Sexual Function Measurement and Outcomes in Cancer Survivors and Matched Controls.

Researchers and cancer survivor advocates are focusing increased attention on sexual function as a fundamental component of quality of life. This focus is warranted by the ever-increasing numbers of cancer survivors, with a relative rate of over 50% of people diagnosed with cancer now living five or more years past initial diagnosis (American Cancer Society, 1999). While findings are still rudimentary and vary by diagnosis, type of treatment, and gender, difficulties with sexual function are some of the more prevalent long-term complications following cancer treatment (Ganz, Rowland, Desmond, Meyerowitz, & Wyatt, 1998; Syrjala et al., 1998).

A major barrier to documenting sexual problems and needs in these populations has been the lack of appropriate, well-standardized tools with which to measure explicit behaviors, specific problems, and subjective experience of sexual function appropriate for cancer survivors (Cull, 1992; Rosen, 1998). As researchers initiate clinical trials to treat sexuality difficulties, adequate measurement for evaluating outcomes is essential. To fit this purpose, we have developed and tested a measure in adult cancer survivors as well as in matched, noncancer control subjects. While the instigation for this measure derived from work with cancer survivors the tool itself is not specific to such survivors, and we believe it could be utilized in research on other populations, including physically healthy groups.

Evaluating Sexual Difficulties in Cancer Survivors

Research into the sexual lives of cancer survivors has almost exclusively focused on the prevalence of various types of sexual problems reported by these survivors. This information assists in defining types of problems that need to be assessed but does not facilitate understanding how cancer survivors adapt to these difficulties, or whether they are able to achieve sexual satisfaction despite these difficulties.

Using the phases of sexual response (American Psychiatric Association [APA], 1994), research on cancer survivors has indicated that lack of sexual desire is reported by 3% to 11% of survivors, arousal problems by 9% to 15%, and orgasm infrequency or inability by 4% to 12% of the survivor population surveyed (Andersen, 1993; Andersen, Anderson, & deProsse, 1989; Andersen, Van der Does, & Anderson, 1992; Schover, Fife, & Gershenson, 1989; Spector & Carey, 1990). These deficits within phases do not fully reflect the diversity of problems cancer survivors have reported. Furthermore, prevalence data are subject to the possible measurement inadequacies described in this paper.

As a normative comparison, Lauman, Paik, and Rosen (1999) examined rates of sexual dysfunction within a national probability sample in the United States. They found that 43% of women and 31% of men reported some component of sexual dysfunction. Lower education, not being married, and emotional or stress-related problems increased the risk of sexual dysfunction for both genders. Poor health increased risk only for dyspareunia in women. The high rates of reported sexual difficulties in normative samples and the varying rates reported by cancer survivors highlight the necessity of standardizing assessment tools to permit comparisons across diseases and with noncancer norms.

Most sexual function research in oncology has been investigated separately by gender and disease. For women, assessment has focused on psychosexual problems following treatments for breast and gynecologic cancers (Andersen, 1990; Andersen et al., 1989; Bergmark, Avall-Lundqvist, Dickman, Henningsohn, & Steineck, 1999; Bines, Oleske, & Cobleigh, 1996; Ganz, 1997; Ganz et al., 1998; Kaplan, 1992; Lamb, 1995; Loprinizi et al., 1997; Schag, Ganz, Polinsky, Fred, Hirfi, & Petersen, 1993; Schover, 1994; Schover et al., 1995). For example, 23% to 28% of breast cancer survivors reported vaginal discomfort to be very severe during intercourse (Loprinizi et al., 1997). Symptoms may be most common in the first year after treatment, as Schag and colleagues (1993) found that from 40% to 57% of breast cancer survivors experienced difficulties with vaginal lubrication or reaching orgasm during sexual activity in the first year after breast cancer treatment. In women with cervical cancer, lubrication (26%) and vaginal elasticity (23%) were the most common problems (Bergmark et al., 1999). Type of treatment had little if any effect on the prevalence of vaginal changes reported after cervical cancer (Bergmark et al., 1999), whereas with breast cancer, type of treatment had more substantial influence on sexual outcomes (Ganz et al., 1998).

For men, as with women, sexual side effects are usually assessed according to the site of and treatment for the disease, with instruments specific to disease, or with sexual function as a small component of broader quality of life evaluation (Baruch et al., 1991; Heinrich-Rynning, 1987; Jonker-Pool et al., 1997; Little & Howard, 1998; Schover, 1987). After lung cancer, prostate cancer is the most common form of cancer in males (Heinrich-Rynning, 1987). Its treatment has had varying reported effects on the sexual function of male cancer survivors. Even with this variability, however, over 60% of prostate cancer survivors report sexual dissatisfaction regardless of the form of treatment (Shrader-Bogen, Kjellberg, McPherson, & Murray, 1997). Following radical prostatectomy, retrograde ejaculation has been the most common sexual side effect, occurring in 75% to 80% of patients (Heinrich-Rynning, 1987); while anywhere from 70% to 90% of men report they cannot achieve erections sufficient for sexual penetration (Schover, 1987; Shrader-Bogen et al., 1997). Research on prostate cancer patients indicates those treated with radiotherapy experience sexual side effects, with a widely varying range of 22% to 84% reporting some form of erectile dysfunction (Schover, 1987; Shrader-Bogen et al., 1997). Over 50% of male bladder cancer survivors also report sexual difficulty or dysfunction, with erectile dysfunction, decreased libido, or sexual dissatisfaction rates depending on treatment (Little & Howard, 1998; Schover, 1987). Finally, 10% to 20% of men treated for testicular cancer noted a loss of interest in sexual activity, decrease in libido, or erectile dysfunction (Jonker-Pool et al., 1997; Schover, 1987).

High-dose chemotherapy treatments are being used increasingly across diseases to attack poorer prognosis malignant cells both earlier and more aggressively. Consequently, studies have begun to look in more detail at sexual function outcomes after cancer treatments that involve these high-dose chemotherapies (Baruch et al., 1991; Marks, Crilley, Nezu, & Nezu, 1996; Marks, Friedman, Carpini, Nezu, & Nezu, 1997; Mumma, Mashberg, & Lesko, 1992; Syrjala et al., 1998; Wingard, Curbow, Baker, Zabora, & Paintadosi, 1992). Blood or marrow transplantation (BMT) represents the most aggressive end of the continuum of cancer treatment. BMT uses supralethal doses of chemotherapy, or chemotherapy combined with total body irradiation, followed by the "rescue" of the patient's eradicated immune system through the infusion of stored bone marrow or stem cells (Thomas, Blume, & Forman, 1999). Sixty-seven percent of female and 20% of male survivors continue to report sexual difficulties three years after this treatment (Syrjala et al,, 1998).

In our research on BMT, we found that we could reliably measure the sexual satisfaction of survivors. But once measured, this satisfaction rating did not inform us whether the person was sexually active, or which phases of sexuality were most affected; nor did the assessment identify which problems might require focused treatment (Syrjala et al., 1998). We also discovered that our data reflected substantially different rates of difficulties than those reported by other researchers looking at sexuality as one component of quality of life outcomes after BMT. Researchers have reported rates of 25% to 44% across genders (Bush, Haberman, Donaldson, & Sullivan, 1995; Marks et al., 1997; Mumma et al., 1992; Wingard et al., 1992). Although we can only speculate, we suspect that these differences reflected measurement effects. Since past investigators used different tools, measurement methodology may have been responsible for any or all of these disparities.

