Pantarhei Oncology announces the publication of its scientific paper “Testosterone suppression combined with high-dose estrogen as potential treatment of serious COVID-19 infection” (Heliyon 8 (2022) e12376)

COVID-19 infections are more serious and have a higher mortality in males compared to females especially at ages above 50 years. This is related to the 10-20x higher testosterone (T) levels in males. Suppression of T in males with serious COVID-19 has no consistent effect on the clinical outcome. However, by suppressing T in males, also their estrogen levels are decreased while estrogens have a favorable inhibitory effect on the factors responsible for the COVID-19 infection. Therefore, we hypothesize that a combination of T suppression by androgen-deprivation therapy (ADT) and high-dose estrogen (HDE) treatment may be an effective treatment of serious COVID-19, to be confirmed in in seriously ill COVID-19 patients.

The scientific background of this hypothesis

Most studies report a higher incidence of serious COVID-19 infections in males compared to females especially at ages above 50 years, which may be due to sex-related immunomodulation. A resulting higher mortality rate has been published in Maturitas, both in a meta-analysis performed in May 2020 and in a recent retrospective analysis. These observations could be associated with the 10-20x higher testosterone level in males, since testosterone has unfavourable effects on the immune system, and also stimulates angiotensin converting enzyme-2 (ACE2) and the androgen-regulated protease transmembrane protease serine 2 (TMPRSS2), which both facilitate the entry of the COVID-19 virus into the cell. Testosterone suppression by ADT decreases the effects of ACE2 and TMPRSS2. Estrogen treatment (ET) has the same beneficial suppressive effect on ACE2 and TMPRSS2 as ADT. Both ADT and ET (ADET) have been investigated separately as possible treatments of SARS-CoV-2. We hypothesize that the ADET combination may be more effective than its components alone, as also suggested in our Research Letter in European Urology (2021), entitled ‘Treatment of Serious COVID-19 with Testosterone Suppression and High-dose Estrogen (HDE) Therapy‘. The ADET co-treatment has been investigated successfully by Pantarhei Oncology in patients with advanced prostate cancer (Eur Urol Open Science, 2021 & 2022). We searched the literature for evidence of COVID-19 treatment benefits with estrogens, progesterone, androgen deprivation, and anti-androgens. Data supporting the effect of ADT on SARS-CoV-2 are sparse, but the favorable effects of estrogens in relation to COVID-19 have been shown in various cohort studies.

Based on the outcome of our review and the mode of action of the ADET combination, we hypothesize that a combination of ADT and HDE may be an effective and safe treatment of serious SARS-CoV-2 and we propose to test this ADET hypothesis in a clinical trial.

Pantarhei Oncology proudly announces that its paper ‘Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study’ has been published in the journal European Urology Open Science after comprehensive review. This journal is an international peer-reviewed, scientific, open access journal in the field of urology.

This paper summarises the very important data on the beneficial effects of high dose estetrol (HDE4) on the Quality of Life of prostate cancer patients treated with androgen deprivation therapy (ADT).

Positive results of E4 co-treatment with androgen deprivation therapy for advanced prostate cancer has been published in European Urology Open Science

Pantarhei Oncology proudly announces that its paper ‘Estetrol Cotreatment of Androgen Deprivation Therapy in Infiltrating or Metastatic, Castration-sensitive Prostate Cancer: A Randomized, Double-blind, Phase II Trial (PCombi)’ has been published in the journal European Urology Open Science after comprehensive review. This journal is an international peer-reviewed, scientific, open access journal in the field of urology.

The research paper reports the results of the PCombi study, a phase II, double-blind, randomised, placebo-controlled, multi-centre study in males recently diagnosed with locally advanced or metastatic prostate cancer, who started ADT treatment with an LHRH agonist. The ADT-treated patients were co-treated for 24-weeks with 40 mg E4 or placebo. The high dose E4 treatment was well-tolerated and no treatment-related cardiovascular adverse events were observed. Patient treated with E4 reported fewer complaints of estrogen deficiency symptoms and better quality of life than patients who received placebo. With E4, 6% of the patients reported hot flushes compared to 55% of patients treated with placebo. Total and free testosterone, prostate-specific antigen (PSA), and follicle-stimulating hormone (FSH) were suppressed more rapid and profound, suggesting enhanced disease control by E4. In addition, bone turnover was substantially reduced in the E4-treated patient implicating a bone-sparing effect. The study results have now been published in European Urology Open Science (EUROS).