Discussions Regarding Reproductive Health for Young Women With Breast Cancer Undergoing Chemotherapy
http://www.100md.com
《临床肿瘤学》
Brown University and Rhode Island Hospital, Providence, RI
ABSTRACT
PATIENTS AND METHODS: A total of 166 premenopausal women aged ≤ 50 years were recruited from oncology offices in academic and private practices in four northeastern states, as part of a randomized controlled clinical trial aimed at stress reduction. Women were asked a variety of questions regarding diagnosis and treatment, including whether they received any counseling regarding early menopause and fertility issues.
RESULTS: Sixty-eight percent and 34% of women reported recalling a discussion with a physician regarding early menopause or fertility, respectively. In multivariate analysis, hormonal therapy and early stage of disease were associated with significantly increased odds of recall of a discussion regarding menopause. Difficulty communicating with medical team was associated with increased odds of recalling a discussion regarding fertility, whereas older age and anxiety in medical situations were associated with decreased odds.
CONCLUSION: Many women fail to recall discussions regarding the reproductive health impact of chemotherapy. Demographic, psychological, and disease-related variables are related to recalling such discussions. Counseling about premature menopause and fertility changes is an overlooked aspect of preparation for adjuvant chemotherapy in young premenopausal women with breast cancer. Future research should explore this issue further.
INTRODUCTION
While chemotherapy can improve survival for younger women, it also can cause premature menopause and infertility.10-14 Young women who undergo menopause after a cancer diagnosis appear to have poorer quality of life and health perceptions.15 Estrogen deprivation due to premature ovarian failure not only affects fertility, it also causes significant side effects such as hot flashes, osteoporosis, and sexual dysfunction.16-19 These side effects appear to be more severe in women who undergo chemotherapy-induced ovarian failure.20-23 Finally, qualitative research with breast cancer survivors has suggested fertility and menopause are important issues for young women with breast cancer treated with chemotherapy.24-27
Research exploring communication between health care professionals and patients regarding the effects of adjuvant chemotherapy has focused on patients' satisfaction, patients' understanding of the impact of chemotherapy treatment on prognosis, alternative treatments, or short-term benefits and risks of treatment.28,29,30,31 However, in order to make informed decisions regarding treatment, women should also be apprised of the potential reproductive health effects of chemotherapy. The little research concerning knowledge and discussions regarding chemotherapy-induced reproductive health changes has mostly focused on childhood cancer survivors and adult men undergoing gonadal toxic chemotherapy.32-34 Studies have suggested that young cancer survivors often do not recall counseling regarding reproductive health changes.25,35
We were interested in examining the reproductive health counseling young women receive before undergoing chemotherapy for breast cancer. Since women diagnosed with breast cancer often see a variety of physicians including oncologists, surgeons, radiologists, and primary care providers, we examined women's recall of discussions with any of these providers. In addition, we sought to explore what factors were associated with recalling a discussion regarding reproductive health counseling. We anticipated women would report low rates of fertility counseling33,34 and that younger, childless, early-stage, insured women with breast cancer would be more likely to have had these discussions, consistent with previous literature32,33 exploring sperm banking in male cancer patients.
PATIENTS AND METHODS
Women were recruited between April 1996 and November 1999 from a network of sites in Rhode Island (31 oncology practices and four hospital oncology departments), Massachusetts (two hospital oncology departments in southeastern Massachusetts), Pennsylvania (one university oncology clinic in Philadelphia), and New Jersey (two hospital oncology departments in Newark). Brown University's institutional review board approved the research protocol.
Detailed information regarding the recruitment for the main study is presented elsewhere.36 In brief, oncologists and their staff presented information regarding the study to eligible women. Women were given a brief explanation of the study as a problem-solving intervention for women newly diagnosed with breast cancer. Women who agreed to participate and provided informed consent were asked to complete a baseline telephone interview and to complete mailed questionnaires. These interviews and questionnaires included demographic information, information regarding the diagnosis and treatment of cancer, and various psychosocial scales. For the present study, only women who reported that their last menstrual period was within the previous 6 months of baseline interview date were included. For our analysis regarding fertility discussions, we further restricted our analysis to women aged 45 years or younger, as few women conceive after this age.37
Variables
Demographic information including age, racial/ethnic background, educational attainment, marital status, health insurance, income, and family characteristics were all self-reported to the interviewer over the telephone. Details of diagnosis and disease were obtained at the same baseline interview, except for stage at diagnosis, which was extracted from the patient's medical record. A three-level variable for stage was created: early stage (stage I-II), late stage (stage III), or missing (medical record abstraction not performed). Interviewers recorded the study site.
