Forum Sneak Peak (Continued):

“A lot of people with long Covid notice that their symptoms get worse just before their period happens,” when estrogen levels are lowest, says Louise Newson, a general practitioner and menopause specialist. She says an additional sign hormones may be involved are long-Covid symptoms like “brain fog, fatigue, dizziness, joint pain — these are also symptoms of menopause.”

Newson has 842 patient responses so far to a pilot survey, and she says the results “confirm my thoughts that long Covid is likely to be related to low hormone levels (estrogen and testosterone), which so far have been neglected with research.” Estrogen plays a key role in women’s health, and having abnormally low levels can lead to infertility, osteoporosis, lack of sex drive, and depression.

Newson says that anecdotally, patients with long Covid from her menopause clinic have improved with the right dose and type of hormone replacement therapy. “They all had low oestradiol and low testosterone results before treatment,” she says.

Long Covid can also significantly impact male reproductive systems and testosterone levels. “Absolutely, reproductive systems have been overlooked during the pandemic,” says Geoff Hackett, a professor of sexual medicine at Aston University in Birmingham, UK. He explains that during acute illness, the testes can be attacked by the virus directly.

“The testes are one of the highest sites of ACE2 expression,” writes the British Society of Sexual Medicine (BSSM) in its position paper on Covid-19. (This ACE2 enzyme is the primary way SARS-CoV-2 enters cells.) The BSSM adds that SARS-CoV-2 also damages cells on the inner surface of blood vessels called endothelial cells, a condition which is “frequently present in men with erectile dysfunction and testosterone deficiency.”

Several recent studies have pointed to testosterone, which in men is produced in the testes, as playing an important role in coronavirus patients: A study in Germany found that the majority of men admitted to the hospital with Covid-19 had low testosterone levels and high inflammatory markers. (This study was unable to determine if these low testosterone levels predated their coronavirus infection.)

A similar study in Italy found low testosterone levels predicted worse outcomes in hospitalized patients. A third study, in Wuhan, China, also found low testosterone levels in coronavirus patients, which they said required “more attention to gonadal function evaluation among patients recovered from SARS-CoV-2 infection, especially the reproductive-aged men.”

Hypogonadism, when sex organs don’t produce sufficient hormones, affects both the production of testosterone and sperm. Another recent paper, published in The Lancet, found the production of sperm was impaired in Covid-19 patients, which they said might be explained by an immune response in the testes. In some patients, they also found auto-immune orchitis, or inflammation of the testis with specific anti-sperm antibodies. “There does seem to be some evidence for relative infertility afterward,” Hackett says, though he cautions it’s too early to say if it would be permanent.

In general, “attacking the cells of the testes will have an adverse effect on erections,” Hackett says. Even beyond a direct effect, endothelial disorder and inflammation may affect the arteries in the penis, making erections more difficult. “Erectile dysfunction is going to be highly prevalent, particularly if you look at the groups at high risk of Covid-19,” Hackett says. “Seventy-five percent of diabetics have erectile dysfunction anyway.” Based on anecdotal evidence, the next Patient-Led Research Group survey will include questions on shrinkage, erectile dysfunction, and testicular pain.

Erectile function is a sign of overall health, and urologist Ryan Berglund of the Cleveland Clinic recently made a statement that for young and healthy people who develop this problem after having Covid-19, “this can be a sign of something more serious going on.”

The BSSM is concerned that these reproductive effects may have lasting implications, warning that low testosterone levels in men “are associated with increased mortality,” and that those “who may have survived the current pandemic … may be at considerable risk from second and third wave infection, or future viral pandemics.”

Beyond Covid-19, research suggested a connection between viral infections of the central nervous system and pituitary dysfunction. A significant number of viruses have previously been associated with the onset of Type 1 diabetes, and it appears there may have been an increase in diabetes diagnoses during the pandemic.

Recognizing these impacts may help doctors find effective treatments; Hackett says a common erectile dysfunction treatment, Tadalafil, improves all markers of endothelial disease. “If it didn’t give men an erection, it would be treated as a serious cardiovascular drug,” he says. He notes that mountain climbers often take Tadalafil before big climbs to avoid altitude sickness, as it lowers pulmonary artery pressure and improves the endothelium of arteries — effects that might significantly help Covid-19 patients.

But Hackett says even as the UK National Health System rolls out long-Covid clinics, he’s been disappointed to see these symptoms overlooked. “Their strategies include things like eating healthy, hydrating, and mindfulness,” he says. “How is this going to go down with seriously ill people? All they’re offering is platitudes.”

The full article is a long read, but fascinating nonetheless: