The effects of phytoestrogen therapy on the endometrium in postmenopausal women

AIM: The purpose of the present study was to carry out a comparative histological analysis of the endometrium in postmenopausal women who made use of phytoestrogens in order to assess the efficacy and possible side effects of this therapy. METHODS: This study was carried out by forming 2 groups in order to compare the results. One group was given a dietary supplement of phytoestrogens for 24 months, whereas the other was given a placebo for the same period of time. At the beginning of this study endometrial bioptical samples were taken from those patients who had been previously selected at our University Centre. This study was started only with those postmenopausal patients whose bioptical sample was histologically suitable, and it was neither hyperplastic, nor cancerous and nor secretive. During these 24 months there have been frequent contacts aimed at verifying the standard therapeutic behaviour, symptoms and appearance of side effects. At the end of the study new and final bioptical samples of endometrium were taken from both groups. RESULTS: One-hundred and forty-one patients completed the study. Five patients (3.4%) who were submitted to phytoestrogens therapy showed a weak proliferative endometrium bioptical sample. All the other biopsies at the beginning and at the end of the study showed an atrophic and inactive sample. Hot flushes, night sweats, vaginal dryness and dyspareunia improved at the end of the study for the group treated with phytoestrogens as compared to the one treated with a placebo. Although there have not been very significant differences ias to symptoms and side effects, it was noted that insomnia was the most common symptom in the group treated with non-hormonal therapy based on phytoestrogens. CONCLUSIONS: Phytoestrogens did not cause any sensitive and worrisome stimulation of the endometrial mucosa. Insomnia was more frequent in the group treated pharmacologically in the 24 months of the study, whereas hot flushes, night sweats, vaginal dryness and dyspareunia persisted or increased as compared to the beginning of the study in the group treated with a placebo, but this did not occur for the group treated with phytoestrogens.     

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.     

A pilot study of the effects of phytoestrogen supplementation on postmenopausal endometrium

OBJECTIVE: This study was designed to assess endometrial histology in postmenopausal women not taking hormone replacement therapy, to evaluate side effects and efficacy of phytoestrogens in treating menopause-associated symptoms, and to determine whether 6 months of phytoestrogen supplementation altered endometrial histology.METHODS: We performed a prospective, double-blinded, randomized, placebo-controlled trial comparing the effects of 6 months of dietary phytoestrogen supplementation versus placebo in postmenopausal women. Baseline endometrial biopsies were performed and, if adequate, nonhyperplastic, noncancerous, and nonovulatory, subjects were randomly assigned to receive daily placebo or soy cereal supplementation for 6 months. Study subjects completed baseline and weekly dietary, symptom, and side effect logs. Repeat endometrial biopsies were obtained at 6 months.RESULTS: Subjects were recruited from January 1998 through June 2000. Twenty-seven subjects were randomized, and 19 completed the study. One (3.7%) baseline endometrial sample was weakly proliferative. All other baseline and final biopsies were consistent with atrophic, inactive endometrium. The maximum risk of endometrial stimulation with phytoestrogens is 35%. Hot flushes, night sweats, and vaginal dryness were significantly less severe at the final week of the study compared with baseline in the placebo group. Insomnia was more common in the treated group. There were no other statistically significant differences in symptoms or side effects.CONCLUSION: Phytoestrogens did not cause stimulation of the endometrium. Insomnia was more frequent over the 6-month study in the soy group, whereas hot flushes, night sweats, and vaginal dryness improved from baseline in the placebo group but not in the soy group.     

