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© 1999 American Society for Clinical Oncology Effect of Tamoxifen on Sexual Functioning in Patients With Breast CancerFrom 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
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.
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
Center for Epidemiologic Studies–Depression Scale
Sexual History Form
Breast Cancer Prevention Trial Symptom Checklist
Gynecologic Status
Statistical Methodology
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.
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.
This trial was undertaken as a pilot study to determine whether women on tamoxifen experience specific problems in sexual functioning that may be induced by treatment. Although the numbers are small, the data are provocative. The frequency of intercourse reported in this series is similar to the levels reported by Frank et al16 in a younger population. In comparing our patients with norms established in participants in the NSABP BCPT, it seems that sexual desire, arousal, and the ability achieve orgasm were unaffected in our breast cancer population. Using the end points of emotional distress, body image, sexual satisfaction, and survival, significant differences have not been found between women treated with breast-conserving therapy and women treated with modified radical mastectomy. The available data suggest that the disfiguring surgery is not a major obstruction to the emotional adjustment of women with localized breast cancers.20-23 The 54% incidence of dyspareunia reported seems higher than one might predict in this age group and may reflect a toxicity of adjuvant therapy. Lindley et al24 evaluated the quality of life in breast cancer survivors within 2 to 5 years of treatment with adjuvant therapy. Most of the 86 patients (65%) received chemotherapy, 38% also received tamoxifen, and 36% were treated with tamoxifen alone. Only 11% of the patients reported pain or difficulty with intercourse before adjuvant therapy, compared with 44% after adjuvant therapy. Likewise, the incidence of vaginal dryness increased from 19% to 54%. Changes in sexual functioning were more common in women who became menopausal with adjuvant therapy.20 Schover et al25 addressed psychosocial adjustment, body image, and sexuality in women treated with either breast-conserving therapy or mastectomy and immediate reconstruction. Surgical treatment of the primary tumor had no effect on sexual functioning. However, the women who received adjuvant chemotherapy reported a higher incidence of sexual dysfunction (vaginal dryness, dyspareunia, and decreased libido) than the women who received either adjuvant tamoxifen or no additional systemic therapy. The incidence of sexual dysfunction in women treated with tamoxifen was similar to that of patients who received no systemic therapy. Chemotherapy may affect sexual function by producing vaginal mucositis or by inducing menopause. In our series, adjuvant chemotherapy did not predict sexual dysfunction. Dyspareunia was reported in 13 of 23 women who received chemotherapy (57%) and seven of 18 women who did not receive chemotherapy (39%) (P = .26). Table 2 lists commonly reported symptoms from three series, all of which used the BCPT Symptom Checklist. The baseline data on NSABP P-01 was obtained on a population of women at high risk for the development of breast cancer, none of whom was taking hormone therapy. Their median age of 52 years is comparable with the median age of 53 years in our series. The incidence of hot flushes, forgetfulness, and early wakening was significantly more common in our patients.2 Women in the breast cancer survivor series were older (median, 57 years), 80% were postmenopausal, and all had been treated for breast cancer. The majority of them (56%) had received tamoxifen, and 38% had been treated with chemotherapy. Compared with the women in our series, the breast cancer survivors were more likely to complain of muscle stiffness and breast sensitivity and to express dissatisfaction with their bodily appearance.1 Our patients, all of whom were on tamoxifen, noted hot flushes more often. The association of tamoxifen with dyspareunia is suggested by our data. The frequency with which participants desired sex was similar to the frequency of having sex. Despite this, women reported a significant incidence of "negative feelings" during intercourse (P = .02). If dyspareunia persists, these negative feelings may lead to avoidance of sexual relations. A decrease in frequency of intercourse was not seen in our participants, which raises the possibility that the dyspareunia was a recent development. The mechanism of action and the toxicities of tamoxifen in premenopausal women may differ from those in postmenopausal women. After menopause, tamoxifen has been shown to increase bone density and decrease serum cholesterol levels. These effects and the increased incidence of uterine cancer in women treated with tamoxifen are indicative of tamoxifen's estrogen effects.4-11 In contrast, tamoxifen seems to act as an antiestrogen in premenopausal women, who have been shown to lose bone density and who demonstrate no significant change in serum cholesterol.26 In our trial, we found an inverse correlation between age and estrogen effect on the vagina, although this did not achieve statistical significance (P = .054). This raises the possibility that tamoxifen may have estrogen agonist effects on the vagina of postmenopausal women and antagonist effects on younger women. The results of this pilot study indicate that women with breast cancer treated with tamoxifen experience symptoms of sexual dysfunction. Clearly, other factors, such as the cancer diagnosis and chemotherapy, may contribute to these symptoms, and these have not been systematically addressed. The individual contributions of chemotherapy and tamoxifen to sexual dysfunction warrant further investigation. A prospective assessment of sexual functioning that includes evaluation of physiologic status (eg, vaginal mucosa and hormone levels) before and after institution of systemic therapy is warranted.
