A. Sanjuán

Quality of life after the menopause: a population study

OBJECTIVE To assess the impact of menopause and some sociodemographic variables on quality of life (QoL). MATERIALS AND METHODS Four hundred and eighty-one women aged 40-59 years attending the Southern Metropolitan Health Service in Santiago de Chile were studied using the Specific Quality of Life Questionnaire for Menopause from Toronto University. RESULTS Univariate analysis showed that menopausal women have worse QoL scores than women conserving cycles in the four areas of the questionnaire: They show a 10.6-fold higher risk for suffering vasomotor disorders affecting QoL, a 3.5-fold higher risk for psychosocial impairment, a 5.7-fold higher risk for physical disorders, and a 3.2-fold higher risk for sexual disorders (P < 0.0001). Regarding the influence of social markers (age, marital status, school years, work, number of children and sexual activity), housewives were found to have higher, worse, scores than working women in all test components (vasomotor, 3.11+/-1.90 versus 2.57+/-1.71, P < 0.003; psychosocial, 3.44+/-1.59 versus 2.92+/-1.45, P < 0.0007; physical, 3.45+/-1.36 versus 2.96+/-1.20, P < 0.0001; sexual, 3.63+/-2.23 versus 2.49+/-1.95, P < 0.0001). However, logistic regression demonstrated that the only variable found to cause a significant impairment in QoL was menopause. CONCLUSION Menopause causes a decrease in quality of life, which is independent from age and other sociodemographic variables.

Comparative effects of estrogens plus androgens and tibolone on bone, lipid pattern and sexuality in postmenopausal women.

BACKGROUND The main goals of estrogen replacement therapy (ERT) are the prevention of osteoporosis and cardioprotection and the improvement of quality of life (QL). Androgens and tibolone therapy may increase bone mineral density (BMD) to a greater extent than ERT and offer an increase in QL. Lipid and cardiovascular effects, however, are still a major concern. AIM To evaluate whether the addition of a weak androgen to ERT may improve postmenopausal bone loss and sexual activity without adverse effects on lipid pattern and to compare these effects with those observed after tibolone therapy. SUBJECTS AND METHODS This prospective study enrolled 120 surgical postmenopausal women; of these, 96 completed the 1-year follow-up. Patients were allocated to one of four groups. The first group (A; n = 23) received 4 mg of estradiol valerate plus 200 mg of enanthate of dihydroandrosterone im monthly. The second group (E; n = 26) received 50 microg/day of transdermal 17-b-estradiol continuously; the third (T; n = 23) received 2.5 mg of tibolone every day; and finally, the fourth group (C; n = 24) constituted a treatment-free control group. Bone mass (dual X-ray absorptiometry), serum total cholesterol, HDL, LDL, triglycerides, apolipoproteins A1 and B and sexual activity were evaluated before starting therapy and at the end of follow-up. RESULTS All active treatment groups showed an increase in BMD. This increase was higher in the A treatment group (4.08% P < 0.01). Sexuality improved significantly with therapy; however, tibolone and androgens increased scores to a greater extent than ERT. Androgen therapy was associated with significant increases in total cholesterol, LDL and triglycerides. Cholesterol and LDL fall into groups E and T, HDL into groups A and T and triglycerides in group T only. CONCLUSION The combined regimen of androgens and ERT increased vertebral bone mass and enhance sexual activity in postmenopausal women equal to that of tibolone and to a greater extent than ERT alone; its effects on lipids, however, are clearly adverse.

Laparoscopic ovarian transposition in patients with early cervical cancer

The aim of this study was to evaluate the feasibility, efficacy, and morbidity of laparoscopic ovarian transposition on the preservation of hormonal function in patients younger than 45 years operated for early cervical cancer. According to risk factors on pathologic evaluation of the specimen, some of them will receive postoperative pelvic radiotherapy. This subset of patients could benefit from taking the ovaries away from the irradiation field in an effort to preserve their functionality. This prospective study included 28 FIGO stage IB1 cervical cancer patients, 45 years old or younger, maintaining menstrual cycles, who were considered suitable for conservation of the ovaries. The ovarian transposition was performed by laparoscopy as a part of the same celio-Schauta operation. Twelve patients underwent adjuvant pelvic radiotherapy. No intraoperative or postoperative morbidity related to the ovarian transposition was observed, and the procedure only entailed a minimum delay of the operative time. There were no cases of ovarian metastasis. At a mean follow-up of 44 months, 63.6% of patients receiving radiotherapy and 93% of those who nonirradiated maintained normal ovarian function. Two patients developed benign ovarian cysts, requiring oophorectomy, but no other long-term adverse effects of the transposition were identified. To the best of our knowledge, this is the largest series of the laparoscopic procedure reported to date in this setting. According to our results, laparoscopic ovarian transposition is a safe and effective procedure for the preservation of ovarian function in young patients with early cervical cancer undergoing adjuvant radiotherapy after surgery

Two-year prospective and comparative study on the effects of tibolone on lipid pattern, behavior of apolipoproteins AI and B.

