- © 1999 by American Society of Clinical Oncology
Effect of Tamoxifen on Sexual Functioning in Patients With Breast Cancer
- From the Department of Medicine, Division of Medical Oncology, and Departments of Pathology, Statistics, and Health Psychology, Washington University, St. Louis, MO; and Department of Psychiatry and the Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC.
- Address reprint requests to Joanne Mortimer, MD, Washington University, Box 8056, 660 S Euclid Ave, St. Louis, MO 63110; email joanne{at}visar.wustl.edu
Abstract
PURPOSE: To define the incidence of sexual dysfunction in a population of women with breast cancer treated with tamoxifen.
PATIENTS AND METHODS: Breast cancer patients with a performance status of 0 to 2 who had been treated with tamoxifen for 2 to 24 months completed the following measures: the Center for Epidemiologic Studies–depression Scale, the Sexual History Form, and the Breast Cancer Prevention Trial Symptom Checklist. Forty-nine of the participants underwent gynecologic examinations with vaginal smears for determination of estrogen effect.
RESULTS: Fifty-seven women were entered onto the trial. Sexual desire, arousal, and ability to achieve orgasm were comparable to norms established in participants in the Tamoxifen Prevention Trial (National Surgical Adjuvant Breast and Bowel Project P-01). Pain, burning, or discomfort with intercourse was reported in 54% of patients and did not correlate with age, surgical treatment of the primary cancer, or chemotherapy. Estrogen effect was seen on the vaginal smears of 34 of 49 participants and was more common in older patients (P = .054). The presence of estrogen effect correlated with negative reactions during sex (P = .02) and vaginal dryness or tightness (P = .046).
CONCLUSION: Women treated with tamoxifen in the adjuvant setting experienced symptoms of sexual dysfunction. The individual contributions of chemotherapy and tamoxifen to sexual dysfunction warrant prospective study.
BY EXPANDING THE indications for systemic therapy, the survival of women with early-stage breast cancer has improved. However, the number of individuals at risk for chronic toxicities from such treatment has also increased. Because the majority of women diagnosed with breast cancer can be expected to be cured or to live for long periods with their disease, the impact of treatment on quality of life is extremely important. Although sexual functioning has often been overlooked as a component of the cancer survivor's quality of life, most women treated for breast cancer are still sexually active.1,2
Worldwide, tamoxifen is the most commonly prescribed antineoplastic agent. The acute toxicities of hot flushes and night sweats suggest that tamoxifen produces symptoms of the climacteric.3 Yet the drug is recognized for its estrogen agonist effects on bone, uterus, and cardiovascular status.4-11 It is unclear whether tamoxifen has a favorable or adverse effect on sexual functioning. Vaginal smears obtained before and after institution of tamoxifen indicate that the drug has estrogen agonist effects on the vaginal mucosa.12,13 After menopause, a decrease in vaginal lubrication has been attributed to lack of estrogen, and the resulting vaginal dryness produces dyspareunia.14-16 If tamoxifen has estrogen agonist effects on the vaginal mucosa, sexual functioning may be unaffected or improved in women treated with the drug. Because little research had examined this issue, the present study sought to determine whether women on tamoxifen experience symptoms of sexual dysfunction. Issues of sexual desire and functioning were addressed through questionnaires. In addition, vaginal smears were obtained to determine whether tamoxifen produced estrogenic effects on the mucosa. Findings on vaginal smears were then correlated with symptoms of sexual dysfunction.
PATIENTS AND METHODS
Subjects for this study were drawn from the practices of oncologists at two university-based medical centers, Washington University, St Louis, MO, and Georgetown University, Washington, DC. Any woman with a diagnosis of breast cancer was considered eligible provided that she had been treated with tamoxifen for 2 to 24 months and had a performance status of 0 to 2. Women who were actively being treated with chemotherapy or were taking estrogenic hormones were excluded. All participants signed a consent form.
Participants were asked to complete four separate questionnaires: a demographic and medical history form, a depression scale, a sexual history form, and a symptom checklist, each of which is described briefly below.
Medical History Form
In addition to collecting demographic data, this form consisted of 13 questions that addressed the woman's previous breast cancer history, methods of birth control, and concurrent illness and medications.
