Continuous subcutaneous infusion of GnRH agonist: effective dosage in the treatment of endometriosis and its influence on the ovarian response to human menopausal gonadotropin

This study was designed to compare the clinical and hormonal efficacy of the treatment for endometriosis using continuous infusion of three different doses of GnRH agonist (A). In addition, we examined the ovarian responsiveness to human menopausal gonadotropin (hMG) administration during GnRH-A treatment. Thirteen endometriosis patients were divided into 3 groups and given different doses. GnRH-A (Buserelin) was infused continuously through the subcutaneous route at rates of 200 micrograms (Group I; n = 5), 100 micrograms (Group II, n = 4) and 10 micrograms (Group III; n = 4) per day for 24 weeks. After the start of treatment, serum estradiol (E2) was suppressed to the menopausal range within 2 weeks and thereafter maintained this range until 24 weeks in each group. The LH and FSH response to a GnRH Challenge test was completely abolished within 2 weeks in 3 groups. Although serum FSH decreased to below the pretreatment value within a week, the FSH level was significantly lower in groups I and II than in group III until 8 weeks. No difference in the LH level during the treatment was seen among the 3 groups. After completion of the 24 weeks' treatment, FSH increased rapidly, and ovulation returned within 4 to 6 weeks in each group. Pregnancy was achieved in two patients in group I, one patient in group II and one patient in group III during cycles 2 and 5. Serum E2 increased to 200-300 pg/ml in 3 out of 7 patients treated with hMG during GnRH-A infusion, whereas no increase in E2 was seen in the remaining 4 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gonadotropin-releasing hormone agonist plus "add-back" hormone replacement therapy for treatment of endometriosis: a prospective, randomized, placebo-controlled, double-blind trial

OBJECTIVE: To assess the effect of add-back therapy with continuous combined estrogen-progestin on the GnRH agonist-induced hypoestrogenic state and its effectiveness in healing of endometriotic lesions. DESIGN: A prospective, randomized, placebo-controlled, double-blind trial. SETTING: Multiple centers in The Netherlands. PATIENT(S): 41 premenopausal women with laparoscopically diagnosed endometriosis (revised American Fertility Society scores >/=2). INTERVENTION(S): Patients were randomly assigned to receive a subcutaneous depot formulation of goserelin, 3. 6 mg, every 4 weeks, plus oral placebo or oral continuous combined estradiol-norethisterone acetate add-back therapy daily for 24 weeks. MAIN OUTCOME MEASURE(S): Endometriosis response, bone mineral density, transvaginal ultrasonographic changes, endocrinologic effects, and subjective side effects. RESULT(S): The number of endometriotic implants was significantly reduced in both groups. In the group that received GnRH agonist plus placebo, bone mineral density of the lumbar spine decreased by 5.02%. CONCLUSION(S): The effectiveness of GnRH agonist treatment for endometriosis was not decreased by the addition of add-back continuous combined hormone replacement therapy. Bone mineral density of the lumbar spine was maintained and subjective side effects were diminished.     

Treatment of endometriosis with a decreasing dosage of a gonadotropin-releasing hormone agonist (nafarelin): a pilot study with low-dose agonist therapy ("draw-back" therapy)

OBJECTIVE: To evaluate the efficacy of half-dose GnRH agonist therapy for endometriosis. DESIGN: Prospective, longitudinal pilot study. SETTING: Osaka University Hospital. PATIENT(s): Patients with symptomatic endometriosis. INTERVENTION(s): Fifteen patients were randomized to receive either full-dose nafarelin treatment (200 microgram b.i.d.) for 24 weeks (n = 7) or full-dose nafarelin treatment for 4 weeks followed by half-dose nafarelin treatment (200 microgram daily) for 20 weeks (n = 8). MAIN OUTCOME MEASURE(s): Clinical symptoms and the results of physical examinations. Serum E(2) and carcinoma antigen 125 (CA125) levels, lipid profiles, and urinary levels of the N-telopeptide of type I collagen. Bone mineral density of the lumbar spine. RESULT(s): Subjective and objective manifestations of endometriosis were decreased to a similar extent in both study groups. Adverse effects were markedly reduced with half-dose administration. In the half-dose group, the mean serum E(2) level was significantly suppressed by 4 weeks of treatment with full-dose nafarelin and remained at approximately 30 pg/mL with half-dose nafarelin. Loss of bone mineral density was significantly less with half-dose treatment. CONCLUSION(s): Half-dose administration of nafarelin after pituitary down-regulation with full-dose nafarelin ("draw-back" therapy) is a new protocol for the treatment of endometriosis that is effective and associated with fewer adverse effects.     

