The levonorgestrel intrauterine system in menopausal hormone replacement therapy: five-year experience.

OBJECTIVE: To study the long-term effects (5 years) of intrauterine levonorgestrel administration as the progestin part of continuous combined postmenopausal hormone replacement therapy. DESIGN: Prospective clinical study. SETTING: Department of obstetrics and gynecology at a central hospital. PATIENT(S): Twenty postmenopausal women with an intact uterus who had no contraindications to hormone replacement therapy and who wanted to take amenorrhea-inducing hormone replacement therapy to relieve their climacteric symptoms. INTERVENTION(S): A percutaneous E2 gel containing 1.5 mg of E2 was administered daily and a levonorgestrel-releasing intrauterine device was used. Endometrial thickness was measured by vaginal ultrasonography. Endometrial sampling was performed yearly. MAIN OUTCOME MEASURE(S): Clinical compliance, profiles of bleeding, and endometrial thickness and morphology were monitored during 5 years of follow-up. RESULT(S): Eighteen women completed 1 year of follow-up. Fifteen of these women were willing to continue the study, and 12 of them completed 5 years of follow-up. Spotting was frequent during the first 6 months of the study and declined thereafter. At 1 year, 80% of the women were totally amenorrheic. Of the 15 women who continued the study, 12 were totally amenorrheic and 3 had problems with bleeding. The mean endometrial thickness was < or = 3 mm during the study. Endometrial morphology showed epithelial atrophy accompanied by decidualization of the stroma in all 12 of the women who were followed up for 5 years. CONCLUSION(S): Intrauterine administration of progestin through a levonorgestrel-releasing intrauterine device is a good alternative as the progestin part of continuous combined hormone replacement therapy because it effectively opposes the estrogenic effects on the endometrium and induces amenorrhea in most cases.     

Uterine effects of raloxifene in comparison with continuous-combined hormone replacement therapy in postmenopausal women

OBJECTIVE: We sought to compare the uterine effects of raloxifene with those of continuous-combined hormone replacement therapy. STUDY DESIGN: This randomized, double-blind 24-month study involved 136 postmenopausal women who received raloxifene 150 mg/d or conjugated equine estrogens 0.625 mg/d with medroxyprogesterone acetate 2.5 mg/d. After baseline evaluations, endometrial biopsy specimens were obtained, and endometrial thickness was measured annually by means of transvaginal ultrasonography. Statistical analyses were performed with an intention-to-treat approach. RESULTS: In the raloxifene group at the end point of the study 94.4% of biopsy specimens showed normal benign postmenopausal endometrium and 5.6% were classified as benign stimulatory endometrium. In the continuous-combined hormone replacement therapy group at the end point of the study 78.7% of biopsy specimens showed normal benign postmenopausal endometrium, 19. 1% were classified as benign stimulatory endometrium, and 2.1% showed benign abnormal postmenopausal endometrium. Mean endometrial thickness was unchanged from baseline with raloxifene and was increased significantly by 0.5 mm at 12 months with continuous-combined hormone replacement therapy. CONCLUSION: Raloxifene 150 mg/d did not increase endometrial thickness or cause endometrial proliferation in healthy postmenopausal women.     

Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding: is it always necessary to perform an endometrial biopsy?

OBJECTIVE: This study was undertaken to evaluate whether it was possible to abstain from performing an endometrial biopsy when endometrial thickness according to transvaginal ultrasonography was /=50 years who were referred because of postmenopausal bleeding or irregular bleeding during hormone replacement therapy. If endometrial thickness was /=5 mm underwent either curettage or endometrial biopsy. RESULTS: One hundred sixty-three women had an endometrial thickness /=5 mm. The corresponding figure when atypical hyperplasia and endometrial metastases were included was 20. 2%. CONCLUSION: If the false-negative rate of endometrial biopsy techniques is taken into account, then the combination of transvaginal ultrasonography and cervical cytologic examination is an adequate form of management for women with postmenopausal bleeding or irregular bleeding during hormone replacement therapy as long as endometrial thickness is 相似文献   

Transvaginal ultrasonographic assessment of the endometrium in asymptomatic, postmenopausal women using different HRT regimens containing tibolone or estrogen

