Impact on uterine bleeding and endometrial thickness: tibolone compared with continuous combined estradiol and norethisterone acetate replacement therapy

Objective: To evaluate endometrial thickness and the incidence of uterine bleeding in postmenopausal women using either tibolone 2.5 mg or continuous combined 2 mg estradiol and 1 mg norethisterone acetate (E+NETA) daily as hormone replacement therapy. DESIGN: We compared diary records of self-reported uterine bleeding and measurements of endometrial thickness, area, and volume by transvaginal sonography at baseline and after 1, 3, 6, and 12 months in a 1-year, prospective, randomized, double-blind, single-center trial of 100 postmenopausal women aged 46-69 years. Bleeding frequencies and endometrial thickness were assessed by Chi-square tests and analysis of covariance, respectively. RESULTS: Self-reported bleeding was significantly less in the tibolone group. Bleeding episodes were reported by 27.7% of women in the tibolone group and by 59.2% in the E+NETA group. The mean number of days with bleeding was 5.8 +/- 27.0 in the tibolone group and 35.6 +/- 58.6 in the E+NETA group. Six women in the tibolone group and seven in the E+NETA group discontinued the study; three in the E+NETA group because of bleeding. The mean endometrial thickness at baseline was 2.56 +/- 0.81 mm in the tibolone group and 2.58 +/- 1.04 mm in the E+NETA group. After 1 year, the corresponding figures were 3.32 +/- 1.58 mm and 3.07 +/- 1.68 mm. Thus, 86% of women in the tibolone group and 93% in the E+NETA group had an endometrial thickness of less than 5 mm. CONCLUSIONS: Use of tibolone 2.5 mg daily for 1 year was associated with significantly less bleeding and spotting compared with daily continuous combined 2 mg estradiol and 1 mg norethisterone acetate in postmenopausal women in the presence of both minimal and nonprogressive increase of endometrial thickness associated with the two regimens.     

Tibolone versus conjugated estrogens and sequential progestogen in the treatment of climacteric complaints

Objective: Tibolone has been shown to alleviate climacteric symptoms. This study was designed to compare the effect of tibolone (Livial®, 2.5 mg daily) on different climacteric complaints and its impact on the endometrium, determined by vaginal ultrasound, with that of conjugated estrogens (Premarin®, 0.625 mg daily) continuously for 6 months in combination with the progestogen medrogestone (Colpron®, 2 × 5 mg daily for 12 days each month). Methods: One hundred and twenty-nine postmenopausal women were recruited and the severity of climacteric symptoms as well as endometrial thickness were recorded at the pre-trial examination and after 1, 3, and 6 months. Results: With the exception of vertigo, mood depression, mood disorder, loss of libido, and dryness of skin, where tibolone was found to be more effective than conjugated estrogens/medrogestone, climacteric symptoms improved significantly in both groups over the 6-month study period. Endometrial thickness did not increase significantly in the tibolone group, whereas in the conjugated estrogens/medrogestone group there was a highly significant increase after 1 month and still a trend towards significance after 6 months. Recurrence of vaginal bleeding occurred significantly less frequently in the tibolone group than in the comparison group. Conclusion: Tibolone seems to offer a complete treatment of the climacteric complaints whilst avoiding some of the problems associated with classical hormone replacement therapy.     

A 5-year study on the effect of hormone therapy, tibolone and raloxifene on vaginal bleeding and endometrial thickness