As this summary of sexual research in cancer patients indicates, research to date has documented widely diverse rates of problems and has been largely limited to prevalence information. While this is an important starting point for research in the field, more sensitive and multidimensional self-report measurements will permit cross-comparisons, and is essential for clinical trials designed to improve these outcomes (Derogatis & Conklin-Powers, 1998).

Development of the Sexual Function Questionnaire

A number of measures exist for multidimensional assessment of sexual function (Cull, 1992; Derogatis, 1997; Rust & Golombok, 1986; Taylor, Rosen, & Leiblum, 1994). Derogatis and Conklin-Powers (1998) define criteria for evaluating adequacy of sexual function measures in clinical trials. They indicate that assessment within phases of the sexual response cycle is needed as well as assessment of relevant core constructs. Their 11 criteria include multidimensional nature, unique dimensional variance, brief, norms, gender-keyed instruments, multiple interpretive levels (total score, dimensions, items), cost efficient, highly transportable (usually self-report), potentially computer compatible, sensitive to therapeutically induced changes, and sensitive to functional or dysfunctional status. We have defined essential core constructs for cancer patients as the four phases of the response cycle, actual sexual behaviors, specific problems, sexual partner relationship, and treatment impact.

Available measures do not cover these core constructs; most do not meet the criteria set by Derogatis and Conklin-Powers (1998). As an example, we conducted a broad search of the literature on sexual function in which a diagnosis of cancer and/or cancer treatment was included. Researchers either used broad quality-of-life assessment tools that contained few items (or often only a single item) dealing with sexual function, or they used tools that were applicable only to a disease or diagnosis (Bergmark et al., 1999; Jonker-Pool et al., 1997; Krongrad, Litwin, Lai, & Lai, 1998; Little & Howard, 1998; Litwin, McGuigan, Shpall, & Dhanani, 1999). When cancer researchers have reviewed these measures in reports, they identify a need for reliable, valid, multidimensional self-report assessments which are also sensitive to cancer treatment effects. In one such report, Cull (1992) reviewed a range of scales and found no brief, well-researched self-report measure of sexual function to recommend for use in cancer clinical trials. Similarly, Rosen (1998) documented various methods for qualitatively assessing sexual function in males. Four self-report instruments were reviewed. While Rosen indicated that self-report may represent the best available means of attaining assessment of sexual function, each of the measures reviewed was determined to have flaws that limit its use in large clinical trials comparing across populations.

Shrader-Bogen et al. (1997) indicate that quality of life instruments in cancer assessment have limited our understanding of sexual outcomes. Further, the authors note that patients have difficulty understanding questions about sexual function and may not be able to answer questions with accuracy. In our own experience with standardized tools for sexuality assessments designed for general use, we find that cancer patients do not complete the more sensitive or infrequent behaviors assessed or are too fatigued to respond to lengthier instruments. Thus missing data become a large problem. Lastly, measures validated with cancer patients commonly do not fully assess core constructs, or frequency of sexual activity, nor do they permit reference to normative data when attempting to understand the extent or quality of difficulties among the patients evaluated.

Our research indicated the need for a questionnaire with a number of components for cancer patients: (a) self-explanatory, brief, self-report format for use with widely diverse patients; (b) a high degree of reliability, validity, and sensitivity to treatment effects; (c) measurement of specific sexual activities and core constructs across males and females; (d) a problem assessment that can be adapted to specific diseases or targeted treatments; (e) measurement of sexuality in respondents who do not have a regular sexual partner or who are homosexual in orientation; and (f) normative data that allow investigators to compare treatment outcomes in patients versus healthy controls or that enable us to compare sexual functioning across different treatments.

With the initial testing of this instrument, aims were to establish a subscale structure, scoring methodology, reliability, and validity of the tool with cancer and noncancer samples. We tested content, construct, criterion, and discriminant validity. Further, we intended to demonstrate the value of the instrument for medical outcomes evaluation and clinical trials designed to improve sexual function.

In validity testing, we hypothesized that: (a) married responders would report better sexual function than single responders; (b) subjects who report more menopausal symptoms would report more sexual problems, but the majority of variance would remain independent rather than shared between the measures of menopausal symptoms and overall sexual function; (c) subjects who report better overall quality in their committed relationships would report better sexual relationships; (d) those women with poorer observer-rated vaginal health scores would have poorer scores on overall sexual function; (e) those respondents who were sexually active in the past month would report better sexual function than respondents who were not sexually active; and (f) survivors of cancer treatment would report on average poorer sexual function than matched, noncancer control participants.

Medical outcomes hypotheses, based on our prior research with this population, were: (a) survivors would report a decrease in sexual function from pretransplant to one year posttransplant, with women reporting a more significant drop than men; (b) survivors who had been diagnosed with clinically extensive cGVHD would report poorer function than those who had not; and (c) women who were premenopausal would report better sexual function overall than women who were postmenopausal as a result of cancer treatment.

METHODS

Participants

Sampling comprised five cohorts--including cancer survivors and matched control subjects--with a total of 400 participants. Four types of cancer survivors were included: adult survivors of blood or marrow transplants (BMT) at 1 year or 10 years after treatment, adult survivors of childhood BMT for cancer, and adult survivors of childhood leukemia without BMT. The matched control subjects were assessed to establish a normative, noncancer sample for outcome comparisons. Control subjects were all of the same gender, same ethnicity, and within 5 years of age of the matched cancer survivor. No nominated control subjects or survivors refused to participate, although data from all survivors and controls had not been received at the time of data analyses. Demographic information is displayed for each of these cohorts by gender in Tables 1 and 2. Medical data for the survivor cohorts is described in Table 3.

Table 1. Demographic Information for Female Survivors and Matched Controls

                                                   Adult BMT
                                       All           1 year
                                  participants     survivors

N                                   223              63
Age at assessment
  Mean (SD)                       33.47 (11.79)   43.63 (9.77)
  Range                           18-67           27-62
Age at treatment
  Mean (SD)                       24.21 (18.23)   42.46 (9.78)
  Range                            1-61           25-61
Education
  No high school degree              14 (06)          2 (03)
  High school Degree/GED             83 (37)         19 (31)
  2-year college/trade               44 (20)         13 (21)
  4-year college                     59 (26)         16 (26)
  Master's degree or higher          25 (11)         12 (19)
Marital status
  Single                             76 (34)          8 (13)
  Married or cohabiting             132 (58)         43 (68)
  Divorced/separated/widowed         18 (8)          12 (19)
Currently has sex partner
  Yes                               162 (71)         42 (67)
  No                                 65 (29)         21 (33)
Sexually active in past month
  Yes                               148 (65)         32 (51)
  No                                 79 (35)         31 (49)
On HRT
  Yes                                86 (38)         43 (68)
  No                                139 (62)         20 (32)
Self-reported menopausal status
at assessment
  Pre                               144 (63)          9 (14)
  Post                               73 (32)         45 (71)
  Peri                               10 (4)           9 (14)

                                    Adult BMT
                                     10 year       Childhood
                                    survivors         BMT

N                                    16              27
Age at assessment
  Mean (SD)                       45.06 (11.52)   27.00 (5.46)
  Range                           30-67           18-41
Age at treatment
  Mean (SD)                       33.94 (11.59)   11.04 (4.32)
  Range                           19-56            1-17
Education
  No high school degree               2 (12.5)        2 (07)
  High school Degree/GED              2 (12.5)       12 (44.5)
  2-year college/trade                4 (25)          4 (15)
  4-year college                      6 (37.5)        7 (26)
  Master's degree or higher           2 (12.5)        2 (7)
Marital status
  Single                              3 (19)         15 (56)
  Married or cohabiting              12 (75)         12 (44)
  Divorced/separated/widowed          1 (6)           0
Currently has sex partner
  Yes                                10 (62.5)       19 (70)
  No                                  6 (37.5)        8 (30)
Sexually active in past month
  Yes                                 9 (56)         18 (67)
  No                                  7 (44)          9 (33)
On HRT
  Yes                                13 (81)         12 (44)
  No                                  3 (19)         15 (56)
Self-reported menopausal status
at assessment
  Pre                                 0              21 (78)
  Post                               16 (100)         5 (18.5)
  Peri                                0               1 (4)