Effects of trimonthly progestin administration on the endometrium in elderly postmenopausal women who receive hormone replacement therapy: a pilot study

OBJECTIVE: The purpose of this study was to determine the effect of trimonthly progestin administration on the endometrium in elderly postmenopausal women who receive hormone replacement therapy. STUDY DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study at a university teaching program. Twenty-five postmenopausal women who were >or=75 years old with an intact uterus were assigned randomly to receive conjugated equine estrogens (0.625 mg/d plus medroxyprogesterone acetate 5 mg/d for 13 days every 3 months (n = 13) or placebo (n = 12) for 9 months). At the end of the 9 months, patients in the hormone replacement therapy arm continued therapy for an additional 9 months. Statistical analysis was performed with the Student t test, the chi(2) test, and the Fisher exact test. RESULTS: Transvaginal sonography was performed at baseline and at 9 and 18 months. Endometrial biopsy was performed if the endometrial thickness was >4 mm or as clinically indicated at 18 months. Patients in the hormone replacement therapy group demonstrated a significant increase in endometrial thickness between baseline (3.9 + 0.8 mm) and 9 months (8.0 + 4.8 mm). There were no cases of endometrial hyperplasia at the 18-month endometrial biopsy. CONCLUSION: Trimonthly progestin administration in elderly postmenopausal women who receive hormone replacement therapy may be a reasonable alternative to the monthly administration of progestin in hormone replacement therapy.     

Sonographic, hysteroscopic, and histologic evaluation of the endometrium in postmenopausal women with breast cancer receiving tamoxifen

STUDY OBJECTIVE: To evaluate the estrogenic effects of tamoxifen on the endometrium in postmenopausal women with breast cancer. DESIGN: Consecutive study (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Thirty-three women. Interventions. All patients underwent transvaginal sonography (TVS) and color flow Doppler of endometrial vessels, hysteroscopy, and, if necessary, endometrial biopsy or other operative hysteroscopic procedures. MEASUREMENTS AND MAIN RESULTS: In four women the endometrium was thin on TVS and atrophic at hysteroscopic assessment. In 29 women with thick endometrium on TVS, hysteroscopy and endometrial biopsy showed atrophy (11 patients), hyperplasia (5), polyps (11), and well-differentiated adenocarcinoma (2). The two endometrial cancers were present in women with uterine bleeding. In women with positive histologic findings, the endometrium was significantly thicker (p = 0.04) and duration of tamoxifen therapy longer than in those with negative findings, although this was not statistically significant (p = 0.067). CONCLUSION: We believe regular assessment of the endometrium by TVS should be performed in postmenopausal patients at the start of the tamoxifen therapy, and hysteroscopy in women with a thick endometrium or postmenopausal bleeding. We believe that patients with thin endometrium on TVS at the beginning of tamoxifen therapy, who have no abnormal uterine bleeding should be screened with these examinations for 2 years.     

Effects of genistein on the endometrium: ultrasonographic evaluation.

The aim of our study was to evaluate the effects of isoflavones on climacteric-related symptoms and on the endometrium in postmenopausal women, in a prospective, open, randomized, clinical trial performed at the Menopause Clinic of our Department. Seventy postmenopausal women were randomly assigned to two treatment groups receiving 12 cycles of treatment with genistein (group A) or calcium (group B). In all patients ultrasonographic endometrial thickness and Kupperman Index (KI) were evaluated at baseline and after 6 and 12 cycles of treatment. At baseline no significant difference was detected in endometrial thickness and in KI between groups A and B. After 6 and 12 cycles of treatment, no significant difference was observed in endometrial thickness between or within groups. Endometrial thickness was lower than 5 mm in all cases before and during treatment except in two cases in group B and in one case in group A after 12 months. At 6 and 12 months, the KI was significantly (p < 0.05) lower in group A in comparison with baseline values and group B. We conclude that genistein administration reduces climacteric symptoms in postmenopausal women and does not increase endometrial thickness.     

