We conducted a randomized clinical trial among women due for a screening mammogram to test whether mammographic performance could be improved with short-term HT cessation. One in three potentially eligible women who were invited to participate, knowing that this study might improve mammography performance, refused. Very few differences distinguished women who agreed to participate versus those who refused, emphasizing that among current HT users, overall resistance to HT cessation is strong, even when there may be an immediate personal benefit.
Breast cancer is one of the greatest fears for women considering HT use 16, 17
, and this same concern prompts many women to stop HT. 18
Thus, we presumed the majority of women, particularly those taking EPT, would be willing to attempt HT cessation for one or two months on the premise that improved breast cancer screening might be achieved. We were surprised that 54% of women invited to join the study refused and that 59% of women who refused participation did so because of unwillingness to stop HT for 1–2 months, despite recruitment materials explaining that they could resume HT at any time during the study. Perhaps unwillingness to stop HT could be explained by the fact that our study was performed 1–2 years following the major WHI publications describing the risks and benefits of HT. 6, 19
Our other studies have shown the prevalence of HT use in our health plan (and other health plans) fell dramatically after the WHI publications, 3
suggesting that continued HT users are very committed, and might be described as “hard core users”. Indeed, 47% of those who agreed to participate had attempted HT cessation in the past and over 84% acknowledged taking HT for symptoms.
We noted only minor differences in the characteristics of women who refused participation based on use of ET versus EPT, and arguably any statistical differences between these groups were clinically insignificant. Women who refused participation had a lower BMI (predominantly ET) than those who agreed to participate. In addition, women who took EPT and agreed to participate had a higher risk of breast cancer (higher percentage of first degree relatives) than those who refused participation, whereas this finding was not observed among ET users. This finding might suggest that our patients have been educated regarding the Women’s Health Initiative findings and understand that the WHI results showed an increased risk for breast cancer among EPT users and not among ET users. 5, 6, 19
Symptom severity is the most common reason that women report for inability to stop HT. 20
Although the women in our study were not asked specifically if refusal to participate was due to concern for return of severe menopausal symptoms, the work of others would suggest that indeed this is commonly the case. 20, 21
Observational studies show that among women who have been on HT for over 1 year and try to quit, 25% resume HT within 6 months. 22
Ness and colleagues reported that reasons for continued HT use included severe symptoms (34%), personal preference (10%), gynecologist recommended (9%), not documented (11%) and other (3%).21
Although these studies did not specifically address reasons associated with refusal to stop HT for short durations, they suggest that women continue HT use predominantly because of intolerable symptoms, despite known risks. Most likely women who continued or started to use HT following the WHI findings have already made a personal decision that symptom-benefits outweigh risks and potentially they view their personal risks as relatively low.
Others have shown that women who have had a hysterectomy are less likely to quit ET 20
as compared to women who have not had a hysterectomy and are using EPT. Contrary to these findings, we did not find that women taking EPT were more willing to discontinue use for 1–2 months prior to mammogram as compared to those women taking ET (p=0.18), although at baseline, more women overall were taking ET (62%) as compared to women taking EPT (38%). Interestingly, it is well recognized that the characteristics of women who take ET may vary from those of women who take EPT on multiple levels. Women who have had a hysterectomy are more likely to be nonwhite, have higher BMI, lower education and income, increased rates of hypertension, diabetes, hypercholesterolemia and depression, and to be less physically active (all P<0.01). 23,24
Despite these differences, we did not find major differences between those women willing to participate based on estrogen dose or type of HT use (ET versus EPT).
Our study has several limitations. We did not collect data on symptom severity before starting HT, as a number of women had been using HT for many years so we could not fully assess symptom severity as a reason for non-participation. We also did not assess women’s understanding regarding HT risks and benefits, or to what degree they had made an informed decision whether to participate or not, based on their understanding of risks.
Several strengths of the study are noted. Despite multiple publications regarding impact of HT discontinuation on breast density and possible mammographic performance, to our knowledge, no one has investigated women’s willingness to stop HT before screening mammogram. We were careful to maintain details regarding study non-participation. Very little is known about whether a woman would be willing to stop HT for 1–2 months if she might have improved breast cancer screening as a result. Although our study did not find improved recall rates among women who stop HT for 1–2 months before mammogram, versus women who continued HT use, we did find a decrease in breast density, particularly among women who stop HT use for 2 months. 25
If a larger study were to find improved accuracy of mammogram screening with short-term HT cessation, our study is an important reminder that many women are unwilling to stop HT regardless of potential benefits. Currently, targeting HT discontinuation before mammogram to a sub-population of women does not appear feasible as most characteristics between those willing to stop HT for 1–2 months and women unwilling to stop HT varied little. However, with additional patient education regarding breast cancer risks, it is unknown whether high-risk groups (i.e. women on EPT with a first degree relative with breast cancer) might be more willing to attempt short term HT cessation prior to mammogram.