Gynecologic complications of cyclic estrogen progestin therapy

We evaluated the long-term gynecologic risks of postmenopausal estrogen therapy in conjunction with cyclic, monthly progestin (progestin-estrogen replacement therapy, or PERT). Our medical record review showed that incidence of abnormal vaginal bleeding necessitating gynecologic procedures for evaluation was significantly higher (RR, 3.1; 95% CI, 2.1–4.5), as was the rate of endometrial biopsy (RR, 3.4; 95% CI, 2.3–5.1), among women receiving PERT than among women not receiving hormone therapy. We also identified a non-significant trend toward a higher rate of dilation and curettage (RR, 1.5; CI, 0.7-3.3) among women receiving PERT. However, rates of endometrial hyperplasia and hysterectomy were similarly low in both groups. PERT apparently protects women against these serious gynecologic consequences previously seen in women taking unopposed estrogen.     

Effects of progestins on estrogen-induced increase in C-reactive protein in postmenopausal women

Background: C-reactive protein (CRP) represents an independent risk factor for coronary disease and stroke. Because oral estrogens increase CRP levels, with inflammatory and thrombotic consequences, we determined whether the co-administration of a progestin might modify the estrogenic effect on CRP. Methods: In a non-randomized, non-blinded study, we measured C-reactive protein serum concentrations with high-sensitivity technique (hs-CRP) in 163 healthy postmenopausal women divided into groups as follow: 52 not taking hormones (referent group), and 111 taking hormone replacement therapy (HRT) (42 of whom treated with unopposed estrogen, and 69 with an estrogen/progestin combination). Results: Compared with non-users of hormones, median CRP levels were 66% (95% confidence interval: from 44 to 89%) higher and 112% (95% confidence interval: from 89 to 168%) higher among women using a combined estrogen/progestin regimen and, respectively, among women taking unopposed estrogen [1.54 mg/L in the referent group; 2.56 mg/L in the estrogen/progestin group (P=0.032), and 3.27 mg/L in the unopposed estrogen group (P=0.004)]. Furthermore, there was no difference in CRP distributions between women taking different types of progestins. Conclusion: concurrent progestin administration may attenuate estrogen’s pro-inflammatory effects, independently on the type of used progestin.     

Use of unopposed estrogen in women with uteri: prevalence, clinical implications, and economic consequence

OBJECTIVE: Hormone replacement therapy with estrogen/progestin is the treatment of choice for relieving postmenopausal vasomotor symptoms and preventing urogenital atrophy and osteoporosis in women with intact uteri. However, despite the known increased incidence of endometrial hyperplasia when unopposed estrogen is used in such women, this progestin regimen has not been universally adopted. DESIGN: This study was conducted in a managed care organization to determine the extent of the use of unopposed estrogen in women with intact uteri. Pharmacy claims data for all women 55 years or older with claims for estrogen only from September 1, 1996, to December 31, 1996, were reviewed. A total of 5,209 records were identified, from which 480 were randomly selected. A survey of the members' physicians was then carried out to determine hysterectomy status and was confirmed by chart audit. RESULTS: Thirty-three (11%) of the members identified had not undergone hysterectomy. Follow-up physician contact revealed that five women did not have a uterus. Use of estrogen without opposing progestin was documented in a substantial percentage of files reviewed. It is of concern that with the documentation of the risks of endometrial hyperplasia and carcinoma in the intact uterus, unopposed therapy still occurs. In addition to the clinical costs, there are economic consequences to this practice. An economic model of unopposed estrogen use was created. A management cost of $1,504 for 3 years was estimated. CONCLUSIONS: Further educational efforts are needed to ensure the use of opposed estrogen in the woman with an intact uterus.     