Patients were asked about side effects and reproductive health counseling as part of a series of questions regarding their medical doctors which opened with the following statement: "Now I'd like to ask you some questions about the doctors who may be involved in your treatment." They were then asked, "Keeping in mind your consultations with your doctors, were any of the following topics mentioned" These topics included the following: "possibility regarding early menopause due to treatment"; "other fertility issues associated with treatment"; "symptoms or side effects associated with treatment"; and "impact of treatment on ability to perform normal activities." Women answered yes or no to these questions. Interviewers then asked, "With which physician did you discuss this topic" and probed with "any others" to ensure all physicians that discussed the particular topic were recorded.
Measures
All participants were asked to complete several cancer-related scales for the main study including the Cancer Rehabilitation Evaluation System (CARES) for quality of life, the Mental Health Inventory (MHI-5) for emotional distress, and the Impact of Events Scale (IES) for post-traumatic stress disorder symptoms. The CARES is a validated instrument38,39 with normative CARES data on women with breast cancer,40,41 which asks women to rate the degree to which a series of problem-oriented statements apply to their own experience during the last month. The scales yield global severity ratings, which indicate the degree of distress patients generally experienced. The MHI-5 is a five-item subscale of the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) that measures emotional distress in the previous month and is well validated.42,43 The IES assesses psychological reaction to potentially distressing events, and it has been used to measure levels of distress experienced over time following a breast cancer diagnosis.44-46 These instruments were either incorporated into the telephone interview (MHI-5 and IES), or sent to patients by mail for completion (CARES). The {alpha} reliability for all instruments was high, ranging from .79 to .88.
We reasoned that issues of anxiety, avoidance, communication problems, and psychosocial distress may affect recall of medical information as well as physicians' discussions regarding treatment. Therefore, we chose to examine three subscales of the CARES, ("anxiety in medical situations," "difficulty communicating with medical team," and "psychosocial distress"), the avoidance subscale of the IES, and the MHI-5 subscale, in relation to recall of reproductive health counseling.
Analysis
We first examined recall of discussions with providers regarding potential treatment effects, and classified these discussions by provider type. We performed univariate logistic regression to examine individual factors related to reporting a discussion regarding menopause or fertility. Using multivariate logistic regression, we sought to model what factors were associated with receipt of reproductive health counseling. We included age and race, covariates that were found to be significant in the univariate analysis ≤ 0.20 level, and covariates previously identified in the literature as relevant to reproductive health counseling (age, marital status, insurance, stage of disease, and income32-34). Individuals with missing variables were excluded from the analysis. We were unable to use the variable insurance status in our modeling of fertility discussions because nearly all women who recalled a discussion regarding fertility had private insurance. The CARES subscale "difficulty communicating with medical providers" was not normally distributed and was dichotomized into those who reported any difficulty communicating (just more than half of all patients) and those who reported no difficulty.
RESULTS
All women reported seeing an oncologist and surgeon for their breast cancer diagnosis and treatment, and more than half reported seeing a radiation oncologist, obstetrician/gynecologist, or primary care physician also (58%, 57%, and 56%, respectively; Table 2). Sixty-eight percent of women reported having a discussion with at least one physician regarding the possibility of early menopause as a result of treatment. Only 34% of women reported a discussion with a provider regarding fertility. In contrast, more than 98% of women reported a discussion regarding the side effects of treatment, and 90% recalled a discussion regarding the impact of treatment on normal activities. Women most often recalled an oncologist discussing these issues.
Our univiariate logistic regression (Tables 3 and 4) revealed that the odds of recalling menopause discussions were significantly higher in women who were privately insured (odds ratio [OR], 3.24; 95% CI, 1.28 to 8.20), and reported hormones were part of treatment (OR, 2.60; 95% CI, 1.13 to 5.99). Odds were significantly lower for women of lower income (OR, 0.45; 95% CI, 0.21 to 0.97). There were no significant differences on the MHI-5, or relevant CARES or IES subscales between women who reported receiving menopausal counseling and those who did not. For discussions regarding fertility, odds were significantly higher in women who were privately insured (OR, 5.74; 95% CI, 1.24 to 26.60). Odds of fertility discussions decreased with increasing age (OR, 0.88; 95% CI, 0.81 to 0.97) and anxiety (OR, 0.65; 95% CI, 0.42 to 1.01), though the latter just missed statistical significance. There were no significant differences on other CARES subscales, the MHI-5, or the anxiety subscale of the IES.
