Treatment of serious COVID-19 infection by combining suppression of testosterone and using a high dose of estrogens

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.

 

 

“Maintaining bone health by estrogen therapy in patients with advanced prostate cancer: a narrative review”

Pantarhei Oncology proudly announces that its paper “Maintaining bone health by estrogen therapy in patients with advanced prostate cancer: a narrative review” has been published in the journal Endocrine Connections after comprehensive review. This journal is an international peer-reviewed, scientific, open access journal in the field of endocrinology.

In this paper we review the new and safer estrogen therapies, including high dose estetrol (HDE4), to maintain bone mass and prevent fractures in advanced prostate cancer patients treated with androgen deprivation therapy (ADT).

 

Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study

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

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).

 

Research paper on positive results treatment for advanced breast cancer with the fetal estrogen estetrol (E4) has been accepted for publication in the Journal of Cancer Research and Clinical Oncology

Pantarhei Oncology proudly announces that its paper ‘Tumor Suppression, Dose Limiting Toxicity and Wellbeing with the Fetal Estrogen Estetrol (E4) in patients with advanced breast cancer’ has been accepted for publication in the Journal of Cancer Research and Clinical Oncology after comprehensive review. The Journal of Cancer Research and Clinical Oncology is an international peer-reviewed scientific journal in the field of oncology.

The research paper states that treating postmenopausal women diagnosed with advanced breast cancer can be treated safely with high doses of E4. All 12 patients enrolled had progressive, heavily pre-treated advanced breast cancer. No treatment-related serious adverse events  or doses of limiting toxicity (DLTs) occurred during the first 4 weeks of E4 treatment allowing further investigation of all three doses. Five of nine patients completing 12 weeks of E4 treatment showed objective anti-tumor effects and six of nine patients reported improved wellbeing.

Schmidt_et_al-2020-Journal_of_Cancer_Research_and_Clinical_Oncology

Review paper on the risk of breast cancer in relation to gender, breast development and gonadal function published in JCEM

The Journal of Clinical Endocrinology & Metabolism has accepted the manuscript “Breast Cancer and Major Deviations of Genetic and Gender-related Structures and Function” by Herjan J.T. Coelingh Bennink, Jan F.M. Egberts, Jan A. Mol, Kit C.B. Roes, Paul J. van Diest for publication. The review reports of the risk of breast cancer (BC) in relation to gender, breast development and gonadal function in eight populations with different genetic conditions. Main three conclusions are: 1) the presence of an Y chromosome protects against the development of BC; 2) Without menstrual cycles, BC hardly occurs with an incidence comparable to males; 3) BC has been reported only once in genetic females with the Mayer-Rokitansky-Küster-Hauser syndrome, who have normal breasts and ovulating ovaries with normal levels of estrogens and progesterone.

For more information, please read the abstract.

 

 

Review paper on the use of high-dose estrogens (HDE) for the treatment of breast cancer

Review paper on the use of high-dose estrogens (HDE) for the treatment of breast cancer

Estrogens are known to stimulate the growth of breast cancer, whereas on the other hand estrogens are an effective treatment for this disease. The fact that estrogens can effectively be used for the treatment of breast cancer is something that almost has been forgotten about, whereas the fear for estrogens remains. This paper reviews the use of estrogens for the treatment of breast cancer and identifies possible applications for the future.

Coelingh Bennink et al Maturitas 2017 (HDE paper)

Results Dose-Escalating Study With the Fetal Estrogen Estetrol in Healthy Men published in The Journal of Clinical Endocrinology & Metabolism

Luteinizing hormone–releasing hormone agonists have replaced estrogens for endocrine treatment of advanced prostate cancer (PC) because of cardiovascular side effects. The published study with the fetal estrogen estetrol (E4) in healthy males shows promise as a safe and effective drug for use in prostate cancer.

A Dose-Escalating Study With the Fetal Estrogen JCEM 2018