Sexual functioning in patients with hepatocellular carcinoma

Authors


Abstract

BACKGROUND

The objectives of the current study were to assess the rates of sexual dysfunction in patients with hepatocellular carcinoma (HCC) and compare the rates of sexual morbidity with a sample of patients diagnosed with chronic liver disease (CLD) and the general population. It was expected that patients diagnosed with HCC would have a greater prevalence of sexual dysfunction than those diagnosed with CLD and the general population, respectively. Furthermore, those patients who reported a sexual dysfunction would also have a poorer quality of life (QOL).

METHODS

Twenty-one men diagnosed with HCC and 23 men diagnosed with CLD completed a battery of questionnaires that included the Sexual History Questionnaire and the Functional Assessment of Cancer Therapy-Hepatobiliary.

RESULTS

Results indicated that 41% of patients reported a current sexual problem (29% of HCC patients and 71% of patients with CLD) and 43% met the Diagnostic and Statistical Manual of Mental Disorders4th edition (DSM-IV) criteria for at least 1 type of sexual dysfunction (25% of patients with HCC and 75% of patients with LD). Of the total sample, 68% reported being diagnosed with a comorbid medical condition or taking a medication that had potential sexual side effects. After eliminating cases with comorbid medical conditions and/or who were taking medications that contributed to sexual morbidity, the rate of sexual problems were found to be similar to that of the general population. Clinically significant differences were found with regard to the QOL. People who were experiencing sexual problems also reported a poorer QOL.

CONCLUSIONS

Although a large percentage of sexual dysfunction may have been secondary to comorbid medical problems and medications, treatment of the sexual dysfunction is still warranted. Cancer 2005. © 2005 American Cancer Society.

A paucity of research exists regarding the rates of sexual morbidity in people with hepatocellular carcinoma (HCC). Laumann et al. indicated that the prevalence of sexual dysfunction for males in the general population was 31%.1 Risk factors included poor health, emotional problems, and stress-related problems.1 These authors also found that men with erectile dysfunction reported a lower quality of life (QOL) than men with other sexual dysfunctions or those who reported no dysfunction.1

A diagnosis of cancer has been found to be associated with higher rates of sexual dysfunction compared with the general population.2–5 Andersen, in an excellent review, found that individual self-schema (image of self), psychiatric and medical symptoms, psychologic/behavioral status, and extent of disease and treatment contributed to increased rates of sexual dysfunction in people diagnosed with cancer.6 As with HCC, factors such as comorbid medical conditions, medications with sexual side effects, and the neuroendocrine changes associated with the disease and/or treatment should also be considered as possible contributors to increased sexual problems.

Malignancies of the reproductive organs and those that affect body image, such as head and neck or breast carcinomas, would be expected to contribute to increased sexual morbidity for both men and women. HCC, or primary liver carcinoma, is an understudied cancer type, particularly with regard to psychosocial functioning. People diagnosed with HCC would be expected to report higher levels of sexual dysfunction secondary to 1) disease- or treatment-related neuroendocrine changes; 2) changes in body image associated with gynecomastia, cachexia, and ascites; 3) a high level of comorbid medical conditions that may result in increased sexual morbidity (e.g., diabetes); (4) medications that include sexual side effects (e.g., narcotics, antidepressants, benzodiazepines, and hypertension medications); and 5) the psychologic distress associated with a poor prognosis.

The objectives of the current study were: 1) to assess the rates of sexual dysfunction between males with HCC, chronic liver disease (CLD), and the general population; 2) to assess the contribution of medications and/or comorbid medical conditions to sexual dysfunction in these populations; and 3) to examine how sexual dysfunction affects health-related QOL (HRQL). It was expected that the prevalence of sexual dysfunction in male patients with HCC, followed by those with CLD, would be higher than that in the general population. It also was hypothesized that there would be an increased likelihood of sexual dysfunction if the patients had comorbid medical conditions or were taking medications that had potential sexual side effects. Lastly, with regard to investigating the effects of sexual dysfunction on HRQL, it was anticipated that patients reporting a sexual dysfunction would have lower HRQL scores.

