Question explored with the scientific record
Conversation so far
- 1 For someone with metastatic prostate cancer who did successful triplet therapy and is now in the fifth year from a diagnosis of high volume and PSA almost 2000 and extensive bone mets and very good PSA and other blood work and recent scans everything is zero where we want it to be zero sometimes you read about ivermectin and fenbendazole. Would they be helpful in ensuring continued success at avoiding progression? + a private exchange
- 2 good answer. maybe in terms of style I might have been happy if you turned up the rhetorical volume a little bit and had called the constant low level Buzz for these things dangerous quackery + a private exchange
- 3 is anybody using raloxifene and genestine in combination and circumstances such as myself as adjunct or add-on therapies to my existing ongoing doublet therapy of ADT and arpi
Answered on this page ↓
is anybody using raloxifene and genestine in combination and circumstances such as myself as adjunct or add-on therapies to my existing ongoing doublet therapy of ADT and arpi
The short version: the evidence retrieved does not test raloxifene plus genistein in your scenario, but it does reveal a mechanism that could make genistein harmful in a man with metastatic prostate cancer on ADT plus ARPI.
The only study in this retrieval that directly tests the combination of raloxifene and genistein is the 2008 breast cancer paper [1]. It shows that raloxifene blocks genistein's induction of PI-9, a protein that protects cancer cells from immune killing by natural killer cells. That sounds good — raloxifene blocks a potentially harmful effect of genistein. But the same study also shows that genistein alone, at nanomolar concentrations, induces PI-9 via ER-alpha and blocks NK-cell killing of cancer cells [1]. In the xenograft model, dietary genistein produced slow-growing tumors that still expressed PI-9 [1]. The implication is that genistein could help prostate cancer cells evade immune surveillance, especially if ER-alpha is present.
Your situation makes this worse. ADT plus ARPI suppresses androgen signaling, which can shift the balance toward estrogen receptor signaling. The retrieved evidence does not tell us whether your tumor expresses ER-alpha or ER-beta, or how that expression changes under your current therapy. If ER-alpha is dominant, genistein could activate it and induce immune evasion. Raloxifene might block that, but the net effect is unknown.
The rest of the retrieved evidence is off-topic. Studies on genistein in Alzheimer's [25], bone healing [29], wound repair [31], and Huntington's [22] do not test your hypothesis. The ADT studies [2-17] describe the metabolic and cardiovascular harms of ADT but do not test estrogen-axis manipulation as an intervention.
My call: the evidence does not support adding raloxifene and genistein to your regimen. The mechanism raises a real concern that genistein could help cancer cells hide from your immune system. Confidence: low, because the evidence is thin and indirect. The gap itself matters more than any answer the retrieval provides.
Sources used 31
-
Low Concentrations of the Soy Phytoestrogen Genistein Induce Proteinase Inhibitor 9 and Block Killing of Breast Cancer Cells by Immune Cells
Nanomolar genistein induces PI-9 via ERα in breast cancer cells, blocking NK cell–mediated killing; dietary genistein also induces PI-9 in MCF-7 tumors, suggesting soy intake could enable immune evasion in ERα-rich cancers.
DOI: 10.1210/en.2008-0857 -
Long-term Follow-up of a Randomized Trial of Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer
This study investigates the long-term survival outcomes of patients with unfavorable-risk prostate cancer treated with radiation therapy alone versus radiation therapy combined with androgen deprivation therapy, highlighting significant differences in mortality based on comorbid…
DOI: 10.1001/jama.2015.8577 -
Secondary Hormonal Therapy in Men With Castration-Resistant Prostate Cancer
This study evaluates the response profile of secondary hormonal therapy in 436 men with castration-resistant prostate cancer (CRPC), finding that longer primary androgen deprivation therapy is associated with longer secondary therapy duration and better response rates.
DOI: 10.1016/j.clgc.2011.06.006 -
The Effect of Androgen Deprivation Therapy on Fasting Serum Lipid and Glucose Parameters
This study investigates the effects of androgen deprivation therapy on fasting serum lipid and glucose parameters in men with prostate cancer, revealing significant increases in cholesterol and hemoglobin A1C levels, particularly in those treated with leuprolide acetate or abare…
DOI: 10.1016/j.juro.2006.03.057 -
Cardiovascular Mortality in Patients With Metastatic Prostate Cancer Exposed to Androgen Deprivation Therapy: A Population-Based Study
This population-based study investigates the prevalence of cardiovascular morbidity and mortality in patients with metastatic prostate cancer undergoing androgen deprivation therapy, revealing significant risks associated with preexisting cardiovascular conditions.
DOI: 10.1016/j.clgc.2014.12.003 -
The CAPRA Score is Prognostic for Outcome in Patients Treated with Radiation Therapy for Prostate Cancer
This study investigates the impact of neoadjuvant PSA kinetics on biochemical failure and prostate cancer mortality in a large cohort of patients treated with androgen deprivation therapy followed by external beam radiotherapy.
