Attitudes to menopause and hormone replacement therapy among Asian and Caucasian women general practitioners

OBJECTIVE: To look for any differences in attitudes to menopause and hormone replacement therapy (HRT) between Asian and Caucasian women standardised for educational background, socio-economic status and access to medical information. METHOD: Self administered postal questionnaire sent to 144 women doctors (general practitioners) in defined geographical areas. RESULTS: The overall response rate was 61%. Both Asian and Caucasian women responded in a similar manner for most aspects. A high proportion of these women doctors (over 75%) would seek HRT at the climacteric. More Asian respondents reported a fear of breast cancer (P=0.001), and that a woman feels less of a woman after the menopause (P=0.02). More Caucasian respondents felt positively about the potential for HRT to enhance enjoyment of life (P=0.01). CONCLUSIONS: The lack of major differences between the ethnic groups in our sample suggests that variations reported elsewhere may be due to lack of knowledge and/or differences in socio-economic status.     

Important factors for use of hormone replacement therapy: a population-based study of Swedish women. The Women's Health in Lund Area (WHILA) Study

OBJECTIVE: The aim of this study was to delineate the use of hormone replacement therapy (HRT) among women who were born between December 2, 1935, and December 1, 1945, and living in the Lund area of southern Sweden and to analyze factors that contribute to the acceptance and continuation of HRT. METHODS: All women received a generic questionnaire pertaining to demographic background, lifestyle, health behavior, and climacteric symptoms and underwent a personal interview. An interim analysis was carried out on 3,900 women. We mailed a hormone questionnaire to the women who were using HRT (n = 1,875). This hormone questionnaire covered, for example, menopausal status, complaints, and alterations in and efficacy of HRT use, as well as the reasons for discontinuing HRT use. RESULTS: A total of 1,415 (76%) women answered the hormone questionnaire. Forty-eight percent were HRT ever users, and 32% were current users. Mean duration of HRT use was 47 months. The most common incentives for HRT use were alleviation of menopausal symptoms (72%) and prevention of bone loss (50%) and/or cardiovascular disease (31%). Forty-seven percent of HRT users reported that they had changed regimens at least once. HRT users had higher education, full-time work, and a higher consumption of alcohol but less consumption of cigarettes. They reported higher frequencies of climacteric symptoms, past histories of premenstrual syndrome, use of oral contraceptives, and hysterectomy. They also had a higher consumption of healthcare resources. A total of 177 women withdrew from therapy. The most common reasons for discontinuation of HRT were weight gain, anxiety of cancer, bleeding, breast tenderness, and emotional problems. Compared with current users, past users had less positive as well as fewer negative effects of HRT. Several variables contributed to compliance, including education, full-time work, regular exercise, low frequency of persistent climacteric symptoms, and alteration of regimens. CONCLUSION: Education, working conditions, lifestyle, interest in prevention, and severity of the climacteric symptoms are determinants for both acceptance of and compliance with HRT.     

Determinants of hormone replacement therapy duration among postmenopausal women with intact uteri

OBJECTIVE: To investigate factors associated with hormone replacement therapy (HRT) duration among postmenopausal women with intact uteri. DESIGN: A Cox proportional hazard model on time to HRT discontinuation is estimated for 2,632 postmenopausal HRT users with intact uteri who began a new episode of treatment between January 1990 and December 1994 in Saskatchewan, Canada. RESULTS: Major contraindicating medical events were highly associated with HRT discontinuation among postmenopausal women. Women who were diagnosed with uterine cancer while taking HRT were almost four times as likely to discontinue HRT, and women who were diagnosed with breast cancer while taking HRT were nearly five times as likely to discontinue HRT. Other statistically significant factors associated with the duration of HRT episodes include administration mode and the ability to try different types and strengths of HRT. Women initiating HRT with a transdermal patch were 50% more likely to discontinue it. Women who were willing and able to experiment with different HRT reduced their likelihood of discontinuing by one-half to three-fourths. CONCLUSIONS: Although some of the factors associated with the hazard of HRT discontinuation among postmenopausal women who are taking the treatment for preventive benefits are immutable, clinicians may influence HRT continuation rates through initial drug choice or modifications in drug type or regimen over the course of therapy.     