In our multivariate logistic regression for menopause discussions (Table 5), hormonal treatment (adjusted OR, 2.99; 95% CI, 1.04 to 7.29) and early stage of disease (adjusted OR, 5.16; 95% CI, 1.13 to 20.30) were associated with significantly increased odds of recalling a discussion regarding early menopause. Two factors associated with reduced odds of recalling a discussion regarding menopause approached significance; reporting ≤ four physicians visited regarding cancer diagnosis (adjusted OR, 0.45; 95% CI, 0.19 to 1.07), and whether the woman had children (adjusted OR, 0.40; 95% CI, 0 0.14 to 1.14). For discussions regarding fertility (Table 6), difficulty communicating with the medical team (adjusted OR, 4.02; 95% CI, 1.34 to 12.14) was associated with increased odds of recalling a discussion regarding fertility, whereas increasing anxiety in medical situations (adjusted OR, 0.48; 95% CI, 0.26 to 0.88) and increasing age (adjusted OR, 0.88; 95% CI, 0.79 to 0.98) were associated with decreased odds of recalling fertility discussions. In addition, those women who saw fewer physicians (adjusted OR, 0.42; 95% CI, 0.15 to 1.15) had reduced odds of recalling a fertility discussion, although this association was not statistically significant.
DISCUSSION
Risk of menopause and infertility is directly related to the age of a woman at the time of treatment, and the chemotherapeutic agents used.6 Estimates of premature menopause in women treated with cyclophosphamide, methotrexate, and fluorouracil range from approximately 30% to 40% in women younger than 40 years, and 70% to 90% in women 40 years and older.6,10,11,47 Although women who receive doxorubicin and cyclophosphamide regimens are less likely to experience ovarian failure, between 12% and 20% of women younger than 40 years and 50% to 70% of women older than 40 years can expect to become postmenopausal within a year of treatment.47,48 However, even for women who do not immediately undergo ovarian failure, they are likely to have reduced ovarian reserve and fertility problems.13,49
The rather low rates of self-reported reproductive health counseling that we found in this study are consistent with previous research. Schover et al34 examined young male cancer survivors’ knowledge and experiences regarding cancer, infertility, and sperm banking and found that only approximately 60% of the patients recalled a discussion regarding risk of infertility, and only 51% recalled a discussion of sperm banking, before treatment. In addition, the same researchers also surveyed oncologists regarding their attitudes toward sperm banking and found that 48% offered sperm banking as an option less than a quarter of the time to never.33 Though this research is not directly applicable to issues of fertility in women, it does suggest that even in the (comparably) straightforward practice of sperm banking before gonadal toxic therapy, many physicians fail to address important fertility issues.
Sociodemographic factors associated with recall of reproductive health discussions such as age, insurance, and income are consistent with previous studies with men undergoing gonadotoxic chemotherapy. Qualitative research has suggested that younger women may be more concerned about fertility issues.25,27 Given the cost of assisted reproduction, it is perhaps understandable that these discussions would more likely be raised by wealthier, privately insured women. However, it is important to discuss these issues with all patients who are premenopausal, regardless of their income or insurance.
Disease- and treatment-related variables were associated with fertility and menopause discussions in anticipated ways, with earlier stage, hormonal treatment, and number of physicians associated with increased odds of reproductive health counseling, though not all relationships were statistically significant.
Higher levels of anxiety were associated with reduced odds of recalling discussions about fertility changes. This may be because women who have higher levels of anxiety do not recall such discussions, or that physicians are avoiding such discussions in more anxious women. Difficulty communicating with the medical team was associated with increased odds of recalling discussions regarding fertility. The reason for this difference is not entirely clear. It may be that some women raise the topic themselves, and feel resentful that their physician did not address fertility issues. In addition, some women may be dissatisfied with the information obtained.