OBJECTIVE: To assess the effects of hormone replacement therapy (HRT) on endometrial thickness as measured by transvaginal ultrasonography in asymptomatic, postmenopausal women. STUDY DESIGN: Between 1997 and 2001, 307 women who had no risk factors for endometrial cancer or abnormal vaginal bleeding were enrolled in a study. Patients received 1 of the following HRT modalities: (1) oral equine HRT modalities: (1) oral equine estrogen, (2) oral 17beta-estrogen, (3) transdermal 17beta-estrogen, or (4) oral tibolone. All women taking estrogens were also taking a progestin. Only the patients with endometrial thickness >7 mm underwent endometrial biopsy while taking HRT. RESULTS: Although we observed an increase in serum estrogen levels as compared to the levels before tibolone therapy, changes in endometrial thickness were not statistically significant in patients taking tibolone. CONCLUSION: Endometrial thickness with tibolone closely mimics the naturally atrophic postmenopausal state. Thus, tibolone is suggested for those postmenopausal women who have concerns about HRT.     

Continuous combined hormone replacement therapy and risk of endometrial cancer

OBJECTIVE: Postmenopausal women who receive sequential hormone replacement therapy with estrogen combined with progestogen for 10 to 24 d/mo for a prolonged period may have an elevated endometrial cancer risk relative to those who have never received hormone replacement therapy. We investigated whether daily use of estrogen and progestogen (continuous combined hormone replacement therapy) could diminish any excess endometrial cancer risk.Study Design: A population-based study in Washington State obtained interview data from 969 women aged 45 to 74 years with endometrial cancer diagnosed during 1985 through 1991 or 1994 through 1995 and from 1325 age-matched control subjects selected primarily by random digit dialing. Women who had received only continuous combined hormone replacement therapy were compared with women who had only received another hormone replacement therapy regimen or who had never received hormone replacement therapy. RESULTS: The risk of endometrial cancer among users of continuous combined hormone replacement therapy (n = 9 case patients, n = 33 control subjects) relative to women who had never received hormone replacement therapy was 0.6 (95% confidence interval, 0.3-1.3); the risk relative to women who received hormone replacement that included progestogen for 10 to 24 d/mo was 0.4 (95% confidence interval, 0.2-1.1). Most continuous combined hormone replacement therapy use was short-term (<72 months) or recent (in the previous 24 months). CONCLUSION: Women who had received continuous combined hormone replacement therapy for several years did not appear to be at any increased risk for endometrial cancer relative to women who had never received hormone replacement therapy and may in fact be at decreased risk for endometrial cancer.     

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.)     

Estrogen replacement therapy in patients with early breast cancer

OBJECTIVE: Most physicians believe that estrogen replacement therapy is contraindicated once a patient is diagnosed with breast cancer. Recently, several studies have shown that estrogen replacement therapy may be safely used in patients with early breast cancer that has been treated successfully. These women can have severe menopausal symptoms and are at risk for osteoporosis. We reviewed the current status of women in our practice with breast cancer who received estrogen replacement therapy, who did not receive hormone replacement therapy, and who did not receive estrogenic hormone replacement therapy. STUDY DESIGN: The study group consisted of 123 women (mean age, 65.4 +/- 8.85 years) who were diagnosed with breast cancer in our practice, including 69 patients who received estrogen replacement therapy for < or = 32 years after diagnosis. The comparative groups were 22 women who used nonestrogenic hormones for < or = 18 years and 32 women who used no hormones for < or = 12 years. The group who did not receive estrogenic hormone replacement therapy received androgens with or without progestogens (such as megestrol acetate). Of the 63 living hormone users, 56 women are still being treated in our clinic, as are 15 of the 22 subjects who receive nonestrogenic hormone replacement therapy. Follow-up was done through the tumor registry at University Hospital; those patients whose tumor records were not current were contacted by telephone. RESULTS: There were 18 deaths in the 123 patients: 6 patients who received estrogen replacement therapy (8.69%), 2 patients who received nonestrogenic hormone replacement therapy (9.09%), and 10 patients who received no hormone replacement therapy (31.25%). Of the 18 deaths, 9 deaths were from breast cancer (mortality rate, 7.3%); 3 deaths were from lung cancer; 1 death was from endometrial cancer; 1 death was from myocardial infarction; 1 death was from renal failure; and 3 deaths were from cerebrovascular accidents. The 9 deaths from breast cancer included one patient who received nonestrogenic hormone replacement therapy (mortality rate, 4.5%), 6 patients who received no hormone replacement therapy (mortality rate, 11.3%), and 2 patients who received estrogen replacement therapy (mortality rate, 4.28%). The 9 non-breast cancer deaths included 4 patients who received estrogen replacement therapy (endometrial cancer [1 death], lung cancer [1 death], cerebrovascular accident [1 death], and renal failure [1 death]), 1 patient who did not receive estrogenic hormone replacement therapy group (myocardial infarction), and 4 patients who used no hormones (lung cancer, 2 deaths; stroke, 2 deaths). Carcinoma developed in one patient in the estrogen replacement therapy group in the contralateral breast after 4 years of hormone replacement therapy; she is living and well 2.5 years later with no evidence of disease. Metastatic breast cancer developed in one patient after 8 years of hormone replacement therapy; she is living with disease. CONCLUSION: Estrogen replacement therapy apparently does not increase either the risk of recurrence or of death in patients with early breast cancer. These patients may be offered estrogen replacement therapy after a full explanation of the benefits, risks, and controversies.     