Sequential combined transdermal and oral postmenopausal hormone replacement therapies: effects on bleeding patterns and endometrial histology

Objectives: To determine the endometrial response and bleeding patterns in postmenopausal women taking a sequential combined hormone replacement regimen either orally or transdermally. Methods: Seventy-two postmenopausal women with amenorrhea of 6 months or longer with follicle stimulating hormone and estradiol levels in the postmenopausal range and normal endometrium were included in the study. The patients randomly received sequential combined hormone replacement regimen with oral (n=37) or transdermal route (n=35). The total duration of treatment was 6 months (6 cycles of 28 d). The subjects kept daily bleeding diaries, and endometrial biopsies were taken at baseline and after 6 months of therapy. Results: The rates of adequate progestational response (secretory or atrophic) were 83.8% and 82.9% in the oral and transdermal hormone replacement groups, respectively (p>0.05). In the oral hormone replacement group, there were 16.2% of inadequate progestational response, 2.7% had endometrial hyperplasia and 13.5% proliferative endometrium. In the transdermal hormone replacement group, there were 17.1% of inadequate progestational response, 2.9% had endometrial hyperplasia and 14.3% proliferative endometrium. Cyclic bleedings occurred in 92.4% and 92% of all cycles in the oral and transdermal treatment groups, respectively. The mean duration of bleeding per cycle were 3.9±0.9 and 3.8±0.9 d in the oral and transdermal treatment groups, respectively. Conclusion: Sequential combined transdermal hormone replacement therapy is as effective as oral therapy in preventing the development of endometrial hyperplasia. Satisfactory control of bleeding is achieved with both regimens. Received: 6 June 2001 / Accepted: 12 July 2001     

Ultrastructural effects of estrogen replacement on postmenopausal endometrium

Endometrial adenocarcinoma occurs almost exclusively in postmenopausal women, and excessive or unopposed estrogen stimulation is suspect as a causative factor in its pathogenesis. Furthermore, the incidence of endometrial adenocarcinoma has increased in women undergoing estrogen replacement therapy. In the present study, the cellular response of premenopausal and postmenopausal endometrium to estrogenic stimulation was compared with endometrial adenocarcinoma by the electron microscope. Tissues were obtained at hysterectomy, endometrial biopsy, or endometrial curettage and were processed routinely for light and electron microscopy. Ultrastructurally the endometrium from postmenopausal patients undergoing estrogen replacement therapy was similar to normal cyclic endometrium in the late proliferative phase. At least three features of the estrogen-treated postmenopausal tissue resembled those observed in adenocarcinoma of the endometrium: accumulation of lipid droplets, irregular nuclei, and perinuclear whorls of microfibrils.     

Tamoxifen-induced endometrial changes in postmenopausal women with breast carcinoma.

OBJECTIVES: To assess the effects of tamoxifen (TAM) on the endometrium in postmenopausal women. METHODS: A case control study of postmenopausal women with breast carcinoma, who were undergoing treatment in the Department of Radiotherapy and Surgery at the Christian Medical College Hospital, Vellore, India was done. Thirty-five women who were on tamoxifen (20 mg/day) for a period of at least 6 months formed the study group. Thirty-three women who were not receiving tamoxifen, formed the control group. Subjects in both groups had a pelvic examination and transvaginal sonogram followed by endometrial biopsy. RESULTS: There was a statistically significant difference in the mean endometrial thickness between the study group and control group (7.8+/-6.4 mm vs. 4.0+/-2.0 mm, respectively) More women in the tamoxifen group had an endometrial thickness of >5 mm but the number of women with polyps or hyperplasia of the endometrium did not differ significantly between the two groups. There were no women with endometrial carcinoma in either group. CONCLUSION: All patients on tamoxifen need to be evaluated by clinical examination annually. A transvaginal sonogram and endometrial biopsy/hysteroscopy may be performed on patients with abnormal vaginal bleeding, bloody discharge, staining or spotting.     

