Long term effects of Tibolone on postmenopausal women with uterine myomas.

OBJECTIVES: The aim of the present study is to evaluate the long term effects of Tibolone (Livial) on uterine myomas volume as well as on uterine arteries pulsatility index (PI) in postmenopausal women. METHODS: This study included 66 naturally menopausal women. Twenty of them (group A) had no uterine myomas; 23 of them (group B) had a single, asymptomatic, intramural or subserous myoma of a maximum diameter less or equal than 2 cm; 23 of them (group C) had a single, asymptomatic, intramural or subserous myoma of a maximum diameter between 2 and 5 cm. The volume of the myomas as well as the pulsatility index of the uterine arteries was assessed by transvaginal ultrasonography every 6 months after administration of Tibolone (2.5 mg daily). RESULTS: No statistically significant difference on myomas volume was found after a 3-year period of Tibolone administration. The uterine artery basal PI was significantly higher in group A compared to that of groups B and C. After 6 months of Tibolone administration the PI in group A was significantly lower compared to the basal one whereas in groups B and C was significantly higher compared to the basal value. CONCLUSIONS: Our results suggest that treating postmenopausal woman with Tibolone on a long-term basis: (a) does not increase the volume of uterine myomas and (b) has an early effect on uterine haemodynamics (decrease of PI in women without myomas and increase of PI in women with myomas).     

Uterine myoma in postmenopause: a comparison between two therapeutic schedules of HRT

OBJECTIVES: It is still controversial whether hormone replacement therapy (HRT) can affect the onset of uterine myomas or their growth in postmenopause. It is likely that some therapeutic schedules can influence the myometrial growth differently, due to a more potent stimulation of the uterine receptors. The aim of the present study is to evaluate the effects of two different hormonal treatment schedules on the risk of uterine myoma onset or progression. METHODS: In a 2 year prospective randomised study we compared an oral cyclic association of oestradiol valerate and cyproterone acetate versus a sequential combination of transdermal E(2) and per oral medrossiprogesterone acetate on 240 postmenopausal women with and without uterine myomas. RESULTS: Among the patients without uterine myomas treated with the transdermal-oral combination we noted the onset of myomas in 5% of cases after 24 months of treatment, while no new uterine formation was observed for the orally treated women (P<0.01). Among the patients with uterine myomas at the beginning of the study, in the group transdermally treated we found a mean increase in myoma volumes of 25.3% in the following 24 months, which was significantly different compared with the initial volume of myomas. On the other hand, women treated with the oral combination showed no significant modification of myoma volumes at the end of the study. CONCLUSIONS: Percutaneous-oral schedule of HRT seems to affect the growth of uterine myomas more than a single oral combination of oestradiol valerate and cyproterone acetate.     

Cytogenetic abnormalities in uterine myomas are associated with myoma size

Uterine leiomyomata (myomas) are associated with a variety of characteristic cytogenetic abnormalities. The significance of these chromosomal aberrations in the pathobiology of myomas remains to be determined. The present study investigated the relationship between myoma cytogenetic abnormalities and size. A total of 114 myoma specimens were obtained from 92 patients undergoing myomectomy or hysterectomy. The maximum diameter of each myoma was measured and a portion of each myoma obtained for cytogenetic analysis. Karyotypes were analysed and categorized as normal, abnormal (non-mosaic) or mosaic. Cytogenetic analyses revealed 73 (64%) normal, 20 (18%) abnormal (non-mosaic), and 21 (18%) mosaic karyotypes. Mean myoma diameter was 6.5+/-0.44 cm with a range of 0.4-27 cm. Differences between the mean myoma diameter of specimens with normal versus abnormal karyotypes was determined by the Kruskal-Wallis test. The mean myoma diameter among specimens with abnormal (non-mosaic) karyotypes was significantly greater than myomas with normal karyotypes (10.2+/- 5.9 versus 5.9+/-4.2 cm; P < 0.001). The proportion of abnormal (non- mosaic) karyotypes in myomas >6.5 cm was compared to myomas <6.5 cm by chi2-analysis; myomas >6.5 cm demonstrated a significantly higher proportion of abnormal (non-mosaic) karyotypes when compared to myomas <6.5 cm (75 versus 34%; P < 0.02). In summary, a significant relationship exists between clonal cytogenetic abnormalities and myoma size, suggesting that chromosomal abnormalities associated with individual myomas enhance myoma growth.      

