Haemostatic risk factors in healthy postmenopausal women taking hormone replacement therapy

OBJECTIVE: To compare changes in haemostatic parameters in healthy postmenopausal women taking either tibolone or 17beta-oestradiol/norethisterone acetate. METHODS: Factor VIIc, antithrombin, fibrinogen, thrombin-antithrombin complex (TAT), FDP (D-Dimer), tissue plasminogen activator (tPA) and plasminogen activator inhibitor I (PAI-1) were measured in 80 healthy postmenopausal women after 3, 6 and 12 months therapy with either 17beta-oestradiol/norethisterone acetate or tibolone. RESULTS: Both treatments significantly reduced fibrinogen, factor VIIc, antithrombin, tPA and PAI-1 antigen. Significantly lower levels of factor VIIc activity were observed on treatment with tibolone compared with 17beta-oestradiol/norethisterone acetate. TAT was unchanged with both treatments as was tPA activity. FDP (D-dimer) was increased on treatment with both preparations. CONCLUSIONS: The enhanced fibrin turnover and reduced antithrombin activity may play a role in the increased risk of venous thromboembolism in some susceptible women taking hormone replacement therapy (HRT) and could explain the lack of benefit of HRT in the secondary prevention of cardiovascular disease. The decreased levels of fibrinogen and factor VIIc found during treatment with 17beta-oestradiol/norethisterone acetate or tibolone may offer some degree of cardioprotection in healthy woman without pre-existing disease.     

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.     

Significance of incidentally thick endometrial echo on transvaginal ultrasound in postmenopausal women

Postmenopausal bleeding is "cancer until proven otherwise." A thin distinct endometrial echo on transvaginal ultrasound has a risk of malignancy of 1 in 917 and does not require an endometrial biopsy. If the endometrial echo is poorly visualized, then in such women, saline infusion sonohysterography is an appropriate next step. The prevalence of asymptomatic endometrial thickening (mostly due to inactive polyps) is high, approximately 10% to 17% of postmenopausal women. The risk of malignancy in such polyps is low (approximately 0.1%), and in structures that mimic polyps, it is also low (0.3%). The incidence of serious complications from an operative intervention in such postmenopausal women is not insignificant (1.3%-3.6%). Thus, automatic intervention in such women, without any high-risk status, is not warranted.     

Effects of hormone replacement therapy on postmenopausal uterine myoma

OBJECTIVES: To evaluate the effects of sequential continuous hormone replacement therapy (HRT) on myoma size and on pulsatility index (PI) of uterine arteries and to verify the correlation between uterine artery flow impedance and the growth rate of myoma in women receiving HRT. METHODS: In a prospective 1-year study 60 postmenopausal women were enrolled into three study-groups to receive continuous transdermal 17beta-oestradiol 0.05 mg/day plus nomegestrolo acetate 5 mg/day sequentially added: 20 patients (group A) unaffected by uterine myomas, 20 patients (group B) with single asymptomatic myoma <3 cm/14 cm3, 20 patients (group C) with single asymptomatic myoma >3 cm/14 cm3. The changes in myoma volume and in PI were assessed by means of transvaginal ultrasonographic scan every 3 months. The patients with myoma were divided into two subgroups: quiescent myoma (B1, C1) and growing myoma (B2, C2). RESULTS: No significant increase of uterine fibroids volume was found after 1-year HRT (24.14+/-20.02-->28.81+/-30.02 cm3). Six out of eight myomas growing during HRT belonged to group C. The uterine artery basal PI value of group A was significantly higher (P<0.01) than the corresponding PI in group B and C. At 3 months follow-up, uterine artery PI was significantly higher (P<0.01) than the basal value in both group B (1.70+/-0.22-->1.88+/-0.16) and C (1.59+/-0.28-->1.92+/-0.21). The baseline PI values in group B1 and C1 were significantly higher than the baseline values observed in group B2 and C2 (1.76+/-0.17 vs. 1.32+/-0.02, 1.76+/-0.16 vs. 1.24+/-0.08) and significantly lower than those observed in group A (2.39+/-0.47). After 3 months of HRT, the PI values were not significantly higher than the baseline values in groups B1 and C2 (1.76+/-0.17-->1.90+/-0.17; 1.24+/-0.08-->1.74+/-0.16), while they were significantly higher in group C1 (1.76+/-0.16-->2.01+/-0.17). CONCLUSIONS: Sequential continuous HRT does not increase the volume of the uterine myoma. The findings of very low resistance index in the uterine arteries of women with growing myoma may indicate the risk of growth of the neoplasia during HRT. The assessment of PI in the uterine arteries could be helpful in predicting the growth rate of the myomas before starting HRT.     

