Transvaginal ultrasonographic measurement of endometrial thickness in postmenopausal women receiving estrogen replacement therapy

OBJECTIVE: This study was undertaken to evaluate endometrial thickness by transvaginal ultrasonography in asymptomatic postmenopausal women receiving estrogen replacement therapy. The endometrial thickness in this study group was compared with endometrial thickness measurements in a group of women who had abnormal postmenopausal bleeding. The recent literature was reviewed.STUDY DESIGN: Asymptomatic postmenopausal women receiving estrogen replacement, seen for routine examination during the 1-year period from Jan. 1, 1994, to Dec. 31, 1995, had the endometrium evaluated by transvaginal ultrasonography. Women with abnormal postmenopausal bleeding were likewise evaluated and their measurements compared with those of the study group.RESULTS: Twenty-seven different estrogen and estrogen-progestin combinations in 327 asymptomatic women were studied. Additionally, 24 women who were bleeding, not receiving estrogen, and 46 women with abnormal bleeding on estrogen therapy underwent ultrasonography of the endometrium. Endometrial thickness ranged from 1 to 15 mm in women on a regimen of combined estrogen-progestin therapy, 1 to 14 mm in women using sequential estrogen-progestin, and 3 to 15 mm for women receiving unopposed estrogen in the study group. For women with abnormal bleeding not using estrogen, the endometrium measured an average of 12.3 mm (range 2 to 29 mm), with unopposed estrogen 8.3 mm (range 4 to 13 mm), and for estrogen with progestin 6.5 mm (range 2 to 15 mm). Significant pathologic features were found in those women who had bleeding and endometrial measurements between 5.0 and 29 mm.CONCLUSION: There was no significant difference between endometrial thickness measurements in women receiving various combinations of estrogen replacement. In general, expected endometrial measurements can range from 1 to 15 mm. In women with postmenopausal bleeding, however, significant pathologic features may exist with an endometrium measuring as little as 5 mm. (Am J Obstet Gynecol 1997;176:1334-9.)     

雌激素替代疗法对绝经后妇女血浆一氧化氮的影响

目的探讨雌激素替代疗法（ＥＲＴ）对绝经后妇女血浆一氧化氮（ＮＯ）含量的影响。方法测定１７例健康绝经后妇女（健康组）,２１例患高血脂症绝经后妇女（高血脂组）应用ＥＲＴ前及应用ＥＲＴ４周后血浆ＮＯ及血清雌二醇（Ｅ２）含量,并与１０例健康绝经后妇女应用安慰剂（对照组）进行对照。结果对照组应用安慰剂前后,ＮＯ含量无变化;健康组及高血脂组应用ＥＲＴ后,ＮＯ含量明显升高,健康组升高尤其明显;健康组应用ＥＲＴ４周后Ｅ２水平与ＮＯ升高有明显相关性。结论绝经后妇女补充雌激素,可通过升高ＮＯ含量发挥其对心血管的保护作用。     

Indirect evidence that estrogen replacement therapy stimulates nitric oxide synthase in postmenopausal women.

The aim of the study was to investigate the effects of estrogen replacement therapy (ERT) on nitric oxide (NO) activity in healthy postmenopausal women. The study group consisted of 22 postmenopausal women (last menses at least 12 months prior to study entry) who were randomized to receive treatment for 2 months with patches that delivered either 50 micrograms/day of 17 beta-estradiol or placebo in a cross-over design. Blood samples for measurements of serum citrulline and arginine were collected at the start of the study and at the end of each treatment course. Serum citrulline and arginine were measured using high-performance liquid chromatography with fluorometric detection. Arginine levels were significantly lower in the ERT group compared to the placebo group, while citrulline levels did not change. The percentage citrulline/arginine ratio was significantly higher in the ERT group (42.9 +/- 21.6) compared to the placebo group (33.9 +/- 18.5) (p < 0.01). The citrulline/arginine ratio, both at baseline and during either ERT or placebo administration demonstrated a positive linear correlation with body mass index (BMI). No correlations were found between follicle stimulating hormone, estradiol and insulin levels and BMI. No correlations were found between age, time since menopause and baseline arginine and citrulline levels or the citrulline/arginine ratio. These data indirectly demonstrate that transdermal estradiol replacement in postmenopausal women is able to stimulate NO production through the involvement of endogenous L-arginine. A positive linear correlation was found between BMI and the citrulline/arginine ratio, suggesting an additional protective cardiovascular effect in overweight women.     