OBJECTIVE To investigate long-term lipid and lipoprotein changes in postmenopausal women treated with tibolone in a prospective study using appropriate control groups. DESIGN Seventy-six of 105 postmenopausal women initially selected for this study completed the 2-year follow-up. Patients were allocated into three groups. The first received 2.5 mg/day tibolone continuously (n = 27; group T), the second received 0.625 mg/day conjugated equine estrogen plus 2.5 mg/day of medroxyprogesterone (group E-P) continuously (n = 25), and a third group contained an additional 24 women who did not receive replacement therapy; these constituted the untreated control group (group C). Plasma lipids and lipoproteins were determined in all patients before joining the study and also at 12 and 24 months after being included. RESULTS Women treated with tibolone experienced the greatest decreases in cholesterol, both total and high density lipoprotein (HDL), and triglycerides (TG), whereas the highest increase in HDL was observed in the group E-P. A decrease in low density lipoprotein levels was detected in both therapy groups, whereas a significant increase was observed in the control group. TG were increased after E-P therapy. In all the groups, apolipoprotein AI showed parallel trends to HDL and apolipoprotein B to low density lipoprotein. CONCLUSIONS Both therapy groups, tibolone and E-P, induced changes in levels of plasma lipids, lipoproteins and apolipoproteins. Long-term tibolone treatment is associated with a marked and significant decrease in HDL apolipoprotein AI and TG, an effect that defines the major difference with standard HRT. Clearly, further studies are necessary to establish the definite risk/benefit ratio of tibolone with respect to its overall effect on lipid metabolism.

Role of magnetic resonance imaging and cause of pitfalls in detecting myometrial invasion and cervical involvement in endometrial cancer

ObjectiveTo determine the diagnostic accuracy of magnetic resonance imaging (MRI) in detecting myometrial invasion and cervical involvement in endometrial cancer.Study designSeventy two consecutive patients with endometrial carcinoma underwent preoperative MRI. We compared the MRI results with the final histopathological findings. We classify myometrial invasion as <50 or ≥50% and cervical involvement as positive or negative. Standard statistical calculations were used.ResultsThe sensitivity, specificity, and accuracy of MRI for the detection of myometrial invasion ≥50% were 71, 86, and 58%, respectively. Positive and negative predictive values are 77 and 83%, respectively. The sensitivity, specificity, and accuracy of MRI for the detection of cervical invasion were 41, 97, and 46%, respectively. Positive and negative predictive values are 71 and 89%, respectively. The possible causes of misdiagnosis included a tumor isointense with the myometrium, polypoid tumor, myometrial thinning, exceedingly irregular myometrium, presence of adenomiosis, and presence of leiomyomas.ConclusionMRI assists in planning the surgical treatment of endometrial cancer with an acceptable accuracy and a good specificity, although sensitivity is suboptimal.

Long-term postmenopausal hormone replacement therapy effects on bone mass: differences between surgical and spontaneous patients.

BACKGROUND Hormone Replacement Therapy (HRT) begun soon after spontaneous menopause or oophorectomy minimizes or even reverses the loss of bone that occurs normally during those years. The persistence of this HRT protective effect at long-term on bone density, however, is not well documented. AIM to evaluate the effects of 5 years of HRT in postmenopausal women on bone mineral density of the lumbar spine. SUBJECTS AND METHODS The 5-year prospective study enrolled 154 postmenopausal women, of them 136 completed the first year and were considered electible to continue the follow-up. These 136 postmenopausal women were allocated to two groups according their origin: surgical (n=68) and spontaneous (n=68). HRT was prescribed and bone mineral density (BMD) was measured at the lumbar spine prior to commencement of therapy, and then yearly for the duration of the study. All patients received a continuous therapy with standard dose (0.625 mg/day) of conjugated equine estrogen (CEE) or 50 microg/day of 17-beta-Estradiol in transdermal therapeutic systems (TTS). Subjects who experienced natural menopause also received 5 mg/day of medroxyprogesterone acetate sequentially added to the last 12 days of estrogen therapy. Treated groups were compared with two non-treated control groups (surgical n=77; spontaneous n=53). RESULTS Our data showed that HRT increased the BMD of women who had experienced spontaneous menopause. Comparison with a control group revealed that HRT also protected against bone loss in women who had undergone surgical menopause. CONCLUSION Long term hormone replacement therapy increases bone mineral density in women who have experienced natural menopause, and protects against bone loss in surgically postmenopausal women.