MATERIALS AND METHODS

Forty-four patients were recruited from the Liver Cancer Center at the University of Pittsburgh Medical Center and the Center for Liver Disease clinics between October 2001 and October 2002. Twenty-one male patients with HCC and 23 male patients diagnosed with CLD were recruited for participation in this study. To be eligible to participate in the study patients were required to be: 1) age ≥ 18 years, 2) fluent in English, and 3) diagnosed with biopsy-proven HCC or CLD. Exclusion criteria included current symptoms of psychosis or suicidal or homicidal ideation or patients considered to be medically too ill to complete the battery of questionnaires.

The patients were administered a battery of self-report questionnaires. The battery included the Sociodemographic Questionnaire, the Sexual History Questionnaire, and the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep). The Sociodemographic Questionnaire included items such as the participant's gender, age, ethnic group, educational level, marital status, number of children, occupation, income, religious affiliation, family history of cancer, phase in menstrual cycles, hormone replacement or oral contraceptive use, and current and past medications and herbal treatments.

The Sexual History Questionnaire also was included and was comprised of a modified version of the Changes in Sexual Functioning Questionnaire (SFQ)7 and the Diagnostic Statistic Manual4th edition (DSM-IV) criteria for six sexual dysfunctions for men.8 As recognized by the DSM-IV, sexual disorders in males included: 1) hypoactive sexual desire disorder (persistent or recurrently deficient sexual fantasies and desire for sexual activity), 2) sexual aversion disorder (persistent or recurrent extreme aversion to and avoidance of all genital sexual contact with a sexual partner), 3) male erectile disorder (persistent or recurrent inability to attain or to maintain an adequate erection until completion of the sexual activity), 4) male orgasmic disorder (persistent or recurrent delay in, or absence of, orgasm after the normal sexual excitement phase), 5) premature ejaculation (persistent or recurrent ejaculation with minimal stimulation before, on, or shortly after penetration and before the person wishes it), and 6) dyspareunia (persistent or recurrent genital pain with sexual intercourse). Patients with sexual problems were defined as having the symptoms described above without any coexistent psychologic or interpersonal distress.

Information regarding comorbid medical conditions and use of medications was collected from the patients and their medical charts. The side effects of the medications were gathered from the Physician's Desk Reference (PDR).9

The FACT-Hep10, 11 was used to assess HRQL. The FACT-Hep is a combination of the FACT-General and a hepatobiliary cancer module. The FACT-General is a 27-item instrument that measures 4 dimensions of QOL including physical well-being, social/family well-being, emotional well-being, and functional well-being. It is one of the most widely utilized QOL questionnaires used in clinical trials for new cancer treatments and has been demonstrated to be valid and reliable.10 The FACT-Hepatobiliary module includes a module with 18 additional items that are specific for patients with hepatobiliary disease. The module includes questions that pertain to symptoms of the disease as well as side effects of treatment. The FACT-Hep has been demonstrated to be reliable and valid.11 Minimally important differences (MIDs) are often used to describe clinically significant changes in HRQL. Guidelines for the MIDs for the FACT-Hep have recently been developed and are as follows: cancer-specific subscale of 2-3; FACT-General of 6-7; Hepatobiliary Cancer Scale (HPCS) of 5-6; FACT-Hep of 8-9; Trial Outcome Index (TOI) of 7-8; and FACT-Hepatobiliary Symptom Index (FHSI) of 2-3 points (unpublished data).

The study was approved by the Institutional Review Board before the commencement of the study. The patients were referred by their oncologist or hepatologist depending on whether the patient received a diagnosis of HCC or CLD, respectively. If the patient was interested in speaking to someone about the study, the individual was referred to a research associate who explained the rationale, risks, and benefits of the study. If the patient provided written informed consent, the person was administered the battery of questionnaires. The source for the prevalence of “sexual problems” in the general population comes from a large epidemiologic study that assessed the prevalence of sexual dysfunction in the U.S. in 1992.1