OBJECTIVES: To study the effect of standard and low-dose estrogen-progestin therapy (EPT), tibolone and raloxifene on the incidence of vaginal spotting/bleeding and endometrial thickness over a 5-year period. METHODS: Seven hundred eighty-six postmenopausal women were studied in an open prospective design. Vaginal spotting/bleeding and endometrial thickness as assessed by transvaginal ultrasonography was compared between six categories of women over a 5-year period: three categories in women on continuous combined estrogen-progestin therapy, one category under tibolone, one category under raloxifene and one under no treatment. More specifically, women received tibolone 2.5 mg (N = 204), raloxifene HCl 60 mg (N = 137), conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5mg (N = 122), 17beta-estradiol 2mg/norethisterone acetate 1mg (N = 58), 17beta-estradiol 1mg/norethisterone acetate 0.5mg (N = 76) or no therapy (controls, N = 189). Women with suspected endometrial pathology were referred for hysteroscopy. RESULTS: Bleeding/spotting incidence was highest among standard dose EPT users (conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5mg: 40.1%, 17beta-estradiol 2mg/norethisterone acetate 1mg: 44.8%, p < 0.001 compared to controls). Low-dose EPT associated with lower incidence of spotting/bleeding (34.1%). The incidence under tibolone and raloxifene was 22.5% and 2.9%, respectively, while 3.2% of women not receiving therapy reported vaginal spotting/bleeding. Mean endometrial thickness was not significantly affected in any of the groups studied. The drop-out rate due to spotting/bleeding was higher in the two higher dose EPT regimens. After logistic regression analysis, age at baseline was the only significant predictor of subsequent spotting/bleeding (b = -0.25, S.E. = 0.09, p = 0.006), while menopausal age and pre-treatment serum FSH had marginal significance. CONCLUSIONS: EPT, tibolone and raloxifene do not appear to associate with significant changes in endometrial thickness in the majority of cases. The low-dose EPT regimen associated with a decreased incidence of unscheduled spotting/bleeding compared to the standard dose regimens. Tibolone expressed a favorable endometrial profile, as seen in its effect on unscheduled spotting/bleeding and mean endometrial thickness. Raloxifene associated with the lowest incidence in S/B and the lowest drop-out rate.s.     

Absent correlation between vaginal bleeding and oestradiol levels or endometrial morphology during tibolone use in early postmenopausal women

OBJECTIVE: To investigate a potential correlation between vaginal bleeding and oestradiol (E2) levels/endometrial morphology in early postmenopausal women using tibolone (Livial(R)). METHODS: A 2-year randomised placebo-controlled study of 94 healthy women, 1-3 years after spontaneous menopause, receiving either placebo (n=23), 1.25 mg/day (n=36) or 2.5 mg/day (n=35) tibolone. Episodes of vaginal bleeding throughout the 2-year study period were recorded. Age, age of menopause, months since menopause and body mass index were recorded. Serum E2 levels were assessed at baseline and at 3-month intervals throughout the study period. In case of vaginal bleeding, endometrium morphology was assessed by Vabra Curettage. RESULTS: Fifty-one percent (n=18, P<0.05) of women in the 2.5 mg/day tibolone group and 44% (n=16, P=0.07) in the 1.25 mg/day tibolone group presented with at least one period of vaginal bleeding, compared with 22% (n=5) in the placebo group. The women who bled in the placebo group were younger (P<0.01), had menopause at an earlier age (P<0.05), had a shorter duration since menopause (P<0.05) and had a higher median E2 serum level prior to bleeding (P<0.05). In contrast, in both tibolone groups, no determinants could be found for the vaginal bleeding. Ninety percent of the first bleedings occurred within 9 months after starting the treatment. At Vabra endometrium sampling, there was no evidence of endometrial stimulation. CONCLUSIONS: In the present study, early postmenopausal women using 1.25 or 2.5 mg/day tibolone are 2-2.5 times more likely to present with vaginal bleeding compared with placebo (P<0.05) without evidence of higher serum E2 levels or endometrial stimulation.     

