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Review
. 2021 Aug 28;28(5):3331-3346.
doi: 10.3390/curroncol28050289.

Androgen Deprivation Therapy, Hypogonadism and Cardiovascular Toxicity in Men with Advanced Prostate Cancer

Gabriela Silvia Gheorghe  1   2 , Andreea Simona Hodorogea  1   2 , Ana Ciobanu  1   2 , Ioan Tiberiu Nanea  1   2 , Andrei Cristian Dan Gheorghe  1   2
Affiliations
Review

Androgen Deprivation Therapy, Hypogonadism and Cardiovascular Toxicity in Men with Advanced Prostate Cancer

Gabriela Silvia Gheorghe et al. Curr Oncol. .

Abstract

Androgen deprivation therapy (ADT) is successfully used in patients with advanced prostatic cancer, but there are many concerns about its systemic side effects, especially due to advanced age and frequent comorbidities in most patients. In patients treated with ADT there are metabolic changes involving the glycaemic control and lipid metabolism, increased thrombotic risk, an increased risk of myocardial infarction, severe arrhythmia and sudden cardiac death. Still, these adverse effects can be also due to the subsequent hypogonadism. Men with heart failure or coronary artery disease have a lower level of serum testosterone than normal men of the same age, and hypogonadism is related to higher cardiovascular mortality. Many clinical studies compared the cardiovascular effects of hypogonadism post orchiectomy or radiotherapy with those of ADT but their results are controversial. However, current data suggest that more intensive treatment of cardiovascular risk factors and closer cardiological follow-up of older patients under ADT might be beneficial. Our paper is a narrative review of the literature data in this field.

Keywords: QT interval; androgen deprivation therapy; arrhythmia; cardiovascular; hypogonadism; prostate cancer; thrombotic risk.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mechanism of action of antiandrogen therapy GnRH = gonadotropin releasing hormone receptor agonist; LH = luteinizing hormone; LH-RH= luteinizing hormone releasing hormone; GnRH-R = gonadotropin releasing hormone receptor; GnRH antagonist = gonadotropin releasing hormone antagonist; LH-R = luteinizing hormone receptor on testis; NARA = nonsteroidal androgen receptor antagonis; DHT = dihidrotestosterone, CYP 17A1 = cytochrome P450 17 A1; 5–10% of testosterone is transformed by 5-α reductase in the more potent DHT, 0.2% testosterone is transformed by aromatases in 17β-estradiol and the rest of testosterone is inactivated by the liver; GnRH agonists provoke an increase of LH in the first weeks of treatment but finally down regulate LH secretion from the anterior pituitary gland. GnRH antagonists block the GnRH receptors on the anterior pituitary gland thus decreasing the synthesis of LH and FSH. NARA block the activation of the androgen receptor from the prostate cells and augment the effectiveness of GnRH agonists or antagonists, CYP 17 A1 inhibitors decrease the synthesis of testosterone from cholesterol.
Figure 2
Figure 2
PRISMA 2020 flow diagram for the current review.
Figure 3
Figure 3
Supposed mechanisms of cardiovascular toxicity of androgen deprivation therapy (ADT) in patients with prostate cancer. Hypogonadism induced by ADT is involved in the occurrence of the cardiotoxicity by many mechanisms. The direct contribution of ADT is not obvious excepting CYP 17 inhibitors which indirectly induce a surge of mineralocorticosteroid secretion and GnRH agonists.
See this image and copyright information in PMC

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