Data Analysis

Descriptive statistics were performed to obtain data regarding the sociodemographic and disease-specific characteristics of the patients as well as the current prevalence of sexual problems and sexual dysfunction according to the DSM-IV diagnostic criteria. One-way analysis of variance (ANOVA) was performed to assess the difference between patients diagnosed with HCC and CLD with regard to rates of sexual problems and sexual disorders using the DSM-IV. Analysis of covariance (ANCOVA) was performed to determine whether a significant difference in the prevalence of sexual problems or DSM-IV diagnoses of sexual dysfunction as a result of comorbid medical conditions and medications associated with sexual dysfunction existed. The medical conditions and medications were classified into two categories according to the presence or absence of possible sexual problems or side effects. Patients who reported medical conditions (such as diabetes, depression, or hypertension) and/or were prescribed medications with the potential to cause sexual side effects (e.g., antidepressants, hypertensives, or insulin) were eliminated and the prevalence of the six sexual dysfunctions was calculated. Multivariate ANOVA was performed to compare overall HRQL scores between patients in the HCC and CLD samples to determine the influence of sexual functioning on patient HRQL for the HCC and CLD groups. MIDs also were calculated to determine whether there were clinically meaningful differences in the HRQL between patients with and patients without sexual problems in both samples. Using distribution-based and anchor-based methods, clinically meaningful differences for each of the subscales was analyzed to determine if there were differences between patients who reported a SD and those who did not report a SD.

RESULTS

Demographic and Disease-Specific Characteristics

The samples from patients diagnosed with HCC and CLD were found to have similar demographic and disease-specific characteristics with the exception of 1) etiology of the disease, 2) patient age, and 3) income level (Table 1). The patients diagnosed with HCC were significantly older (mean age of 65 yrs) compared with the CLD patients (mean age of 54 yrs). The HCC patients also were more likely to earn less than $20,000 per year (50%) compared with the CLD patients (16%). The lower income may reflect the greater number of patients in the HCC group who were likely older (and retired).

Table 1. Demographic and Disease-Specific Patient Characteristics
CharacteristicHCC (n = 21)CLD (n = 23)
  • HCC: hepatocellular carcinoma; CLD: chronic liver disease.

  • a

    P < 0.05.

Age in yrsa  
 Mean6554
 Range41–8240–79
Ethnicity (%)  
 White6884
 African American268
 Hispanic/Latino50
 Asian American04
 Native American04
Marital status (%)  
 Single1812
 Married5976
 Divorced120
 Separated/widowed64
 Living with partner08
Education (%)  
 High school or equivalent6740
 Vocational/college/university1136
 Graduate or professional1824
Income (%)a  
 < $10,000334
 $10,000–$20,0001712
 $21,000–$40,0002540
 $41,000–$60,0001720
 $61,000–$80,000820
 $81,000–$100,00004
 ≥ $100,00000

The etiology of CLD differed from that of HCC, with the majority of patients who were diagnosed with HCC reporting an underlying etiology of their disease to be related to hepatitis B and/or hepatitis C (57%) whereas no patients with CLD reported hepatitis B and 57% reported being positive for hepatitis C. The remaining patients with CLD had cryptogenic or autoimmune hepatitis. The HCC and CLD samples had approximately equal percentages of patients with cirrhosis (84% and 88%, respectively). Child–Pugh scores for the HCC and CLD patients also were found to be similar. Approximately 73% of the patients diagnosed with HCC and 67% of the CLD patients had a Child–Pugh score of A. Approximately 18% of patients diagnosed with HCC and 27% of patients diagnosed with CLD were found to have a Child–Pugh score of B. Approximately 6% of CLD patients had a Child–Pugh score of C score whereas none of the HCC patients was found to have a Child–Pugh score of C. No information was available for two HCC patients with which to calculate a Child–Pugh score (Table 2).

Table 2. Disease-Specific Characteristics of the Patient Sample
CharacteristicHCC (n = 21)CLD (n = 23)
  • HCC: hepatocellular carcinoma: CLD: chronic liver disease; NASH: nonalcoholic steatohepatitis.

  • a

    P < 0.05.

  • b

    TNM staging.

