Recency and duration of postmenopausal hormone therapy: effects on bone mineral density and fracture risk in the National Osteoporosis Risk Assessment (NORA) study

OBJECTIVES: Results from the Women's Health Initiative showed that postmenopausal hormone replacement therapy (HRT) prevents fractures but has an overall unfavorable risk:benefit ratio, leading to the recommendation that HRT be used only for women with troublesome menopause symptoms, and for as short a time as possible. This recommendation has important implications for the timing and duration of HRT and the prevention of osteoporosis. The large number of women participating in the National Osteoporosis Risk Assessment (NORA) program provided the opportunity to evaluate bone mineral density (BMD) and 1-year fracture risk in analyses stratified by duration and recency of HRT. DESIGN: Participants were 170,852 postmenopausal women aged 50 to 104, without known osteoporosis, who were recruited from primary physicians offices across the US. BMD was measured at one of four peripheral sites, and the 1-year risk of osteoporotic fracture was assessed by questionnaire. RESULTS: At baseline, current HRT users had the highest T-scores at every age. Among current hormone users, women who had used HRT longest had the highest BMD levels. Women who had stopped HRT more than 5 years previously, regardless of duration of use, had T-scores similar to never-users. Current but not past hormone use at baseline was associated with a 25% to 29% lower risk of osteoporotic fracture (P < 0.0001) in 1 year, compared with nonusers. These findings were independent of age, ethnicity, body mass index, lifestyle, years postmenopausal, and site of BMD measurement. CONCLUSIONS: We conclude that postmenopausal BMD and fracture are closely associated with current, but not prior, HRT use. Use of HRT for 5 years or less, as proposed for treatment of symptomatic women during menopause transition, is unlikely to preserve bone or significantly reduce fracture risk in later years.     

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.     

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.     

The effect of the duration of progestin use on the occurrence of endometrial cancer in postmenopausal women.

OBJECTIVE: Women who have ever used estrogen replacement therapy (ERT), even at a low dose, have an increased incidence of endometrial cancer. The addition of a progestin to ERT reduces the incidence of endometrial cancer. The duration of progestin administration is more important than the dose. DESIGN: A MEDLINE review of the literature was performed using the search terms endometrial cancer, epidemiology, and hormone replacement therapy (HRT). RESULTS: Women who have ever used ERT have an increased incidence of endometrial cancer. The use of HRT for more than 5 years, with a progestin use of <10 days per cycle, has a relative risk = 1.8. Continuous combined HRT, or sequential or cyclic HRT with >10 days of progestin per cycle, appears to decrease the incidence of endometrial cancer to that found in nonusers of HRT. CONCLUSIONS: The use of HRT in postmenopausal women with a uterus reduces the incidence of endometrial cancer. The duration of progestin administration should be 14 days or more per cycle based on recent epidemiologic data.     

Effects of physical activity and menopausal hormone replacement therapy on postural stability in postmenopausal women--a cross-sectional study

OBJECTIVES: Poor postural stability and muscular strength in postmenopausal women are associated with increased risk of falls and fractures. This study examined whether these risk factors for falls differed according to habitual physical activity and menopausal hormone replacement therapy (HRT) use. METHODS: Subjects were 117 postmenopausal women (mean age 65.3+/-6.0 years); of whom 70 had taken HRT for at least 5 years (42 tibolone and 28 transdermal oestradiol), whilst 47 had not received HRT. Duration of physical activity was assessed with monitors worn on a waist belt. Subjects were grouped into low (LPA; < or = 15 min day(-1)) or high (HPA; >15 min day(-1)) physical activity. Postural stability was assessed using a swaymeter which measured displacement at the waist. Maximal isometric strength of knee flexors was determined in 23 of the tibolone group, 26 of the oestrogen group and 12 of the no therapy group. RESULTS: Stature and body mass did not differ according to physical activity participation or HRT use, although the more active women were on average 2.5 years younger than the less active women. Body sway was lower in more physically active women in three of the four measurement conditions (P<0.05) and this effect persisted after inclusion of age as covariate. Body sway tended to be highest in the no therapy group, although not significantly so. Mean knee extensor strength was higher in women taking tibolone and oestrogen than in those not on therapy (115.3 (5.2), 118.2 (7.2) and 97.6 (9.3) Nm, respectively), although again this difference was not statistically significant. CONCLUSIONS: The more physically active postmenopausal women had significantly better postural stability than less active women, whilst HRT had no significant effect. Physical activity might thus have a role in reducing the risk of fracture through reducing the risk of falling.     