Menopausal estrogen therapy predicts better nocturnal oxyhemoglobin saturation

OBJECTIVES: The respiratory responses in the few previous studies evaluating the effects of short-term unopposed estrogen therapy on breathing in postmenopausal women have been inconsistent. We performed a study to investigate whether long-term estrogen therapy would prevent age-related decline in nocturnal arterial oxyhemoglobin saturation and whether higher serum estradiol concentration is associated with better arterial oxyhemoglobin saturation. METHODS: Sixty-four healthy postmenopausal women were followed-up for 5 years in a 5-year prospective open follow-up study. The women were users or non-users of estrogen therapy according to their personal preference. RESULTS: Mean overnight arterial oxyhemoglobin saturation was similar at baseline (94.3 +/- 1.1%) and after follow-up (94.5 +/- 1.6%). Present estrogen users had higher mean arterial oxyhemoglobin saturation (95.2 +/- 1.4%) than present non-users (94.0 +/- 1.5%), when adjusted for age and body mass index (p = 0.042). The change in mean arterial oxyhemoglobin saturation during follow-up was not associated with serum estradiol concentration at baseline but associated with estradiol at follow-up (p = 0.042), when adjusted for age and body mass index. At follow-up, women with higher serum estradiol concentration had also higher mean nocturnal arterial oxyhemoglobin saturation (Pearson r = 0.29, p = 0.019) and lower apnea-hypopnea index (Spearman r = -0.28, p = 0.031). The pooled current estrogen users spent proportionally less time with SaO(2) below 90% than non-users (ANCOVA adjusted for age and BMI, p = 0.017). CONCLUSIONS: Estrogen use and especially high serum estradiol concentration predict higher mean overnight arterial oxyhemoglobin saturation. The present data suggest that estrogen therapy has favorable respiratory effects.     

The effects of tamoxifen on proliferation and steroid receptor expression in postmenopausal endometrium

AIM: To study the effects of tamoxifen on the proliferation index and oestrogen receptor (ER) and progesterone receptor (PR) expression in postmenopausal endometrium. METHODS: A total of 125 endometrial specimens of postmenopausal women, comprising benign endometria from tamoxifen users (n = 35) and non-users (n = 24), and endometrial cancer from tamoxifen users (n = 15) and non-users (n = 51), were immunohistochemically examined using MIB-1, anti-ER, and anti-PR antibodies in endometrial epithelium and stroma. RESULTS: In benign endometrium the mean MIB-1 index in the epithelium was higher in tamoxifen users than in non-users (mean, 13% (SD, 13%) v mean, 2% (SD, 2%); p < 0.05), whereas in endometrial cancer the MIB-1 index was higher, but similar in tamoxifen users and non-users (mean, 32% (SD, 24%) and mean, 35% (SD, 18%)). The expression of ER was comparably high in benign epithelium from tamoxifen users and non-users (97% and 92%, respectively), but in endometrial cancer it was lower in tamoxifen users (60% and 88%; p < 0.05). The expression of PR in stromal cells was higher in tamoxifen users, both in benign (84% v 54%) and in malignant endometrium (33% v 10%; p < 0.05). CONCLUSION: The proliferation index (as measured by MIB-1) in benign endometrial epithelium is higher in tamoxifen users than in non-users, and this might play a role in the reported higher incidence of endometrial cancer in postmenopausal tamoxifen users. The increased expression of PR in stroma from tamoxifen users with both benign and malignant endometrium demonstrates an additional oestrogenic effect of tamoxifen on the endometrial stroma.     

Effect of estrogen replacement therapy on speed of sound at multiple skeletal sites

Objectives: To evaluate the effect of estrogen replacement therapy (ERT) on postmenopausal bone loss by multi-site ultrasound measurement. Methods: A cross-sectional comparison of postmenopausal women, ERT users and non-users. The two study groups were enrolled for the reference database collection for the Sunlight Omnisense™ (Omnisense) and were matched by years since menopause. Speed of sound (SOS) was measured at the distal radius (RAD), mid-shaft tibia (TIB), fifth metatarsus (MTR) and proximal phalanx (PLX). Results: 143 ERT users for 5.2±3.6 years were compared with 139 ERT non-users (age: 57.0±5.3 and 57.5±5.5, respectively). Both groups were 7.1±5.0 years since menopause. SOS, expressed in T-score units, was higher at the RAD in ERT users as compared to ERT non-users (−0.55±1.30 and −1.36±1.60, respectively, P<0.0001), and at the TIB (−0.73±1.34 and −1.28±1.45, respectively, P=0.003). Same trend was observed at the MTR and PLX, but not statistically significant because of fewer observations. In early post menopause period, the ERT-non users RAD data shows an annual SOS decrease of 0.17 versus annual increase of 0.12 T-score units (P=0.037). Similar effect is observed at the TIB, though not statistically significant (non-users decrease of 0.20 vs. users increase of 0.08 T-score units/year, P=0.086). Conclusions: SOS measurements by Omnisense at multiple skeletal sites support the ERT protective effect on bone.     

