Sabina Oldani

Levonorgestrel-releasing intrauterine device versus hysteroscopic endometrial resection in the treatment of dysfunctional uterine bleeding

Objective To compare the effect of a levonorgestrel-releasing intrauterine device with that of endometrial resection on menstrual bleeding, patient satisfaction, and quality of life in menorrhagic women during 12 months of followup. Methods Seventy premenopausal women with dysfunctional uterine bleeding were enrolled in a prospective, open, parallel-group, controlled trial. They were randomized to either insertion of an intrauterine system releasing 20 μg/day of levonorgestrel (n = 35) or endometrial resection (n = 35). The women were evaluated at baseline, and thereafter, uterine bleeding was assessed monthly with a pictorial blood loss assessment chart. Clinical gynecologic examination was performed bimonthly, and the hematologic variables were measured at 6 and 12 months. On the latter occasion, the women were requested to rate the degree of satisfaction with the effect of their treatment and to complete the Short Form 36 General Health Survey questionnaire. Results Recurrent menorrhagia was observed at 12 months in four women in the intrauterine device group (including two with partial expulsion of the device) and in three women in the resection group. Compared with baseline values, at 1 year, the pictorial blood loss assessment chart score was reduced by 79% in the former group and by 89% in the latter. Amenorrhea or hypomenorrhea at 12 months was reported by 65% of the women with an intrauterine device compared with 71% who underwent endometrial resection. The degree of satisfaction with treatment was high in both groups, with 29 of 34 (85%) women being satisfied or very satisfied in the intrauterine device group versus 33 of 35 (94%) in the resection group. Health-related quality of life perception was not significantly different in the two treatment groups. Conclusion Somewhat less satisfactory results were obtained with a levonorgestrel-releasing intrauterine system compared with endometrial resection for dysfunctional uterine bleeding at 1 year of follow-up.

Depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol for long-term treatment of pelvic pain associated with endometriosis

OBJECTIVE Our purpose was to evaluate the efficacy and safety of depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol in the long-term treatment of pelvic pain in women with endometriosis. STUDY DESIGN Eighty patients with endometriosis and moderate or severe pelvic pain were randomized to treatment for 1 year with intramuscular depot medroxyprogesterone acetate 150 mg every 3 months or a cyclic monophasic oral contraceptive (ethinyl estradiol 0.02 mg, desogestrel 0.15 mg) combined with oral danazol 50 mg a day for 21 days of each 28-day cycle. The women were asked to grade the degree of their satisfaction at the end of therapy. Variations in severity of symptoms during treatment were determined by a 10 cm visual analog and a 0- to 3-point verbal rating scale. RESULTS Twenty nine of 40 subjects (72.5%) in the depot medroxyprogesterone acetate group were satisfied after 1 year of therapy compared with 23 of 40 (57.5%) in the oral contraceptive plus danazol group (chi 2(1) = 1.37, p = 0.24, odds ratio 1.95, 95% confidence interval 0.76 to 4.97). A significant decrease was observed in all symptom scores in both study groups. At 1-year assessment dysmenorrhea was significantly greater in women allocated to oral contraceptive plus danazol. CONCLUSION Depot medroxyprogesterone acetate seems to be an effective, safe, and convenient low-cost treatment for pelvic pain associated with endometriosis. However, women should be carefully counseled regarding menstrual changes and the potential prolonged delay in the return of ovulation.

Paracervical anesthesia for outpatient hysteroscopy

One hundred seventy-seven women aged 41 +/- 8 (mean +/- SD) years, referred for evaluation of excessive uterine bleeding, were enrolled in an open-label randomized trial to evaluate the efficacy of local anesthesia before hysteroscopy in an outpatient population. The patients underwent hysteroscopy and endometrial biopsy with paracervical block by 10 mL of 1% mepivacaine hydrochloride solution (n = 87) or no local anesthesia (n = 90) and assessed lower abdominal and pelvic pain according to a 10-point linear analog scale. The mean +/- SD pain score was 4.5 +/- 2.0 at hysteroscopy and 5.2 +/- 2.1 at endometrial biopsy in the 87 subjects given a paracervical block versus 4.9 +/- 2.2 and 5.7 +/- 2.4 in the 90 women not given local anesthesia, without statistically significant differences. Paracervical anesthesia for routine outpatient hysteroscopy in premenopausal women may be superfluous.