Mammographic density changes during different postmenopausal hormone replacement therapies

OBJECTIVE: To determine the degree of change in mammographic breast densities during different types of postmenopausal hormone replacement therapies. DESIGN: A retrospective study. SETTING: Ege University Hospital. PATIENT(S): The mammographies of 216 women on various postmenopausal hormone replacement therapies were evaluated. INTERVENTION(S): Estrogen alone (n = 76) or estrogen in cyclic (n = 44) or continuous (n = 61) combination with progestin or tibolone-only (n = 35) replacement therapies were used. Mammographic density was quantified according to the Wolfe classification in patients with different hormone replacement regimens. MAIN OUTCOME MEASURE(S): Mammographic density changes were interpreted. RESULT(S): An increase in mammographic density was much more common among women receiving continuous combination hormone replacement therapy 31.1% (19 of 61) than among those receiving estrogen-only 3.9% (3 of 76) treatment. There were no significant mammographic breast density changes among women receiving cyclic continuous combination hormone replacement therapy or tibolone-only treatment. The increase in density was apparent already at first visit after the start of hormone replacement therapy. In continuous combined postmenopausal hormone replacement therapy with norethisterone acetate, the increase in mammographic density was 34.1% (15 of 44), followed by medroxyprogesterone acetate 23.5% (4 of 17). CONCLUSION(S): Our findings show that mammographic breast density changes related to postmenopausal hormone replacement therapy are dependent on the selected hormone regimen. The continuous administration of the progestin component of the combined-hormone replacement therapy seems to effect the breast density most.     

One-stop clinic for postmenopausal bleeding

OBJECTIVE: To evaluate the role of one-stop clinic for early diagnosis and management of women with postmenopausal bleeding by means of transvaginal ultrasonography, outpatient hysteroscopy and endometrial biopsy. STUDY DESIGN: A prospective analysis was performed on 522 women with postmenopausal bleeding who were referred directly to the gynecology outpatient clinic for evaluation of postmenopausal bleeding. Endometrial thickness of 6 mm, as measured by a transvaginal scan, was considered the cutoff limit for further investigation by hysteroscopy and endometrial biopsy. RESULTS: One hundred ninety-one women were using hormone replacement therapy. Thirty-two were taking tamoxifen. Outpatient hysteroscpoy was performed in 157 (71.3%) cases. Thirty-seven (16.8%) cases had general anesthesia for hysteroscopy. Twenty-four (11%) cases had only an endometrial sample obtained. Twenty-one cases of endometrial carcinoma, 20 of endometrial hyperplasia, 4 of cervical carcinoma and 5 of other genital tract malignancies along with several benign pathologies, including submucosal myomas, were detected. Seven (2.3%) cases of endometrial thickness below the cutoff limit had recurrent bleeding due to benign conditions. CONCLUSION: A one-stop clinic is effective for early diagnosis of genital tract malignancy in a majority of patients with postmenopausal bleeding and significantly help in reducing the hospital waiting list.     