Regression of endometrial thickness in combination with reduced withdrawal bleeding as a progestational effect of tibolone in postmenopausal women on oestrogen replacment therapy

For 176 postmenopausal women on HRT with progestogen addition ‘on demand’ medroxyprogesterone acetate (MPA), noresthisterone and tibolone were used to protect the endometrium in 214 cases. Tibolone is a gonadomimetic steroid with combined progestogenic and estrogenic effects. In this study tibolone has been used as a progestogen. The results of these three progestogens were compared. The endometrial thickness before and after the use of progestogen was determined by vaginosonography. In 175 out of 214 cases progestogen addition during oestrogen therapy caused endometrial regression. Withdrawal bleeding was observed 166 times. If the endometrial thickness on the onset of progestogen addition was 5 mm or more, in nearly all cases withdrawal bleeding occurred when MPA or norethisterone was used. If tibolone was used, no withdrawal bleeding occurred in over half the cases studied. We report the first observation of induced endometrial regression without withdrawal bleeding.     

Endometrial safety with a low-dose intrauterine levonorgestrel-releasing system after 3 years of estrogen substitution therapy

OBJECTIVE: To evaluate the pharmacodynamic effects of a novel intrauterine drug delivery system, FibroPlant-levonorgestrel (LNG), on the endometrium in 24 postmenopausal women using estrogen substitution therapy (EST) to suppress climacteric symptoms. DESIGN: A 3-year non-comparative prospective clinical trial. SUBJECTS: The treatment with the FibroPlant-LNG intrauterine system (IUS), releasing 14 microg of LNG per day, was part of a regimen for estrogen substitution therapy in symptomatic postmenopausal women to prevent endometrial proliferation and bleeding. The majority of women received percutaneous 17 beta estradiol, 1.5 mg daily, or an equivalent dose by patch or orally, on a continuous basis. OUTCOME MEASURES: Menstrual pattern, endometrial histology and ultrasonographic evidence of endometrial suppression, after 3 years of use. RESULTS: The endometrial histology specimen showed profound endometrial suppression with glandular atrophy and stroma decidualization in all women. On transvaginal ultrasound, this corresponds with a thin endometrium (<5 mm) and clinically with a "bleed-free" menstrual pattern or amenorrhoea. CONCLUSION: The results of this 3-year study in 24 postmenopausal women using EST suggest that the FibroPlant-LNG IUS is effective in causing strong suppression of the endometrium during the entire period of EST. Target delivery in the uterine cavity could be the preferred route of administering a progestin to oppose estrogen stimulation of the endometrium.     

Tibolone and risk of endometrial polyps: a prospective, comparative study with hormone therapy

OBJECTIVE: To assess the incidence of endometrial polyps during postmenopausal replacement therapy with tibolone, using an appropriate control group. DESIGN: A total of 485 postmenopausal women were included in this open, prospective, comparative study for a duration of 36 months. Of this group, 249 women received 2.5 mg/day of tibolone and 244 women served as controls, receiving continuous-combined estrogen-progestogen therapy (HT). Transvaginal ultrasound, hysteroscopy, and directed biopsies were performed before treatment was initiated and at the end of the study. RESULTS: Two hundred twenty-one of the women receiving tibolone and 203 receiving continuous-combined HT completed the study. Endometrial polyps were detected in 74 women (33.4%) from the tibolone group and in 22 women (10.8%) from the HT group (P < 0.01). The vaginal bleeding rate did not differ between the groups. The frequency of atrophic polyps was significantly higher in the tibolone group (P < 0.01). No difference was found in the size of the polyps. CONCLUSIONS: Tibolone increases by threefold the risk for endometrial polyps.     

