Hormone replacement therapy in postmenopausal women: utilization of health care resources by new users

Transcription

1 Hormone replacement therapy in postmenopausal women: utilization of health care resources by new users John M. Thorp Jr, MD, a Norma I. Gavin, PhD, b and Robert L. Ohsfeldt, PhD, c Chapel Hill, NC, and Indianapolis, Ind OBJECTIVE: To determine health care resource use by new postmenopausal users of hormone replacement therapy. METHOD: We used the Saskatchewan Health administrative databases, which include a health insurance registration file, a cancer registry, and files with data on outpatient prescription drugs, hospital services, and physician services. Our population included postmenopausal women aged 55 years and over with intact uteri taking hormone replacement therapy for long-term prevention benefits, and an equal number of postmenopausal women with intact uteri with no medical contraindications to hormone replacement therapy but who did not use the therapy during the study period. RESULTS: The population in our analysis included 2632 women with new episodes of hormone replacement therapy, all with at least 3 years of follow-up. Only 42% of new hormone replacement therapy users continuously took HRT during the first year after initiation of their first new episode; a third of these were full-year users in the second year. New users of hormone replacement therapy over a 6-year follow-up period had significantly higher rates of medical care contact for diagnoses of menopausal disorders in the first year of HRT compared with subsequent years. We also found slightly elevated numbers of visits to primary care physicians and obstetrician-gynecologists and slightly increased use of endometrial biopsies and dilation and curettage procedures in the first year of hormone replacement therapy, compared with subsequent years. CONCLUSION: New users of hormone replacement therapy had higher rates of medical care for menopausal disorders in their first year of therapy compared with rates in subsequent years. After discontinuing hormone replacement therapy, utilization of medical care decreased dramatically. ( 2001;185: ) Key words: Health services, menopause, hormone replacement therapy Hormone replacement therapy (HRT) is often used for the symptomatic treatment of menopause and for the prevention of postmenopausal osteoporosis. Rates of use have varied substantially in the past as perceptions have changed about the relative benefits and risks of HRT. However, in the early 1980s, research indicated that the addition of a progestin to estrogen replacement therapy decreased the risk of endometrial cancer; since that time, From the Department of Obstetrics and Gynecology, University of North Carolina School of Medicine a ; Research Triangle Institute b ; and Eli Lilly and Company. c The research was conducted under contract from Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN This study is based in part on data provided by the Saskatchewan Department of Health. The interpretation and conclusions contained herein do not necessarily represent those of the Government of Saskatchewan or the Saskatchewan Department of Health. Received for publication March 23, 2001; accepted April 24, Presented at the Sixty-third Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, Va, January 20-23, Reprint requests: John M. Thorp, MD, University of North Carolina Hospitals, Department of Obstetrics and Gynecology, 214 MacNider, CB #7570, Chapel Hill, NC thorp@med.unc.edu. Copyright 2001 by Mosby, Inc /2001 $ /6/ doi: /mob HRT use has steadily increased. By 1995, more than half of all postmenopausal women in the United States had used HRT (with or without progestin) at least once. 1-3 Despite the popularity of HRT, little is known about the level of medical care resource use associated with the management of adverse events resulting from HRT. Because adverse events may be concentrated at the initiation of HRT, we have focused on the use of medical care resources by new users of HRT. We analyzed medical care resource use among postmenopausal women in Saskatchewan, Canada over an 8-year period from 1990 to 1997, and we estimated the resource use associated with HRT in a retrospective population-based study of new HRT users and nonusers. For simplicity, we focused on women who were potential candidates for combined estrogen-progestin treatment (ie, postmenopausal women with intact uteri). Material and methods Saskatchewan Health funds universal coverage of a wide range of health services for its population of about one million people. Information on health service use is stored centrally in several computerized data files that can be linked. The Saskatchewan administrative data- 318

