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Study Question: What is the current management of women with ovarian endometriomas undergoing assisted reproductive treatment (ART) in the UK?, Summary Answer: It appears that the majority of gynaecologists in the UK offer surgery (mostly cystectomy) for endometriomas prior to ART, regardless of the presence of symptoms., What Is Known Already: The ideal management of endometriomas in women undergoing ART remains controversial and presents a dilemma to reproductive specialists., Study Design, Size and Duration: This was a national cross-sectional survey. A total of 388 gynaecologists completed the questionnaire., Participants, Settings and Methods: All clinicians fully registered with the Royal College of Obstetricians and Gynaecologists were contacted. An 11-item survey was administered electronically using Survey Monkey software. Quantitative data were analysed using descriptive and comparative statistics., Main Results and the Role of Chance: The majority of responders were consultants (65%), 25% practiced ART and 65% performed laparoscopic surgery. Overall, 95% of responders would offer surgery for endometriomas in women undergoing ART, either on the basis of the size (>3-5 cm) of the endometrioma (52%), the presence of symptoms (16%), the presence of multiple/bilateral endometriomas (2%), regardless of the size and symptoms (19%) or only to women undergoing IVF (6%). The remaining 5% of responders would not offer surgery before ART. Excision was the most common surgical modality (68%), followed by ablation (25%). Laparoscopic surgeons were almost twice as likely to 'offer surgery to all patients with endometriomas prior to ART' compared with clinicians performing laparotomy (22 versus 12%, P < 0.001)., Limitations, Reasons for Caution: Our overall response rate, with answers to the questionnaire, was low (15%). However, the response rate amongst reproductive specialists was estimated at 60%. It is possible that there might have been an element of bias towards over-representation of responders who are more concerned about 'normalization' of the pelvic anatomy. Furthermore, our survey relied on self-reporting of practice and it is possible that being presented with a list of 'ideal' options may have resulted in respondent bias., Wider Implications of the Findings: Despite the available evidence that surgery for endometriomas does not improve the outcome of ART and may damage ovarian reserve, it seems that the majority of gynaecologists in the UK offer ovarian cystectomy to their patients.

There have been few appropriately conducted trials to evaluate the effectiveness of laser destruction of endometriosis in relieving pain symptoms, yet the techniques are increasingly being used. Laser destruction has been shown to be more effective than the placebo effect of laparoscopy alone in one trial, at least at 6-month follow-up. Longer-term studies suggest increasing recurrence of symptoms with time [23% at 12 months in one study, and 44% by a mean of 19.7 months (5-60) follow-up]. These recurrence rates are similar to those seen following 6 months medical treatment. It is unknown whether laparoscopic uterosacral nerve ablation (LUNA) in addition to destruction of lesions will produce better results, and appropriate trials are needed in several areas to determine the role of laser therapy.

A 43 year old woman who underwent a hysterectomy and bilateral salpingo-oophorectomy for secondary dysmenorrhoea was found to have bilateral ovarian endometriosis. During the following four years she developed a series of tumour-like vaginal masses, which were locally excised, a pelvic mass causing acute large bowel obstruction, which necessitated an emergency Hartmann's procedure, and a further pelvic mass causing hydronephrosis with a non-functioning kidney. Pathological examination of all the resected specimens showed endometriosis with abundant stromal and glandular elements. Immunoreactivity for p53 protein was detected within endometriotic foci from the initial oophorectomy as well as the latest resection specimens. Immunostaining for p53 may help identify potentially aggressive cases of endometriosis for proactive treatment.