Suspected etiology of disease (%)a  
 Hepatitis B130
 Hepatitis C4457
 Alcohol3110
 NASH130
 Cryptogenic019
 Autoimmune010
Cirrhosis (%)  
 Yes8488
 No1612
Child–Pugh score (%)  
 A7367
 B1827
 C06
 Unknown90
Stage (%)b  
 III5
 IV95

Sexual Dysfunctions and Demographic and Disease-Specific Characteristics

A one-way ANOVA was performed to determine the contribution of demographic and disease-specific characteristics with regard to the prevalence of sexual problems and disorders. The variables that were tested include patient age and ethnicity, etiology of disease, presence of cirrhosis, and Child–Pugh score (by A, B, and C as well as A vs. B/C). None of the demographic or disease-specific characteristics were found to be correlated with an increased prevalence of sexual problems or disorders.

Prevalence of Sexual Dysfunction According to the DSM-IV

When using the diagnostic criteria for assessing sexual dysfunction in patients with HCC, the rate for dyspareunia was 5.9%, premature ejaculation was 5.6%, male erectile disorder was 5.6%, and hypoactive sexual desire disorder was 5.3%. To our knowledge, no studies have been conducted to date using DSM-IV criteria in the general population to compare these rates of sexual disorders. Of the patients with CLD, no patient met the criteria for hypoactive sexual desire disorder, sexual aversion disorder, or male orgasmic disorder. Approximately 16% of the patients met the DMS-IV criteria for male erectile disorder and 5% met the criteria for premature ejaculation and dyspareunia. No significant differences between patients diagnosed with HCC and those diagnosed with CLD were found using the DSM-IV criteria.

Prevalence of Sexual Problems

People with HCC reported much higher rates of sexual problems compared with the general population, including hypoactive sexual desire disorder (26% vs. 15%), male erectile disorder (17% vs. 11%), and male orgasmic disorder (13% vs. 8%). The patients diagnosed with HCC were found to have lower rates of premature ejaculation compared with the general population (17% vs. 30%). There was no data for the general population to compare the rates of HCC for sexual aversion disorder (18%) and dyspareania (12%).

With regard to the differences between HCC patients and those with CLD with respect to sexual problems, the rates of sexual morbidity were found to be higher in patients diagnosed with HCC for the majority of the sexual problems, including hypoactive sexual desire disorder (26% vs. 18%), sexual aversion disorder (18% vs. 5%), male orgasmic disorder (13% vs. 5%), premature ejaculation (17% vs. 5%), and dyspareunia (12% vs. 5%). The only disorder in which CLD patients reported a higher prevalence than HCC patients was male erectile disorder (21% vs. 17%; Table 3). The only statistically significant difference found with regard to the prevalence of sexual problems between patients diagnosed with HCC and those diagnosed with CLD was for sexual aversion [F(1,43 = 6.9, P = 0.01], in which a greater number of patients diagnosed with HCC reported significantly more problems with sexual aversion than patients with CLD (17.6% vs. 4.5%).

Table 3. Rates of Sexual Problems and DSM-IV-Related Diagnoses in the General Population, Patients with HCC, and Patients with CLD
Sexual dysfunctionDSM-IV criteriaGeneral populationaHCCCLD
Sexual problemDSM-IV diagnosisSexual problemDSM-IV diagnosisSexual problemDSM-IV diagnosis
  • DSM-IV: Diagnostic and Statistical Manual of Mental Disorders–4th edition; HCC: hepatocellular carcinoma: CLD: chronic liver disease.

  • a

    The general population prevalence of sexual problems (not including level of distress for Diagnostic and Statistical Manual of Mental Disorders–4th edition criteria) was adapted from Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States. JAMA. 1999;281:537–544.

Hypoactive sexual desire disorderPersistently or recurrently deficient sexual fantasies and desire for sexual activity1526.35.318.20
Sexual aversion disorderPersistent or recurrent extreme aversion to and avoidance of all genital sexual contact with a sexual partner17.604.50
Male erectile disorderPersistent or recurrent inability to attain, or to maintain until completion of the sexual activity, an adequate erection1116.75.621.115.8
Male orgasmic disorderPersistent or recurrent delay in, or absence of, orgasm after the normal sexual excitement phase812.505.30
Premature ejaculationPersistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the person wishes it3016.75.64.84.8
DyspareuniaPersistent or recurrent genital pain associated with sexual intercourse11.85.95.05.0

Finally, with regard to the differences between CLD patients and the general population, individuals diagnosed with CLD reported a higher prevalence of hypoactive sexual disorder (18.2% vs. 15%), and male erectile disorder (21.1% vs. 11%). The CLD patients reported lower rates of male orgasmic disorder (5.3% vs. 8%) and premature ejaculation (4.8% vs. 30%) compared with the general population. No prevalent data for the general population exist to compare with the rates of sexual aversion disorder (4.5%) and dyspareunia (5%) in patients with CLD (Table 3).