Predicting Non-Sentinel Lymph Node Status in Breast Cancer Patients with Sentinel Lymph Node Involvement: Evaluation of Two Scoring Systems

Abstract:  The aim of this study was to validate a nomogram and a scoring system to predict non‐sentinel lymph node status in breast cancer patients with sentinel lymph node (SLN) involvement. A total of 516 breast cancer patients underwent sentinel lymph node biopsy at our institution from January 2001 to August 2006. A prospective database was used to identify breast cancer patients with a positive SLN biopsy examination who underwent a completion axillary lymph node dissection. A total of 114 patients were identified. The Memorial Sloan‐Kettering Cancer Center (MSKCC) nomogram and an axilla scoring system from Paris (Hôpital Tenon) were used to predict the probability of having non‐SLN involvement. One hundred fourteen patients were included in the study. The areas under the receiver operating characteristics (ROC) curves were 0.671 (95% CI: 0.552–0.790) for the MSKCC nomogram and 0.703 (95% CI: 0.596–0.811) for the Tenon score. The univariate analysis shows that size of SLN metastases, the number of positive and negative SLN and the proportion of positive SLN were statistically significant. On multivariate logistic regression analysis, the size of SLN metastases and the proportion of positive SLN were statistically significant. The two scoring systems are similar according to their area under ROC curves, but should be improved to be valid and determinant to the general population. Meanwhile, the use of scoring systems could be applied in an individual manner in some patients.

Raloxifene inhibits cholesterol aortic content but not atherosclerotic plaque size in oophorectomised cholesterol-fed rabbits

Raloxifene, a selective oestrogen receptor modulator, is effective in the treatment of osteoporosis without stimulating the breast and the endometrium. Although it is associated with a decrease of cardiovascular risk markers the effect of these changes on atherogenesis, is not clear. In this study, we aimed to investigate the effect of raloxifene on aorta atherogenesis. A total of 32 cholesterol-fed New Zealand white rabbits were studied for 4 months. Twenty-four rabbits underwent bilateral ovariectomy; of these eight received raloxifene (group OR), eight received oestradiol valerate (group OE) and eight received placebo after sterilisation (group OP). Finally, another eight were sham-operated (non-ovariectomised) and received placebo with a hypercholesterolaemic diet (group SP). After the diet, total levels of cholesterol increased in group SP from 111.25 ± 34.8 mg/dl to 1112.25 ± 364.2, in group OP from 122.62 ± 27.7 mg/dl to 1367.37 ± 348.4, in group OE from 65.25 ± 17.01 to 1710.5 ± 356.2 and in group OR from 108.88 ± 15.54 mg/dl to 1407.86 ± 397.7 (no significant differences). At 4 months, in both treated and untreated rabbits, the cholesterol-rich diet caused atherosclerotic lesions affecting 24.51 ± 16.1% for group SP, 30.47 ± 12.2% for group OP, 30.31 ± 18.07% for group OR and 17.91 ± 10.19 for group OE (P < 0.05) of the aortic surface, respectively. Aortic cholesterol expressed as mg of cholesterol/mg aortic weight was found to decrease in raloxifene-treated rabbits: 3.82 ± 2.14 mg col/aortic mg versus 8.55 ± 4.63 (group OP) and 11.97 ± 11.33 (group SP). P < 0.001. Raloxifene reduced aortic cholesterol content but not the atherosclerotic plaque extension in cholesterol-fed ovariectomised rabbits.