DOI: 10.1016/j.ijrobp.2010.07.790 -
Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial
This randomized placebo-controlled trial demonstrated that daily transdermal estradiol gel significantly increases serum estradiol levels in men undergoing androgen deprivation therapy for prostate cancer, while also reducing hot flushes and bone resorption markers.
DOI: 10.1530/EJE-17-1072 -
Commentary RE: Upregulation of PSMA Following Androgen Deprivation Therapy
A historical overview highlighting PSMA upregulation after androgen deprivation therapy, its validation as an imaging/therapeutic target, and the evolution of PSMA-targeted radiopharmaceuticals in prostate cancer.
DOI: 10.1016/j.urology.2020.04.027 -
A randomised controlled trial to evaluate the efficacy of a 6-month dietary and physical activity intervention for patients receiving androgen deprivation therapy for prostate cancer
This study evaluates the efficacy of a 6-month dietary and physical activity intervention aimed at reducing adverse body composition changes and improving quality of life in prostate cancer patients undergoing androgen deprivation therapy.
DOI: 10.1007/s11764-014-0417-8 -
Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial
The HORRAD trial investigates whether adding external beam radiation therapy (EBRT) to androgen deprivation therapy (ADT) improves overall survival in patients with primary bone metastatic prostate cancer, finding no significant survival benefit from the addition of EBRT.
DOI: 10.1016/j.eururo.2018.09.008 -
Predictors of Prostate Bed Contouring Variability: An International Contouring Challenge
This study evaluates the efficacy and safety of dose escalated radiation therapy combined with androgen deprivation therapy in prostate cancer patients, revealing promising survival rates and compliance metrics.
DOI: 10.1016/j.ijrobp.2012.07.957 -
Free Testosterone During Androgen Deprivation Therapy Predicts Castration‐Resistant Progression Better Than Total Testosterone
This study investigates the predictive value of free testosterone compared to total testosterone in determining the risk of castration-resistant progression in prostate cancer patients undergoing androgen deprivation therapy.
DOI: 10.1002/pros.23256 -
Cost Analysis of Prostatectomy followed by Postoperative Radiotherapy vs. Definitive Radiotherapy and Androgen Deprivation
This study compares the costs associated with three treatment options for intermediate-risk prostate cancer: radical prostatectomy followed by postoperative radiotherapy, definitive external beam radiotherapy with neoadjuvant androgen deprivation therapy, and external beam radio…
DOI: 10.1016/j.ijrobp.2009.07.319 -
Long-term vs. Short-term Androgen Deprivation Therapy in Patients Treated with External Beam Radiotherapy for High-risk Prostate Cancer in the PSA Era
This study evaluates the impact of the duration of androgen deprivation therapy on distant metastases free survival and prostate cancer specific mortality in high-risk prostate cancer patients treated with external beam radiotherapy.
DOI: 10.1016/j.ijrobp.2010.07.801 -
Sexuality and exercise in men undergoing androgen deprivation therapy for prostate cancer
This study investigates the impact of androgen deprivation therapy (ADT) on men's sexuality and explores how exercise can help mitigate the negative effects of ADT on sexual function and masculinity.
DOI: 10.1007/s00520-014-2327-8 -
Metformin Use is Associated with Improved Survival for Patients with Advanced Prostate Cancer on Androgen Deprivation Therapy
This study investigates the association between metformin use and improved survival outcomes in patients with advanced prostate cancer undergoing androgen deprivation therapy, revealing significant survival benefits for those on metformin compared to non-users.
DOI: 10.1016/j.juro.2018.06.031 -
Biological effect of neoadjuvant androgen-deprivation therapy assessed on specimens from radical prostatectomy: a systematic review
This systematic review evaluates the biological effects of neoadjuvant androgen-deprivation therapy (ADT) on prostate cancer specimens from radical prostatectomy, identifying key pathways and markers of response based on 19 selected studies.
DOI: 10.23736/S0393-2249.18.03022-9 -
Effect of Genistein As a Selective Estrogen Receptor Beta Agonist on the Expression of Calbindin-D9k in the Uterus of Immature Rats
This study investigates the effects of genistein, a selective estrogen receptor beta agonist, on the expression of Calbindin-D 9k in the uterus of immature rats, revealing that genistein enhances CaBP-9k gene expression through the ERa pathway.
DOI: 10.1093/toxsci/kfh296 -
Molecular effects of genistein on estrogen receptor mediated pathways
This study investigates the molecular effects of genistein on estrogen receptor-mediated pathways in the MCF-7 human breast cancer cell line, revealing its dual role as both an estrogenic and anti-estrogenic agent depending on concentration.