Dose-response evaluation of cyclic estrogen/gestagen in postmenopausal women: Placebo-controlled trial of its gynecologic and metabolic actions

In order to study dose-response relationships of estrogen in normal postmenopausal women, 100 volunteers were randomized to 12 months' treatment with placebo or one of three different doses (high, medium, or low) of natural estrogens (17β-estradiol and estriol), sequentially combined with norethisterone acetate for 10 of the 28 cycle days. A total of 87 women completed the trial with examinations every 3 months. Relief of climacteric symptoms was dose related, being 70%, 56%, and 33% in the high, medium, and low estrogen groups and unchanged in the placebo group. Regular vaginal bleeding occurred in 78% receiving high-dose in 64% receiving medium-dose, and in 40% receiving low-dose estrogen. Bone mass increased in the high and medium groups, was unchanged in the low group, and declined in the placebo group. Dose-related decreases in serum cholesterol of 10%, 5%, and 3% occurred in the three respective estrogen groups. Serum triglyceride levels, blood pressure, and body weight remained unchanged in all groups.     

Cardiovascular risk assessment with oxidised LDL measurement in postmenopausal women receiving intranasal estrogen replacement therapy

Objective.?To investigate the effect of intranasal estrogen replacement therapy administered to postmenopausal women alone or in combination with progesterone on markers of cardiovascular risk.

Methods.?The study was conducted with 44 voluntary postmenopausal women. In group I (n?=?15), the patients were treated with only intranasal estradiol (300?μg/day estradiol hemihydrate). In group II (n?=?11), the patients received cyclic progesterone (200 mg/day micronized progesterone) for 12 days in each cycle in addition to continuous intranasal estradiol. Group III (n?=?18) was the controls. Serum lipid profiles, oxidised low-density lipoprotein (LDL) and other markers of cardiovascular risk were assessed at baseline and at the 3rd month of the treatment.

Results.?Lipid profile, LDL apolipoprotein B, lipoprotein a, homocysteine, oxidised LDL values and oxidised LDL/LDL cholesterol ratio were not observed to change after 3 months compared to baseline values within each group (p?>?0.016). In comparison to changes between the groups after the treatment, only oxidised LDL levels and oxidised LDL/LDL cholesterol ratios of group II were increased compared to control group (p?<?0.05).

Conclusions.?Intranasal estradiol alone did not appear to have an effect on markers of cardiovascular risk in healthy postmenopausal women. However, the addition of cyclic oral micronized progesterone to intranasal estradiol influenced the markers of cardiovascular risk negatively in comparison to non-users in healthy postmenopausal women.     

Tibolone versus four estrogen replacement therapy protocols and plasma lipid levels in postmenopausal women.

OBJECTIVES: To compare tibolone therapy with four different estrogen replacement therapy protocols, with regard to the effects on plasma lipid profiles. METHODS: The plasma lipid levels of 178 postmenopausal women in five different therapy groups were compared with each other as well as their baseline levels with 6-month intervals during 2-year follow-up. Student's t-test, paired t-test and Pearson correlation analysis were utilized for statistical analysis. RESULTS: HDL cholesterol levels increased significantly from baseline in groups using oral estrogen (P<0.05) but a slight non-significant decrease was seen in tibolone therapy (P>0.05). LDL cholesterol levels significantly decreased at the end of the second year in oral estrogen and tibolone users (P<0.05). Triglyceride levels increased non-significantly with estrogen therapy (P>0.05), whilst decreased significantly in the tibolone group (P<0.05). CONCLUSION: Tibolone may be a good alternative to estrogen replacement therapy in postmenopausal women, as it has beneficial effects on LDL cholesterol and triglyceride levels, which play important role in atherosclerosis.     