2 Volume 185, Number 2 Thorp, Gavin, and Ohsfeldt 319 bases include a health insurance registration file, a cancer registry, and files with data on outpatient prescription drugs, hospital services, and physician services. We obtained data from each of these files for a set of women meeting our inclusion criteria. We included postmenopausal women with intact uteri who were taking HRT primarily for its long-term prevention benefits and an equal number of postmenopausal women with intact uteri who had no medical contraindications to HRT but who did not use HRT during the study period. The study population was restricted to women aged 55 years and over, and women who took HRT primarily for the alleviation of symptoms during perimenopause were excluded. We included women who were 55 by January 1, 1990, and women turning 55 between January 1, 1990 and December 31, However, we only included the woman s HRT experience from after her 55th birthday. We also excluded women who had conditions that are often considered contraindications to HRT use: women who had been hospitalized for hysterectomy, thrombophlebitis, or a thromboembolic disorder between 1970 and 1990, and women recorded in the cancer registry with a diagnosis of breast cancer or uterine cancer between 1967 and Because of incomplete data, we excluded women residing in long-term care facilities, women whose prescriptions were paid for by a government agency other than Saskatchewan Health, and women with <4 years of coverage under Saskachewan Health (1 year before HRT and 3 years after initiating HRT). For the purpose of our study, an HRT user was defined as having had at least one prescription filled from January 1, 1990 through December 31, 1994, for the following: (1) a progestin (medroxyprogesterone acetate, micronized progesterone, norethindrone, or other progestin-only oral contraceptive) plus at least one estrogen (chlorotrianisene, estradiol, conjugated estrogen, diethylstilbestrol, estropipate, or ethinyl estradiol) within 90 days of the progestin prescription; (2) a combination estrogen-progestin transdermal treatment; or (3) an oral contraceptive. A woman did not qualify as an HRT user if her only estrogen prescription was for a vaginal estrogen cream or her only progestin prescription was for an injectable progestin. Our inclusion criteria were met by 77,278 women. Among women who turned 55 years old from 1990 to 1994, we identified new HRT episodes on the basis of the purchase of an estrogen prescription preceded by 12 months of no HRT use. From the period from 1990 to 1994, 3238 episodes were identified among 2632 women. In this analysis we look at the 6 years after HRT initiation, regardless of discontinuation of treatment. We divided the 6-year follow-up period into 6 successive 12-month periods and categorized women in each 12- month period according to whether they were taking HRT for the entire 12 months, part of the 12-month period, or not at all during the 12-month period. Because we considered all episodes of HRT, a woman could be a part-year user or a nonuser in one year and a full-year user in a subsequent year. Part-year users are women with disruptions in HRT use, including those who ended an episode during the year, those who ended an episode and began another with two or more months without HRT, and those who started a subsequent new episode after 12 months of no HRT use. Resource use was estimated from claims paid by Saskatchewan Health to providers of care: clinicians, pharmacies, and hospitals. Physician service records in the Saskatchewan Health database contain a single 3- digit ICD-9 diagnosis code. (Codes used to estimate resource use are available from the authors.) We tabulated visits to primary care physicians and obstetrician-gynecologists. To reflect the Canadian health care system, obstetrician-gynecologists were not considered primary care physicians. From the Saskatchewan Health coding book, we chose selected medical procedures for monitoring and treating complications of HRT, menopausal disorders, osteoporosis, and cardiovascular disease. We searched the prescription records of the Saskatchewan Health database for use of alternative prevention drugs for osteoporosis (ie, biophosphonates and sodium fluoride), for cardiovascular disease (ie, antilipidemic drugs), and medications to relieve menopausal symptoms (ie, antidepressants and sedatives). Finally, we determined the percentage of women who received physician services or hospital care who had diagnoses related to osteoporosis, cardiovascular disease, menopausal disorders, or complications of HRT use. We investigated the annual use of medical resources among postmenopausal women in the first 6 years after initiation of a new HRT episode. We looked at