Comparison of transvaginal ultrasonography and saline infusion sonohysterography in evaluating the endometrial cavity in pre- and postmenopausal women with abnormal uterine bleeding

OBJECTIVE: To compare the diagnostic accuracy of transvaginal ultrasonography (TVUS) and saline infusion sonohysterography (SIS) of the endometrial cavity in pre- and postmenopausal women with abnormal uterine bleeding. DESIGN: In a prospective study, TVUS and concurrent SIS findings of 100 pre- and 33 postmenopausal women were recorded. The pathological diagnoses of the specimens, obtained by means of dilatation and curettage, hysteroscopy, and hysterectomy, were taken as reference and compared with the results of TVUS and SIS. RESULTS: When TVUS and SIS findings were compared with pathological results, the sensitivity and specificity of TVUS in diagnosing endometrial pathologies were 83% and 70.6%, respectively, whereas the sensitivity and specificity of SIS were 97.7% and 82.4%, respectively. The sensitivity and specificity of SIS in the diagnosis of endometrial polyps were 100% and 91.8%, respectively, and in the diagnosis of fibroids were 95% and 100%, respectively. CONCLUSION: SIS is more accurate than TVUS alone in the evaluation of the endometrial cavity in women with abnormal uterine bleeding.     

Ascorbic acid status in postmenopausal women with hormone replacement therapy.

OBJECTIVES: Hormone oral contraceptives affected ascorbic acid status adversely in young women. In vitro, estrogens and progesterone inhibited ascorbic acid accumulation in intestinal cells. This is a pilot study to examine the relation between hormone replacement therapy (HRT) and plasma ascorbic acid levels among a group of healthy non-smoking postmenopausal women. METHODS: Healthy non-smoking postmenopausal women aged 48-72 years, 34 with HRT and 21 without HRT, were recruited in summer, 1997. Their fasting plasma ascorbic acid levels were measured and information on ascorbic acid intakes (diet and supplements) was collected through questionnaires. RESULTS: Women taking HRT in this study did not have significantly lower plasma ascorbic acid levels compared with non-HRT users. When subjects were further divided into groups based on ascorbic acid supplementation, HRT users without supplement had a lower mean plasma ascorbic acid level (54+/-16 microM, n=10) compared with non-HRT users (66+/-14 microM, n=12) (P=0.08 for the effect of therapy). HRT users and non-users taking ascorbic acid supplement had similar plasma levels (66+/-10 microM, n=24; 66+/-12 microM, n=9, respectively). CONCLUSION: HRT does not affect ascorbic acid status of healthy well-nourished non-smoking postmenopausal women that are using ascorbic acid supplement. Future larger case-control or supplement intervention study is needed.     