Treatment with nafarelin for endometriosis in young women. Efficacy, safety and lipid metabolism. Niigata Nafarelin Study Group

OBJECTIVE: To assess the efficacy, safety and effect on lipid metabolism of treatment with nafarelin acetate for clinical endometriosis symptoms in young women. STUDY DESIGN: A multicenter, open-label, nonrandomized clinical trial was conducted on subjects who were 19-29 years of age with clinical symptoms and signs of endometriosis demonstrated by laparoscopy, ultrasonography, magnetic resonance imaging, computed tomography or pelvic examination. For 24 weeks, 34 women received intranasal nafarel, 200 mg twice daily. The main outcome measures were changes in signs and symptoms, lumbar bone mineral density by dual energy X-ray absorptiometry and serum parameters of lipid metabolism. RESULTS: Symptoms and signs of endometriosis decreased significantly during treatment and at the first posttreatment menses. CA-125 level decreased significantly, from 84.0 +/- 20.2 U/mL at baseline to 13.4 +/- 1.9 at the 24th week (P = .0014). The mean high density lipoprotein cholesterol, total cholesterol, apoprotein A-I and A-II, lipoprotein (a) and remnant lipoprotein cholesterol levels significantly increased, and cholesterol ester transfer protein activity slightly increased, by the 24th week but fell to baseline values by the first posttreatment menses. Despite a low mean serum estradiol level (20 pg/mL) at the end of treatment, the reported incidence of hot flushes was low (24%), and only one woman withdrew because of hypoestrogenic symptoms. CONCLUSION: Twenty-four-week nafarelin treatment for clinical endometriosis symptoms in women < or = 29 years was safe and effective.     

Treatment of endometriosis with a long-acting gonadotropin-releasing hormone agonist plus medroxyprogesterone acetate

Highly potent agonists of gonadotropin-releasing hormone (GnRH) have been shown to reduce pelvic pain due to endometriosis and the size and number of implants seen at laparoscopy. The accompanying symptoms and problems associated with the hypoestrogenism induced by the agonist have reduced its acceptability and raised questions about its safety. In an attempt to optimize this form of therapy, we treated eight women with endometriosis with daily subcutaneous injections of a potent agonist of GnRH plus a daily oral dose of 20-30 mg of medroxyprogesterone acetate for 24 weeks. Ovarian estrogen secretion was reduced to levels seen in castrated women throughout the course of treatment. Markers of hypoestrogenism, such as hot flashes and loss of calcium from bone, were diminished with this regimen compared with previous findings with GnRH agonist alone. Blinded evaluation of laparoscopic photographs failed to reveal improvement or suppression of active endometriosis. The results of this pilot study indicate that the addition of medroxyprogesterone acetate decreases the hypoestrogenic effects of GnRH agonist alone but fails to affect pain or endometriotic implants.     