                                   Childhood       Noncancer
                                    leukemia       normative
                                    non-BMT        controls

N                                    55             66
Age at assessment
  Mean (SD)                       24.44 (4.45)   31.26 (10.45)
  Range                           18-39          18-64
Age at treatment
  Mean (SD)                        6.95 (4.69)      NA
  Range                            1-16             NA
Education
  No high school degree               6 (11)         2 (3)
  High school Degree/GED             30 (55)        20 (31)
  2-year college/trade               10 (18)        13 (20)
  4-year college                      8 (14.5)      22 (34)
  Master's degree or higher           1 (2)          8 (12)
Marital status
  Single                             28 (51)        22 (34)
  Married or cohabiting              24 (44)        41 (63)
  Divorced/separated/widowed          3 (5)          2 (3)
Currently has sex partner
  Yes                                34 (62)        57 (86)
  No                                 21 (38)         9 (14)
Sexually active in past month
  Yes                                36 (65.5)      53 (80)
  No                                 19 (34.5)      13 (20)
On HRT
  Yes                                 9 (17)         9 (14)
  No                                 44 (83)        57 (86)
Self-reported menopausal status
at assessment
  Pre                                54 (98)        60 (91)
  Post                                1 (2)          6 (9)
  Peri                                0              0

                                        p(*)

N                                      <.001(a)
Age at assessment
  Mean (SD)
  Range
Age at treatment                       <.001(b)
  Mean (SD)
  Range
Education                              <.001(a)
  No high school degree
  High school Degree/GED
  2-year college/trade
  4-year college
  Master's degree or higher
Marital status                         <.001(c)
  Single
  Married or cohabiting
  Divorced/separated/widowed
Currently has sex partner              <.006(d)
  Yes
  No
Sexually active in past month          <.002(d)
  Yes
  No
On HRT                                 <.001(c)
  Yes
  No
Self-reported menopausal status
at assessment                          <.001(c)
  Pre
  Post
  Peri

Note. Differences between sample cohorts were tested between 3 groups: adult survivors, child survivors, and matched controls. Age was tested with one-way ANOVA, other variables were tested with [chi square]. Data in parenthesis are percentages.

Post-hoc comparisons of differences between cohorts:

(a) matched noncancer normative controls and adult survivors higher than child survivors;

(b) only adult vs. childhood survivor groups compared, difference is significant;

(c) adult survivors significantly different from childhood survivors and normative controls;

(d) normative controls significantly different from adult and childhood survivors;

(e) each group differs significantly from the others;

(f) childhood survivors significantly different from adult survivors and normative controls.

Table 2. Demographic Information for Male Survivors and Matched Controls

                                                Adult BMT
                                    All           1 year
                                participants    survivors

N                                 173             36
Age at assessment
  Mean (SD)                     32.51(9.90)    41.17 (9.36)
  Range                         19-69          25-69
Age at treatment
  Mean (SD)                     21.03(16.2)    40.06 (9.37)
  Range                         1-68           24-68
Education
  No high school degree            4 (02)         0
  High school Degree/GED          58 (34)         7 (19)
  2-yr college/trade              37 (22)         9 (25)
  4-yr college                    53 (31)        10 (28)
  Master's degree or higher       19 (11)        10 (28)
Marital status
  Single                          58 (34)         4 (11)
  Married or Cohabiting          102 (60)        31 (86)
  Divorced or Separated           11 (06)         1 (03)
Currently has sex partner
  Yes                            127 (73)        30 (83)
  No                               6 (27)         6 (17)
Sexually active in past month
  Yes                            131 (76)        26 (72)
  No                              42 (24)        10 (28)

                                 Adult BMT
                                  10 year       Childhood
                                 survivors         BMT

N                                  14             29
Age at assessment
  Mean (SD)                     43.64 (8.07)   27.66 (3.98)
  Range                            30-57          20-34
Age at treatment
  Mean (SD)                     32.36 (7.69)   11.00 (4.32)
  Range                            19-45           4-17
Education
  No high school degree            2 (14)            0
  High school Degree/GED           2 (14)        14 (48)
  2-yr college/trade               1 (07)         4 (14)
  4-yr college                     8 (57)      10 (34.5)
  Master's degree or higher        1 (07)         1 (03)
Marital status
  Single                           1 (07)        15 (52)
  Married or Cohabiting           11 (79)        12 (41)
  Divorced or Separated            2 (14)         2 (07)
Currently has sex partner
  Yes                             11 (79)        16 (55)
  No                               3 (21)        13 (45)
Sexually active in past month
  Yes                             11 (79)      19 (65.5)
  No                               3 (21)      10 (34.5)

                                 Childhood      Noncancer
                                  leukemia      normative
                                  non-BMT        controls

N                                  39
Age at assessment
  Mean (SD)                     25.08 (4.40)   31.81 (9.06)
  Range                            19-34          19-61
Age at treatment
  Mean (SD)                     6.85 (4.47)         NA
  Range                             1-16            NA
Education
  No high school degree             2 (05)
  High school Degree/GED           19 (49)       16 (30)
  2-yr college/trade                9 (23)       14 (26)
  4-yr college                      8 (20.5)     17 (32)
  Master's degree or higher         1 (03)        6 (11)
Marital status
  Single                           23 (59)       15 (28)
  Married or Cohabiting            14 (36)       34 (64)
  Divorced or Separated             2 (05)        4 (07.5)
Currently has sex partner
  Yes                              23 (59)       47 (85.5)
  No                               16 (41)        8 (14.5)
Sexually active in past month
  Yes                            24 (61.5)       51 (93)
  No                             15 (38.5)        4 (07)

                                  p(*)

N
Age at assessment               <.001(a)
  Mean (SD)
  Range
Age at treatment                <.001(b)
  Mean (SD)
  Range
Education                       <.006
  No high school degree
  High school Degree/GED
  2-yr college/trade
  4-yr college
  Master's degree or higher
Marital status                  <.001(e)
  Single
  Married or Cohabiting
  Divorced or Separated
Currently has sex partner       <.001(f)
  Yes
  No
Sexually active in past month   <.001(d)
  Yes
  No

Note. Differences between sample cohorts were tested between 3 groups: adult survivors, child survivors, and matched controls. Age was tested with one-way ANOVA, other variables were tested with [chi square]. Data in parentheses are percentages.

Post-hoc comparisons of differences between cohorts:

(a) matched noncancer normative controls and adult survivors higher than child survivors;

(b) only adult vs. childhood survivor groups compared, difference is significant;

(c) adult survivors significantly different from childhood survivors and normative controls;

(d) normative controls significantly different from adult and childhood survivors;

(e) each group differs significantly from the others;

(f) childhood survivors significantly different from adult survivors and normative controls.

