From trends so far, men have appeared likelier than women to die of COVID-19. While the reason remains an open question, reports from the US over the last two days have described trials that will seek to find out whether the answer lies in two sex hormones in women — estrogen and progesterone.
The trends & the theories
Various studies have captured a trend that appears to prevail in many countries and regions. In mid-February, a paper by Chinese researchers analysed data from Wuhan, Hubei, and China as a whole and calculated a fatality rate of 2.8% for men, as compared to 1.7% for women. Since then, Italy, Iran, South Korea, Germany, France and the UK have released data that showed a similar trend. Data from the UK’s national statistics office, in fact, suggested that men were twice as likely as women to die of COVID-19. And daily data from Australia’s Health Department show a visibly higher death rate among men in the age groups 70-79 and 80-89.
India does not release sex-aggregated data on COVID-19 cases and deaths.
As for the cause, there have been various since the trend became obvious, including the possibility that women’s sex hormones help them fight the infection better than men. Among other theories related to biology, one draws from the fact that a woman’s genetic makeup consists of two X chromosomes (a man has only one of those). Because X chromosomes contain most of the genes related to the immune system, the inference is that women are better equipped to mount an immune response.
Other theories are based on lifestyle and perceptions — men are likelier to smoke and take risks, which could include not taking enough precautions against infection.
Estrogen and progesterone are the two main sex hormones that characterise a woman. Estrogen helps her develop female physical features and also maintains her reproductive system. Progesterone is secreted by a temporary endocrine gland that the body produces during the second half of the menstrual cycle, and helps prepare the body for possible pregnancy after ovulation. The male body too has estrogen and produces progesterone, both in smaller amounts.
Now, two teams in the US are testing the theory that these hormones help women fight COVID-19 better. One team, at Stony Brook University, New York, has already started treating male patients of COVID-19 with mild doses of estrogen. The other team, at Cedars-Sinai Medical Center in Los Angeles, will conduct trials with progesterone on men infected with the coronavirus.
More candidates are being recruited for the estrogen trials. “The purpose of this study is to find out if estrogen… given as a patch placed on skin of COVID19 positive or presumptive positive patients for 7 days can reduce the severity of COVID19 symptoms compared to regular care,” the US National Library of Medicine says.
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The New York Times quoted Dr Sara Ghandehari, principal investigator for the progesterone study of Cedars-Sinai, as saying that men are clearly doing worse than women in ICU, and that pregnant women (who have high levels of estrogen and progesterone) tend to have mild courses of the disease. “So something about being a woman is protective, and something about pregnancy is protective, and that makes us think about hormones,” she told The NYT.
Women produce the most estrogen and progesterone during reproductive age, and the levels of both fall drastically after menopause. So, if these hormones were responsible for the lower fatality rate among women, the trend should not have shown itself among older women. However, even elderly women have shown a better survival rate than elderly men.
As such, some experts who study sex differences in immunity have warned that hormones may fail to be the magic bullet that some are hoping for, The NYT report said. Sabra Klein, who studies sex differences in viral infections and vaccination responses at the Johns Hopkins Bloomberg School of Public Health, told The NYT: “We see this bias across the life course. Older men are still disproportionately affected, and that suggests to me it’s got to be something genetic, or something else, that’s not just hormonal.”
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The disproportionate fatality rate among men shows itself very prominently among 70-89-year-olds in graphics released by the Australian government.
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