Progesterone helps men fight COVID-19

Dr. Weeks’ Comment: All people – man and women need progesterone. But now we see it helps men fight COVID-19.

Progesterone in addition to standard of care versus Standard of care alone in the treatment of men hospitalized with moderate to severe Covid-19: a randomized controlled pilot trial.

Chest Journal   Feb 20th2021

Progesterone at a dose of 100 mg, twice daily by subcutaneous injection in addition to SOC may represent a safe and effective approach for treatment in hypoxemic men with moderate to severe COVID-19.

ARTICLE Abstract


Severity of illness in COVID-19 is consistently lower in women. Focus on sex as a biologic factor may suggest a potential therapeutic intervention for this disease. We assessed whether adding progesterone to standard of care would improve clinical outcomes of hospitalized men with moderate to severe COVID-19.

Research Question

Does short-term subcutaneous administration of progesterone safely improve clinical outcome in hypoxemic men hospitalized with COVID-19?

Study Design and Methods

We conducted a pilot, randomized, open-label, controlled trial of subcutaneous progesterone in men hospitalized with confirmed moderate to severe COVID-19. Patients were randomly assigned to receive standard of care (SOC) plus progesterone (100 mg subcutaneously twice daily for up to five days) or SOC alone. In addition to assessment of safety, the primary outcome was change in clinical status at day 7. Length of hospital stay and number of days on supplemental oxygen were key secondary outcomes.


Forty-two patients were enrolled from April – August 2020; 22 were randomized to the control group and 20 to the progesterone group. Two patients from the progesterone group withdrew from the study prior to receiving progesterone. There was a 1.5-point overall improvement in median clinical status score on a seven-point ordinal scale from baseline to Day 7 in patients in the progesterone group as compared to controls (95%CI:0.0-2.0; P=0.024). There were no serious adverse events attributable to progesterone. Patients treated with progesterone required 3 fewer days of supplemental oxygen (median of 4.5 vs 7.5 days) and were hospitalized for 2.5 fewer days (median of 7.0 vs 9.5 days) as compared to controls.


Progesterone at a dose of 100 mg, twice daily by subcutaneous injection in addition to SOC may represent a safe and effective approach for treatment in hypoxemic men with moderate to severe COVID-19.

Progesterone Eases Severe COVID-19 in Hospitalized Men

Mitchel L. Zoler, PhD

March 20, 2021

Women hospitalized with severe COVID-19 generally do better than men, which led to the notion that perhaps men hospitalized for COVID-19 could be treated with female hormones.

This concept has shown “very encouraging” results in a single-center, US pilot study that randomized 42 men hospitalized for severe COVID-19. Those who received up to 5 days of treatment with injected progesterone had significantly better outcomes than those who received standard of care, researchers report in Chest.

The new findings “suggest that administration of progesterone at a dose of 100 mg twice daily by subcutaneous injection may represent a safe and effective approach to treatment of COVID-19 by improving clinical status of men with moderate to severe illness,” write Sara Ghandehari, MD, and coauthors, most of whom work at Cedars-Sinai Medical Center in Los Angeles, California.

“The potential utility of progesterone in treatment of early COVID-19 in men is compelling,” they say.

They caution, however, that further study is needed with greater numbers and a more diverse range of participants, including postmenopausal women, as well as involvement of other treatment locations.

Progesterone, a steroid hormone produced by the ovaries during reproductive cycles, naturally occurs in only premenopausal women. The hormone’s potential role in treating men (or postmenopausal women) with more severe COVID-19 stems from the observation that premenopausal women with COVID-19 have fewer hospitalizations, shorter duration of hospitalizations, and less need for ventilatory support than postmenopausal women.

Higher levels of progesterone may have an immunomodulatory role that dampens the exaggerated inflammatory immune cascade associated with more severe COVID-19, the authors suggest.

Progesterone Doubles Rate of Improvement

The primary study endpoint was change in patients’ clinical status, assessed using a 7-point ordinal scale, from baseline to day 7. Secondary endpoints were hospital length of stay, days of supplemental oxygen use, and need for mechanical ventilation.

Results showed that men who received progesterone had a significant median improvement in clinical score status of 1.5 points at 7 days from baseline compared with controls.

Fourteen men in the progesterone group (70%) improved during the first 7 days, compared with seven (32%) in the control group.

Additionally, during the first 7 days of the study, the cumulative probability of clinical improvement was 0.76 among the 20 men who received progesterone compared with 0.55 among the 22 controls who received placebo, a significant difference.

The progesterone group also had a 3-day decrease in median time on supplemental oxygen and a 2.5-day drop in median length of hospital stay. The need for mechanical ventilation was also lower in the progesterone vs control group (0 vs 4 patients).

No patient had a serious adverse event attributable to progesterone, no adverse events occurred that required progesterone discontinuation, and the treatment seemed well tolerated.

Two thromboembolic events occurred in one patient in the progesterone group, and one thromboembolic event occurred in each of two patients in the control group. Patients in each of the two subgroups reported comparable numbers of serious adverse events, and one patient in each group died.

The study enrolled hospitalized adult men in April to August 2020 who tested positive for SARS-CoV-2, had evidence of lower respiratory tract involvement, had an oxygen saturation of 94% or less on room air, and who were on supplemental oxygen. The study excluded men on mechanical ventilation. Patients received chemoprophylaxis for thromboembolism, a precaution recommended for all patients hospitalized for COVID-19. There is currently no evidence that exogenous progesterone at the dosage used promotes thromboembolism, the authors note.

The treatment regimen called for twice-daily injections of 100-mg progesterone for up to 5 days, but patients could stop treatment early if they improved enough for hospital discharge. The protocol also allowed for use of other treatments with presumed benefit for COVID-19. Patients in the control group who had significant deterioration after 7 days could crossover to receive progesterone. Patients were followed for up to 15 days or until hospital discharge.

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