Pharmacology of the Luteinising Hormone-Releasing Hormone (LHRH) Analogue, Zoladex

Furr, B. J. A.

doi:10.1159/000181318

Cited by 32 publications

(16 citation statements)

References 12 publications

(17 reference statements)

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“…One such form of androgen and estrogen withdrawal in prostate and breast cancer patients, respectively, is the use of the luteinizing hormone (LH)-releasing hormone (LH-RH) agonist Zoladex (goserelin acetate). Zoladex reduces sex hormone concentrations to castrate levels by desensitizing the pituitary gland to LH-RH (16). Zoladex occupies LH-RH receptors on the pituitary, which causes a downregulation of LH-RH receptors.…”

mentioning

confidence: 99%

Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats

Hydock

Lien²,

Schneider³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Reducing testosterone and estrogen levels with a luteinizing hormone-releasing hormone agonist such as Zoladex (i.e., chemical gonadectomy) is a common treatment for many prostate and breast cancer patients, respectively. There are reports of surgical gonadectomy inducing cardiac dysfunction, and exercise has been shown to be cardioprotective under these circumstances. Minimal research has been done investigating the effects of chemical gonadectomy and increased physical activity on cardiac function. The purpose of this investigation was to examine the effects of chemical gonadectomy and physical activity on cardiac function. Male (M) and female (F) Sprague-Dawley rats received either Zoladex treatment (Zol) that suppressed gonadal function for 8 wk or control implants (Con) and either were allowed unlimited access to voluntary running wheels (WR) or remained sedentary (Sed) throughout the treatment period. In vivo and ex vivo left ventricle (LV) function were then assessed, and myosin heavy chain (MHC) expression was analyzed to help explain LV functional differences. Hearts from M Sed+Zol exhibited significantly lower aortic blood flow velocity, developed pressure, and maximal rate of pressure development and higher beta-MHC expression than M Sed+Con. Hearts from F Sed+Zol exhibited significantly lower LV wall thicknesses, fractional shortening, and developed pressure and higher beta-MHC expression than F Sed+Con. This cardiac dysfunction was not evident in hearts from M or F WR+Zol, and this was associated with a preservation of the MHC isoform distribution. Thus an 8-wk chemical gonadectomy with Zoladex promoted cardiac dysfunction in male and female rats, and voluntary wheel running protected against this cardiac dysfunction.

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mentioning

confidence: 99%

Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats

Hydock

Lien²,

Schneider³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…ADT implants were administered subcutaneously (s.c.) at the scruff of the neck, and this time-released treatment suppresses sex hormone synthesis for a period of 28 days (Furr 1989;Han et al 2013). Beginning on day 15 of the protocol, animals underwent a 10 day intraperitoneal (i.p.)…”

Section: Drug Treatments and Exercise Trainingmentioning

confidence: 99%

Endurance exercise attenuates cardiotoxicity induced by androgen deprivation and doxorubicin

Parry

Hydock

Jensen

et al. 2014

Can. J. Physiol. Pharmacol.

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Doxorubicin (DOX) is associated with cardiac dysfunction and irreversible testicular damage. Androgen deprivation therapy (ADT) is administered prior to DOX treatment to preserve testicular function. However, ADT may exacerbate DOX-induced cardiac dysfunction. Exercise is cardioprotective, but the effects of exercise on cardiac function during combined ADT and DOX treatment are currently unknown. In this study, male Sprague-Dawley rats were randomly assigned to experimental groups: control (CON), ADT, DOX, or ADT+DOX. Animals received ADT or control implants on days 1 and 29 of the 56-day protocol. Animals remained sedentary (SED) or engaged in treadmill endurance exercise (TM) beginning on day 1. On day 15, the animals received DOX at 1 mg·(kg body mass)(-1)·d(-1) by intraperitoneal injection for 10 consecutive days, or an equivalent volume of saline. On day 57, cardiac function was assessed in vivo and ex vivo. Animals treated with DOX alone, or with combined ADT+DOX, showed significant (P < 0.05) reductions in left ventricular developed pressure (-21% and -27%), maximal rate of pressure development (-29% and -32%), and maximal rate of pressure decline (25% and 31%), respectively when compared with the sedentary control animals. Endurance exercise training attenuated (P > 0.05) cardiac dysfunction associated with combined ADT+DOX treatment, indicating that exercise during simultaneous ADT+DOX treatment is cardioprotective.

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“…One 3.6 mg depot formulation of Zoladex has been shown to be effective at depressing testosterone concentrations to castrate levels in rats for 28 days. 4 Animals received implants on days 1 and 29. Testosterone production was blocked for a total of 56 days (8 weeks).…”

Section: Drug Treatmentmentioning

confidence: 99%

“…1 The goal of ADT is to reduce testosterone concentrations, and this may be accomplished by orchiectomy (surgical castration) or by the administration of estrogen, luteinizing hormone releasing hormone (LHRH) agonists, LHRH antagonists, or antiandrogens. 4 The LHRH agonist Zoladex (trade name goserelin acetate) has been shown to reduce prostate tumor size to the same degree as orchiectomy. 4 However, it is becoming more common for nonmetastatic disease, asymptomatic patients with signs of biochemical recurrence to receive ADT, and currently there are no recommended treatment limitations for this approach.…”

Section: Introductionmentioning

confidence: 99%

“…4 The LHRH agonist Zoladex (trade name goserelin acetate) has been shown to reduce prostate tumor size to the same degree as orchiectomy. 4 However, it is becoming more common for nonmetastatic disease, asymptomatic patients with signs of biochemical recurrence to receive ADT, and currently there are no recommended treatment limitations for this approach. 5 Long-term ADT treatment can lead to numerous side effects including hot flashes, sexual dysfunction, gynecomastia, changes in body composition, altered metabolism, osteoporosis, anemia, and negative cardiovascular system adaptations, 6 which can have deleterious effects on PC patients' quality of life.…”

Section: Introductionmentioning

confidence: 99%

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Androgen deprivation therapy and cardiac function: effects of endurance training

Hydock

Wonders

Schneider

et al. 2006

Prostate Cancer Prostatic Dis

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Pharmacology of the Luteinising Hormone-Releasing Hormone (LHRH) Analogue, Zoladex

Cited by 32 publications

References 12 publications

Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats

Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats

Endurance exercise attenuates cardiotoxicity induced by androgen deprivation and doxorubicin

Androgen deprivation therapy and cardiac function: effects of endurance training

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