Factors associated with intention to use hormone replacement therapy among Thai middle-aged women

OBJECTIVES: To examine the differences among those who express their intentions to use hormone replacement therapy (intenders), those who express their intentions not to use hormone replacement therapy (non-intenders), and those who are undecided, and to examine the factors associated with hormone replacement therapy (HRT) intention among Thai middle-aged women. METHODS: A total of 420 women aged 40-59 years, recruited from one hospital in Bangkok were asked to complete a self-administered questionnaire. RESULTS: Compared to intenders and non-intenders, the undecided were significantly less knowledgeable about menopause and HRT, and perceived the highest level of decisional uncertainty. Being inadequately informed was the most important factor that distinguished the undecided from intenders and non-intenders. When looking at intenders and non-intenders, no significant differences in perceived information inadequacy, level of knowledge, and perceived risks of HRT were found. However, it was found that intenders perceived higher benefit over risk of HRT (OR = 1.05, 95% CI = 1.02, 1.07), held more negative beliefs towards menopause (OR = 1.61, 95% CI = 1.03, 2.53), and were approximately two times more likely to have ever used oral contraceptives (OR = 1.99, 95% CI = 1.13, 3.47) than non-intenders. CONCLUSION: The findings reveal the importance of being informed about menopause and HRT in making decision about HRT use. Changes in knowledge, and beliefs are promising avenues to study to see how these impacts HRT use.     

The influence of hormone replacement therapy (HRT) on serum leptin concentration in postmenopausal women

OBJECTIVE: This study aimed to evaluate the influence of hormone replacement therapy (HRT), the estradiol concentration and body mass index (BMI, kg/m(2)) on the serum leptin concentration in postmenopausal women. SUBJECTS AND METHODS: 352 healthy postmenopausal women (mean age, 60.9 +/- 8.5 years) participated in this comparative study. 71 (30%) women (mean age 55.9 +/- 8.3 years) had taken HRT, while 281 (70%) women (mean age, 59.1 +/- 10.6 years) had not. Baseline characteristics -age, weight, height, BMI (greater than or = 25 or <25), follicle stimulating hormone, estradiol, and leptin values-were compared in the two groups. In a second analysis to evaluate the influence of HRT, estradiol concentrations, and BMI on leptin concentrations, these data were analysed in women allocated to one of four groups: (a) postmenopausal women not on HRT with a BMI <25 (n = 130); (b) postmenopausal women not on HRT with a BMI greater than or = 25 (n = 151); (c) postmenopausal women on HRT with a BMI<25 (n = 48); and (d) postmenopausal women on HRT with a BMI greater than or = 25 (n = 23). Leptin concentrations were subsequently analysed in relation to BMI and age and BMI and estradiol concentrations to determine any independent effect of these variables. RESULTS: The women taking HRT had a significantly lower mean age, weight, BMI and follicle stimulating hormone concentration than those who were not taking HRT. Furthermore, they had a higher mean height and serum estradiol value, but a significantly lower serum leptin concentration. After controlling for BMI, neither the use of HRT nor the estradiol concentration was found to be related to the leptin value (group (a) versus (c) and group (b) versus (d)), but there were significant differences in leptin concentrations between HRT users with BMI greater than or = 25 and BMI <25 and between women not taking HRT with BMI greater than or = 25 and BMI <25 (groups (a) versus (b) and (c) versus (d)). Furthermore, women with a BMI greater than or = 25 had significantly higher leptin concentrations than women with a BMI<25, irrespective of the HRT use. CONCLUSIONS: Leptin concentrations are significantly higher in obese postmenopausal women than in their non-obese counterparts. Serum leptin concentrations are not influenced by HRT use or estradiol concentrations. Further studies are needed to elucidate the role of HRT and estrogen on serum leptin concentrations.     

