How do we define “castration” in men on androgen deprivation therapy?

Itty, Sarin; Getzenberg, Robert H.

doi:10.4103/aja.aja_139_19

Cited by 7 publications

(3 citation statements)

References 32 publications

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“…The aim is to provide therapeutic benefits similar to traditional testosterone replacement therapy (TRT) with potentially fewer adverse effects on tissues such as the prostate and hair follicles. [2][3][4][5] Some clinical trials have explored the use of SARMs in hypogonadism, primarily focusing on assessing their safety, tolerability, and effectiveness in increasing muscle mass and improving physical function. However, research in this area is still in its early stages, and more extensive studies are needed to establish the longterm safety and efficacy of SARMs compared with existing treatments such as TRT.…”

Section: Selectivementioning

confidence: 99%

Effect of selective androgen receptor modulator RAD140 on prostate and testosterone levels in Wistar strain rats with bilateral orchidectomy

Budaya,

Nurhadi,

Anita

et al. 2024

Med J Indones

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BACKGROUND Selective androgen receptor modulators (SARMs) have been investigated as a potential treatment for hypogonadism, a condition characterized by low testosterone levels in men. The idea is to provide therapeutic benefits similar to traditional testosterone replacement therapy. However, research in this area is still in its early stages, and more extensive studies are needed to establish the efficacy of SARM. This study aimed to determine the impact of SARM RAD140 on testosterone levels, fibromuscular stroma, and prostate mass in rats undergoing bilateral orchidectomy. METHODS This was an in vivo study using posttest-only control group design in rats (Rattus norvegicus). The positive and negative control groups consisted of rats with and without bilateral orchidectomy, respectively. The treatment groups were rats given SARM RAD140 with and without orchidectomy. Testosterone levels, histopathology, and prostate mass were examined at the end of week 6, and the quantitative data were analyzed using one-way ANOVA. RESULTS This study found no difference in prostate mass (0.598 [0.05] g versus 0.590 [0.07] g, p = 0.984), fibromuscular stroma ratio (0.483 [0.094] versus 0.463 [0.057], p = 0.984), and testosterone level (0.006 [0.005] ng/dl versus 0.014 [0.004] ng/dl, p = 0.098) compared to positive control with orchidectomy and SARM RAD140 administration 6 weeks after treatment. CONCLUSIONS There were no differences in testosterone levels, prostate mass, or the ratio of fibromuscular stroma to epithelium area in rats undergoing bilateral orchidectomy and placebo surgery with the administration of SARM RAD140.

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Section: Selectivementioning

confidence: 99%

Effect of selective androgen receptor modulator RAD140 on prostate and testosterone levels in Wistar strain rats with bilateral orchidectomy

Budaya,

Nurhadi,

Anita

et al. 2024

Med J Indones

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“…At baseline (n 5 42), the mean total testosterone concentration measured among male patients (n 5 37) was 309.09 ng/dL (range, 7.00-784.00 ng/dL) compared with 11.20 ng/dL (range, 7.00 to 21.00 ng/dL) among females (n 5 5; Table 4). Although the female total testosterone level is considered castrate (conventionally defined as # 50 ng/dL), the female baseline free testosterone mean of 2.02 ng/dL (range, 0.29-7.00 ng/dL; n 5 4) is higher than the 0.17 ng/dL cutoff for castration in some studies, 20 suggesting that active testosterone might have been available to engage AR. Both total (n 5 36) and free testosterone levels (n 5 30) increased by a mean value of 161.2% (range, -40.1% to 1411.9%) and 148.8% (range, -90.0% to 1407.5%), respectively, at the first on-treatment measurement relative to baseline.…”

Section: Total and Free Testosteronementioning

confidence: 99%

Phase II Study of Enzalutamide for Patients With Androgen Receptor–Positive Salivary Gland Cancers (Alliance A091404)

