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.     

Effects in post-menopausal women of transdermal estrogen associated with progestin upon the removal from the plasma of a microemulsion that resembles low-density lipoprotein (LDL)

Objective: To evaluate the effects of transdermal estradiol and medroxyprogesterone acetate (MPA) treatment on the removal from the plasma of a cholesterol-rich microemulsion (LDE) that roughly resembles low-density lipoprotein (LDL) structure and that binds to LDL receptors. Methods: Ten healthy post-menopausal women were studied before and after 3-month treatment with transdermal estradiol in the following dosages administered every 3.5 days: 25, 50, 50, 100, 100, 50, 50 and 25 μg. From the 15th to the 21st day and from the 22nd to the 28th day of estrogen treatment, respectively, 10 and 5 mg q.d. MPA per oral were associated to the transdermal estrogen. The emulsion labeled with ¹⁴C-cholesteryl oleate was injected after 12 h fasting and its fractional catabolic rate (FCR) was calculated from the plasma decaying curves of the isotope. Results: Treatment reduced LDL-cholesterol levels by 8% only (149.0 ± 36.0 mg/dl, 138.0 ± 27.0 mg/dl; P = 0.046), but the FCR of LDE expressed in medians (25%; 75%) increased from 0.0054 (0.003; 0.052) h⁻¹ to 0.021 (0.009; 0.10) h⁻¹, P = 0.002. Conclusion: The association used in this study so as to mimic the increasing–decreasing pattern of the hormonal ovarian production reduced modestly LDL-cholesterol levels but pronouncedly increased the lipoprotein removal as tested by LDE FCR.     

The effect of dietary soy supplementation compared to estrogen and placebo on menopausal symptoms: A randomized controlled trial

Objectives

To compare the effects of daily ingestion of dietary soy supplementation, low-dose hormone therapy (HT) and placebo on psychological, somatic and urogenital symptoms in postmenopausal women.

Study design

A double-blind, randomized, controlled trial. Sixty healthy, symptomatic, postmenopausal women of 40–60 years of age were allocated to use dietary soy supplementation (containing 90 mg of isoflavone) or HT (1 mg estradiol and 0.5 mg norethisterone acetate) or placebo. Main outcome measures: the Menopause Rating Scale (MRS) was used to assess menopausal symptoms at baseline and after 16 weeks of treatment. Intention-to-treat analyses were performed using the chi-square test, Fisher's exact test, the Kruskal–Wallis non-parametric test and analysis of variance (ANOVA).

Results

No statistically significant differences were found between the groups with respect to baseline clinical and sociodemographic characteristics. The psychological, somatic and urogenital symptoms analyzed in the MRS improved during treatment in all the groups, except for urogenital symptoms in the placebo group in which no significant changes were detected. Comparison between groups revealed a statistically significant improvement in somatic symptoms (hot flashes and muscle pain) in the users of HT (−45.6%) and dietary soy supplementation (−49.8%). Urogenital symptoms (vaginal dryness) improved significantly in HT users (−38.6%) and in users of the dietary soy supplementation (−31.2%). There was no statistically significant difference between the groups with respect to overall MRS score or to scores obtained in the psychological symptoms subscale.

Conclusion

Dietary soy supplementation may constitute an effective alternative therapy for somatic and urogenital symptoms of the menopause.     

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.     

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.     

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.     

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.     

Hormone replacement therapy and hemostasis: effects in Brazilian postmenopausal women