Prevalence of Sexual Problems and DSM-IV Sexual Dysfunction in Patients Diagnosed with HCC after the Elimination of Comorbid Medical Diseases and Medications Associated with Sexual Dysfunction

In HCC patients using the definition of sexual problems, the prevalence of erectile dysfunction was found to decrease significant when medical conditions and medications associated with sexual dysfunction were considered [F(1,20) = 5.8; P = 0.03]. The following rates of dysfunction were found to decrease when cases were eliminated that included medications or medical conditions with increased sexual morbidity: hypoactive sexual desire disorder (26.3% to 5.3%), male erectile disorder (16.7% to 0%), and premature ejaculation (16.7% to 11.1%).

When using the DSM-IV criteria and eliminating comorbid medical conditions and medications associated with sexual dysfunction from the rates of sexual dysfunction, no statistically significant differences were found between those patients reporting a sexual dysfunction with a medical condition or medication that causes a sexual dysfunction and those reporting the sexual dysfunction but denying a medical condition or medication associated with sexual dysfunction. For patients with HCC, the rates of DSM-IV-diagnosed sexual dysfunctions were found to decrease slightly for hypoactive sexual desire disorder (5.3%to 0%), male erectile disorder (5.6% to 0%), and premature ejaculation (5.6% to 0%). No changes were observed for sexual aversion disorder, male orgasmic disorder, or dyspareunia (Table 4).

Table 4. Rates of Sexual Problems and DSM-IV-Related Disorders in Patients with HCC with and without Patients who Reported Comorbid Medical Conditions or Use of Medications that Increase Sexual Morbidity
 DSM-IV criteriaHCC sexual problemsHCC DSM-IV-related disorders
Cases (+) conditions/medicationsaCases (-) conditions/medicationsbCases (+) conditions/medicationsaCases (-) conditions/Medicationsb
  • DSM-IV: Diagnostic and Statistical Manual of Mental Disorders–4th edition; HCC: hepatocellular carcinoma.

  • a

    Cases + conditions and medications indicates rates of sexual problems/disorders without consideration of medical conditions or medications that may cause sexual morbidity.

  • b

    Cases - conditions and medications indicates rates of sexual problems/disorders with the elimination of those cases who reported conditions or medications with increased sexual morbidity.

Hypoactive sexual desire disorderPersistently or recurrently deficient sexual fantasies and desire for sexual activity26.35.35.30
Sexual aversion disorderPersistent or recurrent extreme aversion to and avoidance of all genital sexual contact with a sexual partner17.617.600
Male erectile disorderPersistent or recurrent inability to attain, or to maintain until completion of the sexual activity, an adequate erection16.705.60
Male orgasmic disorderPersistent or recurrent delay in, or absence of, orgasm after the normal sexual excitement phase12.512.500
Premature ejaculationPersistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the person wishes it16.711.15.60
DyspareuniaPersistent or recurrent genital pain associated with sexual intercourse11.811.85.95.9

Prevalence of Sexual Problems and DSM-IV Sexual Dysfunction in Patients Diagnosed with CLD when Comorbid Medical Diseases and Medications Associated with Sexual Dysfunction were Eliminated

Using the sexual problem definition for patients diagnosed with CLD, the prevalence of erectile dysfunction was found to decrease significantly with the elimination of cases in which medications and/or medical conditions that increase sexual morbidity were present [F(1,22) of 4.9; P = 0.04]. The changes in prevalence were noted with regard to hypoactive sexual desire disorder (18.2% to 9.1%) and male erectile disorder (21.1% to 5.3%). The prevalence of sexual aversion disorder, male orgasmic disorder, and premature ejaculation did not appear to change significantly when medical conditions and medications associated with sexual dysfunction were taken into account.