Effects of estradiol, cyproterone acetate, tibolone and raloxifene on uterus and aorta atherosclerosis in oophorectomized cholesterol-fed rabbits

BACKGROUND Different hormonal replacement regimens are used for treating climacteric complaints; however, not all of them have the same clinical profile. Cardiovascular disease (CVD) is a major health problem and tibolone, raloxifene, estradiol (alone or with cyproterone acetate) have been added to cholesterol-fed rabbits to study atherosclerosis. METHODS A total of 48 cholesterol-fed New Zealand white rabbits were studied for 4 months. Forty rabbits underwent bilateral ovariectomy and the other eight were sham operated (group S). The ovariectomized rabbits were allocated to five groups of eight animals each receiving tibolone (Group T, 6 mg/day), raloxifene (R, 35 mg/day), estradiol valerate (E, 3 mg/day), estradiol valerate plus cyproterone acetate (EC, 3+0.5 mg/day, respectively), and no treatment for the control group (C). The sham group received no treatment too. RESULTS After 4 months the percentage of the extent of atherosclerosis in the aorta was 30.4% in C group, 24.5% in S group, 10.2% in T group, 30.3% in R group, 17.9% in E group and 28.1% in EC group (P<0.05 T vs. C, R, EC). The aortic cholesterol content compared with aortic weight was 8.55 microg/mg in C group, 11.97 microg/mg in S group, 1.86 microg/mg in T group, 3.82 microg/mg in R group, 2.86 microg/mg in E group and 5.24 microg/mg in EC group (P<0.05 T vs. EC, C, S; R vs. C, S; E vs. C, S). Uterine weights in grams were: 1.89 (C group), 2.24 (S), 7.38 (T), 1.94 (R), 9.92 (E), and 5.94 (EC); P<0.05 (C, S, R, vs. T, E, EC; T vs. E; EC vs. T, E). CONCLUSION Our study showed a decrease in the extent of aortic atherosclerosis in oophorectomized cholesterol-fed rabbits treated with tibolone or estradiol, and a decrease in aortic cholesterol content in rabbits treated with tibolone, raloxifene and estradiol. However, rabbits treated with tibolone showed an increased uterine weight, which is contrary to that observed in humans.

Bilateral ovarian metastasis on transposed ovaries from cervical carcinoma

The preservation of ovarian function of young patients with cervical carcinoma is thought to be particularly important to the physiologic and psychosexual well-being of these women [1]. So, the ovarian-sparing radical hysterectomy has become the standard operation for early cervical cancer in young women [2] as the risk of persistence of unnoticed tumor implants in the transposed ovaries is supposed to be extremely unusual. Data are controversial in locally advanced cases [3]. A case of bilateral metastasis on both transposed ovaries in a patient with II-B cervical cancer is exposed. A 33-year old woman was referred to the hospital with a newly diagnosed squamous cell cervical carcinoma. The pelvic exam showed a 45 mm exofitic–ulcerative cervical tumor with proximal infiltration of the left parametrium (IIB FIGO stage). A laparoscopic retroperitoneal left paraaortic lymphadenectomy and the transposition of the ovaries was scheduled before the beginning of the chemo-radiotherapy. The left paraaortic lymphadenectomy produced a total of 10 lymph nodes free of metastasis. Afterwards the patient was started on a chemoradiotherapy scheme with cis-platin alongside with pelvic external beam radiotherapy. The treatment was supplemented with brachytherapy. There was an apparent partial response, and a salvage type II (Rutledges classification) abdominal radical hysterectomy was performed. The transposed ovaries were left in place. There was no evidence of relapse during one year until a progressive increase of the carcinoembryonic antigen (CEA) plasma level raised the suspicion of recurrent disease. The abdominal CT scan showed an enlargement of both transposed ovaries (left 5 cm, right 4 cm) (Fig. 1). A PETCT study also revealed another hypermetabolic left paraaortic focus. A laparotomy was performed which included resection of bilateral solid ovarian masses, and dissection of the retroperitoneal paraaortic space that revealed a 3 cm adenopathy that was unable to be completely removed. Final pathology confirmed metastatic squamous cell cancer on both ovaries and in the paraaortic node, but with a small component of adenosquamous cancer. Revision of the initial specimen (cervical biopsies) revealed also this small component of adenosquamous histological type. The patient then received chemotherapy and paraaortic radiotherapy and died 8 months later. The risk for occult ovarian metastasis in early (less than II stage) squamous cell carcinoma of the uterine cervix is well known to be less than 1% (1). When it comes to the adenocarcinomas, there is a slightly higher (1–2%) risk. Therefore, when planning the surgical treatment of early cervical cancer in young women, the ovarian sparing radical hysterectomy should be borne in mind. Metastatic spread to the ovary does occur in more advanced tumors with some frequency. Data such high as an incidence of 17% has been reported [4]. The combination of radiotherapy with radiosensitizing chemotherapy, achieves the control of the locally advanced disease in more than 70% of cases. However, the loss of ovarian function is one of the usual consequences of this therapy. The ovarian function can be maintained by