Effect of hormone replacement therapy on uterine fibroids in postmenopausal women--a 3-year study

OBJECTIVE: The aim of this prospective 3-year clinical study was to examine the effect of hormone replacement therapy (HRT) on uterine fibroid growth among postmenopausal women. METHODS: Thirty-seven postmenopausal women with uterine solitary fibroids were recruited randomly for HRT in a 3-year program. All participants received 0.625 mg conjugated equine estrogen (CEE) and 5 mg medroxyprogesterone (MPA) daily. Fibroid volume was measured by transvaginal ultrasonography at baseline and then at 12-month intervals for 3 times. Clinically, significant fibroid growth was defined as an increase in volume of more than 25% compared with baseline. Also, 35 postmenopausal women with uterine fibroid were studied as control who did not receive HRT during the study period. RESULTS: Fibroid volume had increased significantly after 1 year both in HRT users and non-users. These increases continued to the second year significantly in HRT users but not in non-users. However, the volumes declined significantly at the third year to similar levels as those measured at baseline in control. In HRT users, fibroid volume though significantly increased at the third year (vs. baseline) but declined insignificantly in comparison with the second year. Clinically, at end of the third year study, one of 34 and three of 34 women increased fibroid volume over 25% compared with baseline in HRT non-users and users, respectively. CONCLUSIONS: HRT does increase uterine fibroid volume statistically. However, its effect appears in the first 2 years of use. The increased fibroid volume begins to decline at the third year both in HRT users and non-users. Clinically, the increased effect of HRT on uterine fibroid of postmenopausal women should be not over-emphasized at least for 3 years of usage.     

Raloxifene therapy does not affect uterine blood flow in postmenopausal women: a transvaginal Doppler study

OBJECTIVE: To monitor the effects of raloxifene therapy on the uterus of postmenopausal women by transvaginal ultrasonography and color flow Doppler. Methods: Twenty-five healthy postmenopausal women were enrolled in this prospective longitudinal study performed at Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeir?o Preto. The patients were treated with raloxifene hydrochloride (60 mg per day) for 6 months. All were submitted to transvaginal ultrasound examination with color flow Doppler (ATL-HDI 3000 equipment) before the beginning and after 1, 3 and 6 months of treatment. Resistance index (RI) and pulsatility index (PI) of the uterine arteries were determined by the Doppler method, being considered as indicators of uterine perfusion. The following variables were analyzed: endometrial thickness, uterine volume, RI, and PI. Data were analyzed statistically by repeated-measures analysis of variance. RESULTS: Before treatment, endometrial thickness was 3.38 +/- 0.73 mm, and similar values were observed after 1, 3 and 6 months of treatment (3.04 +/- 0.82; 3.3 +/- 0.83; and 3.37 +/- 0.79, respectively) (P > 0.05). No significant differences in uterine volume were observed between the pre- and post-treatment periods. Uterine artery perfusion as indicated by RI and PI measured by Doppler also showed no significant variation, with a high impedance flow being maintained throughout treatment. CONCLUSIONS: In the group studied here, raloxifene treatment at the dose of 60 mg per day for 6 months did not induce significant changes in endometrial thickness, uterine volume or uterine artery perfusion, confirming that short-term raloxifene treatment does not affect the uterus of postmenopausal women.     

Comparison of transvaginal ultrasonography and endometrial biopsy in endometrial surveillance in postmenopausal HRT users

Objectives: To compare transvaginal ultrasonography with histological findings in endometrial evaluation of postmenopausal women using hormone replacement therapy and to evaluate endometrial safety of three hormone replacement therapy regimens. Methods: in a randomized, comparative study in postmenopausal women, endometrial safety was evaluated using (1) no hormone replacement therapy, (2) oral micronized 17β-estradiol/oral sequential dydrogesterone, (3) transdermal 17β-estradiol/oral sequential dydrogesterone, or (4) oral tibolone. 85 Non-hysterectomised subjects underwent transvaginal ultrasonography immediately before Pipelle biopsy at baseline and subsequently after 12 and 24 months. Endometrial thickness and uterine dimensions were determined by transvaginal ultrasonography, and endometrial thickness (double-layer) was compared with biopsy results. Results: Endometrial evaluation was conveniently performed by transvaginal ultrasonography, and endometrial thickness correlated well with biopsy findings. If endometrial thickness was <5 mm, the endometrial biopsy sample was either inactive/atrophic or insufficient for histopathological diagnosis. Hyperplastic or malignant changes were not reported. After 24 months, endometrial thickness was increased both in the oral (P<0.001) and transdermal (P<0.001) 17β-estradiol/dydrogesterone groups, whereas with tibolone the change in endometrial thickness was not different from controls. Conclusion: transvaginal ultrasonography of the endometrium reliably predicts the histological picture in hormone replacement therapy users. Using 5 mm endometrial thickness as cut-off point, more than 75% of biopsies could be avoided. All three hormone replacement therapies were safe with respect to the endometrium. With sequential 17β-estradiol/dydrogesterone the expected progestogen-induced secretory pattern was observed, whereas endometrial histology under tibolone closely mimicked the natural atrophic postmenopausal state.     