Studies on endocrine therapy of endometriosis

GnRH agonist and synthetic steroid such as Danazol, Medroxyprogesterone acetate (MPA) and Gestrinone are useful for the treatment of patients with endometriosis. These compounds induce atrophy and regression of endometriotic tissue, but the action mechanisms are still unclear. The present study, therefore, was undertaken to elucidate the mechanisms of these compounds in the treatment of endometriosis. In addition, a combination therapy with these compounds for endometriosis was also evaluated with an experimental animal model. Effects of GnRH agonist, Danazol and GnRH/Danazol combination on experimental endometriosis were evaluated in female rats. Endometrium autotransplanted under the renal capsule markedly decreased in size following castration. Histologic examination indicated atrophy and regression of the endometrial explant. The changes of endometrial explant were also induced by GnRH agonist, Danazol and combination treatment. However, a combination therapy with GnRH agonist and Danazol (93%) was shown to be superior to GnRH agonist (65%) and Danazol alone (45%) to induce atrophy and regression of experimental endometriosis. As expected, GnRH agonist significantly decreased serum E2, but Danazol did not at all. It is suggested that a combination therapy with GnRH agonist and Danazol may be a potential modality in the treatment of endometriosis. In order to evaluate whether Danazol, MPA, and Gestrinone has a direct inhibitory effect to synthesize estrogen, immature female rats were hypophysectomized and the ovaries were stimulated by a daily PMS injection. Administration of Danazol to the rats for two weeks stimulated the synthesis of 17, 20-lyase, 17 beta-HSD and aromatase activity, but did not inhibit any enzyme activities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of estrogen-dependent gynecological disorders with the gonadotropin releasing hormone agonist buserelin.

The authors examined the effect and tolerability of buserelin in 40 women with endometriosis and ten women with uterine leiomyoma. Buserelin was given intranasally, 200 micrograms three times a day for 6 months. Laparoscopy was performed before and after, and ultrasonography during the treatment. Hormone and lipid profiles and other biochemical tests were run during the treatment. The bone mineral density was tested by dual photon absorptiometry before and after therapy in a group of patients. Although most of the patients complained of hot flushes, no women dropped out. AFS mean pelvic score decreased from 24.10 to 6.95 and the size of the fibroids decreased by 69% at the end of 6 months of treatment. In conclusion, our data suggest that the use of GnRH agonist has a place in the treatment of endometriosis and uterine leiomyoma but further studies are needed to conclude that buserelin given intranasally at a dose of 600 micrograms/day for 6 months is an alternative to other conventional medical treatment modalities in terms of pregnancy and recurrence rates.     

Long-term use of gonadotropin-releasing hormone analogs and hormone replacement therapy in the management of endometriosis: a randomized trial with a 6-year follow-up

OBJECTIVE: To identify the effects of long-term GnRH agonist use (6-24 months), with and without add-back therapy, and spontaneous reversibility of bone mass density (BMD) up to 6 years after treatment. DESIGN: A prospective, randomized, long-term follow-up study. SETTING: Obstetrics and gynecology department in a university hospital in the United Kingdom. PATIENT(S): Forty-nine symptomatic women with a laparoscopic diagnosis of endometriosis who had been identified for treatment with long-acting GnRH agonist and volunteered to participate in the study. INTERVENTION(S): Women were randomly allocated to receive hormone replacement therapy (HRT) as a daily oral dose of estradiol, 2 mg, and norethisterone acetate, 1 mg, or no treatment in addition to monthly subcutaneous implants of goserelin acetate for up to 2 years, until cessation of symptoms. Bone mineral density (BMD) at the lumbar spine (C2-C4) and hip (Ward triangle) was measured every 6 months. MAIN OUTCOME MEASURE(S): BMD changes in both groups. RESULT(S): 45 women were followed up for 6 years, at the end of which the groups did not differ significantly in the reduction in mean BMD at the lumbar spine or hip. CONCLUSION(S): BMD reduction occurs during long-term GnRH agonist use and is not fully recovered by up to 6 years after treatment. Use of HRT does not affect this process.     