Attitude towards health and hormone replacement therapy among female obstetrician-gynecologists in Israel

OBJECTIVE: To assess Israeli women gynecologists toward their own health, their health related behaviors and to assess attitude towards and the use of hormone replacement therapy (HRT). METHODS: Ninety five actively employed hospital and community women gynecologist completed a questionnaire on attitude towards self-health, way of life, smoking habits, and regular breast, blood, pap smear examinations and HRT. RESULTS: Mean BMI was 25.3 Kg/m(2)+/-4.2, 61% considered themselves above average weight, and only 39% estimated their weight as appropriate. Fifty six percent were on active weight-loss diets, and 35% were current smokers. Blood tests, pap smears and breast evaluations were regularly done by 73.4, 91.5, and 64.1%, respectively. Overall, 74% of the gynecologists had a positive opinion about HRT; 70% of the menopausal subgroup had ever used HRT, and 93.3% of the perimenopausal subgroup intended to use it. The main reason for starting HRT was climacteric symptoms, and for stopping or avoiding HRT were equally bleeding, fear of cancer and adverse reactions towards HRT. By far the oral HRT mode was the most popular and 90% of users expressed satisfaction with treatment. CONCLUSIONS: Israeli women gynecologists are aware and maintain carefully their health, excluding cigarette smoking. The high rate of use and awareness of HRT among this group is encouraging considering that gynecologist serves as role model for the public and maintains the main source of HRT in the community.     

Screening before and during the use of oral contraceptives and hormone replacement therapy. The ESHRE Capri Workshop Group

Most users of oral contraceptives (OC), and many users of hormone replacement therapy (HRT) are apparently healthy, using a preparation for preventative purposes. It is understandable, therefore, that many clinicians feel that they should screen women using these preparations for hidden disease. Sometimes this has resulted in women being subjected to a variety of procedures. This medicalization of the provision of care can inhibit women from availing themselves of these services. All screening programmes must have evidence that: early detection will affect the natural history of the disease; the performance characteristics of the test must be known; the test should be cost-effective, acceptable to users and providers, should influence clinical decisions, and treatment should exist for abnormal results. The tests time to time suggested before and during the use of OC and HRT do not fulfill these needs. Whether any of the contraindications for OC use are present can be determined simply by taking a history and performing a physical examination including measurement of blood pressure. The same policy applies to the women who will start HRT. If facilities are available for screening mammography this test should be performed prior to starting HRT as the oestrogen can promote the growth of an existing subclinical breast cancer. It is not cost effective to perform an endometrial biopsy in women without abnormal genital bleeding prior to starting HRT. Routine measurement of bone density is also not cost effective or necessary since no current available agent reduces the risk of fractures in women with osteoporosis more than HRT.     

Effective bleeding control and symptom relief by lower dose regimens of continuous combined hormone replacement therapy: A randomized comparative dose-ranging study

Objectives: We compared two different continuous combined hormone replacement therapy (HRT) regimens of estradiol valerate (E₂V) and medroxyprogesterone acetate (MPA) with a combination of micronized estradiol (E₂) and norethisterone acetate (NETA) to determine bleeding pattern, control of climacteric symptoms, lipid profile, endometrial and general safety in a 1-year multicenter study. Methods: 440 postmenopausal women were randomized to three treatment groups to receive: 1 mg E₂V+2.5 mg MPA; 1 mg E₂V+5 mg MPA; or 2 mg of E₂+1 mg NETA. After the first 6 months, the E₂V dose was increased to 2 mg in both E₂V/MPA groups. Information on bleeding was recorded on diaries by the women and intensity of climacteric symptoms was assessed using VAS scales. Physical and laboratory examinations, endometrial biopsy and vaginal ultrasonography were performed at baseline and follow-up visits. Results: Significantly fewer bleeding days were experienced in the first 3 months by women taking E₂V/MPA compared with women taking E₂/NETA. When the dose of E₂V was increased in the E₂V/MPA groups, an increase in maximum bleeding intensity was observed in the group receiving 2.5 mg of MPA, but not in the group taking 5 mg of MPA. All dose combinations effectively relieved climacteric symptoms and beneficial effects on the lipid profile were seen after 6 months in all groups. Tolerability and endometrial safety were good and no cases of hyperplasia were observed. More women discontinued treatment prematurely in the E₂/NETA group compared with either of the E₂V/MPA groups. The overall continuation rates ranged from 70 to 86%. Conclusions: These results confirm that lower dose combinations of continuous combined HRT are usually sufficient to control symptoms or avoid breakthrough bleeding. However, if higher E₂V dose is needed for symptom control, it should be combined with the higher dose of progestin (5 mg) to avoid bleeding disturbances. Flexible treatment regimens should be available for individualized HRT.     