The effect of raloxifene and tibolone on the uterine blood flow and endometrial thickness: a transvaginal Doppler study

OBJECTIVES: To evaluate and compare the effect of different than classical hormone therapy medications, such as raloxifene and tibolone, on the uterine arteries and endometrium of postmenopausal women using transvaginal ultrasonography. METHODS: The prospective study included 62 healthy, postmenopausal women recruited from the Menopausal Clinic of the 2nd Department of Obstetrics and Gynecology of the University of Athens. Subjects were randomly allocated to receive raloxifene HCl in a daily dose of 60 mg orally (Group A-31 women) or tibolone in a daily dose of 2.5 mg orally (Group B-31 women). The study period was 6 months and all subjects were assessed using transvaginal ultrasonography before treatment initiation as well as after 3 and 6 months for evaluation of the endometrial thickness and the pulsatility (PI) and resistance (RI) indices at the level of the uterine arteries. RESULTS: No significant differences in RI, PI and endometrial thickness were observed in the raloxifene group during the 6-month treatment. In the tibolone group, PI and RI values decreased linearly from baseline to the end of the study, whereas the endometrial thickness was significantly increased during the first 3 months remaining unaltered thereafter. Comparisons between the two study groups revealed significant percent change of values in the pre-treatment to month-3 period and no difference with regard to pre-treatment, month-3 and month-6 absolute values. CONCLUSION: Raloxifene and tibolone exert dissimilar effects on uterine blood supply parameters and endometrial thickness.     

Dynamic monitoring of menopause hormone therapy and defining the cut-off value of endometrial thickness during uterine bleeding

The aim of this study was to evaluate the effects of low-dose tibolone therapy on ovarian area, uterine volume and endometrial thickness, and define the cut-off value of endometrial thickness for curettage during uterine bleeding. We followed 619 postmenopausal women, aged 40-60 years, for two years. There were 301 subjects in the low-dose tibolone treatment group and 318 subjects in the control group. The ovarian area, uterine volume and endometrial thickness in all participants were measured by transvaginal ultrasound prior to, one and two years post enrollment, respectively. Endometrial specimens were collected from all subjects with abnormal uterine bleeding during the follow-up period. We found that the uterine volume in the treatment group was greater than that in the control group, and the difference was significant (P<0.05), but there were no significant differences in ovarian area and endometrial thickness between the two groups (P>0.05). When the cut-off value for endometrial thickness was 7.35 mm, the sensitivity and specificity were 100% and 79.07%, respectively, and 85.71% and 93.02% when 7.55 mm was set as the cut-off during tibolone therapy. The results indicate that low-dose tibolone therapy may postpone uterine atrophy and the cut-off value of endometrial thickness may be appropriately adjusted for curettage.     

Transvaginal sonography and hysteroscopy in postmenopausal uterine bleeding

OBJECTIVE: To compare the diagnostic accuracy of transvaginal ultrasound and hysteroscopy in the detection of endometrial pathologies in women with postmenopausal bleeding not using hormonal replacement therapy (HRT). METHODS: Between January 1997 and April 1998, 106 postmenopausal women with uterine bleeding not using HRT underwent a diagnostic work-up including pelvic examination, transvaginal ultrasound, hysteroscopy and endometrial biopsy. Sonographic measurement of endometrial thickness and hysteroscopic findings were compared with histological results. The 'classification tree' method was used to identify cut-off values of sonographic endometrial thickness that could be indicative of a class of uterine pathology. Statistical analysis was performed with the McNemar test. RESULTS: No case of endometrial cancer was found with a cut-off point of 5 mm of endometrial thickness evaluated by ultrasound, whereas all patients with endometrial thickness > or = 15 mm at sonography had an endometrial carcinoma. In the group of patients with endometrial thickness between 6 and 14 mm, we found normal atrophic endometria, benign and malignant pathology. On the other hand, the McNemar test showed a very good correspondence between hysteroscopy and histology (sensitivity 97.5% and specificity 100%), confirming its usefulness in diagnosis of postmenopausal uterine bleeding. CONCLUSIONS: Transvaginal ultrasound has revealed some limitations, mainly in the group of patients with endometrial thickness between 6 and 14 mm. The absence of endometrial malignancy in women with endometrial thickness < or = 5 mm and the high possibility of cancer in those with endometrial thickness > or = 15 mm should be confirmed in larger series. Hysteroscopy proved to be a simple and safe outpatient procedure with a high diagnostic accuracy, and in our opinion it should be considered in all women with postmenopausal uterine bleeding.     