Use of GnRH antagonists in the treatment of endometriosis

Endometriosis is an oestrogen-dependent disease that is treatable by oestrogen withdrawal, a therapy that has been effectively provided by the use of a gonadotrophin-releasing hormone (GnRH) agonist. Complete oestrogen withdrawal results in unacceptable side-effects, in particular in accelerated bone density loss. This problem has been effectively overcome with 'add-back therapy' using low-dose oestrogens and progestins in combination with a GnRH agonist to limit these side-effects, while still allowing regression of endometriotic lesions. The aim of this study was to determine the feasibility of using a subcutaneous injection of GnRH antagonist in the treatment of endometriosis. All patients (15/15; 100%) reported a symptom-free period during GnRH antagonist treatment, including mood changes, hot flushes, loss of libido, vaginal dryness and other symptoms. Serum oestradiol oscillated around a mean concentration of 50 pg/ml during therapy. Diagnostic laparoscopy before GnRH antagonist administration showed a mean stage III of disease. Regression occurred in 60% of cases (9/15) and the degree of endometriosis declined to stage II. Sequential administration of the GnRH antagonist cetrorelix (Cetrotide) in a 3 mg dosage once weekly over 8 weeks creates a new opportunity for medical treatment of symptomatic endometriosis. Preserving basic oestrogen production during the course of treatment apparently does not influence regression of disease, and has no major side-effects.     

Effect of LHRH agonist (buserelin) on pulsatile secretion of LHRH and LH

The LHRH agonist buserelin was administered intranasally to eight patients with endometriosis in doses of 300, 600 or 900 micrograms/day for six months. In all patients buserelin clearly suppressed ovulation. In the patients treated with 900 micrograms/day, estradiol levels declined to less than 30pg/ml, and LH release in response to LHRH testing decreased markedly after 2 months of treatment. A mild decrease in LH release was noted in the premarin test at the end of the treatment. At the end of buserelin treatment baseline levels of plasma LHRH, LHRH pulse amplitude and frequency were not lowered. However, baseline levels of plasma LH and LH pulse amplitude decreased. These results indicate that buserelin may act to decrease pituitary response to LHRH.     

Extending the treatment boundaries: Zoladex and add-back

Objective: To review the evidence that add-back hormone replacement therapy (HRT) can ameliorate the metabolic consequences of gonadotropin-releasing hormone (GnRH) agonist treatment in women with symptomatic endometriosis. Methods: A review of relevant literature. Results: Early studies suggested that add-back HRT maintained bone mineral density (BMD) without reducing the symptomatic benefit of GnRH treatment. Both high-dose progestogen and low dose progestogen plus cyclical etidronate are effective in maintaining BMD. Standard and low dose HRT add-back may be more effective in relieving the hypo-estrogenic side-effects of GnRH agonist therapy. Randomized controlled studies have shown that both low-dose and standard-dose add-back HRT reduce the side-effects of GnRH agonist therapy, and that this benefit extends to 12 months of treatment. Conclusions: GnRH agonist treatment with add-back HRT seems to offer the hope of improved treatment for women with endometriosis, but the optimum treatment duration and time to start HRT have yet to be defined.     

Bone mineral density of the lumbar spine in women with endometriosis

Young women with endometriosis have reduced cortical and trabecular bone mineral density of the wrist compared with age-matched controls. This conclusion was based on 41 subjects from one geographical location. The purpose of this study was to test this finding in a larger, more geographically diverse population. One hundred women with laparoscopically proven endometriosis were enrolled in this study for the evaluation of the efficacy of nafarelin, a gonadotropin-releasing hormone agonist. Patients were recruited from nine investigators across the United States and Canada, and bone mineral density of the lumbar spine was obtained at baseline, with 6 Hologic QDR (Hologic Inc., Waltham, MA) and a Lunar DPX (Lunar Radiation Corp., Madison, WI) instrument. The age of the women was 30.3 +/- 5.8 years (mean +/- SD); 91% were white. Bone mineral density of the lumbar spine was 1.1 +/- 0.11 g/cm2 (n = 85 Hologic QDR) and 1.2 +/- 0.93 g/cm2 (n = 15 Lunar DPX). Hologic bone mineral density was 104.8 +/- 11.0 and Lunar bone mineral density was 103.4% +/- 7.8% of normal values for age. To conclude, in a population based cross-sectional study of patients with endometriosis, we do not observe low bone mineral density of the lumbar spine by techniques that measure a combination of cortical and trabecular bone.     