We feel the present findings are important for several reasons. Previous research suggests that the treatment of breast cancer can have substantial psychosocial sequelae. Ganz et al15 followed a large cohort of breast cancer survivors and found that young women had the lowest social and emotional functioning scores. Treatment-related menopause was particularly problematic for the youngest women. In addition, the treatment-related sexual dysfunction women experience appears to persist over time.50,51 Mor et al52 have postulated that in younger women, changes in the ability to meet role expectations are greater, as younger women are often working fulltime, amid raising a family and caring for others. When treatment induces menopause and infertility, women may struggle with these changes in role expectation.
An important suggestion of our findings is that there may be a failure to fully inform young women of the risks and benefits of adjuvant treatment. Deciding whether to receive adjuvant chemotherapy is an important and complex process. Patients must weigh potential risks and benefits carefully, and in order to make an informed choice, need to be fully informed regarding the side effects of treatment. This surely should include the effects on reproductive health, such as early menopause and infertility. Our results also suggest that uninsured, anxious women may in particular require special attention.
There are some important limitations to the current study. We are relying on self-report of reproductive health counseling. It is possible that women simply forgot they were counseled regarding these issues. The process of cancer work-up and diagnosis occurs at a difficult time when patients may not be able to process all the information provided to them.53 There can be a disconnect between patients' recall of discussions and health care providers' recall.31,54 However, 98% of women reported having a discussion with their providers regarding the side effects of treatment, and 90% reported having a discussion with their providers regarding treatment's effects on normal activities, suggesting that women did recall at least some forms of counseling. We would be surprised if women remembered these discussions, but did not recall discussions regarding chemotherapy's impact on fertility, an issue shown to be salient for younger cancer patients.25,35 Also, our interviews were conducted on average just 3.7 weeks after the patients' first chemotherapy treatments, relatively soon after the time we might expect reproductive health discussions to take place. Finally, the factors associated with increased or decreased odds of reproductive health discussions are consistent with those in previous literature, and make empiric sense. For these many reasons, we feel that poor recall as an explanation is less likely. One might also argue that even if cursory discussions took place that women did not perceive as being related to menopause or fertility (eg, a physician asking if a woman desired more children, or if she had completed her family), such discussions would not be fully informing women of chemotherapy's reproductive health effects, and would not address symptoms or other sequelae of menopause.
Another limitation of our study is the relatively small number of women available for analysis, which hampered the precision of the estimates. Despite this limitation, our study is strengthened by the depth of information we had available on individual women, which allowed us a unique opportunity to explore how demographic, psychological, and disease-related variables are associated with reproductive health discussions.
Our sample was from three relatively small geographic areas, and hence may not be representative of all premenopausal women. Practice patterns regarding reproductive health counseling likely vary widely geographically. Physicians may be less likely to discuss these issues in places where reproductive health centers are not available or are inexperienced with cancer patients. Although the study recruited from three diverse areas, the recruitment was relatively low from New Jersey and Pennsylvania, making sub-analysis not feasible. We also lacked information on physician characteristics, which may be a major determinant of whether or not these discussions take place. These issues call attention to the need for additional research exploring physicians' and patients' knowledge, experiences, and attitudes regarding reproductive health counseling in young women receiving chemotherapy.
Some may argue that discussions regarding chemotherapy treatment's impact on fertility and menopause are premature, as not every woman will experience these side effects, or that these discussions are overwhelming to women facing a life-threatening illness. Some may argue that such discussions can cause unnecessary worry in some women. However, we feel that counseling all women regarding the impact of treatment on their reproductive health is essential from both an ethical and legal standpoint. Others have echoed the importance of adequate counseling for decisions regarding adjuvant chemotherapy.13 Although options for preserving fertility in women with breast cancer are currently somewhat limited,55-57 recent advances such as successful cryopreservation of ovarian tissue58 suggest options for these women are likely to increase and improve. In addition, a Southwest Oncology Group phase III trial (SWOG-S0230) is currently underway evaluating the use of gonadotropin-releasing hormone (GnRH) agonists during chemotherapy to prevent ovarian failure. In order to consider these options, a woman must be informed of changes in fertility and menopause before treatment is initiated. Given the importance of these issues to young women with breast cancer,15,59 we feel this is an important area that calls for future study and intervention.
Authors' Disclosures of Potential Conflicts of Interest
NOTES
Supported in part by a grant from the National Cancer Institute, Grant No. CA64703.
Authors' disclosures of potential conflicts of interest are found at the end of this article.