Objective: To determine the duration of time to the recurrence of pain attributable to endometriosis after the discontinuation of treatment with danazol or a GnRH agonist (GnRH-a) in patients who have had a satisfactory response to the treatment., Design: Retrospective study., Setting: Nine academic medical centers in three countries., Patient(s): Three hundred twenty-seven women with diagnosed and staged endometriosis who were treated with at least 6 months of danazol or a GnRH-a and who experienced significant pain relief with therapy., Intervention(s): None., Main Outcome Measure(s): Duration of pain relief after completion of treatment as determined by a patient-initiated report of pain recurrence or increase in pain severity requiring intervention., Result(s): The median time to the recurrence of pain was 6.1 months for patients treated with danazol and 5.2 months for patients treated with a GnRH-a., Conclusion(s): Although there was a lack of uniformity in treatment effects across sites, the analyses have taken into account major covariant effects. The time to the recurrence of endometriosis-associated pain after danazol treatment was slightly longer than that after GnRH-a treatment.

Objective: To assess whether tibolone can prevent the bone loss and symptomatic side effects normally associated with GnRH agonist (GnRH-a) use and whether tibolone modifies the effect of GnRH-a on endometriosis., Design: Prospective, double-blind, placebo-controlled, group comparative study., Setting: Gynecological research unit in a London teaching hospital., Patients: Twenty-nine patients with endometriosis and two with fibroids., Interventions: Six months of treatment with 3.75 mg/mo IM triptorelin combined with daily tablets of either placebo or 2.5 mg tibolone., Main Outcome Measures: Daily symptom diary for hot flushes and bleeding episodes, laparoscopic scoring of endometriosis, endocrine and biochemical changes, and bone mineral density scans., Results: Lumbar spine bone mineral density decreased significantly from baseline in the placebo group (-5.1%) but not in the tibolone group (-1.1%). The frequency of hot flushes and sweating episodes was reduced significantly by tibolone. There was no difference between the two treatment groups with regard to the endometriosis scores., Conclusions: The addition of tibolone to GnRH-a treatment reduces the bone loss and vasomotor symptoms that normally occur with GnRH-a, thus making long-term treatment with GnRH-a safer and more acceptable. It does not negate the therapeutic effect of GnRH-a on endometriosis.

Objective: To investigate whether there are psychological differences between women with symptomatic as opposed to asymptomatic mild endometriosis., Design: Forty-nine women with minimal or mild endometriosis completed the Beck Depression Inventory, the Speilberger State-Trait analysis, and the Golombok Rust Inventory of Sexual Satisfaction. Women admitted for sterilization acted as normal controls and women complaining of pelvic pain with no organic pathology were studied also., Setting: Tertiary referral centers for endometriosis., Main Outcome Measures: Women with pelvic pain symptoms, whether they had mild endometriosis or a normal pelvis, had similar scores for the Beck Depression Inventory. These scores were significantly higher than those of women with asymptomatic disease and normal women admitted for sterilization., Conclusions: Women with mild endometriosis should not be included as a control group when studies on pelvic pain are planned.

The administration of gonadotrophin-releasing hormone (GnRH) analogs to premenopausal women causes hypoestrogenism and bone loss, but the effects on cancellous microstructure have not been determined. In this study we have assessed bone structure in transiliac biopsies obtained from women before and after treatment for endometriosis with GnRH analogs. Twenty-one premenopausal women were studied, paired biopsies being obtained in 13; five women received both GnRH analogs and Org OD 14 (Tibolone, Livial). Comparison of pre- and post-treatment biopsies in women treated only with GnRH analogs showed a reduction in indices related to connectivity (node-to-terminus ratio, node-to-loop strut length, p < 0.02) and increase in inversely related indices (terminus-to-terminus and node-to-terminus strut length, p < 0.03). No significant changes were seen in any of the structural indices in women receiving both GnRH and Org OD 14 therapy. Activation frequency and bone formation rate at tissue level increased in women treated with GnRH agonists alone, although this change was not statistically significant. Our results suggest that bone loss induced by GnRH analogs may be associated with adverse effects on cancellous microstructure which are unlikely to be reversed following cessation of therapy. Concurrent treatment with Org OD 14 appears to prevent these changes.