Treatment of endometriosis with a potent agonist of gonadotropin-releasing hormone (nafarelin)

Administration of superactive agonistic analogs of gonadotropin-releasing hormone (GnRH) has been shown to induce a paradoxic and reversible suppression of gonadotropins, resulting in suppressed gonadal steroid concentrations. Because there currently is no uniformly successful and acceptable medical therapy for endometriosis, we examined the effects of 6 months of nasal administration (500 micrograms every 12 hours) of the agonistic analog of GnRH, nafarelin, on clinical signs and symptoms and hormonal profiles in eight women with endometriosis. All patients had prompt and near-complete relief from their painful symptoms of endometriosis. Laparoscopy or laparotomy, performed both before and after treatment in seven of the women, revealed complete resolution of active endometriotic lesions in five patients and only a single, small cul-de-sac implant in a sixth woman. A large ovarian endometrioma decreased slightly in response to treatment in the seventh woman. Serum luteinizing hormone and follicle-stimulating hormone concentrations, after a transitory stimulation at the onset of treatment, declined and were suppressed (P less than 0.001) during the remainder of treatment. Serum estradiol concentrations fell to approximately menopausal levels (less than 30 pg/ml) after 1 to 4 weeks. Reversibility of drug effect was prompt, with ovulatory menses returning 47 +/- 8 days (+/- standard deviation) after treatment. Thus, nasal administration of agonistic analogs of GnRH may represent a new treatment modality for endometriosis.     

The effect of physical training on bone mineral density in women with endometriosis treated with GnRH analogs: a pilot study

BACKGROUND: The effect of physical training on bone mineral density (BMD) in women with endometriosis treated with gonadotropin-releasing hormone (GnRH) analogs was studied. METHODS: Nineteen Caucasian premenopausal women aged 23-38 years were included in the study. The subjects were all treated with 21.6 mg goserelin during 6 months. The patients were randomized to physical training n=8 or to a control group n=11. The total period of training was 12 months, whereas GnRH treatment was terminated after 6 months. BMD was measured in the femoral neck area and the lumbar spine using dual X-ray absorptiometry (DEXA). This was performed just before treatment, after 6 months and after 12 months. Six women fulfilled the training during 12 months of observation. In the control group 10 women were followed up for 12 months. RESULTS: After 6 months the women in the physical training group were 2.1% below baseline. Six months later these women had gained BMD in the femoral neck and were 0.6% below baseline. Those in the control group lost 2.8% after 6 months and were 3.6% below baseline after 12 months. The difference in loss of BMD after 12 months between the groups was significant 0.029. In the spine there was no significant difference between the two groups. CONCLUSIONS: Physical training in women with endometriosis was found to rebuild bone after treatment with GnRH analogs when compared to a control group. This effect could be demonstrated 6 months after cessation of GnRH treatment.     

Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis

OBJECTIVE: To evaluate the effect of a 3-month course of GnRH agonist administered immediately before IVF-ET in infertile patients with endometriosis. DESIGN: Prospective, randomized trial. SETTING: Three tertiary care assisted reproductive technology programs. PATIENT(S): IVF-ET candidates with surgically confirmed endometriosis. INTERVENTION(S): Twenty-five patients received three courses of a long-acting GnRH agonist, 3.75 mg i.m. every 28 days, followed by standard controlled ovarian hyperstimulation. Twenty-six patients received standard controlled ovarian hyperstimulation with mid-luteal phase GnRH agonist down-regulation or microdose flare regimens. MAIN OUTCOME MEASURE(S): Response to controlled ovarian hyperstimulation, ongoing pregnancy rates per cycle, group implantation rates, and implantation rate per embryo transfer procedure. RESULT(S): The extent of surgically confirmed endometriosis was greater in patients who received the long-acting GnRH regimen for 3 months before IVF-ET. The groups did not differ significantly in terms of dose or duration of gonadotropin stimulation, number of oocytes retrieved, fertilization rate, or number of embryos transferred. Patients who received the long-acting GnRH regimen had significantly higher ongoing pregnancy rates (80% vs. 53.85%) and a trend toward higher implantation rates (42.68% vs. 30.38%). CONCLUSION(S): Prolonged use of GnRH agonist before IVF-ET in patients with endometriosis resulted in significantly higher ongoing pregnancy rates than did standard controlled ovarian hyperstimulation regimens. No deleterious effect on ovarian response was observed.     