The effects of hormone replacement therapy on lipid peroxidation and antioxidant status

OBJECTIVE: A number of studies have consistently shown a lower cardiovascular risk in women who received postmenopausal hormone replacement therapy (HRT). The aim of our study was to examine the effects of HRT on lipid peroxidation and antioxidant status, which were likely to be involved in the pathophysiology of atherosclerosis. METHODS: We measured erythrocyte and plasma thiobarbituric acid reactive substances (TBARS) levels as expression of lipid peroxidation-end product malondialdehyde, and also erythrocyte reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity as indicators of the antioxidant status of the 35 postmenopausal women with HRT (mean age: 51.81 +/- 4.57 yr; body mass index (BMI): 26.56 +/- 3.78 kg/m(2)) and 35 postmenopausal women without HRT (mean age: 47.50 +/- 3.64; BMI: 27.42 +/-3.43 kg/m2). RESULTS: In the group with HRT, erythrocyte and plasma TBARS levels were significantly lower than in the group without HRT (P < 0.003 and P < 0.001, respectively). Erythrocyte GSH level and GSH-Px activity was found to be increased significantly in the group with HRT in comparison with the group without HRT (P < 0.001 and P < 0.001, respectively). There was not any correlation between the erythrocyte and plasma TBARS and erythrocyte GSH levels and GSH-Px activity with duration of HRT (mean 3.5+/-1.3 yr). CONCLUSION: Our results show that HRT is beneficial in the protection against oxidative damage and can prevent atherosclerotic complications.     

Use of hormone replacement therapy among danish nurses at increased risk of osteoporosis

Observational studies and recent randomized trials have shown that postmenopausal hormone replacement therapy (HRT) may reduce the risk of osteoporotic fractures by about 30 to 40%. In this study we used a log linear graphical model to determine whether women with a known increased risk of osteoporosis were more likely to use HRT than other women and to examine whether women at increased risk modified this risk through their lifestyle. Cox regression analysis was used to analyze if women at risk of osteoporosis used HRT longer than women not at risk. Participants were Danish female nurses who, in 1993, were between 50 and 69 years of age (N=14,865). Data were collected from postal questionnaires. We concluded that nurses with a known family history of osteoporosis more often used HRT than nurses without this risk. No other direct associations were found between biological risk factors and ever use of HRT. The presence of biological risk factors of osteoporosis was not consistently modified by a healthier lifestyle. Nurses with a low body mass index (BMI) with a known family history of osteoporosis continued to use HRT longer than nurses without these risk factors.     

Hormone replacement therapy: knowledge, attitudes, self-reported use - and sales figures in Nordic women

Objectives: To evaluate knowledge about, attitudes towards and use of hormone replacement therapy (HRT) in Norwegian women — and to compare self-reported use with sales statistics of HRT in the Nordic countries during recent years. Material and methods: Random samples of Norwegian women age 16–79 were interviewed by the Central Bureau of Statistics in 1994 (n=737), in 1996 (n=665) and in 1998 (n=680). Statistics on the sale of estrogen were provided by the Norwegian Medical Depot and Nordic Council on Medicines. Results: One in three women had received information about HRT during the last 2 years (1994), mainly through weekly magazines and physicians. The proportion answering in accordance with the prevailing view of HRT’s effects (‘correct knowledge’) varied from 36.4 to 47.2%. Those informed by a physician possessed correct knowledge, had positive attitudes towards HRT and were willing to use HRT more often than women informed through other channels. Women with a high level of education had received information and had correct knowledge more often than others, but they were still less willing to use HRT and did not use HRT more often than the less educated. In the age group 45–69 years the use of HRT was 16.3% in 1994, 19.1% in 1996 and 19.1% in 1998 (P=0.421, trend). In addition to received information, attitudes towards and knowledge about estrogen were the most important factors predicting use of HRT after adjusting for other variables. According to sales figures, the use of systemic estrogen in Norway has increased more than 360% since 1990. Although no other Nordic country has experienced a corresponding increase, Iceland had the highest sales figures in 1997. Conclusions: Based on the limited proportion of women receiving information on HRT and the ambivalence found in groups of educated women, we suggest that more and better information should be given middle-aged women to make them better able to make informed choices regarding use of HRT.     

Does the presence of postmenopausal symptoms influence susceptibility to vertebral deformity?