Center for Epidemiologic Studies–depression Scale
The Center for Epidemiologic Studies–depression Scale is a 20-item, self-report scale that was originally developed to measure depressive symptoms in the general population and has been used to screen for depression in samples of medically ill individuals. Responses on are rated on a four-point scale, and the total score ranges from zero to 60. Scores of 16 or higher are indicators of clinical depression.17,18
Sexual History Form
The Sexual History Form is a 31-item, multiple-choice questionnaire that addresses sexual behavior, frequency, and satisfaction. The questionnaire, developed by Lopiccolo and Schover, has been published with normative data from community couples.19
Breast Cancer Prevention Trial Symptom Checklist
The Breast Cancer Prevention Trial (BCPT) Symptom Checklist is a 43-item list of commonly reported physical and psychologic symptoms (eg, nausea, joint pain, excitability, and short temper) as well as symptoms associated with the climacteric (eg, hot flushes, forgetfulness, and vaginal dryness) and tamoxifen. The checklist was originally designed for use in the large-scale National Surgical Adjuvant Breast and Bowel Project (NSABP) BCPT.1 For the present study, the women were asked to indicate the extent to which they were bothered by a given symptom during the preceding 4 weeks, with responses ranging from 0 (not at all) to 4 (extremely).
Gynecologic Status
Participants from Washington University also underwent complete pelvic examinations, and vaginal smears were obtained to determine estrogen effect by karyopyknotic index. Vaginal smears were reviewed by a single pathologist (L.B.). The predominant appearance of superficial squamous and glandular cells defined the maturation index.
Statistical Methodology
Group differences in age were tested with an independent-samples t test. Group differences for items on the Sexual History Form, which were scored on ordinal scales, were tested with Wilcoxon tests, whereas nominally scaled items (such as yes/no) were tested with Fisher's exact test. All analyses were done with SAS software (SAS Institute, Inc, Cary, NC).
RESULTS
Fifty-seven women who met the entry criteria completed the required questionnaires. At the Barnard Cancer Center at Washington University, 52 consecutive women on tamoxifen who were seen in routine follow-up were asked to participate in this trial. Two women declined participation. An additional seven eligible participants were recruited from the Lombardi Cancer Center at Georgetown University. The median age for all participants was 53 years (range, 36 to 84 years). Mastectomy had been performed in 36 patients and was bilateral in two patients. Twenty-one women underwent breast-conserving surgery and radiation therapy. The median duration of tamoxifen use was 12 months (range, 2 to 24 months). Thirty women had received chemotherapy in the past. Forty-one women were in partnered relationships. The majority of the women (91%) were postmenopausal.
In Table 1, sexual functioning is broken down according to the three phases of sexual response: desire, arousal, and orgasm. Forty-one women were sexually active. Our data are compared with data obtained at baseline from women participating in the BCPT. Overall, the women in our sample reported levels of sexual function that were the same or better than those reported by a comparable group of women entering the chemoprevention trial. However, 22 respondents (54%) complained of pain, burning, or discomfort with intercourse. Thirteen respondents (32%) noted vaginal tightness more than 50% of the time, and 27 respondents (66%) routinely used a vaginal lubricant with intercourse.
Comparison of Sexual Function Between Current Series and BCPT Baseline Data
Information on gynecologic examinations was available for 49 of the 50 women from Washington University. Estrogen effect as reflected in a high maturation index was evident on the vaginal cells of 34 women and was absent in 15 women. The women in whom estrogen effect was seen tended to be older. The median age for patients with estrogen effect was 54.5 years, compared with 49 years for patients without estrogen effect (P = .054). Seventy-six percent of the 49 participants for whom vaginal smears were performed were sexually active. The presence of estrogen effect in these women was associated with negative reactions during sex (P = .02) and vaginal dryness or tightness (P = .046). Estrogen effect was not associated with the duration of tamoxifen, the type of breast cancer surgery, the frequency of intercourse, desire, the ability to be aroused, or the ability to achieve orgasm.
The most common symptoms reported on the BCPT Symptom Checklist are listed in Table 2 and compared with data generated by Ganz et al2 in a population of breast cancer survivors, 47% of whom were on tamoxifen. hot flushes and night sweats were more frequent complaints in our sample than in the survivor sample of Ganz et al. However, it is noted that the frequency of hot flushes in their 50- to 59-year-old group was 78%, similar to that seen here. The lower incidence of physical complaints (eg, general aches, joint pain, muscle stiffness) seen in the present study likely reflects the younger age of our sample compared with that of Ganz et al, in which two thirds of the women were age 50 or older.
Most Frequently Reported Symptoms, Current Series Compared with Breast Cancer Survivors (BCS) and Healthy Women at Risk for Breast Cancer (BCPT)