Preliminary evidence that long-term estrogen use reduces white matter loss in aging

Despite numerous studies showing neurotrophic and neuroprotective effects of estrogen in animal models, the long-term effects of estrogen use on brain morphology in older women are not known. Thus, we compared ventricular, cerebrospinal fluid, white matter, and grey matter volumes estimated from magnetic resonance images of postmenopausal women with more than 20 years exposure to unopposed estrogen, women who were not on estrogen, and young healthy women. Estrogen users had significantly smaller ventricles and greater white matter volumes than non-users, but hormone exposure did not affect grey matter volumes. Young healthy women had significantly smaller ventricles, less cerebrospinal fluid and more grey matter than both groups of older women. However, they had comparable white matter volumes to older women on estrogen. These findings suggest that long-term estrogen protects against white matter loss in aging. This adds to findings from other studies suggesting estrogen is neuroprotective of the hippocampus and other regions in older women.     

Endometrial response to raloxifene compared with placebo, cyclical hormone replacement therapy, and unopposed estrogen in postmenopausal women.

OBJECTIVE: To determine the endometrial effects of raloxifene 60 mg/day in postmenopausal women as assessed by vaginal bleeding and endometrial thickness. DESIGN: Data from 1157 postmenopausal women were analyzed from a database consisting of four independent, double-blind, randomized, placebo-controlled trials (range = 6-30 months duration), a 24-month open-label randomized, cyclical hormone replacement therapy (HRT)-controlled trial, and a 6-month double-blind, randomized, unopposed estrogen-controlled trial. Vaginal bleeding rate was derived from self-reported adverse events collected at least every 6 months. Endometrial thickness was measured by ultrasonography at regular intervals. RESULTS: Raloxifene 60 mg/day was not significantly different from placebo with regard to the incidence of vaginal bleeding, the baseline-to-endpoint change in endometrial thickness, or the proportion of women experiencing an increase in endometrial thickness above baseline after either 12 or 24 months of therapy. Unexpected bleeding was reported significantly more frequently in the unopposed estrogen groups compared with the raloxifene group (raloxifene 60 mg/day, 0% versus estrogen, 50%; p = 0.002). A significantly greater baseline-to-endpoint increase in endometrial thickness was observed in both the HRT and estrogen groups compared with their respective raloxifene comparison group (raloxifene 60 mg/day, 0.01 +/- 2.0 mm versus HRT, 1.8 +/- 3.2; p < 0.001; raloxifene 60 mg/day, 1.1 +/- 1.7 mm versus estrogen, 7.8 +/- 3.8; p < 0.001). No cases of endometrial hyperplasia or cancer were diagnosed in the placebo or raloxifene 60 mg/day groups. Endometrial hyperplasia was diagnosed in one case in the HRT group and in two cases in the estrogen group. CONCLUSION: Raloxifene 60 mg/day for up to 30 months is not associated with vaginal bleeding or increased endometrial thickness in postmenopausal women.     

Endometrial tumorigenesis in Pten(+/-) mice is independent of coexistence of estrogen and estrogen receptor α

Numerous studies support the role for mutations in the phosphatase and tensin homologue (PTEN) tumor suppressor gene and unopposed estrogen stimulation in the pathogenesis of uterine endometrioid carcinoma. However, the relation between PTEN signaling and estrogen/estrogen receptor in endometrial tumorigenesis remains unresolved. We used genetically engineered mice as a model to address this relation. Mice with a single deleted Pten allele (Pten(+/-)) spontaneously develop complex atypical hyperplasia and ~20% develop endometrial cancer. To determine the effect of removing endogenous estrogen, we performed oophorectomies on Pten(+/-) mice. Although there was a reduction in the number and severity of hyperplastic lesions, the endometrial phenotype persisted, suggesting that Pten mutation, independent of estrogen, can initiate the development of complex atypical hyperplasia. To recapitulate the situation in women with unopposed estrogen, we implanted 17β-estradiol pellets in adult female Pten heterozygous mice, resulting in increased carcinoma incidence. Because studies have shown that estrogen largely acts on the endometrium via estrogen receptor ERα, we generated Pten(+/-)ERα(-/-) mice. Strikingly, 88.9% of Pten(+/-)ERα(-/-) mice developed endometrial hyperplasia/carcinoma. Furthermore, Pten(+/-)ERα(-/-) mice showed a higher incidence of in situ and invasive carcinoma, suggesting that endometrial tumorigenesis can progress in the absence of ERα. Thus, the relation between Pten alterations and estrogen signaling in the development of endometrial carcinoma is complex; the results presented herein have important implications for the treatment of endometrial hyperplasia and carcinoma in women.     