Carotid and uterine vascular resistance in short-term hormone replacement therapy postmenopausal users

Objective: To compare the short-term effects of oral hormone replacement therapy (HRT) and placebo on carotid and uterine vascular impedance. Methods: 80 postmenopausal women selected from the outpatient clinic of the Hospital Leonor Mendes de Barros in São Paulo, Brazil, were randomized to oral HRT (estradiol 2 mg/norethisterone acetate 1mg—Kliogest^r) or placebo. Carotid and uterine arteries pulsatility indices (PIs) were assessed by color Doppler at baseline, after 4 and 12 weeks of treatment. Seventy-six women completed the trial, 38 in each group. Results: The carotid PI did not decrease significantly in either group. In the uterine arteries, the drop in PI was steeper and greater for HRT women. Drops occurred despite the supposed counteracting effect of norethisterone acetate. In placebo group, there was no significant difference between 4 and 12 weeks of treatment compared with the baseline. The results did not change when analyzed in a real treatment approach. Conclusion: Oral continuous HRT are effective at 12 weeks in reducing impedance to flow in uterine, but not in carotid circulation. These results suggest that the effects of HRT vary by vascular site, and do not have a detectable short-term vascular effect in the carotid area.     

A morphometric study of the uterine glandular epithelium in women with premature ovarian failure undergoing hormone replacement therapy.

In this study we examined the fine structure of the human glandular epithelium in women with idiopathic ovarian failure in artificial cycles produced by two different types of hormone replacement therapy (oestradiol valerate orally and either intramuscular injection of progesterone or progesterone via vaginal pessary), both of which had been claimed to be capable of supporting successful implantation. Biopsies were performed on day 19 of the artificial cycle. A variety of sterological probes were used to quantify the structural characteristics of these cells and the results obtained were compared with those from normal fertile subjects biopsied on days 2 and 5 after the luteinizing hormone (LH) surge. The glandular epithelial cells from the vaginal group had a less elaborate secretory apparatus when compared with the intramuscular group or with LH + 5 controls. Many of the features of the vaginal group suggested a continued oestrogenic influence, while the intramuscular group seemed to be more advanced than LH + 5.     

Two hormone replacement therapy (HRT) regimens for middle-eastern postmenopausal women

Most previous studies designed to evaluate the efficacy of hormone replacement therapy (HRT) have been carried out in Europe, North America and Australia, involving Caucasian women for 6 months or less. OBJECTIVES: To evaluate the 12-month effects of two different HRT regimens on postmenopausal symptoms of Middle-Eastern women. METHODS: Hundred healthy Libyan women with postmenopausal symptoms, 12 months or more since their last menstrual period, were enrolled in a 12-month prospective study. Participants were randomly prescribed one of the two formulations, 50 in each group. These regimens were a continuous regimen of tibolone 2.5 mg oral tablets and a continuous regimen of 17beta-oestradiol sequentially combined with dydrogesterone (2/10 mg) oral tablets. The presence and severity of short- and intermediate-term symptoms were reported at 0, 3, 6 and 12 months of treatment. Observed symptoms were hot flushes, night sweating, palpitations, insomnia, depression, nervousness, loss of memory, vaginal dryness, loss of libido and joint pain. RESULTS: Forty-nine women (98%) in each group completed the 12-month study period. Participants, in the two groups, experienced a significant improvement within the first 3 months of treatment. The observed symptoms were completely relived by the sixth month without any significant difference between the two groups. Improvements were sustained over the 12-month period of the study. HRT users showed their acceptance to the two regimens. CONCLUSIONS: Tibolone and 17beta-oestradiol/dydrogesterone oral tablets were effective and safe to treat short- and intermediate-term symptoms in Middle-Eastern postmenopausal women, within 6 months, and with no significant differences between the groups. Thus, the use of HRT to relieve menopausal symptoms is highly recommended, at least in this region.     

