Cyclooxygenase-2 expression in the endometrium at the end of 2 years' continuous combined hormone replacement therapy

Objective: To evaluate the change of endometrial histology and the expression of cyclooxygenase-2 (Cox-2) in the endometrium after continuous combined hormone replacement therapy (HRT). Methods: Forty-five postmenopausal women were recruited. All participants received 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone (MPA) daily for 2 years. Endometrial biopsy was performed twice, before medication (baseline) and after 2 years of HRT, respectively. Immunohistochemistry was used to detect the presence of Cox-2 expression. Results: More atrophic and weak secretory features of endometrium were noted after the 2-year HRT. Endometrial hyperplasia and carcinoma were not found and immunohistochemistry results revealed that Cox-2 was not expressed in the endometrium. Conclusion: Cox-2, known to play an important role in the tumorigenesis of cancer, was not stained in endometrium tissue after hormonal induction and more endometrium atrophy was noted after the 2-year HRT. From the results, it is noted that continuous combined HRT may be a relatively safe and appropriate regimen for long-term use in postmenopausal women.     

Plasma leptin levels in obese and non-obese postmenopausal women before and after hormone replacement therapy

Objective: the aim of this study was to investigate the effect of hormone replacement therapy (HRT) on plasma leptin levels in postmenopausal women, and the relationship between the plasma leptin levels and obesity. Methods: premenopausal women with normal cycles (n=30; mean ages, 35.4±8.3 years) and postmenopausal women (n=45; mean ages, 49.5±4.7 years) were randomly selected. Women were classified as obese (BMI>27 kg/m²) and as non-obese (BMI<27 kg/m²). Blood samples were obtained from the premenopausal women at the beginning of cycle, and from the postmenopausal women before and 6 months after HRT. Plasma leptin levels were measured by radioimmunassay. Results: plasma leptin levels were significantly higher in premenopausal women than in postmenopausal women (18.60±5.0; 3.67±2.44 ng/ml, respectively, P<0.001). Obese premenopausal women (n=15) had significantly higher plasma leptin levels (24. 60±7.81 ng/ml) in comparison with the levels of the non-obese premenopausal women (n=15; 12.50±4. 63 ng/ml) (P<0.001). Although there was no significant difference in the plasma leptin levels between obese (n=25) and non-obese (n=20) postmenopausal women before HRT, plasma leptin levels were significantly elevated in both obese and non-obese postmenopausal women after HRT (P<0.001), and the obese women had significantly higher plasma leptin levels than the non-obese (29.05±10.53; 14.78±6.76 ng/ml, respectively, P<0.001). Conclusion: HRT is effective in the elevation of the plasma leptin levels in postmenopausal women, and in obese women the increase of the plasma leptin levels are more marked than the non-obese women after HRT.     

Dry eye in post-menopausal women using hormone replacement therapy

PURPOSE: To evaluate the effect of hormone replacement therapy (HRT) on dry eye in post-menopausal women. METHODS: Forty post-menopausal women with dry eye (20 patients, group 1) and without dry eye (20 patients, group 2), and planning to receive HRT (estrogen plus progesterone), were recruited as the study groups. Forty age-matched untreated women were enrolled as controls (group 3 with dry eye, 5 patients; group 4 without dry eye, 35 patients). Patients having at least one of the symptoms (dryness, itching, photophobia, foreign body sensation, and tearing) together with two of the tests with positive results for dry eye (tear film break-up time (BUT), fluorescein staining of the cornea, analysis of the meibomian gland, and Schirmer I test) in both eyes were considered dry eye positive. Hormonal assay for follicle stimulating hormone, luteinizing hormone, estradiol, and free testosterone was performed. Dry eye statuses in the groups were evaluated statistically. RESULTS: Four patients with incomplete follow-up data were excluded. HRT use increased estradiol levels in the groups. Mean ages of patients (50.2+/-4.8 and 50.7+/-3.9 years, and 50.0+/-4.6 and 53.0+/-3.9 years) were similar (p=0.67). Duration of menopause in groups 1 and 2 (3.2+/-2.2 and 1.4+/-1.2 years; p=0.01), and in groups 3 and 4 (3.0+/-1.6 and 1.7+/-1.3 years; p=0.014) were different. At the third month examinations, all of the patients in group 1, and 11 patients (61.1%) in group 2 had dry eye (p=0.003). CONCLUSION: Duration of menopause and use of HRT may increase the incidence of dry eye in post-menopausal woman.     