Effects of estrogen therapy on hearing in postmenopausal women

OBJECTIVE: This study was undertaken to investigate how hormone therapy affects hearing in postmenopausal women. STUDY DESIGN: This prospective study involved 109 postmenopausal women. Twenty of the women were using estrogen therapy (ET group), 30 women were using hormone therapy (HT group), and 59 had not received hormone therapy of any kind (control group). Otoscopic examination revealed normal tympanic membranes in all 109 subjects. Each individual was tested with low- (250-2000 Hz) and high-frequency audiometry (4000-16000 Hz). Duration of hormone therapy was recorded, and patient characteristics (age, type of menopause, time since onset of menopause), body mass index (BMI), and hearing test results in the ET, HT, and control groups were compared. RESULTS: There were no statistically significant differences between the treatment (ET and HT group) and control groups with respect to age, BMI, or time since onset of menopause. The mean time on HT and ET was 4.13+/-2.41 years and 3.35+/-2.20 years, respectively. The mean air conduction results at low frequencies (250, 500, 1000, and 2000 Hz) in the ET group were significantly higher than the corresponding findings in the control group (P<.001) and than the HT group (P<.001). When the same comparisons were made between the HT group and the control group, none of the differences was statistically significant (P>.05). The mean air-conduction results at high frequencies (4, 6, 8, 10, 12, 14, and 16 kHz) in the ET group were significantly higher than the corresponding results in the HT group (P<.008). ET versus controls and HT versus controls at high frequencies revealed no significant differences (P>.05). The mean bone conduction results in the ET group were significantly higher than the corresponding findings in the control group (P<.016). Analysis of the same comparisons between the HT-ET and HT-control groups revealed no significant differences (P>.05). CONCLUSION: Estrogen therapy may slow down hearing loss in aging postmenopausal women; however, further studies of larger series are needed to confirm this, and the sites of hormonal action must also be explored.     

Vaginal flora in postmenopausal women: the effect of estrogen replacement

Objective:To determine the effect of estrogen replacement therapy (ERT) on the vaginal flora of postmenopausal women.Methods: Vaginal cultures were obtained from 15 postmenopausal women whose hormonal statuses were documented by serum follicle-stimulating hormone (FSH) and serum estrogen levels. After 8 weeks of ERT, consisting of 0.1 mg of estradiol delivered daily by dermal patch, the vaginal cultures were repeated, as were measurements of the vaginal pH, serum FSH, and serum estrogen levels.Results: Vaginal cultures revealed no significant change in the incidence of lactobacilli or of all aerobes. However, the incidence of anaerobic species fell after treatment from 47% to 13% (P = 0.05), and the incidence of anaerobic gram-negative rods declined after treatment from 40% prior to ERT to 7% (P = 0.035). Prior to ERT, the difference in mean vaginal pH between lactobacilli-positive and lactobacilli-negative subjects was not significant, but, following the administration of exogenous estrogen, the lactobacilli-positive subjects exhibited a significantly lower mean vaginal pH (4.4 +/- 0.4) relative to the lactobacilli-negative population (5.2 +/- 0.3) (P = 0.02).Conclusions: We conclude that women on ERT are less likely to have vaginal colonization with anaerobic bacteria when compared with women not using replacement therapy. Estrogen replacement may potentiate the effect of lactobacilli on vaginal pH.     