Effect on endometrium of combined oestrogen-progestogen replacement therapy of 1 mg 17beta-estradiol and 0.5 mg norethisterone acetate

The purpose of the study was to determine the effects of low-dose hormone replacement therapy (HRT) on ultrasound thickness of the endometrium and on endometrial histology in postmenopausal women. Two hundred and fifty-four postmenopausal women were included in the study; 124 completed three years of treatment with continuous HRT containing 1 mg oestradiol and 0.5 mg norethisterone acetate daily, and 130 women did not take HRT during the same time (control group). Ultrasound scan showed that the mean thickness of the endometrium was similar between the groups under investigation at the end of the study. Ninety-one percent of the women in the HRT group and 78% in the control group had an atrophic or unassessable endometrium and no cases of endometrial hyperplasia or malignancy were detected in either group at endometrial biopsy at the end of the study. It seems that low-dose continuous HRT of moderate duration is not associated with either endometrial hyperplasia or malignancy.     

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.     

Oncogenic potential of tamoxifen on endometria of postmenopausal women with breast cancer--preliminary report

Tamoxifen (TAM), a nonsteroidal antiestrogen, is used for pre- and postmenopausal patients with breast cancer. Recent reports suggest that TAM may cause endometrial neoplasia. This study is designed to evaluate the oncogenic potential of low-dose TAM on the endometrium. Initially, endometrial screening of patients with breast cancer who had received TAM therapy for at least 12 months was conducted. Seventy patients were interviewed and office endometrial biopsies were obtained from thirty-eight patients. Seven (18%) had hyperplastic changes, ranging from simple hyperplasia through complex hyperplasia with atypia. The following prospective study was conducted: after breast surgery and prior to initiation of TAM therapy, an office endometrial sampling was obtained as a control. After initiation of TAM therapy, biopsies were repeated every 4 to 6 months as long as the patients remained asymptomatic. Nineteen patients were interviewed. Twelve patients were biopsied and followed from 3 to 15 months. One patient refused additional biopsies. Eleven patients had repeat biopsies after initiation of TAM. New hyperplastic changes were found in 3/11 (27%) patients. The preliminary results of this study (although with a small number of patients) indicate that TAM may have some neoplastic effect on the endometrium of postmenopausal patients with breast cancer. This study is still in progress. Additional prospective studies are warranted before a significant correlation between TAM and endometrial neoplasia is confirmed.     

Endometrial patterns and endocrinologic characteristics of asymptomatic menopausal women

The endometrial histology and endocrinologic and demographic characteristics of 556 asymptomatic postmenopausal women ,who attended the menopause outpatient clinic at Ankara Numune Education and Research Hospital were studied before initiating estrogen replacement therapy. Of these women ,486 (87.4%) had atrophic endometrium ,37 (6.65%) had proliferative endometrium ,27 (4.86%) had endometrial hyperplasia without atypia ,three (0.54%) had endometrial hyperplasia with atypia and three (0.54%) had endometrial adenocarcinoma on their biopsy specimens. When demographic characteristics of the patients were considered, we found that the patients with endometrial adenocarcinoma and endometrial hyperplasia with atypia had potential risk factors for endometrial pathology such as chronic anovulation ,diabetes or hypertension. This study confirms that routine endometrial sampling in asymptomatic postmenopausal women is not warranted ,but patients with associated risk factors should be screened for endometrial pathology before starting estrogen replacement therapy.     

Endometrial patterns and endocrinologic characteristics of asymptomatic menopausal women.

The endometrial histology and endocrinologic and demographic characteristics of 556 asymptomatic postmenopausal women, who attended the menopause outpatient clinic at Ankara Numune Education and Research Hospital were studied before initiating estrogen replacement therapy. Of these women, 486 (87.4%) had atrophic endometrium, 37 (6.65%) had proliferative endometrium, 27 (4.86%) had endometrial hyperplasia without atypia, three (0.54%) had endometrial hyperplasia with atypia and three (0.54%) had endometrial adenocarcinoma on their biopsy specimens. When demographic characteristics of the patients were considered, we found that the patients with endometrial adenocarcinoma and endometrial hyperplasia with atypia had potential risk factors for endometrial pathology such as chronic anovulation, diabetes or hypertension. This study confirms that routine endometrial sampling in asymptomatic postmenopausal women is not warranted, but patients with associated risk factors should be screened for endometrial pathology before starting estrogen replacement therapy.     