Ultrasonographic and morphological studies of the postmenopausal endometrium using unopposed estrogen replacement therapy with regular pause: a prospective preliminary study

Hormone replacement therapy with progestogen is known to have severe side effects or complications in certain patients. OBJECTIVE: The goal of this study is to evaluate the safety and efficacy of an alternative treatment regimen with a mensal pause using both transvaginal sonography (TVS) and endometrial biopsy to follow patients. METHODS: A total of 30 postmenopausal women were treated with unopposed estrogen for 21 days each month followed by a regular pause of 9-10 days, and were studied prospectively for 18 months. The TVS measurements of endometrial thickness and biopsy of the endometrium were done on the 21st day of treatment and the 7th day of the pause at 6-month intervals throughout the study. RESULTS: There was a significant decrease of proliferative activity at all three time points during the study (6, 12 and 18 months) when tested on the 7th pause day (PD7). The percentage of patients with hyperplasia without nuclear atypia and endometrial thickness > or =8mm was 32% at 6 months, but decreased to 22 and 19% at 12 and 18 months, respectively. All cases of hyperplasia regressed after the hormonal pause throughout the treatment period. CONCLUSIONS: This study presents an alternative treatment regimen for select patients having side effects or complications from progestogen administration; however, studies evaluating the safety and efficacy of this regimen over longer time periods are necessary.     

A 5-year follow-up study on the use of a levonorgestrel intrauterine system in women receiving hormone replacement therapy.

OBJECTIVE: To investigate endometrial histology, bleeding, and the effects of replacing the levonorgestrel intrauterine system (LNG IUS, Mirena/Levonova, Leiras Oy, Turku, Finland) after 5 years of combined use with estrogen. DESIGN: Prospective cohort study. SETTING: Private outpatient clinic. PATIENT(S): Forty postmenopausal women started hormone replacement therapy with LNG IUS and either a patch (50 microg/24 h) or oral (2 mg) estradiol valerate protocol. Thirty-nine completed 12 months of treatment. Twenty-nine of them had used LNG IUS with continuous estradiol replacement therapy for 5 years. Seven of them volunteered to a 3-month treatment-free period before reinsertion; 22 opted for immediate reinsertion. INTERVENTION(S): Endometrial sampling for histology, endometrial thickness, and location of the LNG IUS by ultrasound at removal and after washout. The women completed bleeding diaries from 3 months prior to removal to 3 months after reinsertion. MAIN OUTCOME MEASURE(S): Endometrial histology was evaluated and estrogen and progestin effects were also investigated. Endometrial thickness was measured. Bleeding was examined based on bleeding diaries. The investigator and the women evaluated the insertion, removal, and reinsertion of the LNG IUS. RESULT(S): At 6 and 12 months endometrial histology was nonproliferative. At removal, all endometria were suppressed and a strong progestin effect was seen. The thickest endometrium was 3.6 mm. After washout, all seven endometria were atrophic. Before the IUS was replaced, 26 women were amenorrheic, whereas three had minor spotting. After replacement 5 women had no bleeding and an additional 10 women had only spotting. The bleeding or spotting discontinued within 18 days. The insertion of LNG IUS was characterized as easy by the investigator and it was well tolerated by the women. Cervical dilatation and/or paracervical blockade was used in 10 insertions. CONCLUSION(S): Intrauterine levonorgestrel effectively protects against endometrial hyperplasia. In most women it induces amenorrhea, which is only temporarily affected by replacement of the LNG IUS.     

Dose of progestin in postmenopausal-combined hormone therapy and risk of endometrial cancer

OBJECTIVE: We studied the impact of progestin dose on this risk. The pattern and number of days per month that progestin is given in postmenopausal combined hormone therapy appears to affect endometrial cancer risk. We assessed the impact of progestin dose on this risk. STUDY DESIGN: A population-based, case-control study included 647 cases with endometrial cancer and 1209 controls. RESULTS: Among users of estrogen with medroxyprogesterone acetate (MPA) 10 to 24 days/month, women who took >100 mg/month had an endometrial cancer risk that was equal to that of hormone nonusers (95% CI 0.6-1.7). The corresponding relative risk was 0.8 (95% CI 0.5-1.5) in those who used a lower monthly MPA dose for 10 to 24 days/month. Among users of a continuous combined hormone regimen, the risk of endometrial cancer was low relative to hormone nonusers, regardless of MPA dose. CONCLUSION: Among the combined hormone regimens most commonly used by postmenopausal women today, MPA monthly dose bears little or no relation to endometrial cancer risk.     