Prevalence of hormone replacement therapy and user''s characteristics: a community survey in Japan

Objectives: It is quite recently that much interest has been paid to the benefits of hormone replacement therapy (HRT) in Japan. We conducted a community survey in Japan in 1992 to examine the prevalence of HRT use and factors related to HRT use. Methods: A total of 8791 female residents aged 45–64 years old in a city of the Gifu Prefecture, Japan, responded to the questionnaire including medical and reproductive histories, lifetime occupational history, diet, exercise, smoking and drinking habits, and use of vitamin supplements or medications. The response rate was 94.2%. Results: Overall, 2.5% of women reported current use of HRT and 6.3% had used HRT previously. The highest prevalence of current use was found among postmenopausal women with surgical menopause (4.8%). Current users were more likely to have participated in cancer screenings, and to have used vitamin supplements or calcium during the past year. Conclusions: HRT use rate was 2.5% among female residents aged 45–64 years old in a Japanese community in 1992. Current users may have more regard for their health status.     

Beneficial effect of hormone replacement therapy on weight loss in obese menopausal women

Objective: at the onset of menopause, weight-gain and the aggravation of certain cardiovascular risk factors are frequently observed. The aim of this study was to examine the metabolic effects of combined hormone replacement therapy (17β-oestradiol transdermic 50 μg for 21 days and oral medroxyprogesterone acetate 5 mg from day 10 to 21) using, in particular, indirect calorimetry. Methods: patients (21; 12 substituted and nine controls) were studied twice (3 months apart) during an oral glucose load (75 g). Results: total body weight was unaltered after 3 months in the control group, whereas a fat-loss of 2.1±0.2 kg and a decrease of the waist:hip ratio were observed in the substituted group. In the latter group, a significant increase in lipid oxidation was observed (0.58±0.06 mg/kg/min before and 0.75±0.04 mg/kg/min after substitution P<0.05), whilst total energy expenditure and thermogenesis were also increased. Glucose, lipid and protein oxidation remained stable during three months in the control group. The insulin response to an oral glucose load diminished by 30% with hormone replacemnet therapy (102.3±32.8 mμ/l versus 71.4±20.0 mμ/l). Total and LDL-cholesterol improved after hormone replacement therapy whereas plasma triglycerides were not altered. Conclusions: combined hormone replacement therapy not only prevented weight-gain, but favored weight-loss by significantly increasing lipid oxidation after 3 months of treatment. It also favourably influenced the insulin response, plasma lipids and energy expenditure.     

Effect of hormone replacement therapy on lipids in perimenopausal and early postmenopausal women

Objective: To determine the effects of oral sequential hormone replacement therapy (HRT) on lipid-profile in perimenopausal and early postmenopausal women. Methods: We performed a single-center, randomized, placebo-controlled trial. The trial was double blind with respect to 17β-estradiol/desogestrel (17β-E-D) and placebo and open with respect to conjugated estrogens/norgestrel (CEE-N). A total of 125 healthy perimenopausal and early postmenopausal women, aged 43–58 years, were recruited from the general population in Zoetermeer, the Netherlands. The intervention consisted of 6 months treatment with 1.5 mg 17β-estradiol/0.15 mg desogestrel (n=53), 0.625 mg conjugated estrogens/0.15 mg norgestrel (n=36) or placebo (n=36). At baseline, cycle 1, 3 and 6, overnight fasting blood samples were obtained in which lipids were determined. We used linear regression analysis to calculate differences in mean change from baseline in lipids in the active treatment groups compared to placebo. Results: In both treatment groups significant (P<0.05) falls in low-density-lipoprotein (LDL)-cholesterol (17β-E-D: −7.8% and CEE-N: −8.4%) and lipoprotein(a) (17β-E-D: −11.7% and CEE-N: −28.3%) were found compared to placebo. Apolipoprotein A1 (17β-E-D: 6.8% and CEE-N: 7.3%) and HDL-cholesterol (17β-E-D: 6.4% and CEE-N: 8.0%) significantly increased compared to placebo. No significant changes were found in the other lipids. Mean changes from baseline in total cholesterol, LDL-cholesterol and apolipoprotein B were significantly more pronounced in postmenopausal women compared to perimenopausal women, adjustment for age-differences did not change the results. Conclusion: Treatment of perimenopausal and early postmenopausal women with 17β-E-D or CEE-N changes their lipid-profile in a potentially anti-atherogenic direction. Changes appear to be more pronounced in postmenopausal women compared to perimenopausal women.     