clinician visits, selected medical procedures, and prescription medications used for monitoring and treating osteoporosis, cardiovascular disease, or complications of HRT, and the incidence of selected diagnoses potentially related to long-term HRT use. In particular, the following questions were addressed: (1) did observable trends in the annual frequency of visits to primary care physicians, obstetrician-gynecologists, and other physicians occur over time after HRT initiation among postmenopausal women and did these trends vary according to level of HRT use? (2) Did observable trends in the use of selected medical procedures or prescription medications for monitoring or treating osteoporosis, cardiovascular disease, or complications of HRT occur over time after HRT initiation among postmenopausal women and did these trends vary according to level of HRT use? (3) What was the annual and cumulative incidence of selected diagnostic condi-

3 320 Thorp, Gavin, and Ohsfeldt August 2001 Table I. Number of new HRT users according to year since HRT initiation and level of use Level First Second Third Fourth Fifth Sixth All new users (n) Full-year user 1112 (42.2) 895 (34.0) 837 (31.8) 618 (30.2) 416 (29.7) 250 (27.1) Continuous user 1112 (42.2) 809 (30.7) 669 (25.4) 421 (20.6) 251 (17.9) 137 (14.9) Part-year user 1520 (57.8) 654 (24.5) 502 (19.1) 385 (18.8) 242 (17.3) 155 (16.8) Did not use during the year 1083 (41.2) 1292 (49.1) 1040 (50.9) 744 (53.1) 517 (56.1) Data are n (%). tions related to HRT use after HRT initiation among postmenopausal women and did these rates vary over time and according to level of HRT use? Bivariate analyses are presented for all variables, along with the results of χ 2 tests for the significance of differences in proportions and Student t tests for the significance of differences in means. Results The 2632 women with new episodes of HRT comprise our study population. Table I shows the number of women in the study population according to year and level of HRT use. All women had at least 3 years of followup. The population size drops off after the third year because of loss of Saskatchewan Health coverage, death, or the end of the study period (December, 1997). Only 42% of the new HRT users were continuously taking HRT during the first year after initiation of their first new episode, and a third of these women were full-year users in the second year. Of the 1520 women who quit HRT during the first 12 months, 437 (17% of the original group) began another episode in the second 12-month period. Among new users for whom at least 6 years of follow-up data were available, 56% had no use during the sixth year, and 27% used HRT for the entire sixth year, slightly more than half of whom were continuous users for the entire 6 years (137 of 250 women). Most women taking HRT in Saskatchewan obtained their prescriptions from their primary care physicians. Almost all full-year and part-year HRT users had at least one visit to a primary care physician each year, whereas only 13% to 20% had at least one visit to an obstetrician-gynecologist (Table II). The percentage of women with a visit to an obstetrician-gynecologist was higher in the first year of HRT than in subsequent years among both full-year and part-year users. Most new HRT users who were not on HRT in the second through sixth years after HRT initiation also had visited a primary care physician each year (91%-95%). In addition, significantly fewer nonusers had visited an obstetrician-gynecologist each year (6%-7%). Except for part-year users in the first year who had 13 visits on average, the average annual number of primary care physician visits among women with such visits was 11 to 12 visits, regardless of level of HRT use or year from initiation of HRT. Similarly, the average number of obstetrician-gynecologist visits among women with such visits was 3 to 4, regardless of level of HRT use or year from initiation of HRT. In the first 12 months after HRT initiation, 77% of HRT users had on average 10 visits to other physicians. A trend toward decreasing visits to other physicians was evident in all HRT user categories. Differences between user groups were not statistically significant; the only significant difference (in the average number of visits in the sixth year after HRT initiation) may be the result of outliers and small sample sizes. Table III provides percentages of new HRT users who underwent selected medical procedures for monitoring and treating complications of HRT, menopausal disorders, osteoporosis, or cardiovascular disease. The most frequently conducted diagnostic procedure was ultrasonography. The percentage of HRT users with at least one ultrasound procedure in a 12-month period increased from 6% to 