madman
Super Moderator
Abstract
Background: With an increase in the number of cancer survivors each year, male sexual dysfunction becomes an important topic for discussion between patients and providers who treat cancer. The aim of this article is to review the types and mechanisms of sexual dysfunction after cancer therapy and discuss treatment options.
Methods: Contemporary concepts regarding male sexual dysfunction after cancer treatment are reviewed and translated for clinical utility.
Findings: To optimize recovery of erectile capacity after erectile dysfunction causing cancer treatments, a penile rehabilitation protocol involving phosphodiesterase inhibitors, vacuum erection devices, intracorporal injections, or a combination is likely to provide some degree of clinically significant benefit. Treating hypogonadism post-cancer treatment depends on the type of cancer that has been treated and patient comorbidities. Anejaculation after cancer treatments is typically not successfully or reliably treated due to the mechanism and severity of sympathetic nerve injury. Semen cryopreservation prior to cancer treatments that may injure nerve fibers essential for the ejaculatory response is highly recommended.
Conclusion: Management of post-cancer treatment sexual dysfunction requires identification of this problem and referral to a specialist if necessary. There are several management options available that can greatly enhance the quality of life in this often overlooked aspect of post-cancer treatment care.
1. Introduction
Cancer survivors make up a growing population that is expected to reach an estimated population of 26.1 million [1], representing approximately 5.0% of the population. Given this growing segment of our population that is a result of more effective treatments, more attention has been placed on the quality of life during and after cancer treatment. In 2018, 856,370 men were newly diagnosed with cancer, with prostate cancer being the most common cancer diagnosed (164,690) [2]. Unfortunately, the prostate is in a central pelvic location surrounded by essential structures whose integrity is essential for the maintenance of normal sexual function.
The resulting erectile dysfunction (ED) after treatment of prostate cancer serves as a prime example of how cancer treatments can affect sexual function [3]. Even in the prostate cancer setting, sexual dysfunction tends to be undertreated and underreported [4]. Thus, it is not surprising that men with cancers whose pathology and treatments are not traditionally associated with sexual dysfunction are often not screened for sexual dysfunction. For the purposes of this review, male sexual dysfunction can be broadly categorized into ED, hypogonadism, and its associated side effects, as well as ejaculatory complaints.
In this review, we discuss the general pathophysiology of how cancer treatments can affect penile erectile capacity, testosterone production, as well as neurologic function as it pertains to ejaculation. We also discuss management strategies for these distressing conditions.
2. Overview of types and mechanisms of sexual dysfunction after cancer treatment
2.1. ED
2.2. Hypogonadism
Along with surgeries to extirpate the pituitary gland and testicles for oncologic reasons, chemotherapy and radiation can have deleterious effects on testicular and pituitary functions. For example, Imatinib, a tyrosine kinase inhibitor, is known to induce lower testosterone levels likely due to its deleterious effects on testosterone-producing Leydig cells [14]. Radiation effects on testicular function are largely dose-dependent and, although relatively radio-resistant compared to germ cells. Leydig cells can have a substantial change in metabolism at the molecular level with doses as low as 4 Gy. This is worth noting since pelvic radiotherapy uses a total radiation dose significantly greater than 4 Gy [15]. In fact, although it was previously thought that testosterone replacement was likely to be required only at Leydig exposure doses in excess of 20 Gy, more recent literature with long-term followup supports significant Leydig cell dysfunction requiring testosterone replacement with doses lower than 16 Gy [16]. Central hypogonadism can also arise due to external cranial radiotherapy for a variety of brain lesions and nasopharyngeal tumors. It has been documented that up to 2 thirds of adult patients who received such radiation treatment developed some form of hypogonadism [17].
2.3. Ejaculatory complaints
3. Clinical management of male sexual dysfunction after cancer treatment
3.1. ED
3.2. Testosterone deficiency syndrome treatment
Any significant damage to the hypothalamic-pituitary-gonadal axis caused by cancer treatments can lead to testosterone deficiency syndrome (TDS). TDS can be a result of primary testicular failure (e.g., such as that caused by bilateral orchiectomy) or hypogonadotropic hypogonadism leading to a loss of luteinizing hormone signaling of the Leydig cells inside the testicles [42]. It may also be incidentally detected after routine care for ED after treatments such as prostatectomy.
There is no exact laboratory or clinical finding to define TDS but many use a constellation of symptoms (e.g., loss of muscle strength, libido, memory, vitality) and a laboratory value (generally total testosterone). The total testosterone cutoff of <=300ng/dL is often utilized to support a diagnosis of TDS, measured on 2 separate occasions. This level has been shown to be the 5th percentile among healthy non-obese patients between 19 and 39 years old [43].