For patients diagnosed with CLD, no statistically significant changes were found between those patients who reported a sexual dysfunction with a medical condition or medication and those without a medical condition or medication that was associated with a sexual dysfunction. However, the rate of a DSM-IV diagnosis of male erectile disorder was found to decrease (15.8% to 5.3%), whereas the prevalence of the other DSM-IV diagnoses did not appear to change significantly (Table 5).

Table 5. Rates of Sexual Problems and DSM-IV-Related Disorders in CLD Patients with and without Patients who Reported Comorbid Medical Conditions or Medications that Increase Sexual Morbidity
 DSM-IV criteriaCLD sexual problemsCLD DSM-IV-related disorders
Cases (+) conditions/medicationsaCases (-) conditions/medicationsbCases (+) conditions/medicationsaCases (-) conditions/medicationsb
  • DSM-IV: Diagnostic and Statistical Manual of Mental Disorders–4th edition; CLD: chronic liver disease.

  • a

    Cases + conditions and medications indicates rates of sexual problems/disorders without consideration of medical conditions or medications that may cause sexual morbidity.

  • b

    Cases - conditions and medications indicates rates of sexual problems/disorders with the elimination of cases who reported conditions or medications with increased sexual morbidity.

Hypoactive sexual desire disorderPersistently or recurrently deficient sexual fantasies and desire for sexual activity18.29.100
Sexual aversion disorderPersistent or recurrent extreme aversion to and avoidance of all genital sexual contact with a sexual partner4.54.500
Male erectile disorderPersistent or recurrent inability to attain, or to maintain until completion of the sexual activity, an adequate erection21.15.315.85.3
Male orgasmic disorderPersistent or recurrent delay in, or absence of, orgasm after the normal sexual excitement phase5.35.35.35.3
Premature ejaculationPersistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the person wishes it4.84.84.84.8

Sexual Problems and HRQL

Multivariate ANOVA was performed to test differences between patients who reported a sexual problem and those who did not on the overall score for HRQL as well as for each subscale of the FACT-Hep. The only significant difference that was reported was for patients with CLD. Those who reported a sexual problem were found to have lower physical and emotional well-being scores [F(1,23) of 4.9, P = 0.04] and [F(1,23) of 6.1, P = 0.02], respectively (Fig. 1).

Figure 1.

Health-related quality of life (HRQL) for patients with chronic liver disease with and without sexual problems. PWB: physical well-being; SFWB: social and family well-being; EWB: emotional well-being; FWB: functional well-being; AC: additional concerns (symptoms and side effects); FACT-Hep: Functional Assessment of Cancer Therapy-Hepatobilliary.

No significant differences were found for patients diagnosed with HCC; however, on each of the scales of the FACT-Hep, patients who reported sexual problems were found to have a clinically significant or minimally significant difference compared with those patients who reported no sexual problems (Fig. 2; Table 6). For HCC patients, clinically meaningful differences on the physical well-being scale were noted between those patients who reported sexual problems compared with those who did not. For the patients with CLD, clinically meaningful differences on the physical well-being, social and family well-being, emotional well-being, functional well-being, symptoms and side effects, and overall HRQL scales were found between patients who reported sexual problems and those who did not.

Figure 2.

Health-related quality of life (HRQL) for patients with hepatocellular carcinoma with and without sexual problems. PWB: physical well-being; SFWB: social and family well-being; EWB: emotional well-being; FWB: functional well-being; AC: additional concerns (symptoms and side effects); FACT-Hep: Functional Assessment of Cancer Therapy-Hepatobilliary.

Table 6. Clinically Significant Differences with Regard to Health-Related Quality of Life between Patients with and Patients without Sexual Problems
ScaleAll patients HCC CLD 
MeanSDMeanSDMeanSD
  • SD: standard deviation; HCC: hepatocellular carcinoma; CLD: chronic liver disease; PWB: physical well-being; SFWB: social and family well-being; EWB: emotional well-being; FWB: functional well-being; HPCS: Hepatobiliary Cancer Scale; FACT-G: Functional Assessment of Cancer Therapy-General (physical well-being + social and family well-being + emotional well-being + functional well-being).

