GnRH agonists before surgery for uterine leiomyomas. A review.

OBJECTIVE: To clarify whether preoperative treatment with gonadotropin-releasing hormone (GnRH) agonists offers substantial advantages to patients undergoing conservative or definitive surgery for uterine leiomyomas. STUDY DESIGN: A review of data from the most recent English-language literature. RESULTS: Inducing amenorrhea in patients with heavy menorrhagia and severe sideropenic anemia before both conservative and definitive surgery for uterine fibroids raises hemoglobin and hematocrit values to within the normal range, limits homologous blood transfusions and enables operations to be scheduled with the patients in better condition. A temporary 30-50% reduction in mean uterine volume theoretically may convert an abdominal into a vaginal hysterectomy in "borderline" cases or sometimes allow a transverse instead of longitudinal abdominal incision. No trial has yet demonstrated "clinically" significant reductions in operating time, operative blood loss or postoperative morbidity in patients undergoing myomectomy or hysterectomy after a course of GnRH agonists as compared with those operated on immediately. There seems insufficient scientific evidence to justify the routine use of GnRH agonists before myomectomy at laparotomy, except possibly in the case of extremely bulky uteri. GnRH agonist treatment before hysteroscopic myomectomy induces endometrial thinning, reduces bleeding and mucous debris, and decreases the diameter of submucous leiomyomas, improving visibility and limiting operating time and fluid intravasation. CONCLUSION: The available data seem to support the use of GnRH agonist treatment before surgery for uterine leiomyomas in selected circumstances. Administration of GnRH agonist for only two or three months preoperatively seems to achieve all the advantages of this treatment, limiting side effects and cost.

Laparoscopic uterine biopsy for diagnosing diffuse adenomyosis.

OBJECTIVE: To investigate the possibility of diagnosing diffuse adenomyosis with the uterus in situ. STUDY DESIGN: Myometrial needle biopsy was performed on a prospectively evaluated series of 72 women undergoing laparoscopy for infertility and/or chronic pelvic pain. Before surgery the patients completed a questionnaire on the presence and severity of dysmenorrhea according to a linear analog and verbal rating scale. A single specimen was taken from along the median line in the upper third of the posterior uterine wall using a 14-gauge Tru-cut needle inserted through the anterior abdominal wall under laparoscopic guidance. RESULTS: No complications occurred. Adenomyosis was diagnosed in 8 of the 42 subjects with menstrual pain and 5 of the 30 asymptomatic ones (19% versus 17%) and pelvic endometriosis in 27 and 10, respectively (64% versus 33%, P = .02). The frequency of moderate or severe dysmenorrhea was greater in women with adenomyosis than in those without adenomyosis or endometriosis, but the difference was not statistically significant. Conversely, menstrual pain was significantly more frequent and severe in patients with endometriosis as compared with women who had neither endometriosis nor adenomyosis. CONCLUSION: Uterine needle biopsy is simple, rapid and safe, but its overall clinical importance, as well as the predictive value of a normal histologic result, requires further investigation.

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.

Adenomyosis at hysterectomy: a study on frequency distribution and patient characteristics.

To evaluate the prevalence and risk factors for adenomyosis, the clinical records of consecutive women undergoing hysterectomy during a 3 year period were retrieved. Data were collected on indication for the intervention, general sociodemographic characteristics of the patients, age at menarche, parity, abortions, and menopausal status at surgery. Adenomyosis was diagnosed in 332 of the 1334 cases (24.9%). The condition was present in 146 of the 627 patients (23.3%) with fibroids and menorrhagia, 68 of the 265 (25.7%) with prolapse, 21 of the 98 (21.4%) with ovarian cysts, 19 of the 100 (19%) with cervical cancer, 31 of the 110 (28.2%) with endometrial cancer, 16 of the 57 (28.1%) with ovarian cancer, and 19 of the 77 (24.7%) with miscellaneous indications. These differences were not statistically significant (chi 2(6) = 11.14). In comparison with nulliparous women, the odds ratio was 1.3 and 1.5 respectively in women with one and > or = two births (chi 2(1) trend = 5.76 P < 0.05). No relationship was found between age at surgery, age at menarche, indications for surgery, menopausal status at intervention, and presence of endometriosis. Our findings do not support the notion that adenomyosis is more frequently related to particular clinical conditions, and suggest that parity may be associated with an increased frequency of adenomyosis.

Very low dose danazol for relief of endometriosis-associated pelvic pain: a pilot study.