Table 3: Medical Characteristics for Male and Female Cancer Survivors

                                    All cancer     Adult BMT
                                    survivor       1 year
                                    participants   survivors

N                                    279           99
Diagnosis
  Acute leukemias                    140 (50)      14 (14)
  Chronic leukemias                   65 (23)      45 (45)
  Other                               74 (27)      40 (40)
Treatment (conditioning)
  Cyclophosphamide + TBI(*)          127 (45.5)    47 (47.5)
  Chemotherapy only                   97 (35)      47 (47.5)
  Other chemo + TBI                    4 (01)       3 (03)
  Chemo + local radiation therapy     51 (18)       2 (02)
Transplant Type
  MT                                 153 (83)      67 (68)
  PBSC                                32 (17)      32 (32)
Donor
  Autologous                          22 (12)      17 (17)
  Allogeneic related                 121 (65)      43 (43)
  Unrelated                           42 (23)      39 (39)
Clinically Extensive cGVHD(*)
  Yes                                 74 (40)      45 (45)
  No                                 111 (60)      54 (55)

                                    Adult BMT
                                    10 year
                                    survivor    Child BMT

N                                    30         56
Diagnosis
  Acute leukemias                     3 (10)    40 (71)
  Chronic leukemias                  15 (50)     5 (09)
  Other                              12 (40)    11 (20)
Treatment (conditioning)
  Cyclophosphamide + TBI(*)          28 (93)    52 (93)
  Chemotherapy only                   2 (07)     3 (05)
  Other chemo + TBI                      0       1 (02)
  Chemo + local radiation therapy        0          0
Transplant Type
  MT                                30 (100)    56 (100)
  PBSC                                   0          NA
Donor
  Autologous                         3 (100)     2 (04)
  Allogeneic related                 27 (90)    51 (91)
  Unrelated                              0       3 (05)
Clinically Extensive cGVHD(*)
  Yes                                12 (40)    17 (30)
  No                                 18 (60)    39 (70)

                                    Child leukemia
                                       non-BMT

N                                      94
Diagnosis
  Acute leukemias                      83 (88)
  Chronic leukemias                     0
  Other                                11 (12)
Treatment (conditioning)
  Cyclophosphamide + TBI(*)             0
  Chemotherapy only                    45 (48)
  Other chemo + TBI                     0
  Chemo + local radiation therapy      49 (52)
Transplant Type
  MT                                   NA
  PBSC
Donor
  Autologous                           NA
  Allogeneic related                   NA
  Unrelated                            NA
Clinically Extensive cGVHD(*)
  Yes                                  NA
  No                                   NA

Note. MT = Bone Marrow Transplant; PBSC = Peripheral Blood Stem Cell Transplant; TBI = Total Body Irradiation; cGVHD = chronic graft versus host disease.

Cohort 1. Cohort 1 included 99 BMT recipients treated at the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle who had been recruited pretransplant between March, 1996 and April, 1998 to participate in a study evaluating long-term effects of BMT. At 1 year, 93% of the surviving BMT recipients completed the reassessment, from an original accrual of 199 pretransplant patients. Those participants completing 1-year assessments were included in this cohort. Sixty-four percent of this cohort were female between the ages of 27 and 62 years, with a mean age of 43.63; thirty-six percent were male between the ages of 25 and 69, with a mean age of 41.17. The survivors were mostly Caucasian (95%) as reflects the population treated at FHCRC and most transplant sites. Forty-four percent received related donor allogeneic transplants; 39% received transplants from unrelated donors (URD), and 17% received their own stored marrow or stem cells (autologous transplants). At some point during their recovery, 45% had clinically extensive chronic graft-versus-host disease (cGVHD), the most common long-term medical complication following allogeneic or URD transplant. Diagnosis of cGVHD requires long-term immune suppressive medication to prevent the immune system from rejecting body organs. This iatrogenic disease can affect connective tissue, mucosa, and, consequently, sexual function (Schubert et al., 1990; Syrjala et al., 1998). At 1-year assessment, 68% of the women in this cohort were on hormone replacement therapy (HRT), 8% were taking tamoxifen, and 24% were taking neither HRT nor tamoxifen. In addition to pretransplant and 1-year assessments, this cohort also completed assessment at 6 months after BMT.

Cohort 2. Cohort 2 included 30 adult transplant recipients who were 10-year survivors and were recruited between September, 1998 and June, 1999 to participate in a study assessing late effects of BMT. The survivors in this cohort all received marrow transplants at FHCRC between March, 1987 and March, 1989 and had been accrued previously to a study of transplant early effects. The Sexual Function Questionnaire had not been administered in earlier assessments with this cohort. At the time of the latest assessment, all were 10 to 12 years posttransplant. The majority of the survivors in this cohort were Caucasian (97%): 53% were female aged 20 to 67, with a mean age of 45.06 and 47% were male aged 30 to 57, with a mean age of 43.64. Eighty-one percent of the women in this cohort were premenopausal before transplant; 100% were postmenopausal at 10-year assessment. Of these women, 81% were on HRT, while 6% were on tamoxifen; 13% were not taking hormones.

Cohort 3. Cohort 3 included adult survivors at least 5 years posttransplant who received marrow transplants as children at FHCRC between 1972 and 1990. At the time of transplant, these recipients ranged in age from 1 to 17. Age at the time of assessment ranged from 18 to 41, with a mean of 27.3 years. These adult survivors of pediatric marrow transplants were approached for consent to participate in a study assessing late effects of pediatric BMT. Of the 56 patients in this cohort, 52% were male and 48% were female: 91% were Caucasian. At the time of transplant, more than half of the females were prepubescent (59%). At time of assessment 35% of the women were on HRT, 4% were on tamoxifen and 8% were taking birth control pills. As with other cohorts, some of these women did not seem to know their menopausal status since those taking HRT sometimes indicated they were premenopausal.

Cohort 4. Cohort 4 included 5-year or more survivors of childhood leukemia who did not have BMTs but received conventional leukemia treatment at the Children's Hospital Medical Center (CHMC) in Seattle between 1972 and 1995. Their ages at treatment ranged from 1 to 16. At the time of assessment, survivors had a mean age of 27.8 and ranged in age from 18 to 39 years. These adult survivors of pediatric leukemia were approached for consent to participate in a study assessing late effects of treatment in childhood leukemia survivors. Of the 94 survivors in this cohort, 59% were female and 41% were male: the majority was Caucasian (90%). Most of the women in this sample were prepubescent prior to treatment (78%). At the time of assessment, most were premenopausal; 16% were on HRT.

Cohort 5. Cohort 5 included a normative sample of noncancer control subjects who were matched to survivors in cohorts 2, 3, and 4 by age and gender. To maintain an approximate sociocultural match, siblings were selected when available. When no sibling was available the survivor nominated a friend who met the same criteria. For adult cancer survivors, a friend known to the survivor prior to disease diagnosis was selected. This prior friendship was not possible for childhood survivors since most adult friendships did not predate their diagnosis. All were asked for consent to participate in a study comparing quality of life in noncancer controls matched to BMT or pediatric leukemia survivors. Of the 121 subjects in this cohort, 45% were male with a mean age of 31.81, ranging from 19-16 years; 55% were female with a mean age of 31.26 and ranged in age from 18-64 years. Eighty-three percent were Caucasian. Of the women in this cohort, 14% were on HRT.

Procedures

The Institutional Review Board at FHCRC approved all procedures and questionnaires used in the reported research. All participants were contacted first by phone for consent to participate, with the exception of cohort 1 in which all participants were approached for consent in person by a research nurse prior to transplant. All of those approached in cohorts 2 through 5 agreed to participate. In cohort 1, the study consent also required participation in a randomized controlled clinical trial; 81% of those approached consented prior to transplant and all of those approached for 1-year follow up agreed to participate. Pretransplant forms for cohort 1 were completed on site at FHCRC and returned to the research nurse who had consented the patient. For 6-month and 1-year assessments of cohort 1 and for all other cohorts, forms were mailed to each subject with directions about how to fill out the questionnaires, with a toll-free phone number to call for questions and an addressed, stamped return envelope.