  • a

    The minimally important difference estimates for the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep).

PWB      
 Sexual problems18a8.220a7.617a8.6
 Without sexual problems216.1177.6233.5
SFWB      
 Sexual problems224.1204.322a4.0
 Without sexual problems237.61910.4254.5
EWB      
 Sexual problems15a5.3145.615a5.3
 Without sexual problems176.5138.8193.1
FWB      
 Sexual problems196.5168.620a5.2
 Without sexual problems207.3167.2226.4
HPCS      
 Sexual problems2115.02012.122a16.8
 Without sexual problems1711.82216.7147.3
FACT-G      
 Sexual problems7417.47020.575a16.7
 Without sexual problems7820.66526.18611.5

When the entire sample was analyzed, patients reporting a sexual problem reported a clinically significant decrease in physical and emotional well-being compared with those who did not. When patients with HCC alone were analyzed, patients reporting a sexual problem were found to have a clinically significant difference on the physical well-being scale compared with patients who did not report a sexual problem. For the patients with CLD, those patients who reported sexual problems reported a clinically meaningful difference compared with those who did not report a sexual problem on the physical well-being, social and family well-being, emotional well-being, functional well-being, symptoms and side effects of hepatobiliary disease, and overall QOL scales. Patients diagnosed with HCC and CLD who reported a DSM-IV diagnosis of a sexual dysfunction were found to report no clinically significant differences in QOL compared with those who did not report a DSM-IV diagnosis of a sexual dysfunction.

DISCUSSION

Male patients with HCC reported higher rates of sexual problems and disorders compared with the general population, with the exception of premature ejaculation. Similar to previous research concerning sexual dysfunction in cancer patients, patients who were diagnosed with HCC also had higher rates of sexual problems compared with the patients with CLD, with the exception of male erectile disorder, for which patients with CLD reported higher rates than both the general population and patients diagnosed with HCC.

A study conducted by Zifroni et al.12 reported that men with CLD and a Child–Pugh score of A had similar functioning as the general population. However, men with CLD and a Child–Pugh score of B or C reported higher rates of sexual dysfunction and significant reductions in free testosterone levels.12 The rates of sexual problems in the CLD patients may have been less in the current study because the majority of participants (67%) had a Child–Pugh score of A.12 However, we found no significant difference in those men who had a Child–Pugh score of B or C and rates of sexual dysfunction compared with those who had a Child–Pugh score of A in both those patients with HCC and those with CLD. These results may be secondary to the relatively small number of patients with Child–Pugh scores of B and C in both the HCC and CLD samples. Furthermore, we found that none of the demographic or other disease-specific variables, including patient age and ethnicity, etiology of disease, and cirrhosis, were found to be associated with increased rates of sexual dysfunctions or problems.

It appears from the results of the current study that it is likely that medical conditions and medications associated with increased sexual morbidity may be the primary etiology of sexual problems and disorders in patients diagnosed with HCC and CLD. The patients with HCC and CLD reported several medical conditions such as hypertension, diabetes, cardiovascular disease, and depression, in which the disease or its treatments are commonly known to cause sexual problems. Medications with potential sexual side effects also contributed to higher rates of sexual problems. The chronic use of opioids accounted for some of the sexual problems and/or disorders reported in patients with HCC, particularly erectile disorder. Opioids are widely prescribed in patients with HCC and may cause hypogonadism and sexual dysfunction.13 Serum testosterone levels have been found to be reduced in patients receiving chronic opioid therapy.13 Further research concerning the use of opioids for pain management and their sexual side effects is needed.

Although the rates of sexual morbidity were found to decrease when patients with comorbid medical conditions and/or medications that increased sexual morbidity were excluded, it should be noted that not all patients who were receiving these medications or with these medical conditions were likely to experience sexual morbidity. Therefore, the high rate of sexual dysfunction noted in patients with HCC and CLD warrants further research.

