Effects of Medical or Surgical Castration on Erectile Function in an Animal Model

Abstract

The goal of this study was to investigate the effects of medical castration (luteinizing hormone-receptor hormone [LH-RH] agonist treatment) or surgical castration on erectile function in an animal model. New Zealand White male rabbits were either kept intact (control); surgically orchiectomized; or treated for 2, 4, or 8 weeks with the LH-RH agonist leuprolide acetate (107 microg/kg/mo). At 2 weeks, plasma testosterone levels of orchiectomized and leuprolide acetate-treated animals were 12.8% and 57.4% of intact control animals, respectively. Erectile function was assessed by continuously recording systemic arterial pressure (SAP) and intracavernosal blood pressure (ICP) and determining the ICP:SAP ratios in response to electrical stimulation of the pelvic nerve at varying frequencies (2.5-32 Hz). Androgen deprivation by surgical (orchiectomy) or medical (leuprolide acetate) castration reduced ICP at all frequencies tested but did not alter SAP. Administration of the phosphodiesterase type 5 inhibitor vardenafil (10 microg/kg) did not enhance ICP in surgically orchiectomized or leuprolide acetate-treated animals. Nitric oxide synthase and arginase activities in the corpus cavernosum were not significantly altered by surgical or medical castration. Further, Masson trichrome staining of erectile tissue from androgen-ablated animals showed a reduction in smooth muscle content. These data demonstrate that androgen deprivation achieved by surgical or medical castration adversely affects penile hemodynamics and erectile function without producing significant changes in the activities of nitric oxide synthase or arginase. We conclude that androgen deprivation produces structural alterations in the corpus cavernosum leading to corporal veno-occlusive dysfunction.

Hypogonadism is associated with overt depression symptoms in men with erectile dysfunction

“…3 This effect of testosterone is likely due to stabilization of neuronal nitric oxide synthase expression, 19 although other mechanisms such as prevention of smooth muscle cell loss through apoptosis have been proposed. 20 Previous epidemiological studies have found a strong correlation between the presence of ED and depression. In a multinational survey of over 27 000 men, Rosen et al 21 found depression to be twice as common in men with ED than in their potent counterparts.…”

Impact of androgen deprivation therapy on sexual function

“…17,18 In a study performed on rats, androgen deprivation by surgical or medical castration resulted in reduction in smooth muscle content and structural alterations in the corpus cavernosum leading to venous leak. 19 Castrated dogs have also been shown to have significantly higher cavernosal collagen/smooth muscle ratios. 20 A decrease in smooth muscle/collagen ratios in the corpora cavernosal leads to the development of venous leak.…”

Testosterone and Erectile Function: From Basic Research to a New Clinical Paradigm for Managing Men with Androgen Insufficiency and Erectile Dysfunction

“…Castration has been shown to reduce the expression and activity of PDE5 in rabbits and rats [11,27,28], and androgen supplementation has been shown to upregulate the expression and activity of PDE5 [11,[26][27][28]. Further, administration of PDE inhibitor alone to medically or surgically castrated animals has little effect on the intracavernosal pressure in response to pelvic nerve stimulation [27,29], suggesting that androgens are critical not only for regulating NOS activity, but also in modulating PDE5 activity. While these actions may be seen as a paradox, in that androgens are upregulating both signal initiators (NOS) and signal terminators (PDE5), we interpret this to be a homeostatic mechanism that maintains a relatively constant ratio of critical enzymes for this pathway (Fig.…”

“…Androgen deprivation by surgical or medical castration results in a significant reduction in trabecular smooth muscle content and marked increase in connective tissue deposition [26,29]. These structural alterations are also associated with loss of erectile function.…”