Low testosterone

[Hutan]

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.

 

[Hutan]

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."

 

[Hutan]

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.

 

[Hutan]

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.

Testosterone levels suggestive for hypogonadism were observed in 257 (89.8%) patients at hospital admission. In as many as 243 (85%) cases, hypogonadism was secondary. SARS‐CoV‐2 infection status was independently associated with lower tT levels (p < 0.0001) and greater risk of hypogonadism (p < 0.0001), after accounting for age, BMI, CCI, and IL‐6 values.

They discuss five hypotheses that might explain this including:

First, low T levels may simply be a marker of illness severity, thus recapitulating what has been reported for many other severe illnesses, thus potentially including severe viral infections

 

[Milo]

HPA axis dysfunction affecting testosterone maybe?

 

[Hutan]

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?

 

[mariovitali]

FWIW, in the years that I was sick I had low levels of testosterone, equivalent to those of a 70+ year old man. I tried injecting with hCG (Human Chorionic Gonadotropin) for a couple of months. It did raise testosterone but also increased the number of my crashes.

It was then that I realised that my body was not able to metabolise properly much needed nutrients, hormones etc. Metabolism and Oxidative stress come together unfortunately

 

[ringding]

Will have a read of some of the links at some point.

It interests me as I consistently test low for testosterone, either just in or just outside the lower NHS threshold.
I have no idea whether it was low before falling ill with M.E.
I did convince gp to let me boost testosterone with a gel for 3mths to see if it made a difference to my health. Didn't appear to. So I stopped.

 

[Hutan]

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.

HPA axis dysfunction affecting testosterone maybe?

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:

Testosterone deficiency is frequently seen in both men and women with HIV. Endocrine abnormalities, which can affect testosterone production, have long been recognized as a complication of HIV since the earliest days of the pandemic (although it has generally been associated with late-stage disease). However, recent research has shown that nearly one out of every five men with HIV has documented testosterone deficiency, irrespective of CD4 count, viral load, or treatment status. Similarly, testosterone deficiency is seen in one in four HIV-positive women, most often in the context of severe, unexplained weight loss (HIV wasting).

Testosterone is the steroid hormone which is central to the development of the testes (testicles) and prostate in men as well as the promotion of secondary male sexual characteristics (e.g., lean muscle mass, bone mass, hair growth). Testosterone is also important to women in maintaining normal muscle and bone mass, although at levels around 10% less than men.

In both men and women, testosterone is essential to a person's overall health and well-being, contributing to an individual's strength, energy levels, and libido. By contrast, testosterone depletion is associated with:

• Loss of lean muscle mass
• Anemia
• Osteoporosis
• Insulin resistance
• Increased lipids (fat and/or cholesterol) in the blood
• Increased subcutaneous fat in the abdomen

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.

 

[mariovitali]

Of interest in the mention to TMPRSS2 to the paper you mentioned @Hutan . Of course this may be a coincidence but the drug that I was getting before ME/CFS is a 5-alpha reductase inhibtor (the drug is called Finasteride). I started having symptoms AFTER I stopped the medication . Regarding TMPRSS2, Finasteride is an inhibitor :

Background SARS-CoV-2 entry into type II pneumocytes is depended on the TMPRSS2 proteolytic enzyme. The only known promoter of TMPRSS2 in humans is an androgen response element. As such, androgen sensitivity may be a risk factor for COVID-19. Previously, we have reported a retrospective cohort analysis demonstrating the protective effect of 5-alpha-reductase inhibitors (5ARis) in COVID-19. Men using 5ARis were less likely to be admitted to the ICU than men not taking 5ARis. Additionally, men using 5ARis had drastically reduced frequency of symptoms compared to men not using 5ARis in an outpatient setting. Here we aim to determine if 5ARis will be a beneficial treatment if given after SARS-CoV-2 infection.

https://www.medrxiv.org/content/10.1101/2020.11.16.20232512v1.full

We are looking at androgens with a researcher of ME/CFS and I forwarded to him this study. Thanks for pointing it out.

 

[Hutan]

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.

 

[SNT Gatchaman]

Case report with testosterone replacement therapy having little to no beneficial effect on LC symptoms.

Use of testosterone replacement therapy to treat long-COVID-related hypogonadism (2024, Endocrinology, Diabetes & Metabolism Case Reports)

Following the TRT, both serum testosterone level and hypogonadism-related symptoms were improved, but poor effects occurred on general and neuropsychiatric symptoms and QoL. Therefore, hypogonadism does not appear to be the cause of neurocognitive symptoms, but rather a part of the long-COVID syndrome; as a consequence, starting TRT can improve the hypogonadism-related symptoms without clear benefits on general clinical condition and QoL, which are probably related to the long-COVID itself.