Background: Previous reports suggest a possible increased risk of osteoporosis in those with postmenopausal symptoms. There are, however, no data from population samples, exploring the relationship between postmenopausal symptoms and vertebral osteoporosis. Aim: To determine if there is an association between self-reported postmenopausal symptoms and radiographic vertebral deformity. Methods: Women aged 50 years and over were recruited from population registers in 30 European centres and invited to attend for an interviewer administered questionnaire and lateral thoracic and lumbar spine radiographs. The questionnaire sought information about aspects of lifestyle, personal, medical and gynaecological history, including postmenopausal symptoms: flushing, sleep disturbance and ‘other’ symptoms. Radiographs were taken according to a standard protocol and evaluated morphometrically. Vertebral deformity was defined according to the McCloskey–Kanis method. Bone mineral density data were obtained in a subsample of women at both the spine and femoral neck. Results: A total of 4023 postmenopausal women, aged 50–64 years, were studied: 73% reported a history of flushing, 45% sleep disturbance and 23% ‘other’ symptoms, at or around their menopause. The prevalence of vertebral deformity was 8.2%. Those with postmenopausal symptoms were slightly younger and more likely to have ever taken hormone replacement therapy (HRT) than those without symptoms. After adjusting for potential confounders (age, centre, body mass index, cigarette smoking and HRT) there was no association between deformity and any of the postmenopausal symptoms: flushing (odds ratio (OR) 1.0; 95% confidence intervals (CI) 0.8, 1.3), sleep disturbance (OR 1.0; 95% CI 0.8, 1.2), ‘other’ symptoms (OR 0.9; 95% CI 0.7, 1.3). Amongst women who had ever taken HRT, however, those with vertebral deformity were more likely to report a history of flushing (OR 2.1; 95% CI 0.9,4.8). Conclusion: A history of postmenopausal symptoms per se does not appear to be associated with increased susceptibility to vertebral osteoporosis. However, women with more severe symptoms (as suggested by their use of HRT) may be at increased risk.     

Postmenopausal HRT and tibolone in relation to muscle strength and body composition

OBJECTIVES: Sarcopenia, the loss of muscle mass with age, has a great impact on physical function, and especially in postmenopausal women, who experience a greater decline in muscle strength than do men of similar age. Conventional hormone replacement therapy (HRT) may diminish this loss of muscle strength and may even increase muscle strength. However, HRT is not currently promoted for this indication because of its negative side effects, which is why tibolone, a synthetic steroid with oestrogenic, progestogenic, and androgenic activity, may be an alternative option. The aim of this article was to review data on the effect of HRT and tibolone on muscle strength and body composition in postmenopausal women. METHODS: Medline, Pubmed, Embase, and Sumsearch were searched for articles on the effect of HRT and tibolone on muscle strength and body composition, using the Mesh terms hormone replacement therapy and clinical trial combined with muscle strength or body composition. Tibolone was added as search term with clinical trial and muscle strength or body composition. RESULTS: Three of five randomized controlled trials reported a significant positive effect of HRT on muscle strength but not on body composition. Tibolone significantly increased handgrip strength and isometric knee extension strength in one randomized placebo-controlled, double-blind trial and increased mean knee extensor strength in one cross-sectional study. Tibolone also increased the lean body mass and decreased the accumulation of body fat. CONCLUSIONS: HRT and tibolone increase muscle strength. Unlike HRT, tibolone also increases lean body mass and significantly reduces the total body fat content. Further research is recommended to determine whether tibolone is a safe treatment for sarcopenia.     

Postmenopausal changes in production of type 1 and type 2 cytokines and the effects of hormone replacement therapy.