Relationship of myoma cell size and menopausal status in small uterine leiomyomas

CONTEXT: Although myomas shrink after menopause, the cellular mechanism for this phenomenon has received little attention. It was recently demonstrated that fibrous degeneration is significantly associated with postmenopausal status in both small and large myomas. OBJECTIVE: The purpose of the present study was to evaluate whether reduction in myoma cell size is also associated with postmenopausal status in small myomas. DESIGN: Tumor size and patient age have also been related to fibrous degeneration in small (<1 cm) myomas. Therefore, in the present study, 10 pairs of premenopausal and postmenopausal small myomas were matched within 3 years for patient age, within 1 mm for size, and within 1 grade for degree of fibrous degeneration. Most of the women were in their 50s, the decade during which postmenopausal fibrous degeneration in small myomas is most prevalent. Myoma cell size was derived by morphometric evaluation of relative myoma cell area (correcting for percentage of stroma, as measured by point counting) and by direct counting of the number of myoma cells per unit area in trichrome-stained sections. RESULTS: Small myomas from postmenopausal women had significantly (P <.05) smaller cell sizes than did size-matched myomas from age-matched premenopausal women. Myoma cell sizes and nucleus-cell (N/C) ratios were highly variable, especially in premenopausal myomas. CONCLUSIONS: Reduction in myoma cell size is significantly associated with postmenopausal status in small uterine leiomyomas and may be an important mechanism for postmenopausal shrinkage of myomas. In addition, the high variability of myoma cell size and N/C ratio may further support the somatic mutation theory (ie, the theory that diverse mutations may account not only for variations in the growth potential of uterine myomas, but also for variations in their cellular details).     

Pregnancy following treatment of symptomatic myomas with laparoscopic bipolar coagulation of uterine vessels

BACKGROUND: Laparoscopic bipolar coagulation of uterine vessels (LBCUV) has been employed for women with symptomatic uterine myomas, but its effect on subsequent pregnancy has not been characterized. METHODS: Four-hundred and twenty-three women entered the study between March 1999 and December 2001. Of these, 142 women (33.6%) were under the age of 40 years at the time of LBCUV, 36 of whom (36/142, 25.3%) were sexually active without contraception. In a prospective study of 142 patients (<40 years old) undergoing LBCUV for symptomatic myomas, 15 women became pregnant (17 total pregnancies) and were evaluated by physical and ultrasound examinations. RESULTS: The volume of the dominant myoma was 117.4 +/- 118.4 and 36.8 +/- 56.8 cm(3) before and after LBCUV respectively. Volume of the dominant myoma after pregnancy was 46.2 +/- 76.7 cm(3) (mean +/- SD). There was a significant difference in myoma volume before and after LBCUV (P = 0.002), but no significant difference in myoma volume when comparing post-partum size with post-LBCUV size (P = 0.269). Pregnancy outcomes included seven miscarriages in the first trimester and one premature rupture of membrane (PPROM). Although the other pregnancies were regarded as uncomplicated, only two women were delivered of normal neonates as the other seven pregnancies were terminated secondary to patient request. CONCLUSIONS: The pregnancy and term pregnancy rates in sexually active women without contraception were 41.6% (15/36) and 5.6% (2/36) respectively. Because a relatively high rate (7/17, 41.2%) of early miscarriages was observed, we recommend that this procedure be employed only for women who do not desire additional children.     