OBJECTIVE: To evaluate the impact that administration of transdermal estradiol gel combined with medroxyprogesterone acetate (MPA) has on hemostasis. METHODS: In this open prospective longitudinal study, thirty postmenopausal women received transdermal estradiol gel (1 mg/day) continuously combined with oral MPA (5 mg/day) for 12 days/month. The following parameters were determined: prothrombin time (PT), activated partial thromboplastin time (aPTT), factors VII, X, and XII activity, fibrinogen levels, thrombin-antithrombin complex levels, protein C and S antigen, antithrombin activity, plasminogen activator inhibitor type 1 (PAI-1) antigen, tissue-type plasminogen activator (t-PA) antigen, plasminogen activity and fibrin degradation products (FbDP) antigen. They were evaluated before and after 6 months of treatment. RESULTS: There was a significant decrease in factor VII activity (P=0.001), factor X activity (P=0.016), protein C antigen (P=0.022), antithrombin activity (P=0.025), plasminogen activity (P=0.023), t-PA antigen (P=0.043) and FbDP antigen (P=0.048) compared with baseline values. CONCLUSION: The results suggest that the treatment with transdermal estradiol gel combined with MPA avoids any major activation of coagulation and does not produce any overall effect on fibrinolysis. Therefore, this treatment might provide interesting effects on hemostasis in postmenopausal Brazilian women.     

The effects of hormone replacement therapy on echocardiographic basic cardiac functions in postmenopausal women

This prospective study was designed to investigate the effects of hormone replacement therapy (HRT) on systolic and diastolic functions. Twenty-eight non-smoking, healthy postmenopausal women who had not received any kind of HRT for at least three years within the onset of menopause were included in the study. All patients received 0.625 mg conjugated oestrogens and 2.5 mg medroxyprogesterone acetate as daily HRT regimen. Their basic systolic and diastolic functions were investigated echocardiographically using standard positions and windows before and 6 months after initiation of HRT. The means of age, weight and length of postmenopausal period were 49.3 +/- 5.8 years, 63.5 +/- 8.7 kg and 46.3 +/- 7.1 months, respectively. Heart rate and systolic and diastolic pressures were similar during the pre- and post-treatment periods. After 6 months of HRT, the mean left ventricular end-systolic and end-diastolic volumes were decreased significantly (71.3 +/- 16.4 versus 56.3 +/- 22.8 ml, 144.5 +/- 26.1 versus 111.7 +/- 24.0 ml, respectively, P < 0.05). Left ventricular ejection fraction was increased (45.1 +/- 6.2% versus 54.8 +/- 4.1%, P < 0.05). Improvement in diastolic function was significant compared with the pretreatment period (E/A 0.90 +/- 0.2 versus 1.10 +/- 0.4, deceleration time 238 +/- 36.8 versus 201 +/- 24.2 ms, respectively, P < 0.05). Based on our preliminary results, we conclude that besides the known favourable effects on women's lives, HRT may also improve cardiac performance and age-related dysfunctions. The present results further suggest that oestrogens exert many direct effects on the cardiovascular system, other than the metabolic changes related to lipoproteins.      

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.     

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.     

Effect of HRT on hormone responses to resistance exercise in post-menopausal women

Purpose: The purpose of this study was to evaluate the effect of hormone replacement therapy (HRT) on the acute and chronic hormonal responses to resistance exercise in post-menopausal women. Methods: Thirty-two post-menopausal women were recruited for this study; 16 who were currently using HRT and 16 who were not using HRT. Subjects in both the HRT and NHRT groups were randomly assigned to either a resistance training group (N=16; 8 HRT and 8 NHRT) or a control group (N=16; 8 HRT and 8 NHRT). The training group completed a supervised resistance training program three times a week for 12 weeks. To evaluate changes in hormone levels, resting blood samples were drawn at weeks 0, 4, and 13 of the program. In addition, at weeks 0 and 13, post-exercise blood samples were drawn in order to examine the hormone response to an acute bout of resistance exercise. Samples were analyzed for serum growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, estradiol, dehydroepiandrosterone (DHEA), and cortisol. Results: There were no significant changes in resting hormone levels between weeks 0, 4, and 13 of the training program. There was a significant week-by-group interaction for DHEA (P<0.05) and cortisol (P<0.05) with the NHRT-training group having a greater post-exercise increase in DHEA and cortisol after training. Overall, the post-exercise GH levels were significantly greater than pre-exercise (P<0.05) or recovery levels (P<0.01). There were no significant differences between HRT and NHRT groups in the acute hormone response to exercise. Conclusion: These results indicate that HRT will not have an effect on the acute or chronic hormone response to a recreational resistance training program in post-menopausal women.     