Investigators made reminder phone calls to participants whose questionnaires had not been received within 3 weeks of mailing. Rate of return of assessments among the survivors was 89% by the time of data analyses. The most common reasons for not returning assessments were acute physical illness or not having had enough time to complete the forms. Since ill survivors may have reduced sexual function, the results may underreport the extent of dysfunction among survivors. Rate of return of questionnaires among control subjects was 82% by the time of data analyses. The most common reason for controls not returning assessments was lack of time.

In addition to the paper and pencil assessments, female patients from cohort 1 agreed, as part of the study protocol, to a pelvic examination by an FHCRC gynecology nurse practitioner at both pretransplant and 1 year posttransplant, close to the time of filling out the self-report questionnaires. Vaginal health was assessed using the Vaginal Health Assessment (Leiblum, Bachmann, Kammann, Colburn, & Swartzman, 1983). For survivors, the data manager collected data on medical status, cGHVD, diagnosis, and treatment history from research databases at FHCRC or CHMC.

Measures

The Background Questionnaire asks standard, self-report questions about age, sex, marital status, income, employment status, and previous relevant medical history, symptoms, and treatment. Control subjects were given a modified background questionnaire in which questions relating specifically to transplant or cancer treatment were removed.

The Sexual Functioning Questionnaire (SFQ) is a gender-specific measure that assesses sexual functioning with 30 items. For example, a set of items ask "how frequently have you felt an interest or desire to engage in the following specific activities in the past month," followed by a list of activities. Each of five activities (fantasy to intercourse) is rated on a 7-point scale from not at all to more than once a day. A second set of items asks "how frequently have you become aroused by the following sexual activities in the past month." A third set asks "how frequently have you engaged in the following sexual activities." Each set is followed by the same list of activities and response options. Specific events during sexual activity, including problems, are rated on a 6-point scale from not at all through sometimes, about 50% of the time to always. Relationship and other satisfaction items are responded to on 6-point scales from very satisfied to very dissatisfied or 11-point scales from not at all to extremely.

The SFQ was adapted from the Brief Sexual Functioning for Women: BISF-W (Taylor et al., 1994). Developers of the BISF-W reported it had adequate, though not strong, reliabilities and reasonable correlation with the Derogatis Sexual Function Inventory (Derogatis & Melisaratos, 1979). We retained the response format for the activities sets and reduced the number of activities sets assessed with an option to add "other activities." The original measure required 65 distinct responses grouped into 22 questions. This was too long for ill cancer patients, and some questions that queried rare activities were perceived as offensive by some patients. This resulted in unacceptable levels of missing data. To address these issues, rare activities were deleted. Items added included problems common in cancer patients, reasons for lack of sexual activity, whether problems stop or restrict sexual activity, questions about intimacy not previously included in the scale (warmth, intimacy, touching, hugging, holding), an item each on overall sexual interest and sexual satisfaction, worries about impact of sexual activity on health, and a section on perceived treatment impact. After preliminary testing, items were deleted about initiation of activity, changes in sexuality, and role of sexual activity in life since these items did not load on initial factors. Content validity was established in adaptation of the instrument with the last author as an expert in sexuality evaluation, with feedback on the assessment from patients and by identified experts in sexuality and quality of life in cancer patients.

We piloted the revised instrument in a sample of 200 BMT recipients at two time points, before and after treatment. After psychometric analyses to establish reliability, validity, and factor structure, we again revised the instrument to strengthen some of the subscales, to eliminate redundant or poorly performing items, and to include items reflective of problems or comments expressed by the participants in open-ended questions. The surviving BMT recipients completed this revised tool and the other cohorts were then included in the assessment with the revised tool. Since the subscale structure and validity remained the same, and reliability was never under .75 for the subscales of the first or second revisions, data from all assessment points were included in this report.

Questions on the SFQ define actual sexual behaviors and events in the past month. The core questions can be answered in about 10 minutes and a score calculated whether or not a person has a sexual partner, regardless of the sexual orientation of the respondent, and regardless of medical condition. Since many aspects of sexuality do not depend on intercourse-directed behaviors, even those respondents who indicate that they are not sexually active in the past month can answer many questions. The core questions can be scored and compared across as well as within gender. While problems are included which are seen in cancer survivors, the problems are not specific to cancer survivors. We expect that the problems subscale could be modified depending on the outcomes of interest to researchers, similar to disease modules in broad quality-of-life tools (Aaronson, Ahmedzai, & Bullinger, 1991; Cella, 1997). Finally, an SFQ Treatment Impact scale is scored separately to permit tailoring to the medical outcome of interest.

The Postmenopausal Estrogen Progesterone Intervention Scale (PEPI) is a 43-item self-report measure of postmenopausal symptoms among women, including genital and sexual function symptoms (Anonymous, 1995). The measure is currently being used in several large-scale clinical trials with healthy and medical populations, including the Women's Health Initiative. Scores on the PEPI for cohort 1 (n = 96, [is less than] = .84) at pretransplant, 6-month and 1-year assessments are used as criterion validation for the Problem subscale of the SFQ and for discriminant validity testing for the Overall SFQ. We hypothesized that subjects who report more symptoms on the PEPI would also report more problems on the SFQ, but that the majority of variance would remain independent rather than shared between the PEPI and Overall SFQ score.

The Dyadic Adjustment Scale (DAS) (Spanier, 1976) is a widely used 32-item self-report scale that assesses quality of adjustment in marital or committed relationships. The DAS (authors report n = 313, [is less than] = .96) is currently one of the most widely used marital adjustment and satisfaction measures with chronic illness populations, as well as with physically healthy, distressed couples. The DAS includes four subscales: satisfaction, consensus, cohesion, and affectional expression (authors report [is less than] = .73-.94). The DAS is used as validation for the Relationship subscale of the SFQ. We hypothesized that subjects who report better relationships on the DAS will also report better sexual relationships on the SFQ.

Vaginal Health Assessment is a 6-item observer scale that assesses vaginal skin elasticity and turgor, amount of pubic hair present, labial fullness, introital size, vaginal epithelial thickness, and vaginal depth (Leiblum et al., 1983). Each of these areas is rated by an experienced gynecology professional on a 3-point scale, a lower score indicating better vaginal health. A mean score is then calculated to determine overall vaginal health. Chemotherapy, radiation therapy, and cGHVD are known to influence vaginal health (Schubert et al., 1990) as well as sexual function (Ganz et al., 1998; Syrjala et al., 1998). This scale offers a relatively detailed and comprehensive method of assessing observable vaginal changes that may be caused by menopause and/or cancer treatment. Thus the vaginal health assessment was conducted as a validation measure for the SFQ, with a hypothesis that those with poorer scores on the vaginal health assessment would also have poorer scores on the Overall SFQ.

