子宫内膜异位症腹腔镜手术后不同药物巩固治疗的疗效比较

目的:比较中重度子宫内膜异位症腹腔镜手术治疗后加用不同药物巩固治疗的效果。方法:45例患者术后不用药(A组);58例加用达那唑治疗(口服达那唑400mg,每日1次,疗程为6个月,B组);47例加用孕三烯酮治疗(口服孕三烯酮2.5mg,每周2次,疗程为6个月,C组);39例用促性腺激素释放激素激动剂(GnRH-a)治疗(皮下注射戈舍瑞林3.6mg,每月1次,疗程为6个月,D组)。比较4组患者术后复发、妊娠及用药副作用等情况。结果:术后2年A组复发率最高,显著高于其他3组(P<0.01);D组复发率最低,显著低于另3组(P<0.01),差异皆有统计学差异。B组和C组的复发率差异没有显著性(P>0.05)。4组不孕患者术后妊娠情况类似。结论:中重度子宫内膜异位症腹腔镜手术治疗后有必要加用药物巩固治疗,GnRH-a巩固治疗的疗效优于达那唑和孕三烯酮。术后药物治疗未能提高妊娠率。     

The morphologic effect of short-term medical therapy of endometriosis

A clinicopathologic study of a short-term medical treatment of endometriosis with danazol or gestrinone was performed in 50 patients with endometriosis and infertility. The cellular response to the therapy was evaluated and graded according to morphologic, that is, histologic and ultrastructural, criteria. A 2-month therapy with 1.25 mg of gestrinone daily induced a degree of cellular inactivation and degeneration of the endometriotic implants that was more pronounced than after 4 months of therapy with either gestrinone (2.5 mg twice or thrice weekly) or danazol (600 mg daily). There was no correlation between the morphologic response to treatment and either the hormonal response of the foci during the menstrual cycle before therapy or the change in laparoscopic staging of endometriosis at the end of therapy. It is suggested that a short-term medical treatment should be further evaluated clinically in the treatment of endometriosis and infertility.     

Comparison of cyproterone acetate and danazol in the treatment of pelvic pain associated with endometriosis

Twenty-three patients with laparoscopically diagnosed endometriosis and pelvic pain were allocated randomly to treatment with cyproterone acetate 27 mg plus ethinyl estradiol 0.035 mg/day (11 patients) or danazol 600 mg/day (12 patients). All women received treatment for 6 months, except for one in the cyproterone group who suspended treatment for nonmedical reasons and was excluded from analysis of the results. The clinical condition and pain symptoms were monitored in all patients for 1 year after treatment suspension. The intensity of pelvic pain at diagnosis, during treatment, and at follow-up was evaluated by a multidimensional verbal score and an analogue scale. At the end of treatment, a repeat laparoscopy was performed in those patients who agreed (four in the cyproterone group, five in the danazol group); the results showed a partial regression of endometriotic lesions in both groups, with no significant differences between them. Dysmenorrhea disappeared in all patients during treatment. At 6 months after suspension, dysmenorrhea recurred in 66% of the cyproterone group and 58% of the danazol group, and at 1 year in 89 and 92%, respectively. Intermenstrual pelvic pain improved markedly during treatment in both groups; 6 months after treatment withdrawal it was present in four cyproterone subjects and four danazol group patients, whereas after 1 year, only one woman in the danazol group did not have this symptom. Deep dyspareunia was less affected by treatment, and 6 months later had recurred in all the women.(ABSTRACT TRUNCATED AT 250 WORDS)     

Buserelin versus danazol in the treatment of endometriosis-associated infertility

A total of 62 infertile women with a laparoscopic diagnosis of endometriosis were allocated randomly to two treatment groups, one of which (32 patients) received oral danazol 600 micrograms/day and the other (30 patients) received intranasal buserelin 1200 micrograms/day for 6 months. Suppression of serum levels of estradiol was greater with the gonadotropin-releasing hormone agonist treatment. Pain symptoms improved markedly during treatment in both groups. At the end of treatment a repeat laparoscopy was performed only in the patients who agreed to it (12 in the buserelin group and 13 in the danazol group), and it did not reveal significant differences in the effects of the two treatments on the endometriotic implants. All of the patients were followed up for at least 12 months, during which pregnancy was attempted. At 18 months the cumulative pregnancy rate was 48% in the patients treated with buserelin and 43% in those treated with danazol. Pain recurrence was observed in about half of the patients in each group 1 year after treatment suspension. The side effects were more frequent and more severe in the danazol-treated patients, whereas those given buserelin generally reported only symptoms of hypoestrogenism. The results of this study suggests that buserelin is at least as effective as danazol in the treatment of endometriosis when the outcome is considered in terms of restored fertility, and its side effects are less severe.     