Foster

Zoroufy³

et al. 2022

JCO

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PURPOSE The androgen receptor (AR) is expressed (+) in a subset of salivary gland cancers (SGCs). This phase II trial evaluated the efficacy of the antiandrogen enzalutamide in AR+ SGC. METHODS Patients with locally advanced/unresectable or metastatic AR+ SGCs were enrolled. Enzalutamide (160 mg) was given orally once daily. The primary end point was the best overall response rate per RECIST v1.1 within eight cycles. Confirmed responses in ≥ 5 of 41 patients would be considered promising. Secondary end points were progression-free survival, overall survival, and safety. RESULTS Forty-six patients were enrolled; 30 (65.2%) received prior systemic therapy, including 13 (28.3%) with AR-targeted drugs. Of seven (15.2%) partial responses (PRs), only two (4.3%) were confirmed per protocol and counted toward the primary end point. Twenty-four patients (52.2%) had stable disease; 15 (32.6%) had progression of disease as best response. Twenty-six patients (56.5%) experienced tumor regression in target lesions; 18 (39.1%) had partial response/stable disease ≥ 6 months. Tumor regressions were observed in female patients (5 of 6 [83.3%]) and those who received prior AR– (6 of 13 [46.2%]) or human epidermal growth factor receptor 2–targeted therapies (5 of 8 [62.5%]). Three patients remained on treatment at data cutoff (duration, 32.2-49.8 months). The median progression-free survival was 5.6 months (95% CI, 3.7 to 7.5); the median overall survival was 17.0 months (95% CI, 11.8 to 30.0). The most common adverse events were fatigue, hypertension, hot flashes, and weight loss. Total and free testosterone levels increased by a mean of 61.2% and 48.8%, respectively, after enzalutamide. CONCLUSION Enzalutamide demonstrated limited activity in AR+ SGC, failing to meet protocol-defined success in part because of a lack of response durability. Strategies to enhance the efficacy of antiandrogen therapy are needed.

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“…Both surgical and medical castration have shown the same level of potency regarding time to progression to castration-resistant prostate cancer and overall survival (OS) [15][16][17]. Surgical orchiectomy has largely fallen out of favor, given ease of access to medical castration [18]. The principle behind ADT is to achieve castrate levels of serum testosterone (<50 ng/l) in hopes of delaying tumor progression and improving survival rates.…”

Section: Androgen Deprivation Therapy: Backgroundmentioning

confidence: 99%

Cardiometabolic side effects of androgen deprivation therapy in prostate cancer

Lafontaine

Kokorovic

2022

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of reviewAndrogen-deprivation therapy (ADT) is widely employed for treatment of advanced prostate cancer and it is considered the frontline therapy. However, the numerous adverse reactions associated with this treatment option are concerning and its potential association with cardiovascular diseases (CVD) should not be overlooked. In this review, we examine the literature on the cardiovascular side effects of ADT and the physiologic mechanisms underpinning the association with CVD. We will also specifically discuss the different findings regarding the interesting potential disparity in major cardiovascular events among GnRH agonist-treated patients compared with patients undergoing GnRH antagonist treatment.Recent findingsAndrogen-deprivation therapy increases the risk of developing CVD by altering the body composition, metabolism, vascular system, and cardiac physiology. GnRH agonists may pose a higher risk of cardiovascular mortality and morbidity than GnRH antagonists; however, this link remains to be determined. Furthermore, screening for cardiovascular risk factors before and during ADT treatment is a crucial step in preventing major adverse cardiac events in prostate cancer patients. Notably, preexisting CVD and comorbidities have been identified as major key elements predicting cardiovascular events. Early implementation of pharmacological and nonpharmacological treatment strategies is strongly suggested, and regular follow-up visits should be scheduled to continuously assess patients’ cardiovascular risk under ADT.SummaryADT is a very powerful treatment option for advanced prostate cancer that improves survival outcomes but has the potential of considerably impacting patients’ cardiovascular health. Medical optimization and close monitoring are crucial during treatment with ADT.

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How do we define “castration” in men on androgen deprivation therapy?

Cited by 7 publications

References 32 publications

Effect of selective androgen receptor modulator RAD140 on prostate and testosterone levels in Wistar strain rats with bilateral orchidectomy

Effect of selective androgen receptor modulator RAD140 on prostate and testosterone levels in Wistar strain rats with bilateral orchidectomy

Phase II Study of Enzalutamide for Patients With Androgen Receptor–Positive Salivary Gland Cancers (Alliance A091404)

Cardiometabolic side effects of androgen deprivation therapy in prostate cancer

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