Endometrial cancer after combined hormone replacement therapy

Objective: It has been suggested that exposure to relatively high levels of unopposed estrogen is a risk factor for endometrial cancer. Combined therapy of estrogen with cyclic progestagen was therefore highly recommended for menopausal women with an intact uterus. Methods: The cases of two postmenopausal women who developed endometrial cancer after taking continuous sequential HRT for 15 months are reported. Both were without bleeding for more than 2 years and presented with a normal vaginal ultrasound. They had severe menopausal symptoms and asked for HRT. Results: After 15 months irregular bleeding occurred and a hysterectomy was performed. The pathohistological finding in both cases was endometrial cancer. As we measured the serum estradiol levels 4 h after tablet ingestion supraphysiologic values ranging between 418 and 442 pg/ml were found. Conclusion: Our report strengthens the evidence that supraphysiologic estradiol levels despite combination with cyclic progestagen therapy, increase the risk of endometrial cancer.     

The protective role of progesterone in the prevention of endometrial cancer

An association between endometrial hyperplasia and corpus cancer has long been suspected. Genetically predisposed women are at greater risk of developing endometrial cancer if subjected to long uninterrupted periods of estrogen stimulation. Endometrial cancer need not be inevitable if 14 day courses of an oral progestogen are continued for as long as is necessary; in some women, however, the lesions will progress and, therefore, should be carefully followed with repeated endometrial biopsies.Epidemiological evidence suggests a true link between unopposed estrogens and early, less invasive endometrial cancer, and progestogens appear capable of protecting against the development of cancer and hyperplasia, although complete protection has not yet been achieved. The protective action of progestogens is supported by the fact that none developed endometrial cancer in a series of 490 women of reproductive age who received continuous estrogens by way of pellet implants of 17 β estradiol for conception control for 1-10 years. Evidence for the protective action of progestogens in estrogen-treated menopausal women was less solid than in nonmenopausal women but was nonetheless considerable. Our study of 1058 women, 45 years of age and older, receiving continuous estrogens by way of 17 β estradiol pellets over a period varying from 1 to 21 years, revealed that the incidence of cancer was not greater and was possibly less than that expected in an untreated population of menopausal women.     

Management of abnormal genital bleeding in girls and women

Management of abnormal genital bleeding in girls, adolescents and women, in pregnancy, and in postmenopausal women is reviewed under the headings of evaluation and treatment. In childhood all genital bleeding is clinically significant: it is due to acute infection, foreign bodies, trauma, prolapsed urethra or precocious puberty, rarely to tumors. Bleeding in adolescents and adults is most often due to anovulation, usually estrogen-breakthrough bleeding. Other causes are submucosal leiomyomas, cervical or endometrial polyps, lacerations, uterine or cervical cancer, or systemic disorders such as hypothyroidism or bleeding disorders. Evaluation of bleeding in children requires skill and often general anesthesia, especially if peritoneal laceration is suspected. The 1st step in adolescents and adults is to rule out pregnancy. Pap smears are insufficient: biopsies are advised, especially endometrial biopsies in women 40. Hemoglobin, hematocrit and thyroid status, should also be ordered. Specific treatments involve antibiotics for infection, correction of anemia and orthostatic hypotension, reversal of unopposed estrogen, and medical treatment of menorrhagia and dysfunctional bleeding that does not involve hemodynamic instability. Sometimes curettage, endometrial ablation or hysterectomy is needed. Medical management of breakthrough bleeding caused by unopposed estrogen is high dose estrogen followed by progestin therapy to bring about withdrawal, curettage if necessary, then cyclic combined therapy. In young women 4 birth control pills per day for 5-7 days are often prescribed, with cyclic therapy after withdrawal bleeding is obtained. Prostaglandin inhibitors reduce menstrual loss 50%. Endometrial atrophy in post-menopausal women is treated with cyclic conjugated estrogens and then medroxyprogesterone acetate for 10-13 days per month, or continuous combined therapy for those who can tolerate it.     

Reversal by medical treatment of endometrial hyperplasia caused by estrogen replacement therapy.