Neuroendocrine changes that may be associated with the disease and/or treatment of hepatobiliary disease also may contribute to the increased sexual morbidity noted in these populations. Previous research that may be relevant in the study of sexual dysfunction in this cancer population concerns changes in androgens and glucose metabolism. Although the studies are dated, prior research has reported a correlation between cirrhosis and changes in 1) metabolic clearance rates, 2) plasma production and total and free levels of testosterone, 3) reduced testosterone responses to human chorionic gonadotropin stimulation, 4) higher levels of estradiol and luteinizing and follicle-stimulating hormone levels, and 5) higher binding capacities of sex steroid-binding globulin.14–18 Approximately 84% of patients with HCC and 88% of patients diagnosed with CLD in the current study had cirrhosis. The rates of erectile dysfunction were found to be higher in these two populations compared with the general population. Approximately 17% of males with HCC and 21% of males with CLD reported erectile dysfunction in the current study compared with the general population estimate (11%). HCC, as well as chemoembolization, is associated with changes in glucose metabolism and also may be related to sexual morbidity in patients diagnosed and treated for HCC.19–21 Unfortunately, the studies that have compared the levels of prolactin and testosterone in malignant and normal liver tissue have to our knowledge been inconsistent and inconclusive.22

Finally, psychiatric symptoms such as anxiety, depression, and chronic alcohol abuse may be associated with sexual dysfunction.23 It is estimated that approximately 35% of patients with cancer experience psychiatric distress.24 Patients diagnosed with liver carcinoma reported the third highest level of psychiatric distress when compared with patients with eight other cancer types.24 In another study concerning sexual dysfunction, Van Lankveld and Grotjohann concluded that patients reporting a sexual problem have higher rates of lifetime depression and anxiety.25 Furthermore, chronic alcohol use has been associated with male erectile dysfunction.24 However, only approximately 15% of the current patient sample had an etiology of alcohol abuse or dependence. In the current study, people who reported a sexual problem and/or met the criteria for a DSM-IV diagnosis for a sexual disorder had a lower emotional well-being score on the FACT-Hep. It is not known whether the increased psychologic distress was a result of the sexual difficulties or whether the psychologic distress itself contributed to the sexual problems. The temporal correlation noted between the psychiatric symptoms and the sexual problems should be addressed in future research because it is difficult to ascertain whether the psychiatric symptoms or the sexual problems were the first to occur.

The results of the current study also found that people diagnosed with HCC who reported increased rates of sexual problems also reported poorer HRQL.26 Dahn et al. found that men with prostate carcinoma who reported decreasing levels of sexual functioning and increasing levels of sexual desire reported a poorer HRQL.27 It is important to recognize the complexity of the factors that contribute to sexual morbidity. A large percentage of patients who reported sexual problems were not distressed by the symptoms in the current study.

We believe that future research should address the prevalence and etiology of sexual problems and DSM-IV sexual disorders in a larger sample of patients diagnosed with HCC. Although there were no statistically significant differences noted with regard to the correlation between sexual problems and HRQL, the results of the current study did suggest that there were clinically meaningful differences between patients who reported sexual problems compared with those who did not.27

The rates of sexual dysfunction in women diagnosed with HCC also should be explored further. The male-to-female ratio of HCC in North America is 2:1 and therefore there are fewer women available to participate in studies concerning sexual dysfunction. It is expected that similar neuroendocrine as well as psychologic changes occur in women that may contribute to changes in sexual functioning and this warrants further research. The temporal correlations for the medications that had possible side effects and the comorbid medical conditions that are associated with greater sexual morbidity were not explored in the current study. Prospective research should be conducted to explore the temporal correlation between factors such as comorbid medical conditions; medications with sexual side effects; and psychiatric symptoms such as depression, anxiety, and substance abuse. Finally, further research with regard to the prevalence of sexual problems and, particularly, DSM-IV-related disorders need to be conducted to be able to understand the relative difference between the prevalence of sexual problems and disorders in individuals with and without medical conditions. To our knowledge, to date only DSM-IV criteria have been used to assess the prevalence of erectile dysfunction in epidemiological studies,28, 29 whereas other sexual difficulties have been explored only within clinical samples.

Acknowledgements

The authors thank the American Cancer Society for support of this study.

Ancillary