Tibolone: clinical recommendations and practical guidelines. A report of the International Tibolone Consensus Group

An international multidisciplinary panel of experts in the management of the menopause met at the 4th Amsterdam Menopause Symposium in October 2004 to determine the specific place of tibolone, a synthetic steroid with a unique clinical profile, within the wide range of currently available postmenopausal therapy options. The consensus was that tibolone is a valuable treatment option for women with climacteric complaints. As well as relieving vasomotor symptoms, tibolone has positive effects on sexual well-being and mood, and improves vaginal atrophy and urogenital symptoms. Prevention of bone loss with tibolone is comparable to that seen with estrogen therapy (ET) and estrogen/progestogen therapy (EPT). As tibolone rarely causes endometrial proliferation, no additional progestogen is required. It also has good tolerability, being associated with a low incidence of vaginal bleeding and of breast pain. Tibolone does not increase mammographic density. Absolute numbers of women at increased risk for breast cancer are estimated to be low or absent with both tibolone and ET, and the risk with tibolone should be significantly lower than that with EPT. Tibolone might therefore be preferable to EPT in certain women who have not been hysterectomised. Based on the evidence available, the panel proposed a number of subgroups of postmenopausal women with vasomotor symptoms in whom tibolone might have added value; these included women with sexual dysfunction, mood disorders, fibroids and urogenital complaints, as well as those with breast tenderness or high mammographic breast density with EPT use.     

Intra-uterine fluid collection in postmenopuasal women with cervical stenosis

OBJECTIVES: The aim of the study was to assess the clinical significance of intra-uterine fluid collection in postmenopausal women with cervical stenosis with and without vaginal bleeding. METHODS: A group of 82 consecutive postmenopausal women with cervical stenosis and sonographically confirmed intra-uterine fluid collection underwent D&C with or without hysteroscopy. Diagnostic hysteroscopy was performed in all patients with an endometrial thickness (ET) was greater than 8mm, or with irregular endometrium at any degree of ET. The patients were divided and evaluated prospectively into two groups according to the presence or absence of postmenopausal bleeding (PMB). Twenty-six women were with PMB and 56 women were asymptomatic. RESULTS: The groups were similar as far as endometrial thickness and histopathological results were concerned. Atrophic endometrium was found in 69 patients (84%), 23 in the PMB group (89%) and 46 in the other group (82%), proliferative endometrium in 7 (9%) and endometrial polyps were found in 35 patients (43%), 12 in the PMB group (46%) and 23 in the other group (41%). When ET was > or =8 mm, in 93% of the cases an endometrial polyp was found (25 out of 27). No case of endometrial cancer was found. A premalignant condition was diagnosed in one patient with an endometrial polyp in the PMB group. All patients with endometrial thickness of less than 3 mm in ultrasound had atrophic endometrium. The incidence of intrauterine pathology increased with the increasing thickness of endometrium as observed by ultrasound. CONCLUSIONS: The presence of intra-uterine fluid collection in postmenopausal patients with cervical stenosis seems to be a benign condition. Normal endometrium of less than 3mm observed by ultrasound in postmenopausal women without vaginal bleeding does not necessarily need further surgical investigation.     

The ATAC ('Arimidex', Tamoxifen, Alone or in Combination) adjuvant breast cancer trial: baseline endometrial sub-protocol data on the effectiveness of transvaginal ultrasonography and diagnostic hysteroscopy

