Sex hormone therapy may benefit women with long COVID, suggests new research

By Claire Wolters | Fact-checked by Davi Sherman
Published March 18, 2024

Key Takeaways

  • Males and females can experience different symptoms from long COVID.

  • In female patients, symptoms can look similar to those of menopause or perimenopause and may involve depletion of hormones.

  • As such, researchers are evaluating whether hormonal replacement therapy could serve as a treatment for long COVID in female patients.

Research suggests that males and females experience long COVID symptoms differently, with studies showing that women are more likely to experience severe hormonal changes from the virus. Now, researchers are investigating whether hormonal replacement therapy could treat women with long COVID.[]

Studying sex-based differences in long COVID

In a preprint article released on March 2, researchers note “strong sex differences in the frequencies and manifestations of long COVID (LC)” in both the symptom manifestation and organ activity.[]

The researchers note that “[t]estosterone levels were significantly associated with lower symptom burden in LC participants over sex designation.” Additionally, females were more likely to develop LC after an acute COVID-19 infection and to experience more intense symptoms.[]

“These findings suggest distinct immunological processes of LC in females and males and illuminate the crucial role of immune-endocrine dysregulation in sex,” the researchers write.[]

Regarding organ activity, the researchers state that males with LC experienced:

  • Decreased frequencies of monocyte and DC populations

  • Elevated NK cells

  • Plasma cytokines including IL-8 and TGF-β-family members

Females with LC experienced:

  • Increased frequencies of exhausted T cells

  • Cytokine-secreting T cells

  • Higher antibody reactivity to latent herpes viruses, including EBV, HSV-2, and CMV

  • Lower testosterone levels (compared to females without LC)

Sex-based differences in acute and long COVID-19

Researchers have noted sex-based differences in both the long and acute phases of COVID-19. In contrast to findings that females with LC experience more severe symptoms, males are reportedly more vulnerable to the effects of acute COVID-19. For both forms of the disease, researchers say they are still questioning why these differences exist—and that there may be more than one answer.

“Sex-specific risk and ultimately outcomes are multifactorial - a function of the complex interplay between biology, behaviour, and the wider determinants of health,” researchers state in a 2021 article published in The Lancet.[]

The article also looks at the potential of using sex hormones in LC treatment, specifically for women. It pointed to observed menstrual changes during acute COVID-19 and noted overlaps between how some women experience LC and how some experience menopause or perimenopause as examples of hormonal impact. In addition to highlighting the need for more studies on hormonal therapies for LC, the researchers say patients need to be thoroughly evaluated to avoid misdiagnosis.

Is hormonal replacement therapy recommended for long COVID now?

Similarities between LC and menopause symptoms in women “could lead to women with symptoms of the perimenopause and menopause being misdiagnosed with Long COVID,” the article states.

The disproportionate impact of LC—combined with other research on sex-based experiences during long COVID—suggests that hormonal therapy could arise as a potential intervention for females experiencing long COVID.

For now, however, there is not enough research to confirm whether or not this sex-specific treatment will be effective.

According to the recent study, “whether immunological traits underlying LC differ between sexes, and whether such differences explain the differential manifestations of LC symptomology is currently unknown.”[]

What this means for you

Men and women may experience symptoms of long COVID differently. As more research on the condition arises, new treatment options, such as hormonal replacement therapies, could become available.

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