OBJECTIVE: An appropriate defense against infective agents or malignant cells is attributed to the exquisitely balanced T helper 1 type (cellular) and T helper 2 type (humoral) immune reactions. We investigated the effect of hormone replacement therapy (HRT) on postmenopausal changes in the production of interferon (IFN)-gamma and interleukin (IL)-10, a type 1 and a type 2 cytokine, respectively. DESIGN: Both cytokines were measured by ELISA in the supernatant of lipopolysaccharide-stimulated whole blood cells from 72 untreated and 44 HRT-treated women. Thirteen women were examined before and during HRT. RESULTS: The production of IFN-gamma in women in their 40s and in postmenopausal women was significantly higher compared with that of younger women. However, IFN-gamma fell to the lowest level in the late postmenopausal stage, whereas the production of IL-10 increased gradually with age and in parallel with the postmenopausal period. Thus, in women in the mid-and late postmenopausal period, excessive production of type 2 cytokine (IL-10) compared with type 1 cytokine (IFN-gamma) occurred. The IFN-gamma levels of women on HRT were significantly lower than those of untreated women in the early and mid-postmenopausal stages, and IL-10 levels of women on HRT were significantly lower than those of untreated women in the mid-and late postmenopausal stages. HRT induced a significant decrease in the production of IL-10 and tended to lower the level of IFN-gamma. CONCLUSIONS: Production of IL-10 is augmented in postmenopausal women. HRT probably prevents postmenopausal women from an aberration of the immune system by improving the balance of type 1 and type 2 immune reactions.     

Prevalence of hormone replacement therapy in a sample of middle-aged women

A survey based on a postal questionnaire sent to a random sample of Danish women aged 40–59 yr living on the island of Fünen (n = 401, response RATE = 79%) revealed that the overall prevalence of the use of hormone replacement therapy (HRT) was 16%, the highest rate being in the 50–54 age group (21%). Among post-menopausal women the rate was 21% and it was highest of all (37%) in those who had undergone an artificial menopause. The median age at the start of treatment was 44.3 yr among the artificial menopause and 48.9 yr among the natural menopause subjects. About half of the women were treated with natural oestrogen alone and over a third with cyclic natural oestrogen in combination with progestogens.

Almost one-third of the women had consulted their doctor about climacteric complaints and two-thirds of these were current or past users of HRT. The women had ambiguous feelings towards HRT, approximately one third reporting a positive and one-third a negative attitude.     

Serum estrogen level after hormone replacement therapy and body mass index in postmenopausal and bilaterally ovariectomized women

OBJECTIVE: The objective of this study was to determine the relationships of serum estrogen levels after hormone replacement therapy (HRT) every other day and every day with body mass index (BMI) in postmenopausal and bilaterally ovariectomized women. METHODS: Eighty-six postmenopausal and 51 bilaterally ovariectomized women who had been suffering from vasomotor symptoms such as hot flush or atrophy of the vagina were randomly treated with HRT every other day or every day. Seventy-four patients received oral administration of 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) every other day, and 63 patients received oral administration of 0.625 mg CEE and 2.5 mg MPA every day as conventional HRT. RESULTS: Eighty-four postmenopausal and 50 bilaterally ovariectomized women completed this study. Serum estradiol levels after HRT every day in postmenopausal and bilaterally ovariectomized women were significantly (P <0.05 and <0.01, respectively) correlated with BMI, while those after HRT every other day were not correlated with BMI. The differences between estradiol levels after 12 months of treatment and initial estradiol levels were also significantly (P <0.01) correlated with BMI in both postmenopausal and bilaterally ovariectomized women who received HRT every day but not in women who received HRT every other day. Serum estrone level after HRT every day and the difference between estrone level after 12 months of treatment and initial estrone level were significantly (P <0.05 and <0.01, respectively) correlated with BMI only in bilaterally ovariectomized women. CONCLUSION: Serum estradiol levels after HRT every day increase more in overweight women than in non-overweight postmenopausal and bilaterally ovariectomized women. The results of the present study regarding the relationship between serum estradiol levels after HRT and BMI should be useful for selecting dosages of drugs to be used in HRT.     

Prevention of postmenopausal bone loss with exchange for short-term HRT for 1alpha-hydroxycholecalciferol