Follow-up of women after a first episode of postmenopausal bleeding and endometrial thickness greater than 4 millimeters

OBJECTIVE: To estimate the incidence of recurrent postmenopausal bleeding among women who were diagnosed with an endometrial thickness greater than 4 mm. METHODS: We designed a prospective cohort study and included consecutive women not using hormone replacement therapy, presenting with a first episode of postmenopausal bleeding. We evaluated patients who had an endometrial thickness greater than 4 mm at transvaginal ultrasonography and benign endometrial sampling; presence of carcinoma was ruled out by office endometrial sampling, hysteroscopy, and/or dilation and curettage. Time until recurrent bleeding was measured, and diagnosis at recurrent bleeding was recorded. RESULTS: Among 318 patients who had an endometrial thickness greater than 4 mm, 222 patients had benign histology results and were available for follow-up. During follow-up, 47 (21%, 95% confidence interval 16-27%) patients had recurrent bleeding, with a median time to recurrent bleeding of 49 weeks (interquartile range 18 to 86 weeks). There was no difference with respect to recurrence rate between patients with polyp removal, patients with a normal hysteroscopy, and patients with office endometrial sampling alone at the initial workup. Two patients were diagnosed with atypical endometrial hyperplasia upon recurrent bleeding. CONCLUSION: The recurrence rate of postmenopausal bleeding in women with endometrial thickness greater than 4 mm is 20%. This recurrence rate is not related to incorporation of hysteroscopy or polyp removal at the initial workup. LEVEL OF EVIDENCE: II.     

Uterine Blutungen bei internistischen Grunderkrankungen

Clinical management of unscheduled uterine bleeds in women using hormone replacement therapy (HRT) involves reconsideration of the selected individual therapy. Special attention should be given to the dose of the estrogen and progestin, the adequacy of both the progestin phase and the regimen – sequential or continuous combined therapy. A progestin should be administered for at least 10 days. It is unknown whether tibolone is an alternative for women with irregular bleeding on continuous combined therapy. These considerations also apply to women with uterine myoma. Transvaginal sonography may help identify women with thickened endometrium demanding histopathological assessment. Various controlled clinical trials suggest different cut-off values for a “normal” endometrial thickness (double-layer). A threshold of 7 mm appears to offer a reasonable compromise between sensitivity and specificity. A single episode of bleeding in the presence of an endometrial thickness ≤ 4 mm may allow for follow-up without endometrial sampling. Adherence to HRT may be enhanced by selecting the lowest doses of estrogens and progestins, including progesterone, achieving alleviation of climacteric symptoms without compromising endometrial safety. Parenteral use of estrogens and progestins is preferable in women with impaired liver function, as this mode of administration avoids the first-pass effect. This relatively small group of women may be eligible for replacement therapy if hepatic function reaches an equilibrium prior to initiation of therapy. Scarce clinical data indicate that systemic lupus erythematosus appears to deteriorate in women using HRT. However, other studies suggest that biliary cirrhosis does not deteriorate in women on HRT. HRT is possible in women with chronic renal and bone diseases. The outlined management of uterine bleeding also applies to these women. Uterine bleeding may occur with use of tamoxifen and less frequently with raloxifene, which is approved for the prophylaxis and treatment of postmenopausal osteoporosis. Transvaginal sonography may identify women with uterine stimulation, as indicated by the presence of subendometrial cysts and thickened endometrium, and preselect patients for endometrial sampling to exclude hyperplasia and cancer. The sensitivity and specificity of a single measurement of endometrial thickness is limited and additional tests such as saline infusion sonography may enhance the predictive value of the ultrasound assessment. The baseline frequency of postmenopausal bleeding does not appear to be increased in women who use raloxifene. Preliminary data suggest that use of raloxifene is not associated with an increased risk of endometrial cancer as is tamoxifen. SERMs constitute a relative contraindication in women with severe impairment of liver function.     

Postmenopausal endometrial cancer screening: is there a correlation between transvaginal sonographic measurement of endometrial thickness and body mass index?