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25. Thewes B, Meiser B, Rickard J, et al: The fertility- and menopause-related information needs of younger women with a diagnosis of breast cancer: A qualitative study. Psychooncology 12:500-511, 2003
26. Dow KH, Ferrell BR, Haberman MR, et al: The meaning of quality of life in cancer survivorship. Oncol Nurs Forum 26:519-528, 1999
27. Avis NE, Crawford S, Manuel J: Psychosocial problems among younger women with breast cancer. Psychooncology 13:295-308, 2004
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ABSTRACT
PATIENTS AND METHODS: A total of 166 premenopausal women aged ≤ 50 years were recruited from oncology offices in academic and private practices in four northeastern states, as part of a randomized controlled clinical trial aimed at stress reduction. Women were asked a variety of questions regarding diagnosis and treatment, including whether they received any counseling regarding early menopause and fertility issues.
RESULTS: Sixty-eight percent and 34% of women reported recalling a discussion with a physician regarding early menopause or fertility, respectively. In multivariate analysis, hormonal therapy and early stage of disease were associated with significantly increased odds of recall of a discussion regarding menopause. Difficulty communicating with medical team was associated with increased odds of recalling a discussion regarding fertility, whereas older age and anxiety in medical situations were associated with decreased odds.
CONCLUSION: Many women fail to recall discussions regarding the reproductive health impact of chemotherapy. Demographic, psychological, and disease-related variables are related to recalling such discussions. Counseling about premature menopause and fertility changes is an overlooked aspect of preparation for adjuvant chemotherapy in young premenopausal women with breast cancer. Future research should explore this issue further.
INTRODUCTION
While chemotherapy can improve survival for younger women, it also can cause premature menopause and infertility.10-14 Young women who undergo menopause after a cancer diagnosis appear to have poorer quality of life and health perceptions.15 Estrogen deprivation due to premature ovarian failure not only affects fertility, it also causes significant side effects such as hot flashes, osteoporosis, and sexual dysfunction.16-19 These side effects appear to be more severe in women who undergo chemotherapy-induced ovarian failure.20-23 Finally, qualitative research with breast cancer survivors has suggested fertility and menopause are important issues for young women with breast cancer treated with chemotherapy.24-27
Research exploring communication between health care professionals and patients regarding the effects of adjuvant chemotherapy has focused on patients' satisfaction, patients' understanding of the impact of chemotherapy treatment on prognosis, alternative treatments, or short-term benefits and risks of treatment.28,29,30,31 However, in order to make informed decisions regarding treatment, women should also be apprised of the potential reproductive health effects of chemotherapy. The little research concerning knowledge and discussions regarding chemotherapy-induced reproductive health changes has mostly focused on childhood cancer survivors and adult men undergoing gonadal toxic chemotherapy.32-34 Studies have suggested that young cancer survivors often do not recall counseling regarding reproductive health changes.25,35
We were interested in examining the reproductive health counseling young women receive before undergoing chemotherapy for breast cancer. Since women diagnosed with breast cancer often see a variety of physicians including oncologists, surgeons, radiologists, and primary care providers, we examined women's recall of discussions with any of these providers. In addition, we sought to explore what factors were associated with recalling a discussion regarding reproductive health counseling. We anticipated women would report low rates of fertility counseling33,34 and that younger, childless, early-stage, insured women with breast cancer would be more likely to have had these discussions, consistent with previous literature32,33 exploring sperm banking in male cancer patients.
PATIENTS AND METHODS
Women were recruited between April 1996 and November 1999 from a network of sites in Rhode Island (31 oncology practices and four hospital oncology departments), Massachusetts (two hospital oncology departments in southeastern Massachusetts), Pennsylvania (one university oncology clinic in Philadelphia), and New Jersey (two hospital oncology departments in Newark). Brown University's institutional review board approved the research protocol.
Detailed information regarding the recruitment for the main study is presented elsewhere.36 In brief, oncologists and their staff presented information regarding the study to eligible women. Women were given a brief explanation of the study as a problem-solving intervention for women newly diagnosed with breast cancer. Women who agreed to participate and provided informed consent were asked to complete a baseline telephone interview and to complete mailed questionnaires. These interviews and questionnaires included demographic information, information regarding the diagnosis and treatment of cancer, and various psychosocial scales. For the present study, only women who reported that their last menstrual period was within the previous 6 months of baseline interview date were included. For our analysis regarding fertility discussions, we further restricted our analysis to women aged 45 years or younger, as few women conceive after this age.37
Variables
Demographic information including age, racial/ethnic background, educational attainment, marital status, health insurance, income, and family characteristics were all self-reported to the interviewer over the telephone. Details of diagnosis and disease were obtained at the same baseline interview, except for stage at diagnosis, which was extracted from the patient's medical record. A three-level variable for stage was created: early stage (stage I-II), late stage (stage III), or missing (medical record abstraction not performed). Interviewers recorded the study site.