1. Ganz PA, Day R, Ware JE, et al: Base-line quality of life assessment in the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial. J Natl Cancer Inst 87:1372-1382, 1995 2. Ganz PA, Rowland JH, Desmond K, et al: Life after breast cancer: Understanding women's health-related quality of life and sexual functioning. J Clin Oncol 16:501-514, 1998[Abstract] 3. Fisher B, Costantino J, Redmond C, et al: A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med 320:479-487, 1989[Abstract] 4. Love RR, Mazess RB, Barden HS, et al: Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 326:852-856, 1992[Abstract]
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Chang J, Powles TJ, Ashley SE, et al: The effect of tamoxifen and hormone replacement therapy on serum cholesterol, bone mineral density and coagulation factors in healthy postmenopausal women participating in a randomized, controlled tamoxifen prevention study. Ann Oncol 7:671-675, 1996 6. Love RR, Wiebe DA, Newcomb PA, et al: Effects of tamoxifen on cardiovascular risk factors in postmenopausal women. Ann Intern Med 115:860-864, 1991
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Love RR, Wiebe DA, Feyzi JM, et al: Effects of tamoxifen on cardiovascular risk factors in postmenopausal women after 5 years of treatment. J Natl Cancer Inst 86:1534-1539, 1994
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Rutqvist LE, Anders Museum for the Stockholm Breast Cancer Study Group: Cardiac and thromboembolic morbidity among postmenopausal women with early-stage breast cancer in a randomized trial of adjuvant tamoxifen. J Natl Cancer Inst 85:1398-1406, 1993
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Costantino JP, Kuller LH, Ives DG, et al: Coronary heart disease mortality and adjuvant tamoxifen therapy. J Natl Cancer Inst 89:776-821, 1997
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Fisher B, Costantino JP, Redmond CK, et al: Endometrial cancer in tamoxifen-treated breast cancer patients: Findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst 86:527-537, 1994 11. Jordan VC, Morrow M: Should clinicians be concerned about the carcinogenic potential of tamoxifen? Eur J Cancer 30A:1714-1721, 1994 12. Boccardo F, Bruzzi A, Rubagtti G, et al: Estrogen-like action of tamoxifen on vaginal epithelium in breast cancer patients. Oncology 38:281-285, 1981[Medline] 13. Ferrazzi E, Cartei G, Mattarazzo R, et al: Oestrogen-like effect of tamoxifen on vaginal epithelium. BMJ 1:1351-1352, 1977 14. Leiblum S, Bachmann G, Kemmann E, et al: Vaginal atrophy in the postmenopausal woman. JAMA 249:2195-2198, 1983[Abstract] 15. Semmens JP, Wagner G: Estrogen deprivation and vaginal function in postmenopausal women. JAMA 248:445-448, 1982[Abstract] 16. Frank E, Anderson C, Rubinstein D: Frequency of sexual dysfunction in "normal" couples. N Engl J Med 299:111-115, 1978[Abstract] 17. Radloff LF: The CES-D Scale: A self-report depression scale for research in the general population. Appl Psychol Meas 1:385-401, 1977 18. Rodin G, Craven J, Littlefield C: Depression in the Medically Ill. New York, NY, Brunner/Mazel Publishers, 1991 19. Schover LR, Jensen SB: Sexuality and Chronic Illness: A Comprehensive Approach. New York, NY, Guilford Publications, 1988, p 59 20. Bloom JR, Cook M, Fotopoulis S, et al: Psychological response to mastectomy. Cancer 59:189-196, 1987[Medline] 21. Wolberg WH, Romsaas EP, Tanner MA, et al: Psychosexual adaptation to breast cancer surgery. Cancer 63:1645-1655, 1989[Medline] 22. Schain WS, d'Angelo TM Dunn ME, et al: Mastectomy versus conservative surgery and radiation therapy. Cancer 73:1221-1228, 1994[Medline]
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Omne-Pontén M, Sjödén PO: Psychosocial adjustment among women with breast cancer stages I and II: Six-year follow-up of consecutive patients. J Clin Oncol 12:1778-1782, 1994
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Lindley C, Vasa S, Sawyer WT: Quality of life and preferences for treatment following systemic adjuvant therapy for early-stage breast cancer. J Clin Oncol 16:1380-1387, 1998 25. Schover LR, Yetman RJ, Tuason LJ, et al: Partial mastectomy and breast reconstruction: A comparison of their effects on psychosocial adjustment, body image, and sexuality. Cancer 75:54-64, 1995[Medline] 26. Powles TJ, Hickish T, Kanis JA, et al: Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol 14:78-84, 1996[Abstract] Submitted August 26, 1998; accepted January 6, 1999. This article has been cited by other articles:
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Copyright © 1999 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