Pregnancy at forty and over: a case-control study.

We compared obstetric prognosis in 327 women > or = 40 years old (148 nulliparas, 279 multiparas) with 20-30-year-old matched controls who delivered at our department between 1988 and 1990. Gestational diabetes and chronic hypertension were the only more frequent antepartum complications in cases than controls (2.4% vs. 0.3% and 3.4% vs. 0.3%, respectively). There were more premature deliveries in cases than controls (19% vs. 8%) but no difference in postdate deliveries. Cesarean section was more frequent in cases than controls in both nulliparas (64% vs. 30%) and multiparas (43% vs. 12%). Incidence of abdominal delivery for acute obstetrical indications was not increased in older gravidas. Significant differences were observed in low birthweight (17% vs. 5%) and 5-min Apgar score < 7 (8% vs. 2%). Most of the abnormal Apgar scores were recorded after cesarean section; values for vaginally-delivered infants were comparable in older and younger women. Perinatal mortality was similar in the two groups.

Analysis of p53 and ras Gene Mutations in Endometriosis

No activating mutations in codons 12, 13 and 61 of ras genes nor inactivating mutations in exons 5-9 of the p53 tumor suppressor gene were detected by polymerase chain reaction and single-strand conformation polymorphism methods in either eutopic or ectopic endometrium from 10 women with severe endometriosis.

Adenomyosis: A Déjà Vu?

Adenomyosis is a relatively frequent finding in series of hysterectomies performed for menorrhagia and dysmenorrhea. Evident selection biases of the available studies on adenomyosis have always limited the possibilities of defining the real clinical importance of the condition. Until now the only certain diagnoses have been made by histopathologists on uteri removed at surgery, but recently various sufficiently accurate techniques have been suggested which allow diagnosis on the uterus in situ. With the these methods it might be possible to obtain correct information on the epidemiologic characteristics of adenomyosis and to clarify whether it has a pathogenic role in unexplained ovulatory menorrhagia and juvenile dysmenorrhea. Furthermore, resectoscopic treatment has been proposed in some mild forms of adenomyosis to avoid hysterectomy, whereas it seems improbable that medical treatment can offer a definitive solution. The adoption of standard histologic criteria for adenomyosis seems important. Until this is done, it will be difficult to establish whether adenomyosis is really a disease or merely a paraphysiologic condition.

Randomized comparison of vaporizing electrode and cutting loop for endometrial ablation.

OBJECTIVE To compare endometrial ablation using a vaporizing electrode with resection using a standard cutting loop, evaluating distension fluid absorption, operating time, and ease of procedure. METHODS Premenopausal menorrhagic women with normal hysteroscopic and endometrial biopsy findings were allocated randomly to endometrial vaporization (n = 47) or resection (n = 44). Distension medium deficit, operating time, and degree of difficulty of the procedure were determined at surgery. Menstrual pattern of women in both groups was also assessed after 1-year follow-up. RESULTS Mean +/- standard deviation (SD) distension fluid deficit was 109+/-126 mL in the vaporization and 367+/-257 mL in the resection group (mean difference 258 mL; 95% confidence interval 175, 341 mL; P < .001, unpaired t test). Mean +/- SD operating time was, respectively, 9.2+/-3.1 minutes versus 10.7+/-2.5 minutes. The surgeon classified intraoperative difficulties as none in 32, minimal in 11, moderate in four, and severe in none in the vaporization group, and 17, 14, seven, and six in the resection group. Menstrual pattern at 1 year in the former group was amenorrhea in 17 (36%) cases, hypomenorrhea or spotting in 20 (43%), normal flows in 10 (21%), and menorrhagia in none compared with, respectively, 21 (48%), 14 (32%), seven (16%), and two (5%) in the latter group. CONCLUSION Endometrial ablation with the vaporizing electrode limited fluid absorption compared with resection by the standard cutting loop. Long-term effects on uterine bleeding were similar.