Womens attitudes and knowledge about the climacteric period and its treatment. A Swedish population-based study

Objectives: The aim of the study was to investigate womens knowledge and attitudes about the menopause and hormone replacement therapy (HRT). Material and methods: Women aged 46, 50, 54, 58 and 62 years, born on uneven days, resident in Göteborg, Sweden (n=5.990) were invited by letter to complete a questionnaire concerning the menopause and HRT. Results: The response rate was 76% (n=4504). Current estrogen use was reported by 21%. Another 20% had stopped estrogen use e.g. because of a fear of cancer (9%) or other side-effects (14%). The most common reasons to refrain from HRT were minor climacteric symptoms (27%), fear of cancer (9%) or side-effects (15%) and the opinion that the menopause is a natural process (20%). A majority (67%) preferred HRT without withdrawal bleedings, especially elderly women (80%). Thirty-five per cent could accept life-long HRT if treatment was free from withdrawal bleedings. Almost 70% received their information about the menopause and HRT from a physician. Forty-five percent of the women considered the menopause to be a relief. Approximately 60% had a regular sex-life. The most common reasons for not having a regular sex-life were irrespective of the womans age, the absence of a partner (43%). Loss of sexual desire (29%) or partners loss of desire (12%), both of which showed an increase with age, were other reasons given. Only 8% of the total population had no sexual activity because of vaginal dryness but in the oldest cohort (62 years old) 32% gave this as a reason. Conclusion: Physicians require more time for counselling of patients about the menopause and HRT. Many women refrain from therapy because of fear and misconceptions. To achieve better long-term compliance epecially in elderly women the use of `non-bleeding' regimes requires further attention.     

The basal and TRH stimulated levels of prolactin in low risk climacteric patients with increased breast density: a matched pair case control trial

OBJECTIVE: To detect any significant alteration of basal and TRH stimulated circulating prolactin levels in those with an extremely dense breast composition as compared to ones with a fatty pattern in mammography in climacteric patients with a low risk probability for developing invasive breast cancer within five years according to a validated risk model. MATERIALS AND METHOD: In this matched pairs case-control trial a total of 67 climacteric patients with an extremely dense breast composition were compared to a control group of 71 climacteric patients with an almost entirely fat pattern composition in terms of basal and TRH stimulated circulating prolactin levels. All participants in the study had an estimated 5 years breast cancer risk less than 1.67% according to the validated model of Gail. Subgroup analysis was done according to menopausal status (premenopausal versus postmenopausal) and according to the hormone replacement therapy (HRT) in postmenopausal patients (current users of HRT versus never used HRT). RESULTS: We did not detect any statistically relevant differences between groups or subgroups in terms of basal, stimulated and Delta levels (stimulated-basal) of prolactin (ng/ml). The differences between groups of extremely dense composition versus almost fatty pattern in terms of DeltaPRL (ng/ml) (+/-S.D.) were not statistically significant (68.1+/-34.5 versus 69.1+/-43.0; unpaired t test, Welch corrected p=0.88, 95% CI -12.1 to 14.0). CONCLUSION: Our results do not suggest a contribution of circulating prolactin to increased mammographic density in climacteric patients with low risk probability to develop breast cancer. A study of similar kind is warranted in high risk patients.     

Endometrial response to raloxifene compared with placebo, cyclical hormone replacement therapy, and unopposed estrogen in postmenopausal women.