Endoscopic management of uterine myoma

This study was undertaken to evaluate the various gynecologic endoscopic surgical techniques including resectoscopic myomectomy, laparoscopic myomectomy, and laparoscopy assisted vaginal hysterectomy (LAVH) used in the treatment of uterine myomas. The medical records of 136 cases of uterine myomas treated using one or more of the gynecologic endoscopic surgical techniques in the Department of Obstetrics and Gynecology at Yonsei University were retrospectively reviewed from March 1997 to September 1998. Of the 136 cases reviewed, there were 40 submucosal myomas and 96 intramural and subserosal myomas. For statistical analysis, Student's t-test was used. Submucosal myomectomy using the resectosope was performed in 35 cases (mean age: 39 +/- 1.5 years), laparoscopic myomecotmy in 35 cases (mean age: 36 +/- 1.9 years), and LAVH in 66 cases (mean age: 42 +/- 1.1 years). In cases of huge myomas, the GnRH agonist was used prior to surgery, and in cases of heavy uterine bleeding, angioblock of the uterine artery was undertaken before the endoscopic procedures. The mean operating time was significantly shorter in resectoscopic myomectomy (41 +/- 12 min), followed by laparoscopic myomectomy (85.0 +/- 10.3 min) and LAVH (123 +/- 5.3 min). The mean hospital stay for resectoscopic myomectomy, laparoscopic myomectomy, and LAVH was 1.9 +/- 0.5, 2.5 +/- 0.5, and 3.4 +/- 0.8 days (p < 0.001), respectively. There were 3 cases of complications including pulmonary edema and uterine perforation in the resectoscopic myomectomy group, and 4 cases of complications including bladder, ureter, and epigastric vessel injury in the LAVH group. In conclusion, the therapeutic effect of various gynecologic endoscopic surgical techniques can be maximized in terms of shorter operation time, shorter hospital stay, faster recovery, and less blood loss by the appropriate management of uterine myoma in well-chosen patients.     

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

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

Comparison of the Inhibitory Effect of Gonadotropin Releasing Hormone (GnRH) Agonist,Selective Estrogen Receptor Modulator (SERM), Antiprogesterone on Myoma Cell Proliferation In Vitro

Uterine myomas are the most common gynecologic tumor in women of reproductive age. Treatment options of uterine myomas consist of surgical, medical and interventional therapy such as uterine artery embolization or myolysis. Given that it is the most common type of tumor in women of reproductive age, the treatment of uterine myomas must prioritize uterine conservation. There are several drugs for medical treatment of uterine myoma such as gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM) and antiprogesterone. The objective of this study was to compare the effect of GnRH agonist, SERM, and antiprogesterone in the treatment of uterine myomas in vitro. The effect of drugs was evaluated through the cell viability assay in cultured leiomyoma cells, western blot analysis of proliferating cell nuclear antigen (PCNA), and BCL-2 protein expression. As a result, mifepristone single-treated group represents the most significant reduction in myoma cell viability and proliferation. When pretreated with leuprolide acetate, raloxifene shows more significant reduction in myoma cell viability and proliferation than mifepristone. This study suggests one of the possible mechanisms how medications act on uterine myoma, especially at the molecular level.     

Laparoscopic myomectomy: indications, surgical technique and complications

The indications and complications of laparoscopic myomectomy were evaluated with regard to its limitations, benefits and feasibility. Surgical technique with related difficulty was also reported. From a population of 89 patients, a total of 104 myomas were removed laparoscopically. A retrospective study was carried out of 54 patients with myomas >3 cm. Indications for surgery were pain or abnormal bleeding (37%), increase in size of the myoma in infertile patients (48.1%) and infertility requiring assisted reproductive technology (14.9%). A total of 57 myomas >3 cm were removed from these patients. The number of myomas per patient varied from 1 to 4. The myomas were intramural (n = 34), subserosal (n = 19) and submucosal (n = 4). The size of the dominant myoma ranged from 3-8 cm (mean 4.16). In all cases the uterine wall was sutured either in one (n = 42) or two planes (n = 15) depending on the depth of the myometrial defect. The laparotomy conversion rate was 1.8% (n = 1); mean blood loss was 84 ml; average hospital stay was 2.09 days and the overall complication rate was 1.8%. Five patients went on to conceive; the pregnancy was uneventful and proceeded to Caesarean section at 38 weeks. No adhesions at myomectomy sites were observed in these patients. At 6 months follow-up, 18 out of 20 patients with pain or haemorrhagic disorders prior to surgery showed remission of their complaints. Our study confirms the feasibility of laparoscopic myomectomy as a technique leading to a low complication rate and remission of symptoms. At the present time, statistically significant data concerning post-surgical adhesion formation or pregnancy outcome are not available.      