OBJECTIVE: The aim of this study was to correlate the body mass index with transvaginal sonographic measurement of endometrial thickness in a cohort of postmenopausal women who were admitted for endometrial cancer surveillance. MATERIAL AND METHODS: Transvaginal sonographic measurement of endometrial thickness was performed in 97 postmenopausal women who attended the gynecology clinic for endometrial cancer screening with no history of hormone replacement therapy and correlated with body mass index. Baseline characteristics including age, years since menopause and body mass index were recorded for each subject. The relationship between transvaginal sonographic endometrial thickness and baseline characteristics was assessed in each. RESULTS: Body mass index was significantly correlated with years since menopause (r = 0.292, p = 0.004) and age (r = 0.243, p = 0.01) but not with endometrial thickness (r = -0.07, p = 0.454). Endometrial thickness versus time since menopause correlation was found to be significant (r = 0.274, p = 0.03) in patients with a body mass index lower than 30. CONCLUSION: The present findings indicate that endometrial thickness does not differ with body mass index in the screening of postmenopausal women for endometrial cancer.     

Ovarian cysts in postmenopausal tamoxifen-treated breast cancer patients with endometrial thickening detected by transvaginal sonography

OBJECTIVE: To investigate the frequency of ovarian cysts in tamoxifen-treated postmenopausal breast cancer patients with endometrial thickening detected by transvaginal sonography. METHODS: Medical records and transvaginal sonographies of 38 postmenopausal women treated for breast cancer with adjuvant tamoxifen therapy who had undergone endometrial sampling due to abnormal endometrial thickness were reviewed retrospectively. RESULTS: During the study period five of 38 tamoxifen-treated postmenopausal patients (13.2%) had ovarian cysts. The mean tamoxifen treatment interval of the patients with an ovarian cyst was 22.4 +/- 18.4 months (p = 0.17). The mean endometrial thickness of the patients with an ovarian cyst was 12.6 +/- 5.9 mm (p = 0.17). Endometrial biopsy detected six cases of abnormal endometria, including endometrial carcinoma (n = 1), endometrial polyp (n = 1) and simple endometrial hyperplasia without atypia (n = 4). Three patients with ovarian cysts underwent laparatomy revealing simple cysts on histopathological examination. Two patients with ovarian cysts declined laparatomy and are currently under follow-up. CONCLUSION: Ovarian cysts a common side-effect of tamoxifen treatment in postmenopausal tamoxifen-treated breast cancer patients. Transvaginal sonography should be performed to detect any concomitant endometrial pathology.     

The effect of submucous fibroids on the dose-dependent modulation of uterine bleeding by trimegestone in postmenopausal women treated with hormone replacement therapy

Objective To assess the value of identifying endometrial structural abnormalities at baseline hysteroscopy in predicting the pattern of bleeding in postmenopausal women treated with hormone replacement therapy.
Design A randomised, double-blind, dose-ranging study.
Setting A teaching hospital in the UK.
Population One hundred and seventy-six healthy postmenopausal women.
Methods Women were randomised to receive one of four doses of oral trimegestone (0.05, 0.1, 0.25 and 0.5 mg per day), from day 15–28, and a daily dose of 2 mg oral micronised oestradiol for six treatment cycles. Women completed diaries in which the bleeding episodes were recorded. Hysteroscopy under local anaesthesia and endometrial biopsy were performed at baseline and on day 24 of the last treatment cycle.
Results Women with submucous fibroids had more prolonged (   P = 0.026  ) and heavier (   P = 0.002  ) progestogen-associated bleeding (odds ratio 4.54). The incidence of intermenstrual bleeding, but not its duration or severity, was higher in women with submucous fibroids (   P = 0.017  ). There was a clear dose-dependent effect of trimegestone, with a consistently later onset of progestogen-associated bleeding occurring with increasing doses of trimegestone (   P < 0.001  ), and such episodes became progressively lighter and of shorter duration over time (   P < 0.001  ).
Conclusion Hysteroscopic evaluation of the endometrial cavity in women treated with hormone replacement therapy, predicts the occurrence of heavy and unscheduled bleeding.     

Transvaginal sonography of the endometrium in postmenopausal women

The purposes of this study were to compare transvaginal sonographic scanning of the uterus and endometrium with histology obtained by endometrial biopsy or curettage and to determine whether the sonographic technique might be useful in the evaluation of postmenopausal women. Eighty postmenopausal women were studied. Of these, 65 were asymptomatic (38 on no hormone therapy and 27 on hormone replacement). Fifteen women underwent evaluation because of postmenopausal bleeding. In both groups, endometrial thickness of 4 mm or less as depicted by sonography correlated well with endometrial characteristics of decreased estrogen stimulation. However, in women with measured endometrial thickness between 5-8 mm, proliferative endometrium could not be distinguished from hyperplastic endometrium or, in one case, low-grade carcinoma. Large polyps and invasive carcinoma with myometrial extension were easily recognized.     