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.     

The effects of hormone substitution in depot form on the uterus in a group of 50 perimenopausal women — a vaginosonographic study

The aim of our study was to examine the effects of hormone replacement on the size of the uterus and the development or increase of myomatas. Fifty perimenopausal women were included in the study (53.8 ± 5.0 years). Patients received a substitution therapy composed of a combination of 4 mg estradiolvalerate and 200 mg prasteronenantate (Gynodian^® Depot cartridges) given as a muscular injection in 6–10 week intervals (mean 7 weeks ± 4 days). Prior to the onset of therapy with Gynodian^® and after a period of 12 months (± 13 days) vaginosonography was performed. Measurements taken were length, thickness, height of endometrium, size of ovaries and of myomas. Data obtained were correlated with baseline findings. Within 1 year, significant increases in uterus length from 73.4 mm to 88.2 mm, in uterus thickness from 33.9 mm to 43.5 mm and in endometrium height from 4.1 mm to 6.7 mm were observed (median values). There was an increase in both the number (from 2.2 to 3.5) and the size of the myomatas (29.4–35.0 nm diameter). A statistical analysis conducted by means of the Wilcoxon matched pairs signed-rank sum test showed P < 0.001. No significant change occurred in the size of the ovaries. Our study shows that hormone substitution may have an impact on uterus growth and that therefore vaginosonographical monitoring can be recommended.     

Effect of estrogen replacement therapy on natural killer cell activity in postmenopausal women

Objective: To evaluate the impact of menopause and estradiol substitution on natural killer cell activity. Methods: Natural killer cell activity and antibody-dependent cellular cytotoxicity were measured in peripheral blood of 53 postmenopausal and 20 premenopausal women in an interval of 3 weeks. Postmenopausal patients were randomly assigned to receive either estradiol valerate (2 mg daily) orally (n = 18), estradiol (50 μg/24 h) transcutaneously (n = 18) or no substitution (n = 17), and the testing was repeated 3 weeks later. Results: Natural killer cell activity but not antibody-dependent cellular cytotoxicity was significantly (P < 0.01) higher in unsubstituted postmenopausal compared to premenopausal subjects. Natural killer cell activity decreased both in orally and transcutaneously estradiol-treated patients (mean [S.D.] before vs. after 3 weeks; oral: 60.8 [9.2]% vs. 52.8 [8.2]% P < 0.01; transcutaneous: 61.5 [10.6]% vs. 54.3 [9.1]% P < 0.01; no substitution: 60.6 [10.6]% vs. 59.3 [8.9]% P > 0.1), whereas antibody-dependent cellular cytotoxicity showed no changes. The addition of 0.1 to 10 ng/ml estradiol to peripheral blood mononuclear cells of untreated postmenopausal women in vitro had no influence upon natural killer cell activity. Conclusion: Postmenopausal women receiving no estrogen replacement exhibited an increased natural killer cell activity which decreased during estrogen substitution.     

Influence of estrogen replacement therapy on cardiovascular responses to stress of healthy postmenopausal women

Two experiments were conducted to understand the influence of estrogen exposure on cardiovascular responses to acute stress measured by impedance cardiography. Study I compared stress responses of 29 postmenopausal women who used postmenopausal hormone replacement therapy (HRT) and 29 who did not use HRT. Women who did not use HRT had higher systolic blood pressure and pulse pressure responses to the tasks relative to HRT users. Study 2 compared stress responses of 38 healthy postmenopausal women not initially on HRT who were randomly assigned to transdermal estradiol or placebo treatment for 6-8 weeks. HRT assignment did not influence substantially women's cardiovascular responses to stress. Characteristics correlated with HRT use, not HRT itself, or differences in type, duration, and dosage may account for the discrepancy in results.