OBJECTIVE: The present study investigated bone turnover with exchange of hormone replacement therapy (HRT) by treatment with 1alpha-hydroxycholecalciferol in early postmenopausal women. METHODS: Subjects included a total of 75 postmenopausal women between 49 and 59 years of age who visited the Department of Obstetrics and Gynecology at Osaka Medical College Hospital for regular gynecological checkups and menopausal disorder, postmenopausal osteoporosis or hyperlipidemia, and were diagnosed with menopausal disorder or osteopenia. Changes in bone turnover and vertebral bone mineral density (BMD) in 28 patients who had undergone HRT; conjugated equine estrogen 0.625 mg daily and medroxyprogesterone acetate 2.5 mg daily) for at least 2 years and then switched to 1alpha-hydroxycholecalciferol (0.5 microg orally twice daily) and in 26 patients who were observed without drug administration after discontinuation of HRT were compared with those in 37 patients who continued HRT. BMD of the lumbar spine (L2-4) was determined using Dual Energy X-ray Absorptiometry. RESULTS: While we observed a significant decrease in vertebral bone mass in the HRT-no medication group at 12 months (P=0.049) and 18 months (P=0.013), there was no significant decrease in vertebral bone mass in either the continuous HRT group or the group with change of HRT to 1alpha-hydroxycholecalciferol. In the group with change of HRT to 1alpha-hydroxycholecalciferol, although urinary pyridinoline level increased significantly from the baseline level throughout the study period (P<0.05), serum propeptide of type-1 procollagen (P1CP) level also increased significantly from the baseline level throughout this period (P<0.001). Furthermore, significant increase from the baseline value (P<0.01) was observed in serum osteocalcin level at 6, 12 and 18 months. CONCLUSIONS: These results indicate that switching to 1alpha-hydroxycholecalciferol therapy after short-term HRT increased both bone resorption and bone formation, and permitted maintenance of increase in bone mass due to HRT for at least 18 months, though this switching accelerated bone turnover. This may have occurred because stimulation of bone formation induced by HRT was maintained by 1alpha-hydroxycholecalciferol, though bone turnover was slightly promoted because of withdrawal of HRT. This method was thus found to be very effective in preventing bone loss in patients who have discontinued HRT and are considered relatively contraindicated for use of estrogen.     

Breast carcinoma developing in patients on hormone replacement therapy: a histological and immunohistological study

AIM: To study the histopathological features of breast carcinoma developing in postmenopausal patients on hormone replacement therapy (HRT). METHODS: The sample comprised 60 patients with invasive breast carcinoma including 31 who had received HRT at or shortly before presentation, and 29 who had not. Details concerning their tumour size, histological type and grade, lymph node status, and oestrogen and progesterone receptor status were compared. Immunoperoxidase staining for Bcl-2, p53, and E-cadherin was carried out on paraffin sections of all 60 patients. The results were then statistically analysed. RESULTS: Tumours detected in HRT patients were significantly smaller (mean 17 mm v 25 mm; p = 0.0156) and of a lower histological grade (p = 0.0414) than those detected in non-HRT patients. The incidence of invasive lobular carcinoma was slightly higher in HRT patients (19% v 14%). Immunohistologically, 87% of HRT tumours were Bcl-2 positive (compared with 79% in the control group), 29% were p53 positive (45% in the control), and 48% were E-cadherin positive (72% in the control group). Although the differences were not statistically significant there was a trend towards higher incidence of p53 negative and E-cadherin negative tumours in HRT patients. CONCLUSIONS: Breast carcinomas detected in patients on HRT have a significantly higher incidence of two favourable prognostic features (small size and a low histological grade). They also show a trend, statistically not significant, of being p53 negative and E-cadherin negative; this may be related to the slightly higher incidence of invasive lobular tumours in these patients.     

Impaired ovarian function and risk factors for atherosclerosis in premenopausal women

Objectives: The aim of the study was to obtain information on the possible relationship between impaired ovarian function and risk factors for cardiovascular disease. Material and methods: Serum lipid levels, plasma fibrinolytic potential and histological and biochemical changes in the intima of the uterine artery were investigated in premenopausal women with irregular menstrual cycles, and the results were compared with those from regularly menstruating women. In addition, the same parameters were studied in postmenopausal women on hormone replacement therapy (HRT) and in postmenopausal women who had never used HRT. In total 64 patients undergoing hysterectomy for benign reasons were included the study. Results: Plasma fibrinogen concentration was significantly higher in irregularly menstruating women as compared with women with regular cycles. In women with irregular cycles thickened or sclerotic arterial intima was a significantly more common finding as compared with regularly menstruating women. A significant positive correlation was observed between plasma fibrinogen concentration and intimal esterified cholesterol content in women with thickened or sclerotic uterine artery. Conclusions: These data suggest an important role for normal ovarian function in the prevention of atherosclerosis.