Modulation of the sleep electroencephalogram by estrogen replacement in postmenopausal women

OBJECTIVE: We performed an examination of the effects of estrogen replacement on the sleep electroencephalogram in postmenopausal women. STUDY DESIGN: A sleep electroencephalogram was recorded in 11 postmenopausal women with and without estrogen administered by skin patch (50 microg of estradiol per day). RESULTS: Estrogen enhanced rapid-eye-movement sleep (50 +/- 4 vs 39 +/- 5 minutes, P <.05) and reduced time awake (12 +/- 5 vs 20 +/- 6 minutes, P <.05) during the first 2 sleep cycles. The normal decrease in slow-wave sleep and delta activity from the first to the second cycle (in percentage from the first cycle) was restored by estrogen (-56% +/- 9% vs -5% +/- 14% and -20% +/- 6% vs -2% +/- 5%; P <.05, respectively). Sigma electroencephalographic activity was increased by estrogen from the first to the second half of the night but decreased during baseline. CONCLUSION: Estrogen treatment after menopause can help to restore the normal sleep electroencephalogram pattern, which in turn might contribute to improved cognitive functioning.     

Effect of estrogen replacement therapy on the serum osteocalcin level in the postmenopausal and castrated women

Osteocalcin (OC), the major noncollagenous bone protein, is a vitamin K-dependent protein which is synthesized in osteoblasts. Serum OC is increased in patients with certain metabolic bone diseases, but little is known about the effects of menopause, castration, and the estrogen-replacement therapy on serum OC. In this study, we attempted to determine the serum OC level before and after menopause and castration, and the effects of estrogen on serum OC were also studied. Mean serum OC in women who underwent menopause or castration within 5 years was 4.56 +/- 1.74 ng/ml (mean +/- SD) and the concentration was significantly higher than that of premenopausal women. Serum OC was then, transiently reduced but increased again when estrogen deprived conditions lasted for more than 10 years. Estrogen replacement therapy (conjugated estrogen 0.625 mg/day for 6 months) could decrease not only serum Ca. P and ALP but also the serum OC from 4.45 +/- 1.40 to 2.97 +/- 1.43 ng/ml (p less than 0.001). There was a significant correlation between the percent changes in serum OC and ALP before and after estrogen administration (r = 0.60, p less than 0.05).     

Effect of estrogen replacement therapy on cardiac function in postmenopausal women with and without flushes.

Left ventricular heart function and its response to long-term estrogen replacement therapy was assessed in 30 postmenopausal women, 20 of whom had modest to severe hot flushes and 10 of whom had never had them. Continuous transdermal estradiol was given to women who had surgically induced menopause, and a combination of transdermal estradiol and sequential medroxyprogesterone acetate was given to those who had spontaneous menopause. Left ventricular systolic and diastolic function was evaluated by complete two-dimensional M-mode and pulsed Doppler echocardiography before and after 6 and 12 months of therapy. The parameters assessed were: systolic and diastolic blood pressure, heart rate, cardiac septal and posterior wall dimensions, left ventricular end-systolic and end-diastolic dimensions and volumes, ejection fraction (EF), ejection time, peak left ventricular outflow velocity (PFV), flow velocity integral (FVI), acceleration time (AT), mean acceleration of systolic flow (MA), duration of early and late filling phase, peak velocity of the early (E) and late (A) mitral flow, and A/E velocity ratio. Although no difference in chamber and wall dimensions between flushers and non-flushers was found, women with hot flushes had lower (not significantly) EF, PFV, FVI, MA, blood pressure and heart rate before therapy. Twelve-month estrogen replacement therapy significantly reduced cardiac wall dimensions and improved systolic function in both flushers and non-flushers. However, stroke volume, EF and MA were increased whereas systolic blood pressure and heart rate were decreased more in flushers. Also, the increase in E mitral flow and decrease in A/E were more pronounced in flushers. Thus, although estrogen replacement therapy significantly improves heart function in healthy postmenopausal women, there appears to be some minor differences in response between flushers and non-flushers.     