Patients were asked about side effects and reproductive health counseling as part of a series of questions regarding their medical doctors which opened with the following statement: "Now I'd like to ask you some questions about the doctors who may be involved in your treatment." They were then asked, "Keeping in mind your consultations with your doctors, were any of the following topics mentioned" These topics included the following: "possibility regarding early menopause due to treatment"; "other fertility issues associated with treatment"; "symptoms or side effects associated with treatment"; and "impact of treatment on ability to perform normal activities." Women answered yes or no to these questions. Interviewers then asked, "With which physician did you discuss this topic" and probed with "any others" to ensure all physicians that discussed the particular topic were recorded.
Measures
All participants were asked to complete several cancer-related scales for the main study including the Cancer Rehabilitation Evaluation System (CARES) for quality of life, the Mental Health Inventory (MHI-5) for emotional distress, and the Impact of Events Scale (IES) for post-traumatic stress disorder symptoms. The CARES is a validated instrument38,39 with normative CARES data on women with breast cancer,40,41 which asks women to rate the degree to which a series of problem-oriented statements apply to their own experience during the last month. The scales yield global severity ratings, which indicate the degree of distress patients generally experienced. The MHI-5 is a five-item subscale of the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) that measures emotional distress in the previous month and is well validated.42,43 The IES assesses psychological reaction to potentially distressing events, and it has been used to measure levels of distress experienced over time following a breast cancer diagnosis.44-46 These instruments were either incorporated into the telephone interview (MHI-5 and IES), or sent to patients by mail for completion (CARES). The {alpha} reliability for all instruments was high, ranging from .79 to .88.
We reasoned that issues of anxiety, avoidance, communication problems, and psychosocial distress may affect recall of medical information as well as physicians' discussions regarding treatment. Therefore, we chose to examine three subscales of the CARES, ("anxiety in medical situations," "difficulty communicating with medical team," and "psychosocial distress"), the avoidance subscale of the IES, and the MHI-5 subscale, in relation to recall of reproductive health counseling.
Analysis
We first examined recall of discussions with providers regarding potential treatment effects, and classified these discussions by provider type. We performed univariate logistic regression to examine individual factors related to reporting a discussion regarding menopause or fertility. Using multivariate logistic regression, we sought to model what factors were associated with receipt of reproductive health counseling. We included age and race, covariates that were found to be significant in the univariate analysis ≤ 0.20 level, and covariates previously identified in the literature as relevant to reproductive health counseling (age, marital status, insurance, stage of disease, and income32-34). Individuals with missing variables were excluded from the analysis. We were unable to use the variable insurance status in our modeling of fertility discussions because nearly all women who recalled a discussion regarding fertility had private insurance. The CARES subscale "difficulty communicating with medical providers" was not normally distributed and was dichotomized into those who reported any difficulty communicating (just more than half of all patients) and those who reported no difficulty.
RESULTS
All women reported seeing an oncologist and surgeon for their breast cancer diagnosis and treatment, and more than half reported seeing a radiation oncologist, obstetrician/gynecologist, or primary care physician also (58%, 57%, and 56%, respectively; Table 2). Sixty-eight percent of women reported having a discussion with at least one physician regarding the possibility of early menopause as a result of treatment. Only 34% of women reported a discussion with a provider regarding fertility. In contrast, more than 98% of women reported a discussion regarding the side effects of treatment, and 90% recalled a discussion regarding the impact of treatment on normal activities. Women most often recalled an oncologist discussing these issues.
Our univiariate logistic regression (Tables 3 and 4) revealed that the odds of recalling menopause discussions were significantly higher in women who were privately insured (odds ratio [OR], 3.24; 95% CI, 1.28 to 8.20), and reported hormones were part of treatment (OR, 2.60; 95% CI, 1.13 to 5.99). Odds were significantly lower for women of lower income (OR, 0.45; 95% CI, 0.21 to 0.97). There were no significant differences on the MHI-5, or relevant CARES or IES subscales between women who reported receiving menopausal counseling and those who did not. For discussions regarding fertility, odds were significantly higher in women who were privately insured (OR, 5.74; 95% CI, 1.24 to 26.60). Odds of fertility discussions decreased with increasing age (OR, 0.88; 95% CI, 0.81 to 0.97) and anxiety (OR, 0.65; 95% CI, 0.42 to 1.01), though the latter just missed statistical significance. There were no significant differences on other CARES subscales, the MHI-5, or the anxiety subscale of the IES.