7% in the first year after HRT initiation to 8% in the third and fourth year, and fell back to below first-year levels in the sixth year. Women who discontinued HRT and remained off for the entire year were significantly less likely to have had an ultrasound in the third through fifth years after HRT initiation, but were equally likely to have undergone the procedure in the second and sixth years. A slightly increasing trend in the use of breast biopsy and a slightly declining trend in the use of endometrial biopsy are evident among full-year HRT users. Compared with full-year users, slightly more part-year users had breast biopsies and slightly fewer had endometrial biopsies; both user groups had more breast and endometrial biopsies than women who had discontinued HRT. Differences in the frequency of diagnostic procedures according to level of HRT use were not consistently significant and were evident primarily in the middle years (second through fourth years) of the study period. No consistent pattern in the use of deep vein thrombosis scans or hysteroscopies was obvious. Dilation and curettage procedures and hysterectomies were also more frequent among users than nonusers, although the differences were not statistically significant (Table III). A slight trend toward fewer dilation and

4 Volume 185, Number 2 Thorp, Gavin, and Ohsfeldt 321 Table II. Percentage of new HRT users with physician visits and average number of visits among women with visits according to physician type, year since initiation of HRT, and level of use First Second Third Fourth Fifth Sixth Percentage of women with visits Primary care physicians Full-year user Part-year user Did not use during year P value Obstetrician-gynecologists Full-year user Part-year user Did not use during year P value Other physicians Full-year user Part-year user Did not use during year P value Average number of visits among women with visits Primary care physicians Full-year user Part-year user Did not use during year Obstetrician-gynecologists Full-year user Part-year user Did not use during year Other physicians Full-year user Part-year user Did not use during year curettage procedures was evident over time. No significant differences or trends were discernible in the percentages of women who underwent fracture repairs or revascularization procedures. Bisphosphonates and sodium fluoride are alternative therapies for the prevention of osteoporosis. Although very few women took either bisphosphonates or sodium fluoride, HRT users were just as likely to use bisphosphonates as were nonusers (Table IV). In addition, the slight trend toward increasing use of bisphosphonates was equally evident in all 3 user groups. These data do not suggest that many women took these medications as an alternative to HRT upon discontinuation of HRT. No difference in the percentages of women taking cardiac and vasodilating drugs or antilipidemic drugs was evident (Table IV). Women who had discontinued HRT in the first half of the 6-year period were more likely than users to have taken antihypertensive medications. However, an increasing trend in the use of these drugs was evident among users. By the fourth year after HRT initiation, current users were as likely as women who had discontinued HRT to be taking hypertensive drugs. The use of antidepressants and sedatives was fairly common among the new users of HRT (Table IV). These may have been prescribed to treat the mood swings and hot flushes that accompany menopause or to treat depression and insomnia, independent of menopause. Women with disruptions in HRT usage both part-year users and nonusers were significantly more likely than full-year HRT users to have been prescribed antidepressants in the first 2 years after HRT initiation and to have been prescribed sedatives in the first 4 years after HRT initiation. Antidepressant use increased over time among full-year users from 12% in the first year to 16% in the sixth year. Finally, we determined the percentage of women who received physician services or hospital care for diagnoses related to osteoporosis, cardiovascular disease, menopausal disorders, or complications of HRT use (Table V). The annual incidence of diagnoses for osteoporosis and bone fractures was highest in the first year of HRT (9% and 5%, respectively). After the first year, these percentages decreased somewhat and remained fairly stable to the end of the follow-up period; no significant differences were found among the HRT user groups. Over the course of the 6-year