Once the diagnosis is established, a clinician then has several modalities available to address TDS. First, patients must be counseled on the short and long-term side effects of testosterone. Although controversial in methodology, 1 prominent study associated testosterone replacement with increased rates of myocardial infarction and stroke in a population of men with a history of coronary angiography [44]. However, other studies of equal quality have not made this association and in fact, have presented opposite results [45]. It is also important to discuss the expected benefit of testosterone replacement with most contemporary literature suggesting improvements in sexual function, particularly libido, and improved bone mineral density [46]. Lastly before initiating testosterone replacement one must advise patients of absolute and relative contraindications including a history of breast or prostate cancer, those planning fertility in the near future, PSA >4 ng/ml, elevated hematocrit, untreated severe obstructed sleep apnea, uncontrolled heart failure, myocardial infarction, or stroke within the last 6 months or thrombophilia [47].
Options for testosterone replacement include transdermal, injection, intra-nasal, and implantable. A contemporary practical guide on testosterone replacement is referenced below [48]. Post cancer treatment critical considerations include avoiding the promotion of the patient’s baseline cancer, especially if there is concern it has not been completely eradicated (e.g., prostate), and the increased risk for thrombotic complications in patients with oncologic histories.
3.3. Ejaculatory complaints
4. Conclusion
Although commonly overlooked, treatment of male sexual dysfunction after cancer treatment can significantly improve a patient's quality of life. For patients with a primary complaint of ED, it has been shown that to optimize recovery of erectile capacity, while preserving penile length and girth, a penile rehabilitation protocol involving PDE5i, VED, ICI, or a combination is likely advantageous. This protocol is likely beneficial during the recovery period that is estimated to be around 2 years for both surgical and radiation pelvic treatments. At our institution, a common rehabilitation protocol involves the used of daily tadalafil 5mg and either VED or ICI to obtain maximally rigid erections at least 3 times weekly. Treating hypogonadism is more complex especially in the setting of treatment of androgen-sensitive cancers such as prostate cancer. Furthermore, although testosterone replacement has been shown to improve all aspects of sexual function, its positive effect on erections is rarely enough to lead to satisfactory erections given the severity of the mechanisms leading to ED after cancer treatment. Thus, it is difficult to recommend screening for low testosterone in patients presenting solely for the post-cancer treatment ED although the American Urological Association recommends screening for low testosterone in men with ED in general. Testosterone replacement is less ambiguous in the setting of ablative procedures to the testicles or pituitary gland where testosterone replacement is essential to maintain quality of life due to extremely low serum levels. Lastly, anejaculation after cancer treatments is typically not successfully or reliably treated due to the mechanism and severity of sympathetic nerve injury. Thus in patients of fertile age, it is imperative to promote semen cryopreservation prior to cancer treatments that may injure nerve fibers essential for the ejaculatory response.
Background: With an increase in the number of cancer survivors each year, male sexual dysfunction becomes an important topic for discussion between patients and providers who treat cancer. The aim of this article is to review the types and mechanisms of sexual dysfunction after cancer therapy and discuss treatment options.
Methods: Contemporary concepts regarding male sexual dysfunction after cancer treatment are reviewed and translated for clinical utility.
Findings: To optimize recovery of erectile capacity after erectile dysfunction causing cancer treatments, a penile rehabilitation protocol involving phosphodiesterase inhibitors, vacuum erection devices, intracorporal injections, or a combination is likely to provide some degree of clinically significant benefit. Treating hypogonadism post-cancer treatment depends on the type of cancer that has been treated and patient comorbidities. Anejaculation after cancer treatments is typically not successfully or reliably treated due to the mechanism and severity of sympathetic nerve injury. Semen cryopreservation prior to cancer treatments that may injure nerve fibers essential for the ejaculatory response is highly recommended.
Conclusion: Management of post-cancer treatment sexual dysfunction requires identification of this problem and referral to a specialist if necessary. There are several management options available that can greatly enhance the quality of life in this often overlooked aspect of post-cancer treatment care.
1. Introduction
Cancer survivors make up a growing population that is expected to reach an estimated population of 26.1 million [1], representing approximately 5.0% of the population. Given this growing segment of our population that is a result of more effective treatments, more attention has been placed on the quality of life during and after cancer treatment. In 2018, 856,370 men were newly diagnosed with cancer, with prostate cancer being the most common cancer diagnosed (164,690) [2]. Unfortunately, the prostate is in a central pelvic location surrounded by essential structures whose integrity is essential for the maintenance of normal sexual function.
The resulting erectile dysfunction (ED) after treatment of prostate cancer serves as a prime example of how cancer treatments can affect sexual function [3]. Even in the prostate cancer setting, sexual dysfunction tends to be undertreated and underreported [4]. Thus, it is not surprising that men with cancers whose pathology and treatments are not traditionally associated with sexual dysfunction are often not screened for sexual dysfunction. For the purposes of this review, male sexual dysfunction can be broadly categorized into ED, hypogonadism, and its associated side effects, as well as ejaculatory complaints.
In this review, we discuss the general pathophysiology of how cancer treatments can affect penile erectile capacity, testosterone production, as well as neurologic function as it pertains to ejaculation. We also discuss management strategies for these distressing conditions.