Influence of hormone replacement therapy on proteomic pattern in serum of postmenopausal women

OBJECTIVES: Proteomics approaches to cardiovascular biology and disease hold the promise of identifying specific proteins and peptides or modification thereof to assist in the identification of novel biomarkers. METHOD: By using surface-enhanced laser desorption and ionization time of flight mass spectroscopy (SELDI-TOF-MS) serum peptide and protein patterns were detected enabling to discriminate between postmenopausal women with and without hormone replacement therapy (HRT). RESULTS: Serum of 13 HRT and 27 control subjects was analyzed and 42 peptides and proteins could be tentatively identified based on their molecular weight and binding characteristics on the chip surface. By using decision tree-based Biomarker Patternstrade mark Software classification and regression analysis a discriminatory function was developed allowing to distinguish between HRT women and controls correctly and, thus, yielding a sensitivity of 100% and a specificity of 100%. The results show that peptide and protein patterns have the potential to deliver novel biomarkers as well as pinpointing targets for improved treatment. The biomarkers obtained represent a promising tool to discriminate between HRT users and non-users. CONCLUSION: According to a tentative identification of the markers by their molecular weight and binding characteristics, most of them appear to be part of the inflammation induced acute-phase response.     

Determinants of the intention to adopt hormone replacement therapy among premenopausal women

Objective: To identify the psychosocial factors that influence the intention to adopt hormone replacement therapy (HRT) at menopause. Methods: Random Digit Dialing was used to recruit 644 premenopausal non-hysterectomized women aged 45–54. Data were collected using a telephone questionnaire previously developed according to the theory of planned behaviour. Variables measured were: intention to adopt HRT (INT); attitude towards HRT (Aact); perceived social norm (SN); perceived behavioural control (PBC); and personal normative belief (PNB). Socio-demographic data were also obtained. Results: Stepwise multiple regression of INT on the theoretical variables yielded an R² of 0.70. The determinants were Aact (β=0.39, P<0.001), PNB (β=0.25, P<0.001), PBC (β=0.23, P<0.001) and SN (β=0.12, P<0.001). Women with a strong intention to adopt HRT represented 25% of the sample. These women were more likely to believe that adopting HRT would have the following positive consequences: an improvement in general well-being, the prevention of health problems, an improvement in interpersonal relationships, an increase in productivity, the regulation of mood swings and a reduction of hot flashes. They were also more likely to believe in the following negative consequences: side-effects, an increased risk of cancer, the likelihood of weight gain, and interference in the natural course of menopause (all at P<0.001). Conclusion: Actions that target behaviourial beliefs regarding HRT and perceived barriers to its adoption are most likely to influence adoption of HRT.     

Associations between the number of natural teeth in postmenopausal women and hormone replacement therapy

ObjectivesIncreasing research suggests that periodontal status is associated with hormone replacement therapy in postmenopausal women. This study was performed to assess the relationship between the number of natural teeth and ever use of hormone replacement therapy in postmenopausal women using nationally representative Korean data.MethodsData from the Korea National Health and Nutrition Examination Survey between 2010 and 2012 were used, and the analysis in this study was confined to a total of 4869 respondents over 19 years old who had gone through menopause and who had no missing data for the reproductive factors and outcome variables in that study. The total number of natural teeth was then calculated after excluding third molars. The time of day when tooth brushing was done was recorded as representative oral health behavior. Multiple logistic regression analyses were used to assess association between the number of natural teeth and the use of hormone replacement therapy.ResultsAmong participants who had ever used hormone replacement therapy, the proportions (percentage and standard error) with no teeth, 1–9 teeth, 10–19 teeth, 20–27 teeth, and 28 teeth were 5.0 ± 2.4%, 6.7 ± 1.4%, 12.5 ± 1.7%, 18.9 ± 1.0%, and 20.7 ± 1.6%, respectively (P < 0.05). The adjusted odds ratio and 95% confidence interval for having fewer than 20 teeth <20 was 0.624 [0.464–0.840] for the individuals using hormone replacement therapy, after adjustments.ConclusionsThe analysis revealed that the use of hormone replacement therapy by postmenopausal women showed positive effects for retention of natural teeth. Lack of hormone replacement therapy may be considered to be an independent risk indicator for tooth loss in Korean postmenopausal women.     