5 322 Thorp, Gavin, and Ohsfeldt August 2001 Table III. Percentage of new HRT users who underwent selected medical procedures according to year since initiation of HRT and level of use First Second Third Fourth Fifth Sixth Breast biopsy Full-year user Part-year user Never used during year P value Endometrial biopsy Full-year user Part-year user Never used during year P value DVT scans Full-year user Part-year user Never used during year P value Ultrasound Full-year user Part-year user Never used during year P value Hysteroscopy Full-year user Part-year user Never used during year P value Dilation and curettage Full-year user Part-year user Never used during year P value Hysterectomy Full-year user Part-year user Never used during year P value Fracture repairs Full-year user Part-year user Never used during year P value Revascularization procedures Full-year user Part-year user Never used during year P value DVT, Deep vein thrombosis. period, 17% of new HRT users required medical care for osteoporosis and 18% required care for bone fractures. New full-year and part-year HRT users were diagnosed with menopausal disorders. Diagnosis coding in the Saskatchewan Health data sets precludes us from discerning whether these symptoms were attributable to hypoestrogenism (eg, vasomotor instability) or to side effects of HRT use (eg, abnormal vaginal bleeding). Comment The most important finding in this investigation of medical resource use by new users of HRT over a 6-year follow-up period was that of significantly higher rates of medical care contacts for diagnoses of menopausal disorders in the first year of HRT compared with subsequent years. Our data set was limited with regard to the etiology of menopausal disorders. Saskatchewan Health physician services files contained only 3-digit ICD-9 codes; thus, we could not distinguish between hypoestrogenic (eg, hot flashes) menopausal disorders and hyperestrogenic (eg, vaginal bleeding) menopausal disorders. These differences were accompanied by slightly elevated numbers of visits to primary care physicians and obstetrician-gynecologists and slightly increased use of endometrial biopsies

6 Volume 185, Number 2 Thorp, Gavin, and Ohsfeldt 323 Table IV. Percentage of new HRT users with selected prescription medications according to year since HRT initiation and level of use First Second Third Fourth Fifth Sixth Bisphosphonates Full-year user Part-year user Never used during year P value Sodium fluoride Full-year user Part-year user Never used during year P value Cardiac and vasodilating drugs Full-year user Part-year user Never used during year P value Hypertensive drugs Full-year user Part-year user Never used during year P value Antilipidemic drugs Full-year user Part-year user Never used during the year P value Antidepressant drugs Full-year user Part-year user Never used during the year P value Sedative hypnotic drugs Full-year user Part-year user Never used during the year P value and dilation and curettage procedures in the first year of treatment. After women discontinued HRT, the frequency of medical care contacts for menopausal disorders decreased dramatically. Women who used HRT were as likely as women who discontinued HRT to take other prescription medication for prevention of osteoporosis, but were less likely to take either antidepressants or sedative hypnotics for treatment of symptoms accompanying menopause. Nevertheless, the percentage of women who took these latter medications was high, even among fullyear HRT users. Despite the differences in first-year resource use, we found few trends in aggregate levels of medical care use over the first 6 years after initiation of HRT. The overall use of physician services in the first year of HRT was similar to that in the sixth year. Prescription medication use increased somewhat over time, whereas hospital care declined. Women taking HRT for the entire year had higher prescription medication use but equal or lower physician service use and hospital care compared with women with disruptions in their HRT use, resulting in little difference in overall resource use. The menopausal disorders experienced by new users of HRT, as evidenced by physician visits and procedure use, have implications for clinicians who prescribe HRT. To optimize HRT compliance so that the long-term benefits in prevention of cardiovascular disease and bone loss are realized, women who initiate HRT will need access to clinicians who are skilled in the management of menopausal disorders. Clinicians and patients will need open lines of communication and must accept that there will be more physician visits and procedures during the first year of HRT use. Conversely, clinicians or patients who wish to obtain the benefits of HRT but minimize side effects in the first year of use may wish to consider alternatives to HRT, such as biophosphonates, lipid-lowering drugs, selective estrogen receptor modulating agents, or lifestyle changes in diet and activity.