Statistical Analyses

Data were analyzed using SPSS for Windows 9.0. Initial scale structure, reliability, and validity were tested with males and females separately since we did not assume identical scale structure across genders and since problem lists differed. Once principal components were identified as the same between males and females, final analyses combined the samples. Subscales for the SFQ were initially established a priori based on theoretical foundations as described under the Sexual Function Questionnaire in Measures. Individual subscales, as well as the Treatment Impact scale, were confirmed using principal components factor analysis, with varimax rotation, across all cohort samples. Internal reliability was tested with Cronbach's alpha. Once initial scale structure and internal reliability testing was completed, test-retest reliability was tested with a Pearson correlation between 6-month and 1-year scores for cohort 1. Construct validity was confirmed with principal components analyses and t tests or correlations on demographic variables known to differ in rates of sexual dysfunction (i.e., married vs. single: Laumann et al., 1999). Criterion validity was evaluated by correlation of the global 0 to 10 satisfaction rating with the Overall SFQ, the SFQ Relationship subscale with the overall DAS score, and the PEPI with SFQ Problems, as well as the vaginal exam with Overall SFQ. Using t tests, discriminant validity was tested between normative controls versus survivors and comparing those participants who reported being sexually active in the past month versus those reporting no sexual activity in the past month. In addition, Pearson correlations between the Overall SFQ versus the PEPI tested discriminant validity. All analyses using the DAS, PEPI, and vaginal exam were done with cohort 1 only, for whom we had repeated measures data at pretransplant, 6 months and 1 year posttransplant. This permitted confirmatory validity testing at the different time points.

To demonstrate the potential value of the SFQ as an outcome measure, analyses tested several hypothesized differences between groups. We compared those who were premenopausal versus postmenopausal on Overall SFQ using t tests. Since differences were found, a stepwise multiple regression was used to determine the relative predictive contribution of menopausal status and other related factors to the Overall SFQ. Also, as a medical outcome, we used t tests to analyze SFQ differences between survivors who had or who had not had clinically extensive cGVHD. Repeated measures ANOVA were used to analyze change over time in men and women in cohort 1. Since subscale structure and reliabilities were nearly identicaI in males and females, testing across time for cohort 1 combined males and females in analyses.

RESULTS

Differences Between Cohorts

Cohorts differed in age, education, income, likelihood of being married, and likelihood of being sexually active in the past month (Tables 1 and 2). The two childhood survivor cohorts had less education, had lower incomes, and were more likely to be single. The control subjects were more likely to have been sexually active than the survivor cohorts. As seen in the tables, these demographic variables were similar between the male and female samples. The notable exception was that males were more likely to report being sexually active in the past month than females ([chi square] = 5.59, p = .02). Although there were no differences between control subjects in rates of sexual activity, among one year survivors men were more likely to be sexually active ([chi square] = 4.34 p [is less than] .04).

Among women, 91% of the age-matched normative control subjects were premenopausal when assessed, while the large majority of the adult BMT respondents were postmenopausal at the time assessed. Adult survivors who were postmenopausal were more likely to be on HRT than childhood survivors who were postmenopausal, but responses also demonstrated that many participants on hormone replacement after cancer treatment believed they were still premenopausal, perhaps because they were still menstruating.

Subscale Structures and Reliabilities

Initial subscale structure for the SFQ was established separately for males (Table 4) and females (Table 5). Subscale and internal reliabilities of the SFQ were consistent across both genders and across survivor and normative control samples. Since no differences were found between cohorts in factor structure or relative strength of factor loadings, the cohorts were combined across genders for final factor analyses (Tables 6 and 7). Content differences by gender occurred only in the Problems subscale where male items included erection and ejaculation difficulties and female items included vaginal lubrication or vaginal tightness difficulties. Principal components factor analyses with varimax rotation demonstrated that all items within each subscale loaded on one factor with loadings above .5 for all items in all subscales for males and females separately and combined. Subscale and Overall SFQ internal reliabilities were above .80 in all cases for males and females. The masturbation items did not load within any of the related phases of sexual function, but loaded highly on their own subscale for both males and females among survivors and control subjects (Table 6). As seen in the tables, the SFQ Treatment Impact scale had high factor loadings and high reliability within both genders for survivors.

Table 4: Description and Internal Reliabilities for Males on the Overall SFQ, Subscales and Treatment Impact Scale

                        Mean (SD)
Scale                   survivors        Norm

Overall SFQ Score      3.23 (1.24)   3.93 (0.80)(***)
Subscales:
  Interest             3.62 (1.30)   3.73 (1.33)
  Desire               3.93 (1.66)   4.67 (1.12)(***)
  Arousal              2.12 (1.24)   2.69 (0.87)(***)
  Orgasm               4.32 (2.27)   5.46 (0.88)(***)
  Satisfaction         3.52 (1.62)   4.20 (1.12)(**)
  Masturbation         1.55 (1.41)   1.96 (1.65)
  Relationship         3.27 (2.06)   4.19 (1.47)(***)
  Behavior             2.49 (1.68)   3.40 (1.35)(***)
  Problems             5.19 (0.95)   5.40 (0.68)
SFQ Treatment Impact   2.92 (0.96)     NA

                       # Items   [Alpha]
                         All       All
                       cohorts   cohorts

Overall SFQ Score         30       .93
Subscales:
  Interest                 4       .81
  Desire                   3       .89
  Arousal                  4       .87
  Orgasm                   2       .93
  Satisfaction             2       .87
  Masturbation             3       .92
  Relationship             3       .87
  Behavior                 4       .90
  Problems                 5       .84
SFQ Treatment Impact       5       .84

Note. Higher scores indicate better sexual function and fewer problems.

(*) p < .05; t test comparing survivor and control.

(**) p [is less than or equal to] .01; t test comparing survivor and control.

(***) p [is less than or equal to] .001; t test comparing survivor and control.

Table 5. Description and Internal Reliabilities for Females

                        Mean (SD)
Scale                   survivors          Norm

Overall SFQ Score      2.62 (1.28)   3.33 (1.03)(***)
Subscales:
  Interest             2.13 (1.44)   2.63 (1.32)(*)
  Desire               3.15 (1.79)   3.91 (1.30)(***)
  Arousal              1.36 (1.20)   2.00 (1.03)(***)
  Orgasm               2.97 (2.03)   3.94 (1.77)(***)
  Satisfaction         3.40 (1.61)   4.07 (1.21)(***)
  Masturbation         0.62 (1.09)   0.89 (1.18)
  Relationship         3.12 (2.03)   3.91 (1.54)(**)
  Behavior             2.23 (1.68)   2.89 (1.47)(**)
  Problems             4.50 (1.09)   5.04 (0.67)(***)
SFQ Treatment Impact   2.65 (1.08)     NA

                       # Items   [Alpha]
                         All       All
Scale                  cohorts   cohorts

Overall SFQ Score        30        .94
Subscales:
  Interest                4        .86
  Desire                  3        .89
  Arousal                 4        .88
  Orgasm                  2        .93
  Satisfaction            2        .87
  Masturbation            3        .91
  Relationship            3        .84
  Behavior                4        .88
  Problems                5        .81
SFQ Treatment Impact      5        .84

Note. Higher scores indicate better sexual function and fewer problems.

(*) p [is less than or equal to] .05; t test comparing survivor and control.

(**) p [is less than or equal to] .01; t test comparing survivor and control.

(***) p [is less than or equal to] .001; t test comparing survivor and control.