BACKGROUND: The 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial is a randomized, double-blind trial comparing anastrozole ('Arimidex'), alone or in combination with tamoxifen, relative to tamoxifen alone as 5 year adjuvant treatment for post-menopausal women with early breast cancer. Since tamoxifen is associated with endometrial pathology, the ATAC endometrial sub-protocol was initiated to establish the background prevalence of intrauterine pathology, and to assess prospectively the incidence and nature of intrauterine changes following endocrine therapy. Another aim was to provide data from which advice could be generated on the best endometrium screening method for patients receiving tamoxifen. METHODS: Patients underwent endometrial assessments at entry to the sub-protocol. The baseline investigations comprised transvaginal ultrasound scanning (TVUS), a hysteroscopy and an endometrial biopsy. RESULTS: A total of 285 gynaecologically asymptomatic women from 31 centres in 10 countries entered the endometrial sub-protocol. The mean uterine volume was 47.7 cm3. The median endometrial thickness overall was 3 mm. Twenty-four histologically confirmed, pathological changes were observed. Twenty-three pathologies were confirmed by TVUS, and 21 were identified by hysteroscopy and confirmed by histopathology. Women with or without intrauterine pathology had median endometrial thickness of 5 and 3 mm respectively. CONCLUSIONS: The presence of pathology was associated with increased endometrial thickness. The relative sensitivity and specificity of hysteroscopy and endometrial thickness for the diagnosis of endometrial pathology was comparable to other studies. If screening of the endometrium prior to treatment is appropriate, this study supports the use of an endometrial thickness of 3 mm, as assessed by TVUS, as a threshold for needing further investigation. This study demonstrates that if the endometrial thickness is >3 mm, hysteroscopy and biopsy is the optimal method of detecting intrauterine pathology in women with breast cancer who are about to commence endocrine treatment.     

Effects of ospemifene, a novel SERM, on hormones, genital tract, climacteric symptoms, and quality of life in postmenopausal women: a double-blind, randomized trial

OBJECTIVE: Ospemifene, a novel selective estrogen receptor modulator, shows a potential for prevention and treatment of osteoporosis in postmenopausal women. We studied the effects of ospemifene on hormone levels, genital tract organs, climacteric symptoms, and quality of life. DESIGN: A double-blinded study in which 160 postmenopausal women were randomly allocated to receive either ospemifene at three different daily doses (30, 60, or 90 mg) or placebo for 3 months. RESULTS: No significant differences were observed among the study groups in clinical characteristics or parameters reflecting estrogen action at baseline. Ospemifene reduced follicle-stimulating hormone and insulin-like growth factor I levels, whereas estradiol failed to change at all, and luteinizing hormone was reduced only in the 90-mg group of ospemifene. In the vast majority of participants, the endometrium remained atrophic after 3 months of treatment with ospemifene. Although the rate of proliferative endometrium slightly increased in all groups, including placebo, no hyperplasia or bleeding occurred in any participant. Ospemifene had no effect on the appearance of proliferation marker Ki-67 in the endometrium as compared with placebo, and endometrial thickness increased by mean 0.4 to 0.6 mm (P < 0.01, P < 0.05 and P < 0.05 for 30, 60 and 90 mg ospemifene, respectively). Uterine volume slightly increased (8.4%-14.7%) in the ospemifene groups (P > 0.05), perhaps as a result of increased uterine blood flow. The most conspicuous finding was the significant estrogenic effect on vaginal epithelium, as evidenced by an increase in intermediate and superficial cells in repeat Pap smears. Ospemifene was not observed to aggravate climacteric symptoms or cause adverse events, nor did it suppress climacteric symptoms. CONCLUSIONS: Ospemifene at daily doses of 30 to 90 mg did not stimulate endometrium or aggravate hot flashes but clearly had a rather strong estrogenic effect on the vaginal epithelium during a 3-month treatment period. Such effects would be advantageous if ospemifene were found to be effective in the long-term prevention of osteoporosis.     