OBJECTIVE: To determine the endometrial effects of raloxifene 60 mg/day in postmenopausal women as assessed by vaginal bleeding and endometrial thickness. DESIGN: Data from 1157 postmenopausal women were analyzed from a database consisting of four independent, double-blind, randomized, placebo-controlled trials (range = 6-30 months duration), a 24-month open-label randomized, cyclical hormone replacement therapy (HRT)-controlled trial, and a 6-month double-blind, randomized, unopposed estrogen-controlled trial. Vaginal bleeding rate was derived from self-reported adverse events collected at least every 6 months. Endometrial thickness was measured by ultrasonography at regular intervals. RESULTS: Raloxifene 60 mg/day was not significantly different from placebo with regard to the incidence of vaginal bleeding, the baseline-to-endpoint change in endometrial thickness, or the proportion of women experiencing an increase in endometrial thickness above baseline after either 12 or 24 months of therapy. Unexpected bleeding was reported significantly more frequently in the unopposed estrogen groups compared with the raloxifene group (raloxifene 60 mg/day, 0% versus estrogen, 50%; p = 0.002). A significantly greater baseline-to-endpoint increase in endometrial thickness was observed in both the HRT and estrogen groups compared with their respective raloxifene comparison group (raloxifene 60 mg/day, 0.01 +/- 2.0 mm versus HRT, 1.8 +/- 3.2; p < 0.001; raloxifene 60 mg/day, 1.1 +/- 1.7 mm versus estrogen, 7.8 +/- 3.8; p < 0.001). No cases of endometrial hyperplasia or cancer were diagnosed in the placebo or raloxifene 60 mg/day groups. Endometrial hyperplasia was diagnosed in one case in the HRT group and in two cases in the estrogen group. CONCLUSION: Raloxifene 60 mg/day for up to 30 months is not associated with vaginal bleeding or increased endometrial thickness in postmenopausal women.     

Hormone replacement therapy and previous use of oral contraceptives among Swedish women

Objectives: To assess the current and previous use of hormone replacement therapy (HRT) and alternative remedies in a postmenopausal population and to relate HRT use to previous use of oral contraceptives. Material and methods: All 1323 women living in Linköping of 55 or 56 years old during 1995 were sent a questionnaire asking for data with relation to health and climacteric symptoms as well as to previous and current use of HRT, oral contraceptives and alternative remedies. Results: Current use of HRT was more common among women who previously used oral contraceptives (41.3 %) than among women who had never used oral contraceptives (23.1%). HRT users were also more often physically active, had undergone hysterectomy and had lighter occupation than non-users. Of all women 35% were current users of HRT, half of them for at least 2 years, whereas only 5% had tried HRT and abandoned therapy. Alternative remedies were used by 5% of the women as therapy for climacteric complaints, and about four times as many women had tried such therapy but abandoned it. The only characteristic about use of alternative medicines was that they were used less often by women who had been hysterectomized. No woman treated for breast cancer used HRT and only few of them used alternative remedies. Conclusions: The prevalence of HRT use, as well as compliance, was high. Previous use of oral contraceptives probably affected the attitude towards using HRT.     

Hormone replacement therapy for African American women: missed opportunities for effective intervention.

OBJECTIVES: Because of the potential benefits and risks of hormone replacement therapy (HRT), information about the efficacy of HRT in different groups of women is important to patients and providers. The objectives of this study were to review the evidence on the benefits and risks of HRT in African American women and to present a quantitative analysis of the potential reduction in mortality from osteoporotic fractures and coronary heart disease and the potential increase in risk of breast and endometrial cancer. METHODS: A MEDLINE search of English-language observational studies and clinical trials on the effects of HRT on osteoporotic fractures and coronary heart disease (CHD) was conducted for the time period from 1966 to September 1998. Using available CHD mortality data for African American women and white women, potential reductions in mortality with HRT were explored for African American and white women. RESULTS: In the 30 studies on CHD and HRT, African American women were known to comprise only 173 (0.1%) of 148,437 participants. In 11 studies of HRT and osteoporotic fractures, only 128 (0.4%) of 40,299 participants were known to be African American women. An analysis of CHD mortality by decade intervals indicated that African American women, aged 55 to 64, are more likely to die from CHD each year than white women. Despite a lower incidence of breast and endometrial cancer among African American women, the mortality rates of African American women with these cancers is higher compared with white women. CONCLUSIONS: With the higher underlying CHD mortality rate among African American women, HRT is an important potential preventive therapy. The absence of African American women and other non-white women from clinical studies of HRT makes it difficult to fully assess the risks and benefits of HRT in this group of women.     