Management of pelvic endometriosis with low-dose danazol

Thirty-eight women with pelvic endometriosis diagnosed by laparotomy or laparoscopy were enrolled in a double-blind study utilizing danazol. Danazol was administered for 6 months in four doses schedules: 600, 400, 200, and 100 mg/day. At the completion of 6 months of therapy, repeat laparoscopy was performed and 71% of the women were found to have improvement of pelvic endometriosis. Minimal and moderate pelvic endometriosis appeared to respond well to doses of danazol of less than 400 mg/day, whereas severe endometriosis appeared to be best treated with danazol doses of greater than 400 mg/day. Symptomatic relief of pain, dysmenorrhea, and dyspareunia occurred in 89% of the women. The over-all pregnancy rate in women attempting conception was 28% (8 of 28). Fifty-four per cent of the women had recurrence of symptoms within 1 year of discontinuation of danazol.     

Photocoagulation of early pelvic endometriosis with the Nd: YAG laser through the laparoscope

Our prospective study evaluated the efficacy of the Nd:YAG laser (MMB-AT MediLas 2) for early-stage clinical endometriosis. Patients with suspected endometriosis underwent diagnostic laparoscopy, and if mild or moderate pelvic endometriosis was discovered, the lesions were treated with the Nd:YAG laser at a power setting of 20 w with intermittent, one- to three-second exposures. All the patients are being treated postoperatively with danazol (800 mg/day) for three to nine months. At this writing, 14 of 24 patients selected for laparoscopy were eligible for treatment with the Nd:YAG laser. Six weeks after treatment all the patients reported relief of their initial symptoms. To date, two patients have had repeat laparoscopy after Nd:YAG photocoagulation of mild endometriotic lesions. Neither patient had evidence of disease at the second laparoscopy.     

An open randomized comparative study of the effect of goserelin depot and danazol in the treatment of endometriosis. Zoladex Endometriosis Study Team.

OBJECTIVE: To compare the efficacy and safety of goserelin depot and danazol for endometriosis. DESIGN: Open, randomized comparative trial. SETTING: Multicenter European academic clinical institutions. PATIENTS: A total of 307 patients with laparoscopically diagnosed endometriosis were randomized to goserelin (n = 204) or danazol (n = 103); 249 patients underwent second look laparoscopy (175 received goserelin and 74 danazol) and were analyzed for efficacy. INTERVENTIONS: A 3.6-mg depot of goserelin monthly subcutaneously or oral danazol 200 mg three times a day administered for 24 weeks. MAIN OUTCOME MEASURES: Efficacy assessments were based on changes in visible deposits at laparoscopy before and after treatment and subjective symptom scores at 4-week intervals during treatment and 8-week intervals after treatment for up to 24 weeks. Safety was assessed by adverse event reporting and clinical laboratory measures. RESULTS: There were similar proportions of symptomatic (73%) and asymptomatic (but infertile) (27%) and comparable distribution of different severity of endometriosis randomized to each treatment. Significantly fewer patients randomized to goserelin (6.4%) withdrew during treatment compared with 20.4% randomized to danazol (P less than 0.05). There were significantly reduced visible deposits of endometriosis found post-treatment (P less than 0.0001) within each group but no differences between the treatments. The mean total subjective symptoms scores remained significantly less than entry at 24 weeks post-treatment (P less than 0.05). Hypoestrogenic side effects were more common in those receiving goserelin, particularly hot flushes, but anabolic/androgenic side effects of weight gain and muscle cramps were more common in those receiving danazol. CONCLUSIONS: The monthly administered 3.6-mg depot preparation of goserelin was highly effective at inducing resolution of endometriotic implants and relieving the symptoms of endometriosis with prevention of their return during 24 weeks follow-up in the majority of patients. However, results were not significantly different from those achieved with danazol 600 mg/d.     

Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery

To evaluate the clinical value of postoperative hormone therapy in endometriosis, 60 patients with advanced disease were randomized to receive in a double-blind study danazol (200 mg, 3 times daily), medroxyprogesterone acetate (MPA) (100 mg daily) or placebo post-operatively for 6 months. Treatment efficacy was evaluated clinically and at laparoscopy 6 months after medication. In relation to placebo, danazol and high-dose MPA treatments, which did not differ from each other in efficacy, significantly alleviated pelvic pain. In addition, the peritoneal endometriosis lesions found at 6-months laparoscopy were significantly smaller in the MPA and danazol groups than in the placebo group. Breakthrough bleeding, weight gain and acne complicated danazol treatment but only breakthrough bleeding complicated MPA treatment. These data suggest that postoperative treatment of advanced endometriosis with high-dose MPA or danazol is clinically beneficial.     