In our multivariate logistic regression for menopause discussions (Table 5), hormonal treatment (adjusted OR, 2.99; 95% CI, 1.04 to 7.29) and early stage of disease (adjusted OR, 5.16; 95% CI, 1.13 to 20.30) were associated with significantly increased odds of recalling a discussion regarding early menopause. Two factors associated with reduced odds of recalling a discussion regarding menopause approached significance; reporting ≤ four physicians visited regarding cancer diagnosis (adjusted OR, 0.45; 95% CI, 0.19 to 1.07), and whether the woman had children (adjusted OR, 0.40; 95% CI, 0 0.14 to 1.14). For discussions regarding fertility (Table 6), difficulty communicating with the medical team (adjusted OR, 4.02; 95% CI, 1.34 to 12.14) was associated with increased odds of recalling a discussion regarding fertility, whereas increasing anxiety in medical situations (adjusted OR, 0.48; 95% CI, 0.26 to 0.88) and increasing age (adjusted OR, 0.88; 95% CI, 0.79 to 0.98) were associated with decreased odds of recalling fertility discussions. In addition, those women who saw fewer physicians (adjusted OR, 0.42; 95% CI, 0.15 to 1.15) had reduced odds of recalling a fertility discussion, although this association was not statistically significant.
DISCUSSION
Risk of menopause and infertility is directly related to the age of a woman at the time of treatment, and the chemotherapeutic agents used.6 Estimates of premature menopause in women treated with cyclophosphamide, methotrexate, and fluorouracil range from approximately 30% to 40% in women younger than 40 years, and 70% to 90% in women 40 years and older.6,10,11,47 Although women who receive doxorubicin and cyclophosphamide regimens are less likely to experience ovarian failure, between 12% and 20% of women younger than 40 years and 50% to 70% of women older than 40 years can expect to become postmenopausal within a year of treatment.47,48 However, even for women who do not immediately undergo ovarian failure, they are likely to have reduced ovarian reserve and fertility problems.13,49
The rather low rates of self-reported reproductive health counseling that we found in this study are consistent with previous research. Schover et al34 examined young male cancer survivors’ knowledge and experiences regarding cancer, infertility, and sperm banking and found that only approximately 60% of the patients recalled a discussion regarding risk of infertility, and only 51% recalled a discussion of sperm banking, before treatment. In addition, the same researchers also surveyed oncologists regarding their attitudes toward sperm banking and found that 48% offered sperm banking as an option less than a quarter of the time to never.33 Though this research is not directly applicable to issues of fertility in women, it does suggest that even in the (comparably) straightforward practice of sperm banking before gonadal toxic therapy, many physicians fail to address important fertility issues.
Sociodemographic factors associated with recall of reproductive health discussions such as age, insurance, and income are consistent with previous studies with men undergoing gonadotoxic chemotherapy. Qualitative research has suggested that younger women may be more concerned about fertility issues.25,27 Given the cost of assisted reproduction, it is perhaps understandable that these discussions would more likely be raised by wealthier, privately insured women. However, it is important to discuss these issues with all patients who are premenopausal, regardless of their income or insurance.
Disease- and treatment-related variables were associated with fertility and menopause discussions in anticipated ways, with earlier stage, hormonal treatment, and number of physicians associated with increased odds of reproductive health counseling, though not all relationships were statistically significant.
Higher levels of anxiety were associated with reduced odds of recalling discussions about fertility changes. This may be because women who have higher levels of anxiety do not recall such discussions, or that physicians are avoiding such discussions in more anxious women. Difficulty communicating with the medical team was associated with increased odds of recalling discussions regarding fertility. The reason for this difference is not entirely clear. It may be that some women raise the topic themselves, and feel resentful that their physician did not address fertility issues. In addition, some women may be dissatisfied with the information obtained.