Estradiol/progesterone-releasing vaginal rings for hormone replacement therapy in postmenopausal women

In order to investigate whether vaginal rings delivering estradiol and progesterone could prevent endometrial hyperplasia and relieve climacteric symptoms ,two variants of rings were used in 20 postmenopausal women with intact uteri for 4 months. One ring designated as PI-002 (n = 8) delivered in vitro estradiol 160 μg/day and progesterone 20 mg/day ,while the other (PI-003; n = 12) delivered the same dosage of estradiol but only half the progesterone (10 mg/day). Serum estrone ,estradiol and progesterone were measured at pretreatment ,weekly for 4 weeks ,and then monthly for 4 months. The incidence of hot flushes ,frequency of night sweats ,mood scores ,vaginal discharge and bleeding profiles were recorded. Endometrial thickness was monitored by ultrasonography. The mean estrone level was 50 pg/ml for 16 weeks. The mean serum estradiol level was 75 pg/ml for the first 4 weeks and gradually decreased to 50 pg/ml at 16 weeks. The mean progesterone level with the PI-002 ring was 5 ng/ml for the first 4 weeks and decreased to 3.5 ng/ml at 16 weeks. With the PI-003 ring ,the mean progesterone level was initially 3.5 ng/ml and then decreased to 2.5 ng/ml thereafter. Significant decreases in the incidence of hot flushes and night sweats as well as a striking improvement in mood scores were noted as early as 2 weeks after insertion. Three of the 20 women discontinued the treatment ,owing to ring expulsion. Increased vaginal discharge was observed with both rings in the first 6 weeks. Vaginal bleeding was more frequently apparent among users of the PI-002 ring ,although bleeding and spotting were confined to the first 6 weeks. Ultrasonographic monitoring of the endometrium constantly revealed a thickness of < 3 mm for both variants throughout use for 16 weeks. An estradiol/progesterone-releasing vaginal ring is a potential alternative to long-term hormone replacement therapy with minimum attention required. It provides effective protection against endometrial hyperplasia.     

Clinical features affecting the results of estrogen replacement therapy on bone density in Japanese postmenopausal women.

Although estrogen replacement therapy (ERT) has been established as an effective treatment for postmenopausal bone loss, the clinical features which predict the effects of ERT have not been well investigated in Japanese postmenopausal women. We analyzed the role of physical factors influencing the effect of ERT on vertebral bone mineral density (BMD) in 94 Japanese postmenopausal women treated for 2 years or longer. The increase in BMD with ERT is 17.6 +/- 27.6 mg/cm(2)/year (mean +/- SD) during the first 2 years. Rates of BMD change were negatively correlated with the estimated initial BMD, and positively correlated with age and years since menopause, while no correlation was noted with the body mass index by a simple correlation analysis. The relationships between BMD change and estimated initial BMD or age also held in a multiple regression analysis. The estimated initial BMD and age together accounted for 34.4% of the BMD change during ERT. Furthermore, there were very few (2.4%) nonresponders with a negative linear regression slope of BMD in the osteoporosis and osteopenia group, although 32.7% of the normal initial BMD group were nonresponders. These results suggest that the initial BMD and age are potent predictive factors of the ERT effect on BMD change in Japanese postmenopausal women.     

Hormone replacement therapy and urogenital disease in postmenopausal women

Estrogen deficit in postmenopausal women causes urogenital atrophy, which is responsible for a wide range of urinary disorders (urinary incontinence, urge incontinence, recurrent urinary infections) and genital disorders (prolapse, dispareunya, vaginal dryness). The efficacy of estrogen therapy on urinary incontinence is not yet demonstrated, but it is widely recognized that the topical use of estrogens lowers the risk of recurrent urinary infections and improves urogenital atrophy.     