Treatment of endometriosis with gestrinone (R-2323), a synthetic antiestrogen, antiprogesterone

Twenty patients with endometriosis diagnosed by laparoscopy were treated with the antiestrogen, antiprogesterone gestrinone (R-2323) for 6 to 8 months. The drug was administered in a dose of 5 mg twice weekly. According to the American Fertility Society's classification of endometriosis, five patients were classified as having mild (Stage I), eight as having moderate (Stage II), and seven as having severe endometriosis (Stage III). All patients became amenorrheic at the end of the second month of treatment, and symptomless at the end of the third month. Of nine women who had the potential and the desire to conceive, three conceived within 3 months after termination of treatment. Two more became pregnant within 1 year, and another, 14 months after termination of treatment. Five pregnancies progressed to term. One patient aborted. Two of the three women who did not conceive had subfertile husbands. Major side effects recorded were seborrhea and acne, which subsided after discontinuation of therapy. Treatment of endometriosis with gestrinone offers the advantage of effective clearing of lesions with relatively low dosage and frees the patient from the daily administration of drugs required by similar conservative hormonal therapies.     

Placebo-controlled comparison of danazol and high-dose medroxypro-gesterone acetate in the treatment of endometriosis after conservative surgery

To evaluate the clinical value of postoperative hormone therapy in endometriosis, 60 patients with advanced disease were randomized to receive in a double-blind study danazol (200 mg, 3 times daily), medroxyprogesterone acetate (MPA) (100 mg daily) or placebo post-operatively for 6 months. Treatment efficacy was evaluated clinically and at laparoscopy 6 months after medication.

In relation to placebo, danazol and high-dose MPA treatments, which did not differ from each other in efficacy, significantly alleviated pelvic pain. In addition, the peritoneal endometriosis lesions found at 6-months laparoscopy were significantly smaller in the MPA and danazol groups than in the placebo group. Breakthrough bleeding, weight gain and acne complicated danazol treatment but only breakthrough bleeding complicated MPA treatment. These data suggest that postoperative treatment of advanced endometriosis with high-dose MPA or danazol is clinically beneficial.     

Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis

A prospective, double-blind, placebo-controlled study was designed to evaluate the clinical efficacy and tolerance of danazol and high-dose medroxyprogesterone acetate (MPA) in the treatment of mild-moderate endometriosis. After laparoscopical confirmation of endometriosis, 59 patients were randomized to receive danazol (200 mg 3 times daily), MPA (100 mg daily) or placebo for 6 months. Clinical examinations were done before and 1, 3, 6 and 12 months after the beginning of the study, and a 2nd laparoscopy 6 months after termination of the medication. Eighteen patients in the danazol group, 16 in the MPA group and 17 in the placebo group completed the trial. Total or partial resolution of peritoneal implants was observed in 60% of the patients receiving danazol and in 63% of the patients receiving MPA. In the placebo group, resolution was observed in 18%, while the size of the implants was estimated to be increased in 23% of the patients. In relation to placebo, danazol and MPA significantly alleviated endometriosis-associated pelvic pain, lower back pain and defecation pain, but they did not differ from each other in these actions. The appearance of acne, muscle cramps, edema, weight gain and spotting bleeding complicated MPA treatment. The present results indicate that because of good efficacy and tolerance, high-dose MPA is a useful alternative in the hormonal treatment of endometriosis.     

Evaluation of histological and ultrastructural aspects of endometrium during treatment with gestrinone in women with amenorrhea or spotting

Nineteen patients with a laparoscopic diagnosis of endometriosis were treated with gestrinone at a dosage of 2.5 mg twice a week for 6 months. In 7 who reported spotting in the first 3 months, the dose was increased to 2.5 mg three times a week during the second trimester. An endometrial sample was obtained from each patient at the time of laparoscopy (basal) and at 3 and 6 months of treatment. Endometrial structure and ultrastructure were studied. Areas of hemorrhage and of loss of surface epithelium and a lesser degree of involution of the surface epithelium were observed in the 3-month samples of 7 patients with spotting, compared with 12 with amenorrhea. It is hypothesized that incomplete endometrial involution could be due to differences in gestrinone pharmacokinetics in individual patients, in the quality and/or quantity of endometrial cytosolic receptors for sex steroids, or in endocrine compensation to administration of the drug.     

