadism in Patients with Post COVID-19 Condition, 2022, Yamamoto et al
"Among the 39 patients, 19 patients (48.7%) met the criteria for late-onset hypogonadism (LOH; FT < 8.5 pg/mL: LOH group) and 14 patients were under 50 years of age. A weak negative correlation was found between age and serum FT level (r = −0.301, p = 0.0624). Symptoms including general fatigue, anxiety, cough and hair loss were more frequent in the LOH group than in the non-LOH group (FT ≥ 8.5 pg/mL). Among various laboratory parameters, blood hemoglobin level was slightly, but significantly, lower in the LOH group. Serum level of FT was positively correlated with the levels of blood hemoglobin and serum total protein and albumin in the total population, whereas these interrelationships were blurred in the LOH group.

Collectively, the results indicate that the incidence of LOH is relatively high in male patients, even young male patients, with post COVID-19 and that serum FT measurement is useful for revealing occult LOH status in patients with long COVID."

 

There's the possibility that reduced activity levels might lower testosterone levels, but I don't see much evidence for exercise having a major lasting impact.

 

Severely low testosterone in males with COVID‐19: A case‐control study
That 2021 study found that most men admitted to hospital with acute Covid-19 had low testosterone. It seems pretty accepted that men who have an infection are likely to have low testosterone.

They discuss five hypotheses that might explain this including:

 

I actually thought there might be more papers out there on this. I haven't looked hard, but I haven't come across any good papers on the topic for ME/CFS yet.

One thought is that low testosterone can cause chronic fatigue. So, possibly, sometimes, there are misdiagnoses, and the problem isn't actually CFS. Or, if low testosterone was in fact common in men with ME/CFS, and given some doctors think of ME/CFS as a women's disease, the men might not actually be getting an ME/CFS diagnosis, but instead a diagnosis related to the low testosterone. Is that possible?

 

There are varied accounts on reddit. Some people with ME/CFS or fibromyalgia felt better with testosterone replacement therapy, some stayed the same, and some felt worse. So, pretty much the same as for any touted treatment.

Or perhaps it's not HPA axis dysfunction, perhaps that part of the body (at least) is functioning is exactly as it should when it is coping with a reported immunological challenge. As @mariovitali says, if the body is struggling, it needs to prioritise.

Here's some information from a site about HIV - it says that with HIV, rates of testosterone deficiency are 5 times higher than in the general population - note that low testosterone can also be a problem in women:

They say that most of the low levels of testosterone in HIV are related to neuroendocrine disturbances in which the "interaction between the nervous system and endocrine system is significantly impaired". Although there are rare cases of HIV causing damage to the pituitary gland, HIV itself generally does not cause the impairment. Instead, it is observed in the presence of many chronic illnesses, with persistent inflammation and nonspecific weight loss seen to be associative factors.

 

A report of markedly reduced testosterone in women with LC, somewhat reduced levels in men:
Sex differences in symptomatology and immune profiles of Long COVID, 2024, Silva, Putrino, Iwasaki et al.