7 324 Thorp, Gavin, and Ohsfeldt August 2001 Table V. Annual and cumulative percentages of new HRT users who received medical care for selected diagnoses according to year since initiation of HRT and level of use First Second Third Fourth Fifth Sixth Osteoporosis Full-year user Part-year user Never used during year P value Annual incidence Cumulative incidence Bone fracture Full-year user Part-year user Never used during year P value Annual incidence Cumulative incidence Cardiovascular disease Full-year user Part-year user Never used during year P value Annual incidence Cumulative incidence Stroke Full-year user Part-year user Never used during year P value Annual incidence Cumulative incidence Deep venous thrombosis Full-year user Part-year user Never used during year P value Annual incidence Cumulative incidence Menopausal disorders Full-year user Part-year user Never used during year P value Annual incidence Cumulative incidence Breast cancer Full-year user Part-year user Never used during year P value Annual incidence Cumulative incidence Benign breast disease Full-year user Part-year user Never used during year P value Annual incidence Cumulative incidence Uterine cancer Full-year user Part-year user Never used during year P value Annual incidence Cumulative incidence Uterine hypertrophy Full-year user Part-year user Never used during year P value Annual incidence Cumulative incidence Uterine fibroids Full-year user Part-year user Never used during year P value Annual incidence Cumulative incidence

8 Volume 185, Number 2 Thorp, Gavin, and Ohsfeldt 325 We thank Saskatchewan Health for supplying the data, Patty Beck for working with Research Triangle Institute staff on the data specifications, and Angela Greene of Research Triangle Institute and Harlene Gogan of University of North Carolina for preparing the analytic files from the Saskatchewan data. REFERENCES 1. Leveille SG, LaCroix AZ, Newton KM, Keenan NL. Older women and hormone replacement therapy: factors influencing late life initiation. J Am Geriatr Soc 1997;45: Newton KM, LaCroix AZ, Leveille SG, Rutter C, Keenan NL, Anderson LA. Women s beliefs and decisions about hormone replacement therapy. J Wom Health Gend Based Med 1997;6: Rosenberg L, Palmer JR, Rao RS, Adams-Campbell LL. Correlates of postmenopausal female hormone use among black women in the United States. Obstet Gynecol 1998;91: Discussion DR WILLIAM E. BROWN, Greenville, NC. Dr John M. Thorp Jr should be congratulated on a comprehensive retrospective study of HRT from the Saskatchewan Health administrative database. The study population was restricted to postmenopausal women aged 55 years and over with intact uteri who were taking I-IRT for longterm preventive health benefits and an equal number of postmenopausal women with intact uteri with no medical contraindications to HRT who did not use HRT during the study period. Hormone replacement therapy is considered a major preventive public health strategy for all postmenopausal women. 1 The therapy of estrogen replacement has the potential to reduce central nervous system symptoms, improve sexual function, delay atherosclerotic changes, improve genitourinary function, and aid in the prevention of osteoporosis. Dr Thorp stated that the most significant finding in their investigation of medical resources used by new users of HRT over a year follow-up was significantly higher rates of medical care contacts for diagnosis of menopausal disorders in the first year of HRT compared with subsequent years. During the first year of HRT use, the full-year user had 11.8 visits to a primary care physician and 3.4 visits to an obstetrician-gynecologist. Only 42.2% of the first-year HRT users were compliant. With new starts of HRT at age 55 and poor compliance with HRT, it would be anticipated that there would be problems with vaginal bleeding. 2 Abnormal bleeding would increase visits, ultrasound procedures, endometrial biopsies, dilation and curettage, and hysteroscopy, which were shown to be significantly increased among users versus nonusers of HRT. Older women who were receiving HRT have been noted to be less tolerant of bleeding than younger women on HRT. 3 In an elderly population the continuation rate decreased with increasing age in those women who had a uterus, but not in those women who had undergone hysterectomy. 4 Hormone replacement users were just as likely as nonusers in this study to take other medications to prevent osteoporosis. Osteoporosis was more commonly diagnosed in the users of HRT than in the nonusers. It is not surprising that once the diagnosis of osteoporosis is made that a physician may recommend HRT and a bisphosphonate. Nonusers of HRT were more likely to take antidepressants or sedatives. Estrogen replacement therapy has been noted to be effective in reducing central nervous system symptoms (ie, hot flushes, insomnia, irritability, poor memory, anxiety, and headaches). 5 The long-term benefits of HRT include prevention of osteoporosis, cardiovascular disease, and senile dementia. Dr Thorp suggested minimizing the side effects of HRT and considering alternative medications (ie, bisphosphonates, lipid lowering drugs, estrogen receptor modulating agents) and lifestyle changes in diet and activity. Compliance with therapy is a major challenge if longterm benefits are to be realized. The stopping rate for estrogen replacement therapy has been reported to be 20% at 6 months, 38% at 12 months, 51% at 18 months, and 59% at 2 years. 