Sonographic changes in the endometrium of climacteric women during hormonal treatment

Vaginal sonography of the endometrium is a new method of monitoring the effects of progestogen replacement therapy during the post-menopausal period. The advantages of transvaginal ultrasonic diagnosis are that the uterus can be seen from the fornix vaginae (that is from close range) and that the examination can be carried out whether the bladder is full or not. The differences in the thickness and structure of the endometrium, and the boundary with the surrounding myometrium, enable most of the endometrial changes that occur during the post-menopausal period to be detected sonographically. In the first group of patients we investigated, endometrial carcinoma was detected in 2 out of 60 women suffering from post-menopausal metrorrhagia, the findings subsequently being confirmed histologically. It was observed that post-menopausal women who have regular bleeding during post-menopausal hormone therapy show signs of endometrial proliferation during oestrogen therapy and of secretion during progestogen therapy.     

Percutaneous estradiol gel with an intrauterine levonorgestrel releasing device or natural progesterone in hormone replacement therapy

Objective: To evaluate the bleeding patterns and clinical compliance associated with postmenopausal amenorrhea-inducing forms of hormone replacement therapy using either percutaneous estradiol-gel and a levonorgestrel-releasing intrauterine device or an oral/vaginal natural progesterone. Methods: Sixty postmenopausal women with an intact uterus were followed over 12 months in this open, non-randomised, parallel group study. All patients continuously received a gel containing 1.5 mg of estradiol daily. The women were divided into three groups on the basis of progestin administration. Twenty women (group I) had a levonorgestrel-releasing device (LNG-IUD) inserted at the beginning of the study. Twenty-one women (group II) received oral natural micronised progesterone (oral P) 100 mg daily during 25 calendar days each month, and 19 women (group III) used vaginal natural micronised progesterone (vaginal P) 100–200 mg daily during 25 calendar days each month (higher dose if spotting occurred). Clinic visits were at 0, 3, 6 and 12 months. Bleeding patterns were recorded by the patient in a diary and clinical compliance was evaluated at control visits during the treatment. Symptoms were recorded using a modified Kuppermann index. The serum estradiol concentration was determined at the 0, 6 and 12 month control visits. Results: 80% (n = 16) of the patients in the LNG-IUD group, 67% (n = 14) in the oral P group II and 53% (n = 10) in the vaginal P group were without bleeding at 12 months. Spotting was common during the first 3 months. Symptom relief was good in each group. The LNG-IUD did not cause any serious side-effects. Compliance was good for LNG-IUD and oral progesterone but not for vaginal progesterone. Conclusions: Percutaneous estradiol-gel associated with LNG-IUD is an appropriate method of hormone replacement therapy. The combination of oral natural progesterone with estradiol-gel is also useful, although bleeding episodes complicated the treatment in one third of the patients. The vaginal administration of natural progesterone was impractical due to bleeding disorders..     

The number of proliferating cell nuclear antigen positive cells in endometriotic lesions differs from that in the endometrium

Immunohistochemical expression of proliferating cell nuclear antigen (PCNA) was studied in the endometrium and in endometriotic lesions during the menstrual cycle and in post-menopausal patients. During the menstrual cycle, in the basal layer of the endometrium, an increase in the number of positive indices (PI) of PCNA was observed in epithelial cells from the menstrual phase. It reached a maximum in the proliferative phase and decreased in the secretory phase. However, no change was observed in the stromal cells of the basal layer. In the functional layer of the endometrium, the PI of the epithelial cells showed a high peak in the late proliferative phase, decreased sharply in the secretory phase and remained unchanged thereafter. The PI of the stromal cells in the functional layer showed two peaks, one in the late proliferative and the other in the mid and late secretory phase. In the endometriotic lesions, except for the proliferative phase, the number of PI was significantly higher than that of the corresponding endometrium and no significant changes were observed during the menstrual cycle. In post-menopausal endometriotic lesions, the number of PI was also higher than that of the corresponding endometrium. Thus the numbers of PI differed between the endometrium and endometriotic lesions in the same patients. These results imply that the endometriotic lesions are constantly more proliferative than the endometrium irrespective of the hormonal milieu during both the menstrual cycle and in a post-menopausal environment.     

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.     