Ultra low-dose hormone replacement therapy and bone protection in postmenopausal women

OBJECTIVES: The aim of the present study was to evaluate the effects of low doses of hormone replacement therapy (HRT) in normal young postmenopausal women. METHODS: In an open trial healthy, non-obese postmenopausal women received for 2 years a low-dose continuous combined HRT (LD-HRT) containing 1mg estradiol+0.5 mg norethisterone acetate each pill for 28 days, or 0.5 mg of 17beta-estradiol and 0.25 mg of norethisterone acetate (Ultra low dose, Ultra-LD-HRT) along with 1000 mg of calcium per day. Control group consisted of women receiving only 1000 mg of calcium per day, for 2 years. Menopausal symptoms were evaluated by the Green climacteric scale for the first 12 weeks of the study while bleeding profiles, bone mineral density (BMD) and bone turnover were assessed for 24 months. RESULTS: LD-HRT and Ultra-LD-HRT were effective in reducing menopausal clinical symptoms. In the control group, BMD significantly (P<0.05) decreased at the spine (-2.8+/-0.2%), and femoral neck (-2.8+/-0.7%). In LD-HRT treated group BMD showed a significant (P<0.05) increase at the spine (5.2+/-0.7%), and femoral neck (2.8+/-0.4%) after 24 months. In the Ultra-LD-HRT treated women spine and femoral neck BMD showed a significant (P<0.05) increase (2.0+/-0.3 and 1.8+/-0.3%, respectively) after 24 months. In these women treated with LD-HRT and Ultra-LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women. CONCLUSIONS: LD-HRT and Ultra-LD-HRT can alleviate subjective symptoms providing an effective protection against the postmenopausal decrease of BMD.     

Facial wrinkling in postmenopausal women. Effects of smoking status and hormone replacement therapy

Background: There is some evidence that hormone replacement therapy may produce significant improvements in fine wrinkling, while aging skin is more frequently found in smokers. However, studies of the combined effect of a protective factor, such as HRT, and a damaging factor, such as smoking, are rare. Objectives: To determine in postmenopausal women the relationship between smoking status and the average number of packets of cigarettes since the subject took up smoking (packs-years) on the one hand, and facial wrinkling on the other, and to evaluate the role of hormone replacement therapy in the prevention of wrinkles in smokers and non-smokers. Methods: All subjects were recruited from our menopause clinic at Hospital Clı́nic i Provincial in Barcelona and were placed into one of three groups according to their smoking status: 215 life-long non-smokers, 306 former smokers and 209 current smokers. Smoking status, pack-years and hormone replacement were assessed by direct questioning. Facial wrinkle scores were estimated by standardized visual assessment. Results: The relative risk of moderate–severe wrinkling for current smokers compared to that for life-long non-smokers was 2.57 (confidence interval: 1.83–3.06; P<0.0005). Pack-years was positively related to facial wrinkles. Life-long non-smokers receiving HRT had lower facial wrinkle scores than Life-long non-smokers who had never received HRT. HRT did not, in general, modify the facial wrinkle score in current smokers. Conclusion: Our results suggest that the risk of facial wrinkles is greater in smokers and that HRT does not diminish this risk.     