6 The North American Menopause Society has made the following recommendations: (1) involve the woman in the decision making; (2) explain and personalize benefits and risks; (3) clarify a woman s preferences, modify regimen accordingly; (4) provide education at the appropriate level; (5) help each woman systematize HRT taking; and (6) follow up frequently. 7 Establishing good rapport with ongoing communication between the patient and medical provider is of utmost importance. Questions to Dr Thorp include the following: (1) Does he feel an average of 11 to 12 visits to a primary care provider and 3 to 4 visits to an obstetrician-gynecologist during the first year of hormone replacement therapy is normal and necessary, (2) Do the data provided by Saskatchewan Health appear applicable to us in the United States; and finally, (3) Is hormone replacement therapy cost effective? REFERENCES 1. American College of Obstetricians and Gynecologists. Hormone replacement therapy. ACOG Educational Bulletin No Washington,DC: ACOG; Doren M. Hormone replacement regimens and bleeding. Maturitas 2000;34 suppl 1: Ettinger B, Pressman A, Silver P. Effect of age on reasons for initiation and discontinuation of hormone replacement therapy. Menopause 1999;6: Vestergaard P, Herman AP, Gram J. Improving compliance with hormonal replacement therapy in primary osteoporosis prevention. Maturitas 1997;28: Campbell S, Whitehead M. Oestrogen therapy and the menopausal syndrome. Clin Obstet Gynaecol 1997;4: Berman RS, Epstein RS, Lydick EG. Compliance of women in taking estrogen replacement therapy. J Wom Health 1996;5; Achieving long-term continuance of menopausal ERT/HRT: consensus opinion of the North American Menopause Society. Menopause 1998;5: DR CHARLES HAMMOND, Durham, NC. A question occurs and maybe it is in your manuscript. If one looks at the reasons that patients discontinue hormone therapy, irregular bleeding is one of the top two causes. What regimens did you use? Because I think bleeding is much more common early in menopause with combined continuous recipes than abnormal bleeding with cyclical recipes. I think you re-

9 326 Thorp, Gavin, and Ohsfeldt August 2001 ally have to define for us the therapeutic regimens chosen and whether they are altered during the process. BRENDA PEACOCK, Washington, NC. I probably speak for a number of us in this room about the counseling benefits as far as beginning anyone at any point on estrogen. But I wondered if those visits to the primary care provider versus those to the obstetrician-gynecologist were delineated as far as whether they were referred to the obstetrician-gynecologist after multiple visits with problems initiating the hormone or not, or were these just voluntary visits on the patients part. DR JOHN THORP, JR (Closing). I greatly appreciate the discussion and questions. Dr Hammond s question on what prescriptions were available and what types of hormone replacement therapy is answerable. There was progestin plus at least one estrogen given both in cyclical and in continuous regimens. There is one combined estrogen and progesterone treatment and oral contraceptives. We did analyze these data to see who continued with HRT, and the two biggest predictors of continuation were (1) women who changed medications and did not continue on their initial regimen and (2) women who were not prescribed a transdermal form of estrogen. 1 Dr Peacock s question was about referrals, and to my knowledge one does not see a specialist within the Canadian health care system without a referral, and visits to gynecologists are not patient generated. Dr Brown had three questions. One was on the large number of visits, which is slightly skewed because the women with no visits were excluded. Just ask a football coach in Durham or Chapel Hill how much they would like to get rid of their shutouts. Nevertheless, I believe this high visit frequency is an inherent difference in the Canadian health care system. The second question regarded generalizability of our findings to the United States. I think the populations are generalizable in terms of being Western, well fed, and prosperous. Certainly the health care system is not generalizable. The health care system is what makes the data available and, to my knowledge, there are not region-wide data sets of this type available elsewhere in the Western world. In another manuscript, we show slightly higher costs over the duration of the study for new and part-year users. 2 One could argue that the epoch studied was not sufficiently prolonged to capture evidence of benefit, but I would caution that the long-term compliance is so poor that one wonders how many women will stay on their medicine long enough to accrue said potential benefits. REFERENCES 1. Gavin NI, Thorp JM, Ohsfeldt RL. Determinants of hormone replacement therapy duration among postmenopausal women with intact uteri. Revised and resubmitted to Menopause. 2. Gavin NI, Ohsfeldt RL, Thorp JM. Medical care costs associated with postmenopausal hormone replacement therapy. Submitted to Journal of Managed Care Pharmacy.