We feel the present findings are important for several reasons. Previous research suggests that the treatment of breast cancer can have substantial psychosocial sequelae. Ganz et al15 followed a large cohort of breast cancer survivors and found that young women had the lowest social and emotional functioning scores. Treatment-related menopause was particularly problematic for the youngest women. In addition, the treatment-related sexual dysfunction women experience appears to persist over time.50,51 Mor et al52 have postulated that in younger women, changes in the ability to meet role expectations are greater, as younger women are often working fulltime, amid raising a family and caring for others. When treatment induces menopause and infertility, women may struggle with these changes in role expectation.
An important suggestion of our findings is that there may be a failure to fully inform young women of the risks and benefits of adjuvant treatment. Deciding whether to receive adjuvant chemotherapy is an important and complex process. Patients must weigh potential risks and benefits carefully, and in order to make an informed choice, need to be fully informed regarding the side effects of treatment. This surely should include the effects on reproductive health, such as early menopause and infertility. Our results also suggest that uninsured, anxious women may in particular require special attention.
There are some important limitations to the current study. We are relying on self-report of reproductive health counseling. It is possible that women simply forgot they were counseled regarding these issues. The process of cancer work-up and diagnosis occurs at a difficult time when patients may not be able to process all the information provided to them.53 There can be a disconnect between patients' recall of discussions and health care providers' recall.31,54 However, 98% of women reported having a discussion with their providers regarding the side effects of treatment, and 90% reported having a discussion with their providers regarding treatment's effects on normal activities, suggesting that women did recall at least some forms of counseling. We would be surprised if women remembered these discussions, but did not recall discussions regarding chemotherapy's impact on fertility, an issue shown to be salient for younger cancer patients.25,35 Also, our interviews were conducted on average just 3.7 weeks after the patients' first chemotherapy treatments, relatively soon after the time we might expect reproductive health discussions to take place. Finally, the factors associated with increased or decreased odds of reproductive health discussions are consistent with those in previous literature, and make empiric sense. For these many reasons, we feel that poor recall as an explanation is less likely. One might also argue that even if cursory discussions took place that women did not perceive as being related to menopause or fertility (eg, a physician asking if a woman desired more children, or if she had completed her family), such discussions would not be fully informing women of chemotherapy's reproductive health effects, and would not address symptoms or other sequelae of menopause.
Another limitation of our study is the relatively small number of women available for analysis, which hampered the precision of the estimates. Despite this limitation, our study is strengthened by the depth of information we had available on individual women, which allowed us a unique opportunity to explore how demographic, psychological, and disease-related variables are associated with reproductive health discussions.
Our sample was from three relatively small geographic areas, and hence may not be representative of all premenopausal women. Practice patterns regarding reproductive health counseling likely vary widely geographically. Physicians may be less likely to discuss these issues in places where reproductive health centers are not available or are inexperienced with cancer patients. Although the study recruited from three diverse areas, the recruitment was relatively low from New Jersey and Pennsylvania, making sub-analysis not feasible. We also lacked information on physician characteristics, which may be a major determinant of whether or not these discussions take place. These issues call attention to the need for additional research exploring physicians' and patients' knowledge, experiences, and attitudes regarding reproductive health counseling in young women receiving chemotherapy.
Some may argue that discussions regarding chemotherapy treatment's impact on fertility and menopause are premature, as not every woman will experience these side effects, or that these discussions are overwhelming to women facing a life-threatening illness. Some may argue that such discussions can cause unnecessary worry in some women. However, we feel that counseling all women regarding the impact of treatment on their reproductive health is essential from both an ethical and legal standpoint. Others have echoed the importance of adequate counseling for decisions regarding adjuvant chemotherapy.13 Although options for preserving fertility in women with breast cancer are currently somewhat limited,55-57 recent advances such as successful cryopreservation of ovarian tissue58 suggest options for these women are likely to increase and improve. In addition, a Southwest Oncology Group phase III trial (SWOG-S0230) is currently underway evaluating the use of gonadotropin-releasing hormone (GnRH) agonists during chemotherapy to prevent ovarian failure. In order to consider these options, a woman must be informed of changes in fertility and menopause before treatment is initiated. Given the importance of these issues to young women with breast cancer,15,59 we feel this is an important area that calls for future study and intervention.
Authors' Disclosures of Potential Conflicts of Interest
NOTES
Supported in part by a grant from the National Cancer Institute, Grant No. CA64703.
Authors' disclosures of potential conflicts of interest are found at the end of this article.
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