Clinical usefulness of endometrial screening by ultrasound in asymptomatic postmenopausal women

Objective: The aim of the present study was to evaluate the clinical usefulness of routine use of endometrial ultrasound in asymptomatic, bleeding-free postmenopausal women. Methods: We retrospectively reviewed the data of 850 postmenopausal women subjected to hysteroscopy, focusing our attention on those cases (148) with an ultrasound indication of endometrial thickening. Results: In 850 postmenopausal women, we identified 27 (3.2%) endometrial adenocarcinomas. In these subjects, the indication for office hysteroscopy was abnormal uterine bleeding in 24 (24/27; 88.9%) cases; pathological pap smear with abnormal endometrial cells in 2 (2/27; 7.4%) cases and thickened endometrium upon transvaginal ultrasound (tvUS) only in one (1/27; 3.7%) patient. On the other hand, 148 hysteroscopies were performed on the basis of the tvUS indication in otherwise asymptomatic (bleeding free) postmenopausal women; only 1(0.7%) of these presented an adenocarcinoma. Conclusion: Our findings show that the use of tvUS as a screening tool for endometrial pathology in asymptomatic postmenopausal women generates 93.2% false positive results, so that most of these women undergo this second level invasive procedure uselessly. Our data suggest that, in asymptomatic postmenopausal women, endometrial ultrasound evaluation is not worthwhile as a screening tool, such as it is considered in common clinical practice. The present results call for a larger prospective trial to further elucidate this controversial issue.     

The effects of tibolone on mood and libido

OBJECTIVE: To review published data pertaining to the effects of tibolone on sexual parameters, mood, and cognitive function in postmenopausal women. DESIGN: A review of all relevant published, peer-reviewed studies. RESULTS: Tibolone is a compound that can be selectively metabolized by individual tissues to its estrogenic, progestogenic, or androgenic metabolites and hence exhibits tissue-specific hormonal effects. Tibolone also lowers sex hormone binding globulin, thus increasing free estradiol and testosterone levels. Tibolone alleviates climacteric vasomotor symptoms and displays a dominant progestogenic effect on the endometrium. Tibolone normalizes the vaginal karyopyknotic and maturation indexes and alleviates symptomatic atrophic vaginitis. Women treated with tibolone report significant reductions in vaginal dryness and dyspareunia, effects that may be secondary to both estrogenic and androgenic actions. Randomized studies indicate tibolone has positive effects on mood compared with placebo and alleviates several adverse mood parameters to a similar extent as conventional hormone replacement therapy. Improved mood is associated with increased plasma beta-endorphin. With respect to cognition, tibolone seems to improve semantic memory but does not significantly improve recognition memory. Tibolone is associated with improvements in sexual function that seem to be greater than those achieved with standard hormone replacement therapy. CONCLUSION: Published studies indicate beneficial effects of tibolone on both libido and mood, which otherwise significantly compromise physical, psychological, and social well-being. Hence, tibolone provides another option for menopausal women experiencing loss of libido as part of their symptomatology or who have persistent low libido despite adequate estrogen/progestin replacement therapy.     

Hysteroscopy for asymptomatic postmenopausal women with sonographically thickened endometrium

Endometrial carcinoma is the most common genital cancer in women. While patients usually present with vaginal bleeding, in 10–20% this characteristic symptom is absent. Endometrial thickness (double layer) is measured by transvaginal sonography and thickening indicates an increased risk of malignancy or other pathology (hyperplasia or polyps). Objective: We sought to correlate hysteroscopic and pathological findings in asymptomatic postmenopausal women with sonographically thickened endometrium (>6 mm). Study design: A prospective observational study in a university hospital of 304 postmenopausal women referred between 1996 and 2006 because of a sonographically thickened endometrium in the absence of abnormal bleeding, who underwent continuous flow hysteroscopy (4.5 mm Storz hysteroscope) and fractionated curettage of the uterine cervix and corpus (D & C) in addition to vaginal sonography (5 MHz probe). Results: The mean age of the women was 64.8 (range 57.7–71.9) years. Average endometrial thickness measured by ultrasound was 12 mm ± 6.7 mm. Hysteroscopy suggested the presence of endometrial polyps in 226 women (74.3%), simple endometrial hyperplasia in 34 (11.2%), atrophic endometrium in 18 (5.9%), complex endometrial hyperplasia in 2 (0.7%), atypical hyperplasia in 3 (1%) and leiomyoma in 9 (3.0%). In 12 women (3.9%), the hysteroscopic appearance suggested malignancy and histology revealed endometrial adenocarcinoma. All hysteroscopic results were confirmed by histological examination. Conclusion: Hysteroscopy represents an easy, safe and effective method for the investigation of asymptomatic women with a thickened endometrium found with transvaginal ultrasound. The commonest pathology was endometrial polyps.     