Table 6. Factor Loadings for Subscales that Include All Participants

Item                          Interest   Desire   Arousal   Orgasm

Had sexual thoughts, urges,
  fantasies                     .85
Interest in sexual dreams
  or fantasy                    .90
Interest in sexual thoughts
  or feelings                   .81
Engaged in fantasy              .81
Desire for kissing,
  touching, holding                       .81
Desire for petting                        .94
Desire for vaginal
  intercourse                             .91
Aroused by dreams                                   .59
Aroused by kissing,
  touching, holding                                 .86
Aroused by petting                                  .94
Aroused by vaginal
  intercourse                                       .90
Pleasure from any forms of
  sex                                                        .97
How often reached orgasm                                     .97
Satisfied with warmth &
  intimacy
Satisfied with sexual
  activity
Engaged in kissing,
  touching, holding
Engaged in petting
Engaged in mutual
  masturbation
Engaged in vaginal
  intercourse
Conflict in relationship
Communicate sexual desire
Satisfied with sexual
  relationship
Desire to engage in
  masturbation
Aroused by masturbation
Engaged in masturbation

                              Satisfaction   Activity

Had sexual thoughts, urges,
  fantasies
Interest in sexual dreams
  or fantasy
Interest in sexual thoughts
  or feelings
Engaged in fantasy
Desire for kissing,
  touching, holding
Desire for petting
Desire for vaginal
  intercourse
Aroused by dreams
Aroused by kissing,
  touching, holding
Aroused by petting
Aroused by vaginal
  intercourse
Pleasure from any forms of
  sex
How often reached orgasm
Satisfied with warmth &
  intimacy                        .89
Satisfied with sexual
  activity                        .89
Engaged in kissing,
  touching, holding                            .86
Engaged in petting                             .94
Engaged in mutual
  masturbation                                 .58
Engaged in vaginal
  intercourse                                  .91
Conflict in relationship
Communicate sexual desire
Satisfied with sexual
  relationship
Desire to engage in
  masturbation
Aroused by masturbation
Engaged in masturbation

                              Relationship   Masturbation

Had sexual thoughts, urges,
  fantasies
Interest in sexual dreams
  or fantasy
Interest in sexual thoughts
  or feelings
Engaged in fantasy
Desire for kissing,
  touching, holding
Desire for petting
Desire for vaginal
  intercourse
Aroused by dreams
Aroused by kissing,
  touching, holding
Aroused by petting
Aroused by vaginal
  intercourse
Pleasure from any forms of
  sex
How often reached orgasm
Satisfied with warmth &
  intimacy
Satisfied with sexual
  activity
Engaged in kissing,
  touching, holding
Engaged in petting
Engaged in mutual
  masturbation
Engaged in vaginal
  intercourse
Conflict in relationship          .78
Communicate sexual desire         .85
Satisfied with sexual
  relationship                    .87
Desire to engage in
  masturbation                                 .96
Aroused by masturbation                        .90
Engaged in masturbation                        .95

Table 7: Factor Loadings for Scales that Include Selected Participants

                                                  Treatment
                                                   impact
Item                          Male      Female     [Cancer
                            problems   problems   survivors
                                                    only]

Male problems:
  Delayed ejaculation         .59
  Difficulty getting
    erection                  .84
  Losing erection             .72
  Lack of arousal             .89
  Lack of desire              .82

Female problems:
  Lack vaginal
    lubrication                          .70
  Lack of desire                         .75
  Lack of arousal                        .89
  Difficulty reaching
    orgasm                               .81
  Painful vaginal
    penetration                          .61

Treatment impact:
  Adjust to change in
    sex life                                         .68
  Impact of diagnosis or
    treatment on sex life                            .79
  Impact of treatment on
    interest or desire                               .89
  Impact of treatment on
    sexual arousal                                   .80
  Impact of treatment on
    orgasms                                          .76

Consistency of response was analyzed between the 6-month and 1-year SFQ responses of the adult 1-year survivor sample, across genders. The correlation between time points on the Overall SFQ was .83 and on the SFQ Treatment Impact scale was r = .66. Subscale test-retest reliabilities were Interest r = .74, Desire r = .81, Arousal r = .75, Orgasm r = .68, Satisfaction r = .69, Relationship r = .81, Behavior r = .80, Masturbation r = .60, and Problems r = .74.

Validity

Validity was established by testing for hypothesized relationships between established assessments and the relevant SFQ scores.

Construct validity was confirmed by high factor loadings of the items on scales (Tables 6 and 7). Further supporting construct validity, the Masturbation subscale mean is higher for males than females (t = 7.14, p [is less than] .001) and higher for respondents without sexual partners than for those with partners (t = 4.00, p [is less than] .001). In addition, males reported less dysfunction SFQ scores (t = 5.04, p [is less than] .001), as did those who were married compared with those who were single (t = 4.06 for women, t = 4.63 for men, p [is less than] .001).

Criterion validity was tested with several correlations. Overall SFQ was strongly associated with a Satisfaction single item numerical rating scale (r = .89 for females, r = .82 for males, p [is less than] .001), which has been demonstrated to be a reliable measure of global sexual function (Syrjala et al., 1998). For those participants in a committed relationship, we hypothesized that the SFQ Relationship subscale would be higher in respondents who reported higher levels of overall relationship quality on the DAS. In the survivors with repeated assessments (cohort 1; the adult 1-year sample), we found that the DAS and SFQ Relationship subscale correlated pretransplant (r = .50, p [is less than] .001), at 6 months (r = .51, p [is less than] .001), and at 1 year (r = .38, p = .001). At 1 year and 6 months, women's scores on the PEPI correlated with those on the SFQ Problems subscale which share a focus with the PEPI on symptoms (r = -.38, p = .01 at 1 year; r = -.40, p [is less than] .01 at 6 months; r = -.17, p = .11 pretransplant). At the two time points assessed, female survivors in cohort 1 who had better vaginal health scores also had higher Overall SFQ scores: pretransplant r = .38, p [is less than] .001; 1 year r = .43, p [is less than] .02.

Discriminant validity was tested between survivors and comparison norms, between those sexually active and those not active, and between sexual function and menopausal symptoms in women. T tests between survivors and normative subjects on the SFQ scale scores indicated that all female subscale scores differed significantly between survivors and norms with the exception of Masturbation (Overall SFQ t = 4.29, p [is less than] .001). For males, subscale scores differed significantly between survivors and norms with the exceptions of Masturbation, Interest, and Problems (Overall SFQ t = 3.80, p [is less than] .001). As predicted, Overall SFQ was significantly higher in respondents who reported being sexually active in the past month (t = 14.74, p [is less than] .001 for males, and t = 17.71, p [is less than] .001 for females). Correlations for women between the PEPI and Overall SFQ indicated the two variables did not share a majority of variance (r = -.09, p = ns at 1 year; r = -.31, p = .01 at 6 months; and r = -.22, p = .02 at pretransplant).

Medical Outcomes and Sexual Function

Based on published research, we hypothesized a number of medical variables would demonstrate differences in Overall SFQ. In analyzing change over time in cohort 1, we found main effects for time (F = 6.83, p [is less than] .01) and gender (F = 9.00, p [is less than] .01), with males reporting higher Overall SFQ, but no interaction of gender with time. Decrease in sexual function from pretransplant to 6 months was highly significant (F = 14.36, p [is less than] .001) while decline from 6 months to 1 year was marginal (F = 3.51, p = .065). Finally, for all survivor cohorts at 1 year or longer, years since treatment was correlated with better Overall SFQ score for women, (r = .21, p [is less than] .01), but not for men (r = .01, ns). In another hypothesized outcome, male survivors who had clinically extensive cGVHD reported poorer sexual function than those who had not had cGHVD (t = 2.12, p [is less than] .05) while for females, cGVHD did not have significant effects on Overall SFQ (t = 0.45).