Gonadotropin releasing hormone agonist therapy and its effect on bone mass

The effects on bone mass of a 6 month therapeutic cycle with a gonadotropin releasing hormone agonist (GnRHa) were studied in 22 patients, ten affected by pelvic endometriosis and 12 by uterine fibroids. All patients were subjected to preliminary full examinations to confirm their diagnosis (laparoscopy for the endometriosis group and precise ultrasound volume measurements for uterine fibroids group). Before the beginning of treatment, bone mineral density (BMD) was measured in each patient both on the distal third of the forearm, with single-photon absorptiometry, and on the lumbar spine (L1-L4), with dual photon absorptiometry. The gonadotropin releasing hormone agonist used was buserelin. In the first week of therapy 0.5 mg of the drug was administered subcutaneously thrice daily. In the following 25 weeks the same drug was given intranasally, at a dosage of 300 micrograms again three times a day. Bone mass measurements, both at the peripheral and at the axial site, were repeated at the end of the 26-week therapeutic cycle and then again 6 months later. At the 26th week, a significant decrease of BMD was observed at both sites. The loss was 1.5% (p less than 0.05) on the lumbar spine, and 2.1% (p less than 0.05) on the radius. No bone mass restoration took place in the following 6 months. On the contrary, a less significant but discernible trend towards a further bone loss was apparent in the BMD values measured 6 months after the end of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Current approaches to optimizing the treatment of endometriosis in adolescents

Endometriosis can occur in adolescents and this patient group presents particular challenges in terms of differential diagnosis, variable presentation and symptoms, and choice of treatment. Early diagnosis is essential in order to decrease pain and hopefully prevent disease progression and preserve future fertility. Endometriosis surgery is generally cytoreductive rather than curative, and postoperative medical therapy should be initiated regardless of disease stage. Menstrual suppressive therapy with the use of continuous combination estrogen/progestin is the main treatment for most adolescents with endometriosis. For those with a persistence of pain on this therapy Gonadotropin-releasing hormone (GnRH) agonists (with add-back therapy) can be effective in relieving symptoms. GnRH agonist therapy requires special consideration in adolescents due to possible adverse effects on bone mineralization--an important consideration in adolescents who are at a critical age for accrual of bone mineral density (BMD). However, potential problems of bone loss may be avoided with the use of 'add back' therapy. A recent clinical study found that most adolescents with endometriosis receiving a GnRH agonist plus add-back therapy with norethindrone acetate (NA) or estrogen plus NA had normal BMD at the hip. Add-back therapy appears to be a promising adjunct to GnRH agonist therapy for the prevention of bone loss and may allow a longer duration of therapy than with a GnRH agonist alone. BMD should continue to be carefully monitored after the initial 6-8 month period of therapy and then approximately every two years in adolescent patients (over age 16) receiving long-term GnRH agonist with add-back therapy.     