Bone turnover in young hypoestrogenic women on hormonal therapy

OBJECTIVE: To compare the biochemical markers of bone turnover in hypoestrogenic women who had been on the standard dosage of Premarin 0.625 mg to that of the age-matched women who were menstruating spontaneously. STUDY DESIGN: Chinese women between 25 and 40 years of age with a diagnosis of hypoestrogenism who had been on Premarin 0.625 mg daily for more than 1 year were recruited. The control group comprised age- and parity-matched women who had proven ovulation by mid-cycle serum luiteinising hormone surge. Serum osteocalcin and serum pyridinoline crosslink, markers of bone formation and resorption, respectively, were measured by enzyme-linked immunosorbent assays. RESULTS: Twenty hypoestrogenic Chinese patients with a mean age of 36.2 were recruited as the study group. The same number of controls was recruited. There were no smokers in either group. The body weight, body height and body mass indices were comparable between the two groups. Both biochemical markers of bone metabolism did not differ between the two groups. CONCLUSION: The average bone turn-over rate in young hypoestrogenic Chinese women on Premarin 0.625 mg/day was similar to that of normal menstruating women.     

Compliance with hormone replacement therapy in postmenopausal Sicilian women

OBJECTIVE: To verify the compliance with hormone replacement therapy (HRT) over 2 years in a population of postmenopausal women in East Sicily. STUDY DESIGN: Patients starting hormonal therapy for the first time were enrolled in this study. A telephone survey was then conducted after 3, 6, 12 and 24 months and the reasons for any discontinuation were recorded. RESULTS: Of a total of 138 women who agreed to be enrolled in this prospective longitudinal study 72 were still taking the treatment after 1 year and only 56 at the end of the study, although only three patients reported that they had experienced no benefit. CONCLUSIONS: Type of work, surgical menopause and previous use of oral contraceptives were significantly statistically associated with better HRT compliance. Side effects and fear of breast cancer, which we maintain is exaggerated by the women and their family doctors, were the commonest reasons for early discontinuation of the hormonal treatment.     

Estradiol/progesterone-releasing vaginal rings for hormone replacement therapy in postmenopausal women.

In order to investigate whether vaginal rings delivering estradiol and progesterone could prevent endometrial hyperplasia and relieve climacteric symptoms, two variants of rings were used in 20 postmenopausal women with intact uteri for 4 months. One ring designated as PI-002 (n = 8) delivered in vitro estradiol 160 microg/day and progesterone 20 mg/day, while the other (PI-003; n = 12) delivered the same dosage of estradiol but only half the progesterone (10 mg/day). Serum estrone, estradiol and progesterone were measured at pretreatment, weekly for 4 weeks, and then monthly for 4 months. The incidence of hot flushes, frequency of night sweats, mood scores, vaginal discharge and bleeding profiles were recorded. Endometrial thickness was monitored by ultrasonography. The mean estrone level was 50 pg/ml for 16 weeks. The mean serum estradiol level was 75 pg/ml for the first 4 weeks and gradually decreased to 50 pg/ml at 16 weeks. The mean progesterone level with the PI-002 ring was 5 ng/ml for the first 4 weeks and decreased to 3.5 ng/ml at 16 weeks. With the PI-003 ring, the mean progesterone level was initially 3.5 ng/ml and then decreased to 2.5 ng/ml thereafter. Significant decreases in the incidence of hot flushes and night sweats as well as a striking improvement in mood scores were noted as early as 2 weeks after insertion. Three of the 20 women discontinued the treatment, owing to ring expulsion. Increased vaginal discharge was observed with both rings in the first 6 weeks. Vaginal bleeding was more frequently apparent among users of the PI-002 ring, although bleeding and spotting were confined to the first 6 weeks. Ultrasonographic monitoring of the endometrium constantly revealed a thickness of < 3 mm for both variants throughout use for 16 weeks. An estradiol/progesterone-releasing vaginal ring is a potential alternative to long-term hormone replacement therapy with minimum attention required. It provides effective protection against endometrial hyperplasia.