Endometrial responses to transdermal estradiol in postmenopausal women

In prospective studies, we have determined the endometrial histologic characteristics and patterns of vaginal bleeding in 12 perimenopausal or postmenopausal women during administration of transdermal estradiol, 0.05 mg daily, given either alone or in combination with a progestogen. In the first study, we administered transdermal estradiol in cyclical fashion for 3 months. Outpatient curettage at pretreatment produced no endometrial sample or tissue too scant for assessment from 10 of the 12 patients (83%). At the end of therapy, proliferative or nonsecretory endometrium was diagnosed in nine patients (75%). Eight patients experienced treatment-related vaginal bleeding but no regular pattern, and seven patients reported breakthrough bleeding. Eight patients participated in the second study in which transdermal estradiol was administered continuously and norethindrone, 0.35 mg, was added for 12 days of each calendar month. A further curettage was performed at the end of treatment, and proliferative endometrium was the most common finding. No endometrial hyperplasia was observed. Only one patient experienced breakthrough bleeding. There were no consistent changes with time in the number of patients bleeding each month or in the duration or heaviness of the bleeding.     

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.     

Increased endometrial thickness in women with hypertension

OBJECTIVE: We noticed an increase in endometrial thickness in women with hypertension who were treated with a combination of medications, including beta-blockers. The purpose of this study was to examine whether the endometrium of hypertensive women is thicker than that of healthy women and to determine whether endometrial thickening in hypertensive women is directly related to the antihypertensive beta-blocker treatment. STUDY DESIGN: We compared 3 groups of postmenopausal patients as follows: (1) women with a history of essential hypertension treated with a combination of medications, including beta-blockers; (2) women with a history of hypertension treated with a combination of medications that did not include beta-blockers; and (3) healthy women without hypertension. All patients were interviewed and examined, blood tests were performed, and endometrial thickness in the anterior-posterior diameter was measured by vaginal ultrasonography. Among the exclusion criteria were diabetes or an abnormal fasting blood glucose level, obesity, hormonal medication or replacement hormonal therapy during the previous 6 months, and a history of hormonal disturbances, infertility, or polycystic ovary syndrome. RESULTS: Of 45 hypertensive women enrolled in the study, 22 were treated with a beta-blocker combination medication and 23 were treated with other antihypertensive medications. They were compared with 25 healthy women. There was no statistically significant difference in endometrial thickness between women treated with medications, including beta-blockers, and those who were treated with other hypotensive agents. Twenty percent of women with hypertension and none of the healthy women had endometrium >5 mm thick (P <.017; odds ratio, 8.22; 95% confidence interval, 1.22-infinity). CONCLUSION: Twenty percent of hypertensive postmenopausal women were found to have increased endometrial thickness. However, we were unable to substantiate an association between the type of treatment administered, whether beta-blockers were included, and the increase in endometrial thickness.     

Tamoxifen and endometrial pathologies: a prospective study.