Doppler velocimetry of the uterine arteries after hysteroscopic rollerball endometrial ablation

The aim of this study was to document the Doppler indices [pulsatility index (PI) and resistance index (RI)] of the uterine arteries in 30 patients who underwent hysteroscopic rollerball endometrial ablation for dysfunctional uterine bleeding by transvaginal pulsed Doppler sonography, and to reveal whether treatment failures (persistent menometrorrhagia) can be predicted by the blood flow characteristics of the uterine arteries in advance. On the basis of the outcome of patients at the end of the first postoperative year, the Doppler indices of the uterine arteries were meaningful 1 year after the operation when PI (1.32 +/- 0.11; mean +/- SD) and RI (0.71 +/- 0.04) in six menometrorrhagic patients were statistically different from PI (2.19 +/- 0.28; 1.95 +/- 0.36 and 1.82 +/- 0.37) and RI (0.87 +/- 0.06; 0.82 +/- 0.06 and 0.81 +/- 0.04) in normally menstruating, amenorrhoeic and hypomenorrhoeic patients respectively (P < 0.05). On the other hand, the patients who would be menometrorrhagic one year after the operation had a thicker endometrium in the first post-operative month. These findings suggest that the angiogenetic role of the persistent endometrial islands after endometrial ablation needs at some time to be reflected as changes in the Doppler parameters of the uterine arteries.      

Uterine myomata and outcome of assisted reproduction

The aim of this work was to study the effect of uterine myomata on the implantation rate and outcome in in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Among 406 patients, 51 (12.6%) were found to have uterine corporeal myomata. Twelve patients were excluded from the study as they had large myomata, submucous myomata or intramural myomata encroaching on the cavity. These patients were advised to have myomectomy before being enrolled in the IVF/ICSI programme. The remaining patients (n = 39) were sorted according to the number, site and size of the myomata as assessed by transvaginal sonography. Three patients had more than one myoma. Most of the myomata were subserous (72.7%) and the mean diameter of the myomata was 3.5 +/- 0.9 cm. A control group (n = 367) was chosen with normal uteri and no history of uterine reconstruction surgery. The mean age of myoma patients was 34.7 +/- 3.6 years as compared to 34.0 +/- 4.4 years in the control group. The age, period of infertility, body mass index, duration and number of human menopausal gonadotrophin ampoules needed for stimulation, oestradiol levels, number of oocytes retrieved and the fertilization rate were not significantly different in the myoma patients compared to the control group. Fifteen myoma patients (38.5%) subsequently showed one or more pregnancy sacs on ultrasonography of which three (20%) spontaneously aborted during the first trimester and two (13.3%) had preterm labour, as compared to 123 (33.5%), 19 (15.5%) and nine (7.3%) respectively, among the control group (P = 0.27, 0.33 and 0.21). In conclusion, uterine corporeal myomata, not encroaching on the cavity and <7 cm in mean diameter, do not affect the implantation or miscarriage rates in IVF or ICSI.      

Hysteroscopic resection of submucosal myomas in patients with infertility.

BACKGROUND: Submucosal myomas are associated with infertility, and may be treated by hysteroscopic resection. Improvement of the menstrual pattern after surgery has been examined and compared with pregnancy rate in a group of menorrhagic women with primary (n = 24) and secondary (n = 35) infertility. METHODS: The entire patient group (n = 59) was managed between January 1990 and September 1998. The submucosal myomas were intracavitary (n = 15), intramural class 1 (n = 34) and intramural class 2 (n = 10), and none was multiple submucosal myoma. The mean (+/- SD) age was 36.6 +/- 4.6 years; mean myoma size was 24.5 +/- 13.3 mm; mean duration of the procedure was 40 +/- 23 min; and mean follow-up was 26 +/- 18.8 months. Thirty-five patients had one or more associated infertility factors. RESULTS: An improvement in clinical symptoms was observed in 62% of patients. Sixteen patients (27%) conceived, and of these only six (10%) delivered at term. The pregnancy rate was significantly better when myoma was the exclusive aetiology of infertility (41.6%), and when the lesion was >/=50 mm in size (57.1%). CONCLUSIONS: Hysteroscopic myomectomy appears safe, and is effective in the control of menstrual disorders. However, the effect on infertility seems limited, particularly in terms of delivery rate. The advanced age of the patients may partly explain these results.     