Evidence of similar increases in bone turnover during nafarelin and danazol use in women with endometriosis

Medical 'oophorectomy' by GnRH agonist or danazol is an effective treatment for endometriosis. Since increased bone loss is a potential risk of hypoestrogenism, we compared the effect of nafarelin and danazol treatment on bone metabolism. Twelve patients with laparoscopically confirmed endometriosis received nafarelin (400 micrograms day intranasally) and six patients danazol (600 mg day orally) for 6 months. Both treatments had already led to hypoestrogenism (E2 less than 21.6 pg/ml) after 3 months. They both were accompanied by an approximately 50% rise in 24-h urinary hydroxyproline output, suggesting accelerated bone resorption at 6 months; yet urinary calcium output did not change significantly. Serum osteocalcin rose by 80-120% and bone alkaline phosphatase activity by 34-40%, suggesting stimulated bone formation at the same time. No detectable changes ensued in cortical bone mineral content in the distal radius or in serum levels of calcium, calcitonin, parathyroid hormone, or aminoterminal propeptide of type III collagen. Three months after treatment, hydroxyproline output, serum osteocalcin and bone alkaline phosphatase were still elevated in women taking nafarelin, whereas only serum osteocalcin was elevated in women taking danazol. Our data thus suggest that bone turnover was increased during nafarelin and danazol therapy and that this effect was reversible.     

Protection of ovarian function and fertility using a combination of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist during cancer treatment in young females.

Cytotoxic treatment can cause early loss of ovarian function associated with loss of fertility in younger women. To investigate if co-treatment with a combination of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist may be useful in preserving ovarian function and fertility in younger women during chemotherapy, we prospectively observed nine young patients receiving different chemotherapies for various malignant diseases and other severe medical conditions who also received simultaneous GnRH agonist and GnRH antagonist. Mean age of the patients was 26.56 +/- 8.78 years, all were < or =35 years old. Eight (88.9%) patients regained normal basal hormonal profile within 3 - 6 months after the completion of chemotherapy. Median level of follicle-stimulating hormone, luteinizing hormone and estradiol was 6.3 +/- 8.8 U/l, 8.2 +/- 25.4 U/l and 118.0 +/- 130.8 pg/ml, respectively. Eight (88.9%) patients resumed spontaneous menses within 3 - 11 months following discontinuation of chemotherapy. Two (22.2%) patients conceived: one spontaneously, and the second following induction of ovulation by injection of gonadotropins. It seems that combined usage of GnRH agonist and GnRH antagonist during chemotherapy may be useful in preserving ovarian function and fertility in a group of young females receiving chemotherapy treatment.     

Peritoneal Vascular Density Assessment Using Narrow-Band Imaging and Vascular Analysis Software,and Cytokine Analysis in Women With and Without Endometriosis

The development and onset of endometriosis is associated with angiogenesis and angiogenic factors including cytokines. We analyzed intrapelvic conditions in women with endometriosis via vascular density assessment of grossly normal peritoneum and determination of cytokine levels in peritoneal fluid. Seventy-three patients underwent laparoscopic surgery because of gynecologic disease including endometriosis in our department using a narrow-band imaging system. Each patient was analyzed for peritoneal vascular density using commercially available vascular analysis software (SolemioENDO ProStudy; Olympus Corp, Tokyo, Japan). Each patient was also subjected to analysis of interleukin 6 (IL-6), IL-8, tumor necrosis factor-α, and vascular endothelial growth factor concentrations in peritoneal fluid. We defined 4 groups as follows: group 1, endometriosis: gonadotropin-releasing hormone (GnRH) agonist administration group (n = 27); group 2, endometriosis: GnRH agonist nonadministration group (n = 15); group 3, no endometriosis: GnRH agonist administration group (n = 18); and group 4, no endometriosis: GnRH agonist nonadministration group (n = 13). No significant differences in peritoneal vascular density between the 4 groups were found under conventional light; however, under narrow-band light, vascular density in the endometriosis groups (groups 1 and 2) was significantly higher. Cytokine analysis of the 4 groups determined that IL-6 and IL-8 concentrations were significantly higher compared with the no endometriosis groups (groups 3 and 4). Tumor necrosis factor-α and vascular endothelial growth factor concentrations were not significantly different between groups. In endometriosis, peritoneal vascular density was significantly higher as assessed using the narrow-band imaging system and SolemioENDO ProStudy, whereas GnRH agonist did not obviously decrease vascular density but IL-6 concentration was lower in the GnRH agonist administration group.