The men arriving with severe disease stayed longer, needed more breathing machines
En los primeros meses de la pandemia, una neumóloga de Los Ángeles observó que los hombres hospitalizados por COVID-19 grave morían con mayor frecuencia que las mujeres, y se preguntó si una hormona reproductiva podría explicar —y quizás corregir— esa diferencia. Un pequeño ensayo clínico con cuarenta pacientes sugiere que la progesterona, conocida por sus propiedades antiinflamatorias, podría moderar la respuesta inmune descontrolada que hace tan letal a esta enfermedad. Los resultados son prometedores, pero la ciencia exige paciencia: este es apenas el primer paso de un camino más largo.
- Desde el inicio de la pandemia, los hombres han muerto de COVID-19 a tasas desproporcionadamente altas, una disparidad que urgía explicación y respuesta.
- La hipótesis central es que la progesterona —más abundante en mujeres en edad fértil— podría frenar las tormentas de citocinas que convierten una infección grave en una catástrofe inmunológica.
- En un ensayo aleatorio de cinco días, los veinte hombres que recibieron inyecciones de progesterona mostraron una mejoría clínica 1,5 puntos superior a la del grupo de control al séptimo día.
- Los pacientes tratados también necesitaron menos oxígeno suplementario y pasaron menos días hospitalizados, aunque las diferencias no alcanzaron significancia estadística dado el tamaño reducido de la muestra.
- El estudio fue pequeño, no ciego y realizado en un solo hospital, por lo que sus autores advierten que se necesitan ensayos más amplios y diversos antes de considerar este tratamiento como estándar clínico.
En la primavera de 2020, Sara Ghandehari, neumóloga de Cedars-Sinai en Los Ángeles, notó un patrón inquietante en su unidad de cuidados intensivos: los hombres con COVID-19 grave permanecían más tiempo conectados a respiradores y morían con mayor frecuencia que las mujeres. La disparidad era demasiado consistente para ignorarla.
Ghandehari y su equipo comenzaron a sospechar que la progesterona podría ser parte de la respuesta. Esta hormona esteroide, presente en ambos sexos pero mucho más abundante en mujeres durante sus años fértiles, tiene propiedades antiinflamatorias conocidas. Observaron además que las mujeres posmenopáusicas —con niveles de progesterona más bajos— desarrollaban formas más graves de la enfermedad que las premenopáusicas. La pregunta era lógica: ¿podría suplementar a los hombres con esta hormona mejorar sus probabilidades de sobrevivir?
Entre abril y agosto de 2020, reclutaron a cuarenta hombres hospitalizados con COVID-19 moderado o grave. La mitad recibió atención estándar; la otra mitad recibió además inyecciones de 100 miligramos de progesterona dos veces al día durante cinco días. Al séptimo día, los pacientes tratados mostraron una puntuación 1,5 puntos más alta en una escala clínica de siete niveles, y también requirieron menos oxígeno y tuvieron estancias hospitalarias más cortas, aunque estas diferencias no alcanzaron significancia estadística. Dos pacientes fallecieron —uno en cada grupo—, pero ninguna muerte se atribuyó al tratamiento.
Ghandehari fue cuidadosa al interpretar los resultados. La muestra era pequeña, predominantemente blanca e hispana, y el ensayo no fue ciego. Antes de que la progesterona pueda considerarse un tratamiento estándar, serán necesarios estudios más amplios, en múltiples centros y poblaciones más diversas. Los hallazgos son alentadores, pero preliminares: una primera señal de que una hormona con millones de años de historia evolutiva podría tener un papel inesperado frente a un virus completamente nuevo.
In the spring of 2020, as COVID-19 filled hospital wards across the country, a pulmonologist at Cedars-Sinai in Los Angeles noticed something that troubled her. Sara Ghandehari, working in the intensive care unit, saw a pattern: the men arriving with severe disease stayed longer, needed more breathing machines, and fared worse than the women on the same ward. The disparity was stark enough to demand explanation.