2. Overview of types and mechanisms of sexual dysfunction after cancer treatment
2.1. ED
2.2. Hypogonadism
Along with surgeries to extirpate the pituitary gland and testicles for oncologic reasons, chemotherapy and radiation can have deleterious effects on testicular and pituitary functions. For example, Imatinib, a tyrosine kinase inhibitor, is known to induce lower testosterone levels likely due to its deleterious effects on testosterone-producing Leydig cells [14]. Radiation effects on testicular function are largely dose-dependent and, although relatively radio-resistant compared to germ cells. Leydig cells can have a substantial change in metabolism at the molecular level with doses as low as 4 Gy. This is worth noting since pelvic radiotherapy uses a total radiation dose significantly greater than 4 Gy [15]. In fact, although it was previously thought that testosterone replacement was likely to be required only at Leydig exposure doses in excess of 20 Gy, more recent literature with long-term followup supports significant Leydig cell dysfunction requiring testosterone replacement with doses lower than 16 Gy [16]. Central hypogonadism can also arise due to external cranial radiotherapy for a variety of brain lesions and nasopharyngeal tumors. It has been documented that up to 2 thirds of adult patients who received such radiation treatment developed some form of hypogonadism [17].
2.3. Ejaculatory complaints
3. Clinical management of male sexual dysfunction after cancer treatment
3.1. ED
3.2. Testosterone deficiency syndrome treatment
Any significant damage to the hypothalamic-pituitary-gonadal axis caused by cancer treatments can lead to testosterone deficiency syndrome (TDS). TDS can be a result of primary testicular failure (e.g., such as that caused by bilateral orchiectomy) or hypogonadotropic hypogonadism leading to a loss of luteinizing hormone signaling of the Leydig cells inside the testicles [42]. It may also be incidentally detected after routine care for ED after treatments such as prostatectomy.
There is no exact laboratory or clinical finding to define TDS but many use a constellation of symptoms (e.g., loss of muscle strength, libido, memory, vitality) and a laboratory value (generally total testosterone). The total testosterone cutoff of <=300ng/dL is often utilized to support a diagnosis of TDS, measured on 2 separate occasions. This level has been shown to be the 5th percentile among healthy non-obese patients between 19 and 39 years old [43].
Once the diagnosis is established, a clinician then has several modalities available to address TDS. First, patients must be counseled on the short and long-term side effects of testosterone. Although controversial in methodology, 1 prominent study associated testosterone replacement with increased rates of myocardial infarction and stroke in a population of men with a history of coronary angiography [44]. However, other studies of equal quality have not made this association and in fact, have presented opposite results [45]. It is also important to discuss the expected benefit of testosterone replacement with most contemporary literature suggesting improvements in sexual function, particularly libido, and improved bone mineral density [46]. Lastly before initiating testosterone replacement one must advise patients of absolute and relative contraindications including a history of breast or prostate cancer, those planning fertility in the near future, PSA >4 ng/ml, elevated hematocrit, untreated severe obstructed sleep apnea, uncontrolled heart failure, myocardial infarction, or stroke within the last 6 months or thrombophilia [47].
Options for testosterone replacement include transdermal, injection, intra-nasal, and implantable. A contemporary practical guide on testosterone replacement is referenced below [48]. Post cancer treatment critical considerations include avoiding the promotion of the patient’s baseline cancer, especially if there is concern it has not been completely eradicated (e.g., prostate), and the increased risk for thrombotic complications in patients with oncologic histories.
3.3. Ejaculatory complaints
4. Conclusion
Although commonly overlooked, treatment of male sexual dysfunction after cancer treatment can significantly improve a patient's quality of life. For patients with a primary complaint of ED, it has been shown that to optimize recovery of erectile capacity, while preserving penile length and girth, a penile rehabilitation protocol involving PDE5i, VED, ICI, or a combination is likely advantageous. This protocol is likely beneficial during the recovery period that is estimated to be around 2 years for both surgical and radiation pelvic treatments. At our institution, a common rehabilitation protocol involves the used of daily tadalafil 5mg and either VED or ICI to obtain maximally rigid erections at least 3 times weekly. Treating hypogonadism is more complex especially in the setting of treatment of androgen-sensitive cancers such as prostate cancer. Furthermore, although testosterone replacement has been shown to improve all aspects of sexual function, its positive effect on erections is rarely enough to lead to satisfactory erections given the severity of the mechanisms leading to ED after cancer treatment. Thus, it is difficult to recommend screening for low testosterone in patients presenting solely for the post-cancer treatment ED although the American Urological Association recommends screening for low testosterone in men with ED in general. Testosterone replacement is less ambiguous in the setting of ablative procedures to the testicles or pituitary gland where testosterone replacement is essential to maintain quality of life due to extremely low serum levels. Lastly, anejaculation after cancer treatments is typically not successfully or reliably treated due to the mechanism and severity of sympathetic nerve injury. Thus in patients of fertile age, it is imperative to promote semen cryopreservation prior to cancer treatments that may injure nerve fibers essential for the ejaculatory response.
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