Immunohistochemical localization of telomerase in myomas and in uterine myometrium

Telomerase activity could be a potential marker for the neoplastic process, because it is absent in normal cells and present in tumor cells. Immunohistochemical studies were conducted using samples obtained from 32 uterine myomas, each sample having a size of 3-4cm and obtained from women between 35 and 45 years of age. These studies also concentrated on fragments of macroscopically unaltered myometrium, collected 3-4cm from a uterine tumor. Immunohistochemistry was performed using antibody to the catalytic unit of telomerase (hTERT; clone 44F12, NCL-L-hTERT, Novocastra Laboratories, UK). This study aimed at detecting a possible presence of potentially neoplastic cells in the margins of healthy tissue, which was removed together with the primary tumor. The results were classified according to the number of telomerase-positive cells. Tumors of the first group had up to 50% telomerase-positive cells, while their content in the second group exceeded 50%. Our study demonstrated an almost two-fold increase in the number of telomerase-positive tumor cells compared with myometrial cells 3-4cm from the tumor. Hopefully, investigating the presence of telomerase in both uterine myometrium and myoma could facilitate the diagnosis of the neoplastic process.     

Fertility after laparoscopic myomectomy of large intramural myomas: preliminary results

Fertility outcome following laparoscopic myomectomy was evaluated.A prospective clinical study was carried out between October1990 and October 1993 in 21 infertile patients who underwentlaparoscopic myomectomy for a myoma measuring 3>;5 cm indiameter. The overall rate of intrauterine pregnancy was 333%(seven patients). Out of 12 patients with infertility factorsassociated with uterine myomas, three (25.0%) became pregnant,whereas four (44.4%) out of nine patients with no other associatedinfertility factor became pregnant. No uterine rupture was observed.Out of the seven pregnancies, four were spontaneous and beganwithin 1 year of the operation. The other three were achievedafter in-vitro fertilization in patients with associated infertilityfactors. In the four patients who gave birth by Caesarean section,no adhesions were found on the myomectomy scar. From these preliminaryresults, laparoscopic surgery for myomas seems to offer comparableresults with those obtained by laparotomy.     

腹腔镜下子宫肌瘤剔除术的临床应用

目的探讨腹腔镜下子宫肌瘤剔除术的手术技巧、复发及术后妊娠情况。方法子宫肌瘤患者217例，年龄25～43岁，平均年龄32岁（标准差7．3岁）．其中有蒂浆膜下肌瘤37例．阔韧带肌瘤4例．宫颈肌瘤7例，肌壁间肌瘤及无蒂浆膜下肌瘤169例．行腹腔镜下子宫肌瘤剔除术（laparoscopic myomectomv．LM）。结果217例手术均获成功．无严重并发症．217例中13例失访．204例随访11～47个月，平均（29．00±10．32）个月。术后9～47个月复发71例．占34．80％．有生育要求者49例，妊娠率46．67％．21例（21次）妊娠中．1例流产．1例异位妊娠．1例妊娠高血压疾病早产（剖宫产）．9例足月妊娠，其中7例行剖宫产，2例顺产；9例继续妊娠中[平均（22．00±6．82）周]，无一例子宫切口瘢痕裂开。结论LM后可提高妊娠率，复发率同开腹手术。LM后妊娠是安全的．但剖宫产几率增加。LM具有创伤小、恢复快的优点．是一种安全、可靠的手术方法．     

Sonographic assessment of pregnancy co-existing with uterine leiomyoma in Owerri,Nigeria

Background

Uterine myomas co-existing with pregnancy could cause obstetric complications.

Objectives

To assess sonographically the frequency of occurrence and effect of uterine myomas co-existing with pregnancy.

Methods

A longitudinal study was conducted during a period of 23 months. A convenience sample of 816 consecutive consenting pregnant women who met the inclusion criteria was evaluated during routine prenatal ultrasound scan. The women were referred for prenatal sonography. One hundred of the subjects who had myoma co-existing with pregnancy and another 100 subjects without myoma were selected for follow-up. These groups were followed up till delivery and obstetric complications and outcomes were documented. Any changes in size and growth rate of myoma were documented.

Results

Subjects with myoma co-existing with pregnancy were 12.3%. This was commoner with increasing maternal age. An increase was observed in myoma mean size from 60mm to 63mm from the 1^st scan sequence to the 2^nd scan sequence and a reduction from 63mm to 59mm in the 3^rd scan sequence. Myoma growth rate was 0.667mm per week. Myomas in pregnancy especially large ones caused more complications during delivery when compared to pregnancies without myomas.