Dietary and metabolic differences in pre- versus postmenopausal women taking or not taking hormone replacement therapy

While hormonal fluctuations during the menstrual cycle are known to affect energy intake, changes in dietary intake at menopause and specifically with hormone replacement therapy (HRT) are less well understood. Our objective was to assess dietary macro- and micronutrient intakes in premenopausal women (PEMW) in the luteal and follicular phases and postmenopausal women (PSMW) taking or not taking HRT. Serum estradiol and progesterone as well as resting energy expenditure (REE) and respiratory exchange ratio (RER) were measured. In the 9 PEMW, daily energy intake was 19% higher during the luteal versus follicular phase (2089+/-178 vs. 1752+/-158 kcal/day, p<0.05). The luteal phase was characterized by higher intake of total and saturated fat and a lower micronutrient density. In the 7 PSMW not taking HRT and 6 women taking HRT, there was no significant difference in total energy or macronutrient intake. Neither PEMW nor PSMW met national nutritional recommendations for folate, vitamin D, vitamin E and calcium. Serum progesterone levels were positively correlated with protein intake and negatively correlated with percent carbohydrate in the diet. REE was lower (p<0.05) in PSMW not taking HRT, but not in those taking HRT compared to young women. We confirm increased energy intake in the luteal phase in PEMW but found no difference in energy intake between PSMW taking or not taking HRT. While the quality of the diet in PSMW women was closer to national nutritional recommendations, several at risk nutrients that have been linked to health and disease were found in both groups.     

Effects of hormone replacement therapy on growth hormone secretion patterns in correlation to somatometric parameters in healthy postmenopausal women

Objectives: The aim of the present study was to investigate the influence of a continous estrogen, cyclic progesterone replacement therapy on the secretion of growth hormone (GH) and IGF I as well as of somatometric-GH correlation patterns. Methods: The study included 23 healthy postmenopausal women. Of the proband group 13 randomly selected women were treated with orally applicated 2 mg estradiol-valerat (E2V) and 10 mg dydrogesterone for 10 months. Ten women did not receive any hormonal treatment during this time. After 10 months all probands were reexamined and their GH and IGF I secretion, as well as their somatometric-hormonal correlation patterns, compared with those of a fertile control group. Results: It could be shown, that in postmenopausal women a 10-month oral hormone replacement therapy led to a significant increase of GH- and IGF I levels, however, the treated postmenopausal women did not reach the levels of the fertile controls. Those women who did not receive any hormonal treatment and the postmenopausal women before HRT showed nearly identical GH- and IGF I levels as well as somatometric-GH correlation patterns. Conclusions: The results of the present paper indicate a marked influence of estrogens on GH and IGF I secretion. Furthermore, hormonal replacement therapy (HRT) may influence somatometric GH correlation patterns too.     

Insulin-like growth factor-binding protein-1: a biochemical marker of endometrial response to progestin during hormone replacement therapy

Objectives: To compare immunohistochemical localization of insulin-like growth factor binding protein-1 (IGFBP-1) in endometrial stromal cells with endometrial morphology during three regimens of continuous combined hormone replacement therapy. Methods: Endometrial samples for morphological examination and immunohistochemical staining with monoclonal antibody against IGFBP-1 were obtained from 30 menopausal women before treatment and after 12 and 24 months of continuous combined hormone replacement therapy. All women received percutaneous estradiolgel releasing 1.5 mg estradiol daily. Regarding progestins, patients were divided into three groups: one group (n = 15) had a 20 μg/24 h levonorgestrel-releasing intrauterine device (LNG-IUD); the women in the other two groups received micronised natural progesterone either 100 mg orally (n = 7) or 100–200 mg vaginally (n = 8) daily, 25 days per calendar month. Results: Before treatment the endometrium of all women was atrophic or subatrophic and no IGFBP-1 could be detected in any of the samples which contained enough stromal cells for evaluation. After 12 and 24 months of treatment, epithelial atrophy with decidual transformation in stroma was detected in all specimens in the LNG-IUD group, and IGFBP-1 was localized in decidualized stromal cells in all samples. In the other two groups, no signs of progestin effect were detected by microscopic examination in any of the endometrial samples and IGFBP-1 staining was completely negative in all of them. Conclusion: A striking difference occurred in both morphological and biochemical response in the endometrium of women treated with LNG-IUD compared with those receiving oral or vaginal micronised progesteron during continuous combined HRT. Micronised progesterone at doses used in this study turned out to be ineffective to prevent the proliferative effect of estrogen. Immunohistochemical localization of IGFBP-1 in endometrial stromal cells strongly correlated with decidual reaction in all endometrial specimens exposed to LNG-IUD, suggesting that the immunostaining of IGFBP-1 can be used as a means of assessing the strength of progestin effect in the endometrium during HRT.