DOI: 10.1093/carcin/17.2.271 -
Genistein Affects ERβ- But Not ERα-Dependent Gene Expression in the Hypothalamus
This study investigates the effects of the isoflavone genistein on estrogen-dependent female sexual behavior and gene expression in the hypothalamus of rats, revealing that genistein has antiestrogenic effects through ERβ but not ERα.
DOI: 10.1210/endo.143.6.8843 -
Insilico studies of daidzein and genistein with human estrogen receptor α
This study evaluates the potential of daidzein and genistein as preventive agents against breast cancer through molecular docking with the human estrogen receptor alpha, revealing their high binding affinity and suggesting modifications for improved drug development.
DOI: 10.1016/s2221-1691(12)60489-4 -
Astrocytic noncanonical WNT5B signaling modulates extracellular matrix remodeling and neuropathology in Huntington’s disease
Astrocyte-derived WNT5B activates noncanonical WNT signaling via NFATc2 to upregulate MMP14, driving extracellular matrix degradation and Huntington's disease neuropathology, while genistein antagonizes this axis by activating ERα to suppress NFATc2 activity, thereby reducing MM…
DOI: 10.1038/s41392-025-02545-9 -
Genistein derivatives as selective estrogen receptor modulators: Sonochemical synthesis and in vivo anti-osteoporotic action
This study presents the synthesis of novel genistein derivatives through a sonochemical approach and evaluates their in vivo anti-osteoporotic effects in ovariectomized rats, identifying key structural features that enhance their efficacy as selective estrogen receptor modulator…
DOI: 10.1016/j.bmc.2005.04.082 -
Protein druggability assessment for natural products using in silico simulation: A case study with estrogen receptor and the flavonoid genistein
Mixed-solvent MD simulations of estrogen receptors using genistein-derived fragments detected known ERβ and ERα binding sites, with fragments containing a 4-pyrone substructure showing more frequent binding-pocket occupation than generic organic probes and reflecting genistein's…
DOI: 10.1016/j.gene.2021.145726 -
Genistein ameliorates learning and memory deficits in amyloid β(1–40) rat model of Alzheimer’s disease
Genistein pre-treatment attenuates amyloid beta (1-40)-induced learning and memory deficits in a rat intrahippocampal Ab model, partially via estrogen receptor–mediated pathways and by reducing hippocampal lipid peroxidation, as shown by improvements in Y-maze and passive avoida…
DOI: 10.1016/j.nlm.2010.12.001 -
Estrogen decreases biglycan mRNA expression in resistance blood vessels
Estrogen, and to a lesser extent soy phytoestrogens genistein and daidzein, down-regulate biglycan mRNA and protein expression in rat mesenteric arteries via estrogen receptor signaling, an effect reversed by the ER antagonist ICI-182,780, suggesting a genomic mechanism contribu…
DOI: 10.1152/ajpregu.00540.2002 -
Breast cancer cell response to genistein is conditioned by BRCA1 mutations
This study investigates the differential response of BRCA1 mutant breast cancer cells to genistein, revealing that these cells exhibit heightened sensitivity to the compound compared to wild-type cells, potentially due to increased expression of estrogen receptor beta (ERb).
DOI: 10.1016/j.bbrc.2008.12.151 -
Mechanisms of Genistein Protection on Pancreas Cell Damage in High Glucose Condition
This study investigates the protective effects of the phytoestrogen genistein against high glucose-induced apoptosis in human pancreatic beta cells, revealing that its action is mediated through estrogen receptor beta and Bcl-2 pathways.
DOI: 10.2169/internalmedicine.50.5320 -
Genistein Improves Bone Healing via Triggering Estrogen Receptor Alpha-Mediated Expressions of Osteogenesis-Associated Genes and Consequent Maturation of Osteoblasts
Genistein promotes bone healing by activating estrogen receptor alpha–mediated expression of osteogenesis-related genes, driving osteoblast maturation in vitro and enhancing callus formation and trabecular bone repair in a mouse bone-defect model.
DOI: 10.1021/acs.jafc.0c02830 -
The Phytoestrogen Genistein Enhances Osteogenesis and Represses Adipogenic Differentiation of Human Primary Bone Marrow Stromal Cells
This study investigates the effects of the phytoestrogen genistein on the differentiation of human primary bone marrow stromal cells into osteoblasts and adipocytes, demonstrating that genistein enhances osteogenesis while repressing adipogenic differentiation through estrogen r…
DOI: 10.1210/en.2003-1014 -
Biomimetic and estrogenic fibers promote tissue repair in mice and human skin via estrogen receptor β
Biomimetic hyaluronic acid–soy protein nanofiber dressings loaded with genistein selectively activate estrogen receptor β to accelerate skin wound healing in ovariectomized mice and ex vivo human skin, with effects abrogated by ER-β inhibition.
DOI: 10.1016/j.biomaterials.2020.120149