Ghandehari and her team began to wonder whether a hormone might hold the answer. Progesterone—a steroid hormone best known for its role in the female reproductive cycle—exists in both men and women, but women produce far more of it during their childbearing years. The researchers noticed something else: premenopausal women, who maintain higher progesterone levels naturally, tended to develop milder COVID-19 than postmenopausal women, whose progesterone drops sharply. Could supplementing men with this hormone help them survive?
The mechanism seemed plausible. Progesterone has anti-inflammatory properties. In severe COVID-19, the immune system sometimes spirals into a catastrophic overreaction called a cytokine storm—a cascade of inflammatory signals that can be fatal. If progesterone could dampen that response, it might save lives. The team decided to test the idea.
From April through August of 2020, they recruited forty hospitalized men with moderate to severe COVID-19 and divided them randomly into two groups. Twenty received standard hospital care. The other twenty received injections of 100 milligrams of progesterone twice daily for five days, in addition to standard care. Every patient was tracked for fifteen days or until discharge, with daily assessments using a standard seven-point clinical scale that ranged from "not hospitalized, no activity limitations" down to death.
By the seventh day, the results showed a measurable difference. Patients who received progesterone scored a median of 1.5 points higher on the clinical scale than the control group—a meaningful gap on a seven-point measure. The treated group also spent fewer total days in the hospital and required less supplemental oxygen and mechanical ventilation, though these differences fell short of statistical significance in a group this small. No serious adverse effects emerged from the injections. Two patients died during the study period—one from each group—but neither death was attributed to the treatment.
Yet Ghandehari was careful not to overstate what she had found. The study had significant limitations. The sample size was small. The participants were predominantly white and Hispanic, mostly obese, and carried other medical conditions that already increased their risk of poor outcomes. The trial was not blinded, meaning everyone involved—researchers, doctors, patients—knew who was receiving the experimental treatment, a fact that can subtly influence how people respond and report their symptoms.
Most importantly, this was a single small trial at a single hospital. Before progesterone could become a standard treatment for severe COVID-19 in men, much larger studies would be needed, conducted across multiple centers and in more diverse populations. The researchers would need to test it in postmenopausal women as well. They would need to confirm that the early promise held up at scale and that no hidden safety problems emerged with wider use.
Ghandehari's conclusion was measured: the findings were encouraging, but they were also preliminary. The next phase of research would determine whether this hormone, which has shaped human reproduction for millennia, might also help save the lives of men fighting a novel virus.
Notable Quotes
As a doctor in the ICU, I was struck by the gender disparity—men staying longer and needing mechanical ventilation while women had better outcomes.— Sara Ghandehari, pulmonologist, Cedars-Sinai
While our findings are encouraging, our study has significant limitations. The sample size is relatively small and was composed mainly of white, Hispanic, and obese individuals.— Sara Ghandehari
The Hearth Conversation Another angle on the story
Why did Ghandehari notice the gender difference in the first place? Was it obvious?
She was in the ICU every day, watching who got sicker and who recovered. The men seemed to stay longer, need more machines. It wasn't a statistical hunch—it was something she saw with her own eyes.
And the progesterone idea—did that come from nowhere, or was there already a reason to suspect it might work?
Women naturally have more of it, and premenopausal women were getting less severe COVID. That's not coincidence you can ignore. The hormone also has known anti-inflammatory effects. So the logic was there.
The cytokine storm—that's the body attacking itself, right?
Exactly. In severe COVID, the immune system doesn't just fight the virus. It overreacts catastrophically, flooding the body with inflammatory signals. Progesterone might act as a brake on that spiral.
So why is she so cautious about the results? The treated men did better.
Because forty men at one hospital is not enough to change medical practice. You need hundreds, maybe thousands, across different places, different populations. And you need to know it wasn't just luck or bias in how the study was run.
The fact that it wasn't blinded—does that really matter if the numbers show improvement?
It matters because people respond differently when they know they're getting a special treatment. Doctors might watch them more closely. Patients might report symptoms differently. You can't separate the drug from the expectation.
What happens next?
Larger trials. Different hospitals. Women too, especially older women. And they have to prove the safety holds up when you give this to thousands of people, not twenty.