OBJECTIVE:The purpose of this study was to prospectively follow a group of women with breast cancer, on tamoxifen, for the development of endometrial pathologies. MATERIALS AND METHODS: Eighty women with breast cancer, on tamoxifen, were prospectively followed every 6 months with pelvic examination, Pap smear, vaginal ultrasound, and endometrial biopsy. RESULTS: Nine women were lost to follow-up prior to initiation of treatment and 4 refused biopsies, leaving 67 patients for evaluation. Fifty (74.6%) of the 67 patients were already on tamoxifen for a mean duration of 15.8 +/- 16.6 months and had a baseline benign, unremarkable endometrium at the time of entry into the study. The total duration of treatment was 32.5 +/- 19.6 months (median 30 months). The mean age of the patients was 51.7 +/- 9.9 years (median 52 years). Of the patients, 56.7% were postmenopausal. Sixty-three patients had a benign endometrium (mean age 51.8 +/- 10.1 years, mean duration 33.1 +/- 19.6 months). Two patients had simple hyperplasia (mean age 43.5 years, duration 28.5 +/- 33.2 months), 1 patient had complex hyperplasia with atypia (age 57 years, duration 13 months), and another patient developed adenocarcinoma (grade 3) after 22 months. These 4 patients had abnormal vaginal bleeding. Seven patients developed endometrial polyps (mean age 54.0 +/- 8.5 years, duration 36 +/- 24.2 months). The mean endometrial thickness for patients with histologically unremarkable and abnormal endometrium was not significantly different (7.6 +/- 3.9 vs 8.8 +/- 5.0 mm, respectively) (median 7.0 mm for both groups). No endometrial thickness cutoff point reached statistical significance. The patient who developed endometrial cancer had a thickness of only 3 mm. CONCLUSION: All patients who developed an abnormal endometrium had abnormal vaginal bleeding. There was no correlation between endometrial thickness and endometrial pathology; thus the value of routine screening remains controversial.     

Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study

Objective

To determine the effects of 5 years of treatment with soy phytoestrogens on histological characteristics of endometrium in postmenopausal women.

Design

Randomized, double-blind, placebo-controlled study.

Setting

Centre of Perinatal and Reproductive Medicine, Department of Gynecological, Obstetrical, and Pediatric Sciences, University of Perugia, Italy.

Patient(s)

Three hundred seventy-six postmenopausal healthy women, all with intact uterus.

Intervention(s)

Women were distributed in two different groups using randomized criteria: group A (n = 179) patients received soy tablets (150 mg of isoflavones per day) for 5 years; group B (n = 197) patients received identical appearing placebo tablets for 5 years.

Main outcome measure(s)

Results of endometrial histology from biopsies obtained at baseline, 30 months, and 5 years after the beginning of the treatment.

Result(s)

Two hundred ninety-eight women completed the 5-year treatment. No cases of malignancy were detected during biopsy. Seventy percent of women undergoing treatment with soy phytoestrogens had an endometrium classified as atrophic or nonassessable versus 81% receiving placebo. The occurrence of endometrial hyperplasia was significantly higher in group A (3.37% vs. 0%).

Conclusion(s)

Long-term treatment (up to 5 years) with soy phytoestrogens was associated with an increased occurrence of endometrial hyperplasia. These findings call into question the long-term safety of phytoestrogens with regard to the endometrium.     

Apoptosis in the endometrium of postmenopausal women receiving tibolone

BACKGROUND/AIM: Tibolone, a synthetic derivative of the 19-nortestosterone family, induces atrophy of the endometrium, especially via its progestogenic Delta(4) isomer. The aim of the study was to determine whether tibolone induces apoptosis in the endometrium of postmenopausal women. METHODS: Twenty healthy postmenopausal women (mean age +/- SD 52.4 +/- 4.21 years) who had amenorrhea for at least 1 year and who had no history of any systemic illness and estrogen replacement therapy were enrolled in the study. All patients were offered office endometrial samplings, and then tibolone was prescribed (2.5 mg/day p.o., once daily) to all patients. Repeat endometrial samples were obtained after completion of the 6-month course of tibolone therapy. All samples were immunohistochemically analyzed for the presence of apoptotic cells. RESULTS: There was no significant difference in the median proportion of apoptotic nuclei between the pre- and posttreatment samples (2 vs. 3%; p > 0.05). CONCLUSIONS: The results showed that tibolone did not affect the rate of apoptosis in the postmenopausal endometrium. Further studies are needed to clarify the role of apoptosis in overall effects of hormonal compounds on the postmenopausal endometrium.