The value of cyst puncture in the differential diagnosis of benign ovarian tumours

A prospective collection of serum samples and ovarian cyst fluid was used to assess the use of different tumour markers and cyst fluid cytology in combination with serum tumour markers for the differential diagnosis of benign ovarian cysts. A consecutive series of 108 women of median age 30 years (range 15-75) undergoing laparotomy or operative laparoscopy for presumedly benign ovarian cyst(s) were studied at a teaching hospital at the University of Milan, Italy. The main outcome measures were tumour markers CA 125, CA 19.9 and carcino-embryonic antigen (CEA) in serum and ovarian cyst fluid, oestradiol and progesterone concentrations in cyst fluid, and cytology of the sediment. The studied cysts were endometriotic (55 subjects), dermoid (16), mucinous (12), serous (10) or of miscellaneous histotype (15, including four follicular and one luteal). Serum CA 125 concentrations were significantly higher in the endometrioma patients than in the other groups. The sensitivity of CA 125 in the differentiation of endometriomas from other adnexal tumours was 61.8% and the specificity 94.3%; combining CA 125 and CA 19.9 assays yielded a sensitivity of 83.6% and specificity of 62.3%. Cyst fluid tumour markers values were extremely scattered with ample overlap between different cyst types. Oestradiol and progesterone concentrations were similar in the histological subgroups. Cyst fluid cytology was non-specific. We concluded that the aspiration of fluid from presumedly benign ovarian cysts appears to contribute little to the differential diagnosis of various tumours. The use of combining serum CA 125 and CA 19.9 assays in the diagnosis of endometriomas needs further confirmation.

Randomized Biomarker Trial of Anastrozole or Low-Dose Tamoxifen or Their Combination in Subjects with Breast Intraepithelial Neoplasia

Purpose: In the Anastrozole, Tamoxifen Alone or in Combination trial, the combination arm was inferior to anastrozole alone in terms of disease-free survival possibly due to an adverse pharmacokinetic interaction or a predominant estrogenic effect of tamoxifen under estrogen deprivation. We assessed whether the addition of a lower dose of tamoxifen influenced anastrozole bioavailability and favorably modulated biomarkers of bone fracture, breast cancer, cardiovascular disease, and endometrial cancer risk. The influence of CYP2D6 genotype on tamoxifen effects was also determined. Experimental Design: Seventy-five postmenopausal women with breast intraepithelial neoplasia were randomly allocated to either 1 mg/d anastrozole or 10 mg/wk tamoxifen or their combination for 12 months. Study endpoints were plasma drug concentrations and changes of C-telopeptide, osteocalcin, estradiol/sex hormone binding globulin (SHBG) ratio, estrone sulfate, insulin-like growth factor-I (IGF-I)/insulin-like growth factor binding protein-3 (IGFBP-3), C-reactive protein, antithrombin-III, endometrial Ki-67 expression, and thickness. Results: Anastrozole concentrations were not affected by the combination with low-dose tamoxifen, whereas endoxifen levels were lower in poor CYP2D6 metabolizers. C-telopeptide increased by 20 with anastrozole and decreased by 16 with tamoxifen and by 7 with their combination (P < 0.001); osteocalcin showed similar changes. Compared with anastrozole, the combination arm showed lower IGF-I/IGFBP-3 levels (17 versus 9; P = 0.004) and lower estradiol/SHBG and estrone sulfate reductions (15 versus 29 and 30 versus 38, respectively). However, IGF-I/IGFBP-3 and estradiol/SHBG did not decrease in poor CYP2D6 metabolizers. Endometrial thickness was not greater in the combination than in the anastrozole arm. Conclusions: The addition of a weekly tamoxifen administration did not impair anastrozole bioavailability and modulated favorably its safety profile, providing the rationale for further studies. (Clin Cancer Res 2009;15(22):705360)

Endometrial ablation with a vaporizing electrode

Background. To evaluate histologically and histochemically the physical and thermal effects of a vaporizing electrode as compared with a standard cutting loop in the performance of endometrial ablation.Methods. Operative hysteroscopy was performed on 20 menorrhagic patients immediately before hysterectomy. Part of the posterior uterine wall was treated with a cylindrical, grooved, vaporizing electrode and undamped current set at 200 watts, and part with a standard cutting loop and undamped current set at 100 watts. A mucosal strip of about 1 cm width was left intact between the two treatment areas. Specimens underwent histologic examination after hematoxylin and eosin staining and histochemical assessment of thermal injury was based on detection of the respiratory enzyme dihydronicotinamide adenine dinucleotide diaphorase.Results. The mean (standard deviation) endometrial thickness as determined on the untreated area of the posterior uterine wall was 1.08 (0.36) mm. The mean depth of furrows was 3.10 (0.9...