OBJECTIVES: To evaluate the efficacy and safety of very low dose danazol in improving pelvic pain in women with endometriosis, the benefit of preceding the treatment by a short course of a GnRH agonist, symptoms recurrence after drug withdrawal, and variations in menstrual pattern. DESIGN: Open-label, randomized study. SETTING: University hospital endometriosis center. PATIENTS: Forty-two women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis. INTERVENTIONS: Treatment with oral danazol, 50 mg/d, for 9 months (group I, n = 21) or leuprolide depot for 3 months followed by oral danazol, 50 mg/d, for 6 months (group II, n = 21), and a 6-month follow-up. MAIN OUTCOME MEASURES: Variations in severity of symptoms during treatment and at the end of follow-up as shown by a linear analog scale and a verbal rating scale; menstrual blood loss as assessed by a pictorial chart. RESULTS: Four patients withdrew from the study, one in each group at the fifth month of treatment (for persistent pain) and one in each group during follow-up (they requested additional therapy); one woman in group I was lost to follow-up. Significant improvements were obtained in dysmenorrhea, deep dyspareunia, and nonmenstrual pain in both treatment schedules without differences between the groups. Also menstrual blood loss was significantly reduced in both groups. A temporary fall in high and rise in low density lipoprotein cholesterol was observed in the study population. At the end of follow-up symptoms recurred without significant differences in median pain scores with respect to baseline. CONCLUSION: Very low dose danazol may be an alternative for temporary relief of endometriosis-associated pain. Ovulation is not always inhibited and barrier contraception is needed. Side effects occur but are rarely severe. Further data are required to evaluate the influence of long-term administration on the lipid profile.

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.

Serum and Cyst Fluid Tumor Marker Levels in the Differential Diagnosis of Benign Ovarian Cysts

Serum and cystic fluid levels of CA 125, CA 19.9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) were assayed in 74 consecutive women of median age 30 years (range 15 to 74 years) undergoing surgery for adnexal cysts of presumed benign nature. Median (range) serum levels of CA 125, CA 19.9, CEA and AFP were 46.5 IU/ml (4.3-406), 28.5 IU/ml (1-96.3), 1.4 ng/ml (0.5-3.5) and 2.4 ng/ml (1-9.9) in 44 endometriotic cysts; 22.5 (4.7-82), 4.9 (1-226),1.3 (0.7-4.8) and 4 (0.5-10.5) in 11 dermoid cysts, 14 (8.6-25.1), 3.2 (1-6), 1 (0.3-2.8) and 3.7 (1.9-6) in 9 mucinous cysts, and 6.9 (0.5-104), 18 (1-132), 0.8 (0.1-1.9) and 2.1(1-5.4) in 10 cases with mixed histotypes. Corresponding cystic fluid levels were 342,864 (1,418-3,404,682), 228,000 (117-2,500,000), 106 (0.5-2,908) and 1.3 (0.4-51) in endometriomas; 843,895 (10,842-1,676,948), 740,039 (77-1,280,000), 470 (61-880) and 2.5 (1-4) in dermoids; 3,485 (27.2-149,804), 9,007 (36.4-153,475), 1,631 (402-11,096) and 1 (0.5-2.5) in mucinous cysts, and 13,068 (5,300-43,767), 412 (1-142,700), 0.8 (0.4-5.3) and 2.3 (1-4) in the mixed histotype group. No significant between group differences were detected in serum marker levels. Patients in the mucinous cyst group had significantly lower CA 125 cystic fluid levels compared with women with endometriomas and dermoids (P<0.05). Fluid aspirate tumor marker measurements did not aid in the differential diagnosis of benign ovarian cysts, mainly due to the extremely wide scattering of values.

Gonadotropin releasing hormone agonist treatment before hysteroscopic endometrial resection.

OBJECTIVES: To evaluate the effects of treatment with the gonadotropin releasing hormone (GnRH) agonist goserelin before endometrial resection on absorption of distension medium fluid and technical feasibility of the surgical procedure. METHODS: Fifty-five patients reporting menorrhagia underwent endometrial resection after 2 months of goserelin depot therapy (33 cases) or during the proliferative phase of the cycle (22 controls). RESULTS: In the cases, the mean distension medium deficit +/- S.D. was 511 +/- 196 ml versus 647 +/- 245 ml in controls (P = 0.03), and the operating times were, respectively, 14 +/- 4 versus 18 +/- 5 min (P = 0.002). The intrauterine operating conditions were considered excellent or good in 64% of the cases versus 27% of the controls (chi 2 = 5.60, P = 0.02). CONCLUSIONS: GnRH agonists induce endometrial thinning, so that when administered before intrauterine interventions, mucus cellular debris and bleeding should be reduced during surgery and hysteroscopic visibility increased; the operating time may thus be shorter and fluid absorption decreased. However, more data are needed before considering GnRH agonists a proven effective means of facilitating endometrial resection.