A randomized double-blind prospective trial of two doses of gestrinone in the treatment of endometriosis

The purpose of this randomized double blind prospective trial was to study the efficacy and safety of two doses of oral gestrinone in the treatment of endometriosis. Six patients received gestrinone 1.25 mg twice weekly (group I) and six patients received gestrinone 2.5 mg twice weekly (group II). Patients underwent pretreatment and post-treatment laparoscopies and their endometriosis scores were recorded. The mean total endometriosis scores declined significantly from 20.0 +/- 5.2 (mean +/- standard error of the mean) pretreatment to 9.5 +/- 3.9 post-treatment in group I and from 19.1 +/- 4.8 pretreatment to 7.1 +/- 2.1 post-treatment in group II. A total of 67% of patients reported side effects. This study suggests that oral gestrinone 1.25 mg or 2.5 mg twice weekly is efficacious and safe in the treatment of endometriosis.     

A comparison of nafarelin acetate and danazol in the treatment of endometriosis

Nafarelin 400 micrograms daily and danazol 600 mg daily were compared in a double-blind randomized study. Eighty-two patients with endometriosis were treated for 6 months after an initial laparoscopy and 74 had a second laparoscopy. Twenty-two (30%) patients had complete disease regression, 42 (57%) patients had a partial regression, and in 10 (13%) patients disease was unchanged or worse. Both treatments led to significant regression of active disease but not of adhesions. At 3 months follow-up, 34 (64%) patients reported their symptoms were improved, 15 (28%) reported no change, and 4 (8%) were worse. Nafarelin was associated with more hot flushes and headaches, and danazol with more weight gain. No significant differences, however, were noted in treatment efficacy between the two groups.     

Prolactin and its response to the luteinizing hormone-releasing hormone thyrotropin-releasing hormone test in patients with endometriosis before, during, and after treatment with danazol

Basal levels of prolactin (PRL) were studied in 16 normal women and in 60 women with endometriosis, 37 of whom were infertile. In addition, the authors studied the response to an intravenous (IV) injection of luteinizing hormone-releasing hormone (LH-RH) (100 micrograms) plus thyrotropin-releasing hormone (TRH) (300 micrograms) in the 16 normal women and in 18 endometriosis patients, examining the basal PRL and thyrotropin, and at 15, 30, 45, 60, and 120 minutes after the IV bolus. After laparoscopy and/or conservative surgery, the patients were treated with danazol for 6 months and a second laparoscopy was performed. The LH-RH/TRH test was carried out in the third month of danazol treatment in 6 endometriosis patients and before the second laparoscopy in 11 patients. The results show that there was both an increase in the mean basal levels of PRL and in the percentage of cases of moderate hyperprolactinemia in endometriosis patients. There also was a greater rise in PRL with the LH-RH/TRH test in moderate and severe endometriosis. The PRL response was significantly greater in endometriosis than in normal women, and was not related to TSH response. Danazol treatment reduced significantly the PRL response. The PRL response before treatment was significantly higher in patients who after treatment showed persistent endometriosis at the second laparoscopy. This could suggest a lower effectiveness of danazol in patients with endometriosis and a PRL hyper-response to LH-RH/TRH.     

Comparison between laparotomy and operative laparoscopy in the treatment of moderate and severe stages of endometriosis

A retrospective study was designed to compare the results of treatment of moderate and severe stages of endometriosis by laparotomy and by laparoscopy. Patients were divided into three groups: the first consisted of 42 patients treated by laparotomy followed immediately with danazol treatment for 6-9 months; the second, 44 patients treated by operative laparoscopy followed immediately with danazol treatment for 4-6 months; and the third, 62 patients treated by operative laparoscopy followed immediately with danazol treatment for 6-10 weeks. The cumulative pregnancy rate in the laparoscopy groups was better than that of the laparotomy group. Most patients who failed to conceive underwent a second-look laparoscopy for reevaluation. Residual endometriosis and associated adhesions were noticed least in the third group. It is concluded that operative laparoscopy could be efficiently used for the treatment of moderate or even severe endometriosis.     

Combined laparoscopic surgery and danazol therapy for pelvic endometriosis

The role of combined laparoscopic surgery and postoperative danazol treatment for endometriosis in infertile patients has been reviewed in 66 cases. Thirty-five patients with mild endometriosis and twenty-five patients with moderate endometriosis received a standardized laparoscopic surgical procedure followed by danazol therapy with a minimum of 6 months' follow-up. Six patients with severe endometriosis received 4 months of danazol treatment followed by conservative surgery. Fifty-four per cent of these patients conceived, with 92% delivering a live child. By excluding patients with other significant infertility factors, a "corrected" fertility rate of 68% was obtained. The majority of patients conceiving after danazol treatment did so within the first 6 months after therapy. Reported complications to drug treatment were minimal. Second-look laparoscopy when performed in patients who had not conceived within 6 months revealed a significant decrease in residual endometriosis.     