Women who were postmenopausal reported significantly poorer sexual function, overall and within subscales, than women who were premenopausal (Overall SFQ t = 4.633, p [is less than] .001; all subscales p [is less than] .01 except Relationship p [is less than] .05). Since both age and menopausal status were strongly related to Overall SFQ score, the poorer sexual function reported by postmenopausal women could be related primarily to age or to other factors associated with menopause. To address this question, we analyzed predictors of Overall SFQ with a stepwise multiple regression entering variables potentially associated with both menopausal status and SFQ: menopausal status, age, patient versus normative control, and whether or not a woman was on HRT. In the final model two variables entered the equation, menopausal status entered first ([R.sup.2] = .097), followed by patient versus control status ([R.sup.2] = .023) with p [is less than] .001 for the model. HRT was not associated with sexual function either in the final regression or when comparing mean SFQ for postmenopausal women on versus not on HRT.

DISCUSSION

Inconsistencies or inadequacies in measurement have impeded efforts to fully understand sexual difficulties following cancer treatment. As tested with four cohorts of cancer survivors and matched noncancer controls, the Sexual Function Questionnaire (SFQ) provides a reliable, valid, and sensitive tool for measuring self-reported difficulties and sexual activities in cancer survivor and noncancer adult populations. In testing, the measure supports hypothesized changes over time in sexual function from before to after cancer treatment, differences between genders, differences based on menopausal status, and hypothesized differences based on medical outcomes of treatment.

The rationales for such a measure include inconsistencies in measuring sexual function across diseases, across studies, and across genders as well as insufficient assessment of sexual behavior in most measures used with cancer patients. There remains a lack of clarity about who requires intervention or what areas of sexual function might be targeted with treatments. Since interventions are available that might reduce or eliminate some deficits, a standardized, reliable, and valid tool such as the one presented here could contribute to identifying sexual difficulties and facilitating treatment in cancer survivors and other chronically ill or medically treated populations.

As described in the introduction, Derogatis and Conklin-Powers (1998) define criteria for adequate assessment of sexual function. The SFQ demonstrates adequacy in 10 of the 11 areas; sensitivity to functional status has not yet been tested with the instrument. The SFQ provides multiple dimensions including an overall score plus phases of the response cycle, behaviors, problems, partner relationship, and treatment impact. Scoring allows comparable outcomes for males and females as well as for cancer patients and physically healthy adults. The self-report format is self-explanatory and thus can be sent to participants to complete at home, requiring little research time or cost. The format can be readily computerized. Respondents who do not have regular sexual partners, as well as those with homosexual orientation, can complete the form. The SFQ, while not requiring recent sexual activity, does require respondents to have been sexually active in their lifetimes so that their experience is adequate to recognize and report desire, arousal, orgasm, and satisfaction, even if to report that none of these experiences took place in the past month. Sexual activity that is reported may have taken place with or without a partner and with or without intercourse. Scores can be calculated if respondents complete 75% of the items and at least two items within each subscale. The treatment impact items are separated from the core SFQ, allowing this section to be tailored to the population of concern. The Problems subscale can be augmented with specific areas of difficulty known to occur in the population being tested, creating disease or treatment modules as has been done effectively with the most widely used cancer quality-of-life tools (Aaronson et al., 1991; Cella, 1997; Cella et al., 1993). In summary, initial testing supports the measure's potential value as an outcome measure.

Although the matched noncancer control subjects and cancer survivors reported differences in levels of sexual dysfunction, their patterns of response, reliability, and validity were quite similar across the samples. As tested, the measure had nine reliable subscales as well as two summary scores. One intended subscale, Body Image, proved unreliable (two items; [Alpha] = .52) and so was not included in the final scoring. Two other scales deviated from expectations in principal components analyses. The intended Desire subscale loaded on two factors, Interest and Desire, which are now scored separately. Masturbation items loaded on their own factor rather than with their related phases of sexual activity. Test-retest reliabilities from 6 months to 1 year supported the relative stability of the measure even during the acute recovery period for cancer survivors.

Validity testing confirmed hypothesized relationships supporting content, construct, criterion, discriminant, and confirmatory validity for overall scores and subscales. Results confirmed previously established associations in that married individuals reported overall less sexual dysfunction and males similarly reported lower mean dysfunction compared with females (Laumann et al., 1999).

From a scale development and clinical perspective, it is notable that most of the SFQ subscales are fairly strongly correlated with the Overall SFQ score. Interest, Problems, and Masturbation demonstrate the greatest independence of variance, suggesting that these dimensions fluctuate most independently from the other dimensions of sexuality. Masturbation was a relatively less frequently reported activity, but is of value to retain in measurement because it captures and helps to discriminate sexual function in those respondents who do not have sexual partners. Similarly, mutual masturbation as a behavior was infrequently engaged in, but is valuable to retain because some treatments prescribe this behavior either for improving sexual communication or for patients for whom penetration is problematic. Intercorrelations between response cycle subscales are high. However, by retaining separate evaluation of the subscale areas, it is possible to ascertain where difficulties are focused for diagnosis, treatment, and outcome determinations.

From our experience in administering these questions, we believe it is vital that the method for introducing the measure is attended to with care and standardization. Perhaps more than any other area of self-report, the administration of a sexual function assessment must assure confidentiality and must present a rationale for the responder to invest thoughtful and honest reflection while completing the form. Once we began introducing the form with a statement addressing the sensitive nature of the questions, missing data were rare. We indicated that this sensitive topic area was being assessed because cancer survivors told us this was a major area of concern of theirs. While 400 participants completed the quality-of-life assessment, an Overall SFQ score could be calculated for 391 (96%). Respondents who refused to complete the form were all female, with no consistent reason for nonresponses.

Several limitations in the data presented need to be noted. While the measure was tested and found reliable in cancer survivors and noncancer matched controls, these data do not reflect sexual function for all cancer survivors, nor can they be interpreted as a probability sample for population norms. The cancer survivor cohorts reflect primarily patients with hematological malignancy and childhood or adult survivors of blood or marrow transplantation. The age ranges of participants cluster in the 20s to 30s, with relatively fewer in the 40s to 70s. While data indicate a correlation between time since treatment and sexual function for females, with slight mean improvement over time, survivors are clustered at 1 year and 10 or more years posttreatment. This leaves unanswered questions about course of recovery between 1 and 10 years and whether these differences may be confounded by age or changes in cancer treatment that have occurred over the intervening years. Also notable, the SFQ is designed for use with homosexual as well as heterosexual adults. However, in this testing, we did not ask participants their sexual orientation; thus reliability and validity based on sexual orientation remain untested.

Finally, prospective, longitudinal data are needed to document changes over time and the factors that promote healthy adaptation to sexual changes both in cancer survivors and in noncancer normative groups. As cancer survivors increasingly advocate for their needs, more are requesting information on long term sexuality outcomes prior to selecting treatment. Breast cancer survivors who have been denied hormone replacement therapy are demanding either hormone supplements or alternative treatments for which outcome data are poor. Early diagnosis of prostate cancer is bringing sexual function outcomes to the forefront in the treatment options considered by men. Improved capability to measure sexual function and to compare across studies, treatments, and diagnoses will greatly facilitate valid comparisons between treatment outcomes and, thus, facilitate medical decision-making by cancer patients and health-care providers.

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Manuscript accepted January 24, 2000

Karen L. Syrjala, Thomas C. Schroeder, Janet R. Abrams, Tamara Z. Atkins, Wendy S. Brown, Jean E. Sanders, Mary A. Schubert, and Julia R. Heiman Fred Hutchinson Cancer Research Center and University of Washington School of Medicine

This research was supported by grants from the National Cancer Institute (CA 15704, CA18029, CA 63030, and CA78990).

Address correspondence to Karen L. Syrjala, Ph.D., FM815, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109; e-mail: [e-mail].