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

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

Diagnostic accuracy of hysteroscopy in endometrial hyperplasia

Objectives: To determine the diagnostic accuracy of hysteroscopy in the diagnosis of endometrial hyperplasia in women with abnormal uterine bleeding. Methods: From 1993 through 1995, 980 women referred to our institution for abnormal uterine bleeding underwent diagnostic hysteroscopy with eye direct biopsy of the endometrium in case of macroscopic abnormalities. Hysteroscopic features were compared with pathologic findings in order to detect the reliability of the endoscopic procedure. Statistical analysis was performed with the McNemar test. Results: Positive predictive value of hysteroscopy in the diagnosis of endometrial hyperplasia accounted for 63%. In fact hysteroscopic diagnosis of endometrial hyperplasia was confirmed at pathologic examination in 81 out of 128 patients. Sensitivity and specificity of the endoscopic procedure accounted for 98% and 95%, respectively. Negative predictive value accounted for 99%, as only two cases of atypical hyperplasia were missed at hysteroscopy. Positive predictive value was higher in postmenopausal patients compared to women in the fertile age (72 vs. 58%). Conclusions: Overall, results appear encouraging, since no case of endometrial hyperplasia was missed by hysteroscopy. The high diagnostic accuracy, associated with a minimal trauma, renders hysteroscopy the ideal procedure for both diagnosis and follow-up of conservative management of endometrial hyperplasia.     

Endometrial safety after 5 years of continuous combined transdermal estrogen and intrauterine levonorgestrel delivery for postmenopausal hormone substitution

OBJECTIVE: To investigate endometrial histology and thickness of the endometrium after long-term use of continuous transdermal estrogen substitution combined with intrauterine release of levonorgestrel (LNG) in postmenopausal women. DESIGN: A 5-year non-comparative prospective clinical trial. SUBJECTS: Out of 182 symptomatic postmenopausal women using estrogen substitution therapy (EST) combined with a novel T-shaped LNG-releasing intrauterine system (Femilis Slim LNG-IUS), to prevent endometrial proliferation and bleeding, only those women (n=102) who used two consecutive LNG-IUSs, were isolated with the aim to study the long-term effects on the endometrium. The mean age of the women was 57 years (range 47-71). The majority of women received percutaneous 17beta estradiol, 1.5mg daily, or an equivalent dose by patch or orally, on a continuous basis. MAIN OUTCOME MEASURES: Endometrial histology and ultrasonographic evidence of endometrial suppression, after a period of approximately 5 years of use. The mean duration of use of the regimen was 70 months (range 25-98). RESULTS: The dominant endometrial histologic picture was that of inactive endometrium characterized by glandular atrophy and stroma decidualization (Kurman classification 5b). No cases of endometrial hyperplasia were found. On transvaginal ultrasound, this corresponds with a thin endometrium (< or = 5 mm). CONCLUSION: The results of this 5-year study in 102 postmenopausal women using EST demonstrates that the LNG-IUS effectively opposes the estrogenic effect on the endometrium resulting in strong suppression during the entire period of EST. Due to its high efficacy and absence of systemic effects on organ tissues (e.g., breasts), target delivery in the uterine cavity could be a preferred route to administer a progestagen in women using EST.