B cell subsets in postmenopausal women and the effect of hormone replacement therapy

Objectives: In elderly subjects the capacity for antibody production is depressed. This immunosenescence state of humoral immunity is associated with the occurrence of autoimmune disorders involving CD5⁺ B (B-1) cells. Since estrogen is capable of stimulating the production of autoantibodies, this sex steroid hormone may be a contributing cause of the higher incidence of autoimmune diseases in women. In the present study, B cell subsets in women during the postmenopausal period was determined. The effect of hormone replacement therapy (HRT) on B cell subsets was examined to establish whether the administration of gonadal hormones influence humoral immunity in postmenopausal women. Methods: Forty six untreated pre- and postmenopausal women and 39 women on HRT were studied. The proportion of B-1 (CD5⁺) and conventional CD5⁻ B (B-2) lymphocytes was determined by two-color flow cytometry. Serum autoantibodies to a nuclear antigen and to interleukin (IL)-1 were measured by immunofluorescence and by radioimmunoassay, respectively. Thirteen women were examined prospectively before and during HRT. Results: In late postmenopausal women (≥30 years postmenopausal period), the proportion of B-2 cells was significantly reduced (p<0.01) compared to those of premenopausal and perimenopausal women. HRT induced a significant (p<0.01) increase in the percentage of B-2 cells, while that of B-1 cells remained unchanged. HRT did not affect autoantibody production. Conclusion: HRT may retard the progress of immunosenescence by increasing the production of B-2 cells. Moreover, HRT appears not to increase the risk of autoimmune diseases developing in postmenopausal women.     

Assessment of DNA damage in postmenopausal women under hormone replacement therapy

OBJECTIVE: To evaluate the possible DNA damage in peripheral blood leukocytes of postmenopausal women under different hormone replacement therapies (HRT), comet assay, a standard method for assessing genotoxicity has been used. METHOD: 46 women were categorized in three groups-Group A: 15 surgical menopausal women who underwent surgery for benign conditions, receiving conjugated equine estrogen, 0.625 mg/day (CEE) for 2.3 +/- 1.5 years, Group B: 16 spontaneous menopausal women receiving conjugated equine estrogen, 0.625 mg/day plus medroxyprogesteron acetate, 5mg/day (CEE + MPA) for 2.4 +/- 1.0 years and Group C: 15 spontaneous menopausal women receiving tibolone, 2.5mg/day for 2.4 +/- 1.3 years. Control group consisted of 15 spontaneous menopausal women who never had HRT. RESULTS: Significant differences in terms of DNA damage were observed between Group A and B with controls as mean total comet scores 23.93 +/- 5.84, 19.44 +/- 6.19 and 10.07 +/- 2.40, but no significance (P > 0.05) were detected between Group C and controls as mean total comet scores 12.07 +/- 3.65 and 10.07 +/- 2.40, respectively. CONCLUSION: Reduced DNA damage were observed with tibolone compared to CEE or CEE + MPA therapy. Studies of this approach are needed.     

Role of hysteroscopy with endometrial biopsy to rule out endometrial cancer in postmenopausal women with abnormal uterine bleeding