OBJECTIVE: Endometrial hyperplasia, an entity considered a precursor to endometrial carcinoma, frequently develops in women receiving unopposed estrogens. Progestins used concomitantly with estrogens can largely prevent endometrial hyperplasia and carcinoma. However, the ability of progestins to reverse endometrial hyperplasia induced by estrogens is less well recognized. The purpose of this study was to assess the medical reversal rate of endometrial hyperplasia that develops in women receiving unopposed estrogen replacement therapy (ERT). DESIGN: Review of recent literature (1990-2000). RESULTS: Based on four large series, more than 90% of endometrial hyperplasia caused by ERT can be reversed by medical treatment. Discontinuation of estrogen and oral administration of 10 mg/day of medroxyprogesterone acetate continuously for 6 weeks or cyclically for 3 months (2 weeks of each month) are the two regimens most widely used. Other progestins also have been shown to be effective. CONCLUSIONS: Progestins are highly successful in reversing endometrial hyperplasia caused by ERT.     

Management of patients with non-atypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: long-term follow-up

OBJECTIVES: Levonorgestrel (LNG), delivered locally into the uterine cavity has a profound effect on the endometrium. The aim of the study was to use a LNG intrauterine system to treat non-atypical and atypical endometrial hyperplasia in women and to evaluate the long-term cure (remission) rate. METHODS: Each of the 20 women in the study, of whom eight were diagnosed with atypical hyperplasia, received a LNG-IUS, releasing 20 microg LNG/day. The study is a non-comparative study with long-term follow-up (range 14-90 months). RESULTS: All women developed a normal endometrium, except one asymptomatic woman with atypical hyperplasia who still had focal residual non-atypical hyperplasia at 3 years follow-up in the presence of a thin (< 4 mm) endometrium. CONCLUSION: Continuous intrauterine delivery of LNG appears to be a promising alternative to hysterectomy for the treatment of endometrial hyperplasia and could enhance the success rate when compared with other routes of progestagen administration as well as intrauterine progesterone delivery. The significant reduction of the PR expression observed during treatment with the LNG-IUS appears to be a marker for the strong antiproliferative effect of the hormone at a cellular level resulting in an inhibition of estrogen bioactivity and endometrial suppression.     

Prevention of endometrial cancer with progestogens

Unopposed oestrogen replacement therapy increases the risk of endometrial cancer in post-menopausal women. However, the addition of progestogen to the oestrogen therapy reduces the risk of endometrial carcinoma by preventing and effectively treating hyperplasia of the endometrium. In a 5-yr prospective study with a further 4 yr of follow-up (1975-83), 31 adenocarcinomas of the endometrium were detected over 27243 patient-years of observation, for an incidence of 113.8:100 000 women. The first report on the results of the study appeared in 1978; this paper presents further results. The lowest incidence of endometrial cancer (49.0:100 000) was observed among the oestrogen-progestogen users and the highest (390.6:100 000) among the unopposed oestrogen users. Not only was the incidence of endometrial carcinoma significantly lower in the oestrogen-progestogen users than in those using unopposed oestrogens (P less than or equal to 0.0001), but it was also significantly lower than that among the non-hormone users (245.5:100 000 with P less than or equal to 0.0005). Endometrial hyperplasia had been diagnosed previously in 12 of the 31 patients with adenocarcinoma (38.7%) from 4 mth to 8 yr before the detection of cancer. When given for 7-10 days each month progestogens are effective in reversing hyperplasia and restoring a normal endometrium in 94.5% of patients treated within 3-6 mth. The progestogen challenge test was devised to identify post-menopausal women at greatest risk for adenocarcinoma of the endometrium. It is concluded that the use of this test will reduce the risk of endometrial cancer in both oestrogen-treated post-menopausal women and women with increased endogenous oestrogens.     

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.     

Estrogen use and brain metabolic change in postmenopausal women

OBJECTIVE: We used positron emission tomography to evaluate cerebral glucose metabolic change in postmenopausal women in a naturalistic observational study. METHOD: Women estrogen users (n = 11) and non-users (n = 9) were studied at baseline and 2 years later. Analyses focused on glucose metabolism in regions previously reported to decline in older persons at risk for Alzheimer's disease (AD) (posterior cingulate and lateral temporal cortex). RESULTS: Region of interest (ROI) analysis at baseline showed no regional differences between women estrogen users and non users. ROI follow-up analysis revealed that women non-users declined significantly in the posterior cingulate cortex (P= 0.04). Statistical parametric mapping (SPM) analysis confirmed a significant decrease in metabolism of the posterior cingulate cortex among non-users at 2-year follow-up (P = 0.004). In contrast, women estrogen users did not exhibit significant metabolic change in the posterior cingulate. CONCLUSIONS: Estrogen use may preserve regional cerebral metabolism and protect against metabolic decline in postmenopausal women, especially in posterior cingulate cortex, the region of the brain found to decline in the earliest stages of AD.     