Long term effects of tibolone on the genital tract in postmenopausal women.

OBJECTIVES: To assess the effects of six years tibolone therapy on the genital tract in postmenopausal women against matched voluntary controls. DESIGN: Prospective, non-randomised, open label study of the efficacy of tibolone. METHODS: Symptoms were assessed by questionnaires every six months. Assessment of genital tract cellular activity comprised annual vaginal smear and endometrial biopsy/smear in the tibolone group (n = 58) and vaginal smear alone in the control group (n = 55). As a recent protocol addition, transvaginal ultrasound assessment of endometrial thickness was performed in all women who gave consent. Endometrial biopsy was performed in control women if the endometrial thickness was > 5 mm. Karyopyknotic index and maturation index were calculated from the vaginal smears. RESULTS: The rate of amenorrhoea between six months and six years treatment was 90% in the tibolone group compared with 91% in the controls (P was not significant). There was improvement in reported vaginal symptomatology in the treatment group but not in the controls. Median endometrial thickness increased slightly in the tibolone treated group (3.2 mm tibolone vs 2.5 mm control; P < 0.05). There were no cases of cytologically proven endometrial stimulation in asymptomatic women in either group. Both vaginal karyopyknotic index and maturation index increased significantly in the tibolone treated group over six years, but not in the control group. CONCLUSIONS: Tibolone is effective at maintaining an inactive endometrium while providing oestrogenisation of the lower genital tract over a six year period.     

Intrauterine levonorgestrel delivered by a frameless system, combined with systemic estrogen: acceptability and endometrial safety after 3 years of use in peri- and postmenopausal women.

OBJECTIVE: To evaluate the acceptability and endometrial safety of a novel intrauterine drug delivery system, FibroPlant-levonorgestrel (LNG), combined with estrogen therapy (ET) in 150 peri- and postmenopausal women, followed-up for at least 3 years. DESIGN: This was a prospective, non-comparative study in peri- and postmenopausal women. In the majority of women, treatment with the FibroPlant-LNG intrauterine system (IUS), combined with ET, was initiated during the perimenopausal transitional phase to establish a smooth transition to menopause and suppress the endometrium to prevent endometrial proliferation and bleeding. A 3.5-cm long coaxial fibrous delivery system, delivering approximately 14 microg LNG/day, was used. The calculated duration of release of the system is at least 3 years. The majority of women received percutaneous 17beta-estradiol (Oestrogel), 1.5 mg daily on a continuous basis, which provides sufficient blood levels of estrogen in most women to suppress climacteric symptoms and protect against bone loss. OUTCOME MEASURES: To measure acceptability, women were asked, after they had the IUS in place for a minimum of 3 years, if they would like to continue the combined regimen and if they would accept renewal of the IUS. Endometrial safety was evaluated by transvaginal ultrasound examination and endometrial biopsy in a subset of 101 women prior to replacement of the IUS. RESULTS: Ninety-four insertions were done in perimenopausal and 56 in postmenopausal women aged between 33 and 78 years. Of the total group of 150 women, 132 women (88.0%) accepted replacement of the IUS and ten are waiting for replacement. This group includes nine women who will receive a second replacement. The number of women continuing the method is 142 (94.6%). Histological examinations conducted on endometrial biopsies from 101 postmenopausal women prior to replacement, after an average period of use of the regimen of 40 months (range 25-50 months), showed predominantly inactive endometrium characterized by pseudodecidual reaction of the endometrial stroma with endometrial atrophia, which is in keeping with the effects seen with a progestogenic compound. There were no specimens showing signs of proliferation. CONCLUSIONS: Results suggest that the frameless FibroPlant-LNG IUS is safe, well tolerated, well accepted and effective in suppressing the endometrium during ET. Intrauterine progestogen administration in postmenopausal women can be regarded as fundamentally advantageous compared with systemically applied progestogens, which may have potentially inherent ill side-effects, especially on the breast and cardiovascular system, as reported in the recent literature.