OBJECTIVE: To compare the diagnostic accuracy of ultrasonographic endometrial thickness and outpatient hysteroscopy, to establish the most appropriate exam for the diagnosis of endometrial cancer in postmenopausal women with abnormal uterine bleeding (AUB). The secondary aim was to develop a multivariable approach considering clinical history as an added value for these diagnostic procedures. METHODS: This prospective study was conducted on 220 consecutive postmenopausal patients with AUB, who underwent ultrasonographic evaluation of endometrial thickness, outpatient hysteroscopy and endometrial biopsy. Evaluation of sensitivity, specificity, positive and negative predictive value was performed. Receiver operator characteristic curve (ROC) was calculated to assess the global performance of ultrasonographic measurement of endometrial thickness and diagnostic hysteroscopy as tests for detecting endometrial cancer and atrophy. RESULTS: Histological findings for <4 mm level revealed that atrophy was present in 48 (65%) and in 2 cases (2.7%) endometrial cancer was found; for > or = 4 mm values polyps and myomas were present in 86 (59%) and there were 11 (7.5%) endometrial cancer. Sensibility and specificity for trans-vaginal ultrasound, with a cut-off value > or = 4 mm, was 55.6% and 49.7% while positive predictive value was 83.3% and negative predictive value 98.1% (ROC curve 0.597). Hysteroscopy revealed sensitivity 100%, specificity 49.6%, positive predictive value 81.3% and negative predictive value 100% (ROC curve 0.993). CONCLUSIONS: In conclusion, endometrial thickness <4 mm can miss malignancies but trans-vaginal ultrasound remains the first line diagnostic procedure in postmenopausal women without AUB, because it is not invasive and has high sensitivity for detecting endometrial cancer and other endometrial disease; according to our experience, outpatient hysteroscopy with biopsy is mandatory in all postmenopausal women with AUB.     

Changes in endometrial blood vessels in the endometrium of women with hormone replacement therapy-related irregular bleeding

BACKGROUND: Irregular bleeding affects up to 60% of hormone replacement therapy (HRT) users. The mechanism of this bleeding is not understood. Reduced endometrial microvascular integrity appears to underlie breakthrough bleeding in pre-menopausal women and the aim of this study was to establish whether similar changes are seen in HRT users and hence to elucidate a possible mechanism of irregular bleeding. METHODS: Endometrium from 34 HRT users with amenorrhoea, irregular bleeding or regular bleeding was assessed for endometrial endothelial cell density (anti-CD34), number of blood vessels per mm(2), vascular basal lamina components (laminin, collagen IV and heparan sulphate proteoglycan) and in 32 subjects and 23 controls for perivascular smooth muscle alpha (SMA). Findings were compared with a control population of 29 post-menopausal women not using HRT, other sex steroids or tamoxifen and with no vaginal bleeding. Staining intensity was assessed in a blinded fashion in all immunohistochemical studies. RESULTS: Four significant differences in endometrial blood vessels were observed between HRT users and controls: (i) a significantly lower density of endometrial endothelial cells (EC staining for CD34) per mm(2) was present in HRT users compared with controls (P < 0.001); (ii) endothelial cells (EC) were predominantly organized within blood vessels (83%) in controls but in HRT users EC were dispersed in the tissues with only 29% in organized vessels (P <0.001); (iii) supportive perivascular cell SMA was significantly reduced in 23 post-menopausal HRT users compared with 23 post-menopausal controls (n = 29, P = 0.013) and (iv) an atrophic or inactive histological pattern of endometrium was more frequently seen in the controls (P < 0.001). CONCLUSIONS: These findings support the hypothesis that exposure to HRT profoundly alters endometrial blood vessels, reducing structural integrity thereby predisposing to irregular bleeding in HRT users.     

Endocrinological features and endometrial morphology in climacteric women receiving hormone replacement therapy

Prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), oestrone (E₁), and oestradiol (E₂) levels were determined in 204 women who were receiving hormone replacement therapy for their climacteric symptoms. The changes in these hormone levels and the endometrial morphology were studied in order to determine the effects of the replacement therapy. The women were divided into two groups: the first group of 120 women was treated with conjugated oestrogens administered cyclically, plus norethisterone acetate. The second group of 84 women received oral oestriol succinate, also administered cyclically but without additional progestogens. The oestrogen-progestogen therapy resulted in a disappearance of the climacteric symptoms and a significant decrease of FSH and LH levels. Oestriol therapy was less effective than the conjugated oestrogens as a replacement therapy. Oestriol therapy also resulted in a less remarkable decrease of gonadotrophin levels. There were no significant changes in prolactin levels in either group of women. The endometrial histology did not change significantly after either of the two hormone replacement therapies.