Detection of Male Hypogonadism in Patients with Post COVID-19 Condition, 2022, Yamamoto et al

[Andy]

Abstract

The pathogenesis and prognosis of post COVID-19 condition have remained unclear. We set up an outpatient clinic specializing in long COVID in February 2021 and we have been investigating post COVID-19 condition. Based on the results of our earlier study showing that “general fatigue” mimicking myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is the most common symptom in long COVID patients, a retrospective analysis was performed for 39 male patients in whom serum free testosterone (FT) levels were measured out of 61 male patients who visited our clinic.

We analyzed the medical records of the patients’ backgrounds, symptoms and laboratory results. 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.

Open access, https://www.mdpi.com/2077-0383/11/7/1955/htm

 

[rvallee]

Evidence mounts for an accumulation of relatively small damage all throughout the body. Injured organs all over, shrinking brain and now gonads. It's generally not huge damage, makes it easy to miss, but starting to think there could be something about what all this damage does, how much it could explain the resulting illness.

Some have extensive damage, or significantly reduced organ function, that can be detected with the traditional tools of medicine. But a lot of widespread damage could be very demanding to fix, gets the immune system active having to clean up, and possibly reducing its vigilance, allowing for opportunistic pathogens present in the body to go on the attack. A thousand small cuts vs a large deep wound.

It's frankly hard to agree that even a small measure of damage could be irrelevant when it's so widespread.

 

[CRG]

Correlation looks problematic - is LOH a consequence of COVID19 or does LOH lower male immunity to infection by and/or sequalae of, COVID19 infection ?

 

[Hutan]

Yes, we don't know if people with low testosterone are more likely to get post-Covid ME/CFS, or if Covid-19 causes lower testosterone in some men. This study doesn't tell us anything about the testosterone levels prior to Covid-19.

The authors suggest two possible mechanisms for Covid-19 causing lowered testosterone:

1. Direct damage to the testes

It is well known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets angiotensin-converting enzyme 2 (ACE2) receptors [29], and the testis and its Leydig cells are known to express ACE2 receptors abundantly [30]. Given the fact that SARS-CoV-2 was detected in the testes of cadavers of COVID-19 patients [31], it is possible that SARS-CoV-2 infiltrates into Leydig cells, leading to hyposecretion of androgens by the testis. Prolonged testicular damage after acute COVID-19 was shown in an animal study [32], and other endocrine organs including the hypothalamus, pituitary gland, adrenal gland, and thyroid gland are also likely to be affected by COVID-19 from the acute phase through to the chronic phase [33,34].

2. Damage to the glands that govern testosterone secretion

In addition to pulmonary and neurological damage, direct infiltration of SARS-CoV-2 into the hypothalamus or pituitary gland may activate related autoimmunity and then induce an ME/CSF-like condition through central hypogonadism [14]. From this point of view, not only primary hypogonadism but also secondary hypogonadism should be considered in post COVID-19 condition.

 

[Wonko]

There is another option;

That testosterone and post covid have no connection.

Much like elephants, although it's rumoured some exist, are not likely to have a strong connection to cod stocks in the Atlantic (of much more dubious existence).

 

[Hutan]

Yes, @Wonko's option is possible.
I wish authors would provide good commentary on how their findings compare to population means. These authors don't tell us what levels of testosterone might be expected in the general population. All of the men in the study who had testosterone levels tested were referred by a clinician for the test because of some suspicion that levels might be low. These are relevant normal ranges for testosterone in men that I found:
Serum total and free testosterone level of Japanese men: a population-based study, Okamura et al

The mean +/- 2 SD of ... FT ... 13.2 +/- 7.8) pg/mL (5.4-21.0 pg/mL) .

Compare that with the measured testosterone of the 39 men (divided into LOH and non-LOH groups) who were referred for testing out of 61 male patients attending the clinic:

The median serum FT levels were 7.2 pg/mL (IQR: 5.7–7.4 pg/mL) in the LOH group and 11.0 pg/mL (9.6–14.3 pg/mL) in the non-LOH group, and the difference was statistically significant (p < 0.05).

So, I don't know - maybe there is a higher rate of low testosterone in the men turning up at this clinic than would be expected?
Googling for normal ranges of testosterone produces quite a lot of variation, I think methods of measuring and also the time of day, and of course age affect things.

It is, therefore, important to consider the necessity of measuring serum FT in patients, especially in patients with fatigue, anxiety, or signs of anemia, at an early stage of post COVID-19 condition.

Regardless, this seems sensible, given that low testosterone in men can cause some symptoms such as fatigue that overlap with ME/CFS.