Hormone replacement therapy: the perspectives for the 21st century.

Nowadays different lines of evidence demonstrate the benefits of postmenopausal hormone replacement therapy (HRT). HRT is extremely effective in treating subjective symptoms and can really improve the quality of life of climacteric women. HRT and dementia: Estrogens are potentially relevant to the pathogenesis and treatment of Alzheimer's disease. The effects of different progestogens on cognitive functions and Alzheimer's disease are largely unknown. The prevention of Alzheimer disease might be a major indication to long term HRT. Large prospective, randomized trials will confirm these preliminary data. HRT and osteoporosis: HRT has been strongly correlated with higher bone mineral density and lower fracture incidence. Definite answers in terms of minimum effective dosages, timing and duration of HRT for fracture prevention are needed. HRT and cardiovascular disease: Different lines of evidence suggest that HRT can exert cardioprotective effects with substantial reduction of morbidity and mortality for cardiovascular disease in postmenopausal women. The effects and the role of progestogens in cardiovascular disease prevention are still debated. Prospective, randomized, controlled studies are needed to assess the impact of different HRT regimens on cardiovascular events. HRT and cancer: The major issue in the relationship between HRT and cancer is breast cancer. Long-term and current HRT use are followed by a slight, though significant increase in the risk of breast cancer. Progestogens can modify the cellular response of normal as well as cancer breasts. The possible protective effect of continuous progestogen addition is very interesting and needs further investigation. Alternative to classical HRT: Selective estrogen receptor modulators (SERM). SERMs such as raloxifene (RAL) are a new class of drugs that exert site specific estrogenic or antiestrogenic effects in different target tissues. RAL prevents bone loss and reduces serum cholesterol in postmenopausal women. In contrast to estrogen RAL does not stimulate breast or uterine tissues. In vitro RAL is highly effective at inhibiting the growth of estrogen-dependent breast adenocarcinoma cells. SERMs are expected to represent a major breakthrough for postmenopausal health. CONCLUSION: HRT can be offered either as a preventive tool or as individualized care on the basis of personal needs. New therapeutic options like the SERMs will offer a substantial medical advancement for the treatment of postmenopausal women.     

Postmenopausal hormone replacement therapy: endometrial and breast effects

The history of hormone replacement therapy (HRT) dates back to the late 1800s, when animal extracts of ovaries were first used. With the development of synthetic hormones, widespread use in postmenopausal women extended throughout the industrialized world, so that by the late 1900s roughly one-third to one-half of all postmenopausal women in the United States and Europe were taking HRT. Two events changed the course of use of HRT: the association of an increased rate of endometrial carcinoma with estrogen-only HRT and the association of an increased breast cancer rate with combined estrogen and progestin HRT. This review explores the evidence of the effects of HRT on the endometrium and the breast, with emphasis on the pathologic changes.     

Prevention of postmenopausal bone loss with long-cycle hormone replacement therapy