Depot leuprorelin acetate versus danazol in the treatment of infertile women with symptomatic endometriosis

PURPOSE OF INVESTIGATION: Endometriosis is a common finding in women with infertility, but the mechanism by which it renders a woman infertile remains unclear. The medical treatment of pelvic endometriosis includes hormonal therapy that directly attacks endometriosis lesions or indirectly by inhibiting endometrial proliferation through estrogenic deprivation. The aim of this study was to compare the efficacy and safety of leuprorelin acetate depot and danazol for endometriosis in infertile women. METHODS: This randomized trial involved 81 women 19-41 years old with regular menses and known pelvic endometriosis who were recruited from the Fertility Center of the Second University of Naples between 1992 and 1999. Fifty-four women were given 3.75 mg of leuprolide acetate depot every 28 days for 24 weeks and the remaining 27 took 200 mg of danazol three times daily for 24 weeks. Efficacy assessments were based on pre-admission and end-of-treatment laparoscopic scores and subjective symptoms scores at 4-week intervals during and after treatment. Safety was evaluated by adverse events and clinical laboratory tests. RESULTS: In each group, endometriosis growth and symptoms significantly improved during treatment (p < 0.001). Significantly fewer patients randomized to leuprorelin acetate (5.5%) withdrew during treatment compared with 18.5% randomized to danazol (p < 0.05). After treatment symptoms returned in each group, but severity was less than at admission at all time points (p < 0.02). Hypoestrogenic side-effects were more common in those receiving leuprorelin, particularly hot flushes, but anabolic/androgenic side-effects of weight gain and acne were more common in those receiving danazol. CONCLUSION: Both leuprorelin acetate depot and danazol are effective in the treatment of endometriosis in infertile patients. The hypoestrogenic side-effects of leuprorelin may be better tolerated than the androgenic, anabolic effects of danazol.     

Treatment of endometriosis by vaginal administration of gestrinone

The effectiveness and acceptability of gestrinone administered by vaginal route was evaluated in a group of 110 patients with endometriosis. Patients were divided into four groups. The first three groups were treated by vaginal route. Group I (n = 17) received two 2.5-mg tablets weekly; group II (n = 31) received three 2.5-mg tablets weekly; group III (n = 35) received two 5.0-mg tablets weekly. Group IV consisted of 27 patients who received 2.5 mg of gestrinone orally twice weekly. Ninety-eight women completed the 6- to 8-month treatment period. Amenorrhea developed in all treatment groups, including group I (34%). The disappearance of both dyspareunia and dysmenorrhea occurred in most patients in all treatment groups soon after the second month of therapy. Patients treated by vaginal route had significantly less seborrhea and acne than those treated by oral route. Weight gain was also significantly less in vaginally treated women than in those treated orally. Pregnancy rate following discontinuation was not significantly different for the various groups.     

Comparison of the effects of leuprorelin acetate and danazol treatments on serum CA-125 levels in women with endometriosis

OBJECTIVE: To investigate the effects of danazol and leuprorelin acetate on CA-125 levels during treatment for endometriosis. PATIENTS AND METHODS: Fifty women with laparoscopically diagnosed and treated endometriosis, and 50 women without pelvic disease as a control group. Following surgical treatment, 35 women with endometriosis were divided into two groups. The first group (20 women) received 200 mg danazol three times daily for 6 months; the second group (15 women) received 3.75 mg leuprorelin acetate depot every 28 days for 6 months. Serum CA-125 levels were measured before medical treatment, during the last 15 days of the 6-month treatment course, and 3 months after treatment. RESULTS: Serum CA-125 levels were significantly higher in women with endometriosis than in women in the control group. Before treatment, CA-125 levels in patients with stage III/IV endometriosis were significantly higher than those in stage I/II endometriosis. Six months of danazol or leuprorelin acetate depot treatment decreased serum CA-125 levels. Three months after stopping danazol, CA-125 levels remained significantly lower than pretreatment levels. On the other hand, 3 months after stopping leuprorelin acetate, CA-125 levels returned to pretreatment levels. CONCLUSIONS: (a) Danazol and leuprorelin acetate are equally effective in the treatment of endometriosis. (b) Moreover, the results support the view that the determination of CA-125 levels may assist in evaluating progress of endometriosis treatment.