Conclusion

Routine sonography is important in pregnancy management of uterine myomas co-existing with pregnancy.     

Impact of different hormone replacement therapy regimens on the size of myoma uteri in postmenopausal period: tibolone versus transdermal hormonal replacement system

OBJECTIVES: To assess the effect of different hormone replacement therapy regimens on myoma uteri in postmenopausal period. METHODS: Totally 46 patients with 60 myomas attending to Department of Obstetrics and Gynecology, Akdeniz University School of Medicine between May 2000 and March 2001 because of postmenopausal symptoms and having myoma uteri were included in this study. These patients were randomized for tibolone and transdermal hormonal replacement therapy system. The patients who were taking hormonal replacement therapy, discontinued the treatments and lost for follow-up were excluded from the study. Impact of the treatments on the size of myoma uteri was evaluated 6 months after starting the therapy. Size of myomas were evaluated by transvaginal sonography before and 6 months after onset of the treatment. RESULTS: Mean age was 57.3 (50-70) and mean gravida 3.6 (1-6) for all the patients. Although, increase in the size of myoma uteri was frequent in transdermal HRT, it was not statistically significant. CONCLUSION: There are no statistical significant differences between tibolone and transdermal hormonal replacement therapy regimens in respect to increase in the size of myoma uteri.     

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

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

Increased spontaneous and mitomycin C-induced sister chromatid exchanges in patients with cancer of the cervix uteri, with special reference to stage of cancer

The frequencies of spontaneous and mitomycin C (MMC)-induced sister chromatid exchange (SCE) were examined in 35 patients with cancer of the cervix uteri (stage 0, eight cases; stage I, nine cases; stage II, nine cases, and stage III, nine cases) before they had undergone cancer treatment, as well as in seven patients with uterine myoma and 18 healthy women as controls. The frequency of SCE was analyzed in reference to the stage of cancer in the cancer group and in reference to chromosome group in the cancer and normal groups. The frequencies of spontaneous and MMC-induced SCE in the cancer group were 10.0 +/- 1.8 and 20.7 +/- 2.6, respectively, and both were significantly higher than in the myoma (8.1 +/- 0.8 and 17.6 +/- 1.8) and normal (7.6 +/- 0.8 and 17.6 +/- 2.3) groups. Furthermore, the frequency of SCE in the cancer group increased with cancer stage. All chromosome groups contributed equally to the increase in SCE in the cancer group. These results indicate that an increase in the frequency of SCE in patients with cervical cancer is related to the presence of cancer, but is not related to a predisposition to cancer.     

Effect of postmenopausal hormone replacement on atherosclerosis in femoral arteries.

OBJECTIVES: On the basis of epidemiological and experimental data, it has been supposed that hormone replacement therapy (HRT) inhibits atherosclerosis in postmenopausal women. This randomized controlled trial examined whether 1 mg 17beta-estradiol daily, combined cyclically with 0.025 mg gestodene in every month (HRT 1), or in every third month (HRT 2) slows the increase of intima-media thickness in femoral arteries compared with no HRT. METHODS: Healthy postmenopausal women (n=321) with an increased risk for future vascular disease as indicated by >1 mm of intima-media thickness in the carotid arteries were equally randomized to one of the three groups for 48 weeks. Ultrasound scans of femoral arteries were recorded at study start and study end, together with a thorough clinical examination and laboratory work-up. RESULTS: Complete scans were obtained in 260 of the 264 subjects who participated until study end. Mean maximum intima-media thickness of four femoral artery segments (common and superficial, both sides) was 0.93+/-0.37 mm (mean+/-S.D.) at study start. It increased by 0.02+/-0.05, 0.02+/-0.05, and 0.03+/-0.05 mm in the HRT 1, HRT 2 and no HRT groups, respectively (HRT 1 versus no HRT, HRT 2 versus no HRT; both P>0.2). Compared with no HRT, HRT significantly lowered follicle stimulating hormone, low-density lipoprotein cholesterol, and fibrinogen. CONCLUSIONS: In this 1-year trial, irrespective of the progestogen dose used, HRT with 1 mg 17 beta-estradiol did not inhibit progression of femoral artery atheroslerosis in postmenopausal women with subclinical vascular disease.