Exploring the Role of Testosterone Replacement Therapy in Benign Prostatic Hyperplasia and Prostate Cancer: A Review of Safety

Rizzuti, André; Stocker, Gustavo; Santos, Heitor O.

doi:10.3390/uro2010005

Cited by 7 publications

(2 citation statements)

References 74 publications

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“…Apart from BPH, the association between the serum balance of androgens with age and its link to prostate cancer risk has become a topic of immense research interest, especially in men above 40 years [12,13]. In 2018, about 1.3 million new cases were recorded and over 350,000 deaths were as a result of prostate cancer [14].…”

Section: Introductionmentioning

confidence: 99%

Docking and Molecular Dynamics Identify Leads against 5 Alpha Reductase 2 for Benign Prostate Hyperplasia Treatment

Saah

Sakyi

Adu-Poku

et al. 2023

Journal of Chemistry

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Steroid 5 alpha-reductase 2 (5αR-2) is a membrane-embedded protein that together with other isoforms plays a key role in the metabolism of steroids. This enzyme catalyzes the reduction of testosterone to the more potent ligand, dihydrotestosterone (DHT) in the prostate. Androgens, testosterone, and DHT play important roles in prostate growth, development, and function. At the same time, both testosterone and DHT have been implicated in the pathogenesis of benign prostate hyperplasia (BPH). Inhibition of the DHT formation, therefore, provides a therapeutic strategy that offers the possibility of preventing, delaying, or treating BPH. Currently, two steroidal drugs that inhibit 5αR-2, dutasteride and finasteride, have been approved for clinical use. These two come at a high cost and also portray undesirable sexual side effects which necessitate the need to find new chemotherapeutic alternatives for the disease. Based on the aforementioned, finasteride and dutasteride were subjected to scaffold hopping, fragment-based de novo design, molecular docking, and molecular dynamics simulations employing databases like ChEMBL, DrugBank, PubChem, ChemSpider, and Zinc15 in the identification of potential hits targeting 5αR-2. Altogether, ten novel compounds targeting 5αR-2 were identified with binding energies lower or comparable to finasteride and dutasteride, the main inhibitors for this target. Molecular docking and molecular dynamics simulations studies identify amino acid residues Glu57, Phe219, Phe223, and Leu224 to be critical for ligand binding and complex stability. The physicochemical and pharmacological profiling suggests the potential of the hit compounds to be drug-like and orally active. Similarly, the quality parameter assessments revealed the hits possess LELP greater than 3 implying their promise as lead-like molecules. The compounds A5, A9, and A10 were, respectively, predicted to treat prostate disorders with Pa (0.188, 0.361, and 0.270) and Pi (0.176, 0.050, and 0.093), while A8 and A9 were found to be associated with BPH treatment with Pa (0.09 and 0.127) and Pi (0.077 and 0.033), respectively. Structural similarity searches via DrugBank identified the drugs faropenem, acemetacin, estradiol valerate, and yohimbine to be useful for BPH treatment suggesting the de novo designed ligands as potential chemotherapeutic agents for treating this disease.

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Section: Introductionmentioning

confidence: 99%

Docking and Molecular Dynamics Identify Leads against 5 Alpha Reductase 2 for Benign Prostate Hyperplasia Treatment

Saah

Sakyi

Adu-Poku

et al. 2023

Journal of Chemistry

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“…Testosterone undecanoate (T undecanoate), mentioned as having favorable pharmacokinetics in the Development of methods of male contraception by world health organization (WHO), is a testosterone drug with the longest half-life, approved in more than 100 countries, including the approval by food and drug administration (FDA) in 2014; it is widely used in clinical trials for the treatment of gonad function [ 3 – 5 ]. Today exogenous testosterones were mainly used for testosterone replacement therapy, but the benign prostatic hyperplasia (BPH) and prostate cancer, the side effects of testosterone replacement therapy on prostate enlargement and related disorders, are commonly remained a concern for urologist [ 6 ]. Accordingly, we investigated the potential for extended application of T undecanoate, which is characterized by a long-acting effect in the body, beyond the treatment of hypogonadism.…”

Section: Introductionmentioning

confidence: 99%

Comparative application of testosterone undecanoate and/or testosterone propionate in induction of benign prostatic hyperplasia in Wistar rats

Kong

2022

PLoS ONE

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Testosterone undecanoate is a hormone agent with long-acting potential and is used for testosterone replacement therapy for hypogonadism. This study was designed to investigate application of testosterone undecanoate in maintaining high androgen levels for inducing benign prostatic hyperplasia more conveniently than that for testosterone propionate. We conducted two-part studies to determine the optimal dosage and dosing cycle for efficient and stable induction of benign prostatic hyperplasia using testosterone undecanoate. In the injection dosage substudy, single testosterone undecanoate dose (125, 250, 500, 750, or 1000 mg/kg body weight) was administered, and the optimal concentration was determined for 8weeks by measuring changes in testosterone, dihydrotestosterone, and 5-alpha reductase levels. And then, testosterone undecanoate was administered at the optimal dose at intervals of 1, 2, 3, or 4 weeks for 12weeks to induce benign prostatic hyperplasia. The injection dosage substudy showed dose-dependently higher and more stable levels of testosterone in groups administrated testosterone undecanoate than in groups administered testosterone propionate. In the injection cycle substudy, testosterone undecanoate-administered group stably maintained high levels of testosterone, dihydrotestosterone, and 5-alpha reductase compared with testosterone propionate-administered group for the same injection cycle; moreover, the prostate measurements, an important sign of benign prostatic hyperplasia, were significantly increased. Based on these two substudies, we determined the optimal conditions for inducing benign prostatic hyperplasia stably and more conveniently than that for testosterone propionate. This study suggests an extended application of testosterone undecanoate for inducing benign prostatic hyperplasia that can improve research reliability considering the half-life of testosterone as well as injection dosage and concentration.

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Nonpharmacological Interventions for the Management of Testosterone and Sperm Parameters: A Scoping Review

Santos

Cadegiani²,

Forbes

2022

Clinical Therapeutics

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Exploring the Role of Testosterone Replacement Therapy in Benign Prostatic Hyperplasia and Prostate Cancer: A Review of Safety

Cited by 7 publications

References 74 publications

Docking and Molecular Dynamics Identify Leads against 5 Alpha Reductase 2 for Benign Prostate Hyperplasia Treatment

Docking and Molecular Dynamics Identify Leads against 5 Alpha Reductase 2 for Benign Prostate Hyperplasia Treatment

Comparative application of testosterone undecanoate and/or testosterone propionate in induction of benign prostatic hyperplasia in Wistar rats

Nonpharmacological Interventions for the Management of Testosterone and Sperm Parameters: A Scoping Review

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