Endometrial cancer patients and tibolone: a matched case-control study

OBJECTIVE: To evaluate whether tibolone had adverse effects on the prognosis of endometrial cancer patients. METHODS: In this retrospective matched case-control study, out of 396 patients with endometrial cancer from January 1997 to December 2002, 68 patients who underwent complete surgical staging were identified as tibolone users (cases). For each case, one control as tibolone non-user was matched for stage and grade of disease, in this order of priority (ratio users: non-users, 1:1). RESULTS: There were no significant differences in age (p = 0.11), stage (p = 1.00), grade (p = 0.96) and treatment modality (p = 0.55) between two arms. The mean duration of follow-up for tibolone users and tibolone non-users is 48.0 months and 54.4 months, respectively (p = 0.12). In tibolone users, a total of four patients recurred and two out of four patients died of disease. In tibolone non-users, there were three recurrences and all of three patients died of disease. There were no significant differences in disease free survival (p = 0.52) and overall survival (p = 0.61) between two arms. And there was no significant difference in disease free survival according to the duration of tibolone use (p = 0.14). CONCLUSION: There was no evidence that tibolone had adverse effects on the disease free survival and overall survival of endometrial cancer patients. So, tibolone could be used in these patients.     

Poorer prognosis in older patients with endometrial adenocarcinoma.

It has been suggested that there are two types of endometrial carcinoma: the first arises in younger women who have hyperestrogenism and has a favorable prognosis and the second occurs in older women, is not associated to estrogen stimulation, and has a poorer prognosis. This study examined the hypothesis that more aggressive carcinomas are found in older patients with no evidence of estrogen stimulation. A retrospective review of all patients (N = 82) with endometrial carcinoma diagnosed and treated at our institution between 1978 and 1990 was undertaken. The following data were analyzed: age at diagnosis, stage, race, histologic type, grade, depth of myometrial invasion, absence or presence of associated hyperplasia, and survival. The mean age of the patients was 64.8 years. Sixty (73%) of the 82 patients were considered estrogen-positive either because of obesity (body mass index > or = 27.3) or the use of unopposed exogenous estrogen. There were no statistically significant differences between estrogen-positive and estrogen-negative patients. Patients > or = 65 years had a 5-year survival of 60% compared with 74% for younger patients. There was a trend toward higher histologic grade among the older patients. Otherwise no statistically significant differences were found between these two groups. Estrogen-negative women > or = 65 years had the worst prognosis with a 5-year survival of 29%. As identified by other investigators, age at diagnosis is a significant indicator of prognosis in patients with endometrial carcinoma. In this series, thin, older (> or = 65 years) women who developed endometrial carcinoma had the worst prognosis.     

Hysteroscopic findings in postmenopausal abnormal uterine bleeding: a comparison between HRT users and non-users

Objectives: The aim of our study was to investigate hysteroscopic findings in a sample of 410 menopausal women (hormonal replacement therapy, HRT users n=219 and HRT non-users n=191) and to evaluate the relationship between the presence of intrauterine disease, the use of HRT and the presence of AUB. Methods: Two hundred and nineteen women on HRT underwent standard office hysteroscopy by means of the Hamou hysteroscope (in 94 cases for abnormal uterine bleeding (AUB) and in 125 cases for periodic endometrium monitoring). One hundred and ninety-one women who had never received HRT were submitted to office hysteroscopy (154 for AUB and 37 for other reasons). Results: Intrauterine diseases are more frequent in patients who do not use HRT (P=0.02). Endometrial polyps is a frequent disease present in 30% of the sample (23.7% of HRT users and 30.8% of HRT non-users). Myomas were present in 8.7% of all patients examined (6.8% of HRT users and 11% of HRT non-users). Irregular bleeding in menopause is often associated with endouterine abnormalities: in symptomatic patients the frequency of endouterine diseases was 41% while in asymptomatic patients was 28% (P=0.003). In patients taking HRT (n=219) endouterine disease is demonstrated in 37% with AUB and in 26% without AUB (P=0.07). Conclusion: Benign intrauterine diseases (endometrial polyps and submucous myomas) are more frequent in postmenopausal women who do not use HRT. In patients taking HRT irregular bleeding is associated with intrauterine diseases; however, the absence of AUB does not exclude the presence of endometrial polyps or myomas.