OBJECTIVE: Postmenopausal bone loss and osteoporotic fractures can be prevented by hormone replacement therapy (HRT). However, opposed HRT may increase the risk of breast cancer above that associated with estrogen alone and in non-hysterectomized women estrogen substitution alone increases the risk of uterine cancer, which triggered renewed interest in long-cycle HRT regimens (estrogen replacement therapy with progesterone-free intervals up to 6 months). The effects on bone of such long-cycle HRT regimens are unknown. The objective of the present study was to compare the effects on bone and the endometrium of long-cycle HRT and conventional HRT. METHODS: Seventy-three healthy non-hysterectomized postmenopausal women were randomized to either conventional HRT (estradiol (E2) 2 mg/d during 12 days, E2 2 mg/d plus 1 mg/d of norethisterone acetate (NETA) during 10 days, E2 1 mg/d for 6 days) or long-cycle HRT treatment (two cycles with E2 2 mg/d during 28 days, followed by one cycle of conventional HRT and repeated every 3 months). Primary endpoint was the change in bone mineral density (BMD) at the lumbar spine (LS) over 24 months. RESULTS: BMD at LS increased significantly versus baseline in both treatment groups (conventional HRT +3.8 +/- 0.6%, long-cycle HRT +3.3 +/- 0.5%, p < 0.0001 for both) with no significant difference between treatment groups over 24 months. Similar significant BMD increases versus baseline were observed at the femoral neck, while biochemical markers of bone turnover (osteocalcin and deoxypyridinoline) were significantly decreased over 24 months. There were no endometrial or breast related adverse events reported. CONCLUSION: Long-cycle HRT may be a valid alternative to conventional HRT with regard to protection against postmenopausal bone loss.     

Hormone replacement therapy in cancer survivors

Objective: Thousands of women are treated each year for cancer; many of these are already in menopause, while other younger patients will go into early menopause due to surgery, or chemotherapy, or the need for radiotherapy to the pelvic region. In most cases the oncologist and the gynaecologist would advise these women against the use of HRT. The purpose of this paper is to review biological and clinical evidences in favour and against HRT use in the different tumours and to propose an algorithm that can help choosing the treatment for the single woman. Methods: We performed a systematic literature review through April 2002 concerning: (1) biological basis of hormonal modulation of tumour growth; (2) epidemiological data on the impact of HRT on different cancers risk in healthy women; (3) safety of HRT use in cancer survivors; (4) alternatives to HRT. Results: With the exception of meningioma, breast and endometrial cancer, there is no biological evidence that HRT may increase recurrence risk. In women with previous breast and endometrial cancer HRT is potentially hazardous on a biological basis, even if published data do not show any worsening of prognosis. Conclusions: Even if a cautious approach to hormonal-dependent neoplasias is fully comprehensible and the available alternative treatment should be taken into greater consideration, the reticence to prescribe HRT in women previously treated for other non hormone-related tumours has neither a biological nor a clinical basis. An algorithm based on present knowledge is proposed.     

Variability of breast cancer risk in observational studies of hormone replacement therapy: a meta-regression analysis

OBJECTIVES: A re-analysis of data from 51 epidemiological studies reported a significant 14% increase in the risk of breast cancer associated with the use of hormone replacement therapy (HRT). Unlike randomized trials, these observational studies varied in design and methods. This study was conducted to explore the impact of study design factors on the rate ratio. METHODS: We performed a meta-regression analysis of 39 epidemiological studies of HRT and breast cancer. The rate ratio of breast cancer associated with ever use of HRT was evaluated in relation to study design, study period, country, primary study objective, method of exposure measurement, age control, adjustment factors related to reproduction and menopause, and the presence of breast cancer surveillance. We used stepwise multiple regression analysis, weighted by the inverse of the variance of the logarithm of the rate ratio, to estimate ratios of rate ratios for these factors. RESULTS: Exposure measured by personal interview and/or medical record review was associated with a 14% lower rate ratio estimate as compared with telephone interview or self-administered questionnaire (P = 0.018). Among studies that did not adjust for age at menopause, the rate ratio was 12% lower if the primary objective was HRT effect than not (P = 0.016), while it was 43% higher among studies that adjusted for age at menopause (P = 0.042). An index that included as six desirable design features, breast cancer surveillance, matching of controls, more reliable exposure information, adjustment for age at menopause and reproductive risk factors, and as primary objective the effect of HRT suggests that studies with none of these properties would lead to a rate ratio estimate of 1.14 (95% CI: 1.00-1.29) while studies with all six properties would produce a rate ratio of 0.98 (95% CI: 0.83-1.15). CONCLUSIONS: Design factors of epidemiological studies could be an alternative explanation for the reported 14% increase in the risk of breast cancer associated with the use of HRT.