Objective: To compare dydrogesterone with placebos in the treatment of minimal to mild endometriosis., Design: Prospective, double-blind, randomized study., Setting: Three Obstetrics and Gynaecology Departments in the United Kingdom., Patients: Sixty-two premenopausal women with complaints of pain (n = 12) and infertility with or without pain (n = 50) with minimal to mild endometriosis diagnosed at laparoscopy. Thirty-nine women had a laparoscopy after treatment and 56 women were followed up 12 months after treatment., Interventions: Two high doses of dydrogesterone (either 40 or 60 mg) or a placebo, which was given for 12 days, beginning 2 days after the LH surge for a treatment period of 6 months., Main Outcome Measures: Change between before and after treatment endometriosis scores, pregnancy rates (PRs), and pain., Results: Treatment with dydrogesterone did not alter the natural history of endometriosis or PRs when compared with placebo. Pain was reduced significantly during treatment with 60 mg dydrogesterone and this improvement still was evident at 12-month follow-up., Conclusion: Luteal phase dydrogesterone reduces pain associated with endometriosis.

Medical treatments of endometriosis rely upon the hormonal dependence of endometriotic implants for further growth and extension. The cyclic nature of the symptoms means they may be helped by agents that suppress menstruation both from the endometrium and within the endometriotic lesions. In comparative trials, progestogens have been shown to achieve a similar reduction in symptoms and to induce regression of deposits, but to date there are few long term follow-up data concerning gestrinone. The recent introduction of gonadotrophin-releasing hormone (GnRH) agonists, highly effective at inducing a state of sustained hypoestrogenaemia, is providing another group of compounds suitable for use in the treatment of endometriosis. In comparative trials with danazol, a number of these compounds administered in novel formulations (as intranasal sprays or sustained release depots), have been shown to significantly reduce symptoms both during treatment and for 6 to 12 months post-treatment when compared with baseline. In addition, there are highly significant reductions in revised American Fertility Society (R-AFS) total and implant alone scores following 6 months' therapy. Whilst these changes are not significantly different from danazol, there are fewer patients discontinuing treatment with GnRH agonists than with danazol. The low circulating levels of 17 beta-estradiol seen during GnRH analogue therapy result in alterations of bone mineral metabolism similar to those observed at the menopause. Continued prolonged use would thus result in reduced bone mass and this factor will limit the duration of use of GnRH agonists long term until appropriate combination ('add-back') regimens to protect bone are developed.

To assess the effect of GnRH pretreatment prior to IVF-ET on fertilisation and pregnancy rates in patients with endometriosis compared with tubal infertility, a retrospective analysis of 228 cycles of tubal infertility cases (Group 1) and 92 cycles of endometriosis has been performed. Patients with endometriosis were classified by the revised AFS scoring system to two groups: 37 cycles of minimal and mild endometriosis (Group 2) and 55 cycles of moderate and severe endometriosis (Group 3). The GnRH analogue buserelin was used for pituitary desensitisation in all IVF cycles. Endometriosis patients have a minimum of 6 weeks GnRH treatment prior to superovulation therapy. Although the fertilisation rate per oocyte (51%) was significantly lower in Group 3 (P < 0.001), the percentage of cycles in which fertilisation occurred (86%, 78%, 78%) and the pregnancy rates per embryo transfer (17.7%, 17.2%, 18.6%) for Groups 1, 2 and 3, respectively, were not significantly different. Pretreatment with GnRH analogues allows patients with endometriosis to achieve similar success rates to patients with tubal infertility alone.

Objective: To study some of the metabolic effects of oral gestrinone on plasma lipoprotein risk markers for cardiovascular disease and on bone density, a risk marker for osteoporosis., Design: Randomized double-blind study., Setting: All patients were referred to Gynaecology Clinic of Royal Free Hospital Medical School., Patients: Twenty premenopausal women with laparoscopically confirmed endometriosis., Interventions: Subjects were randomized in a double-blind fashion to receive either 1.25 mg or 2.5 mg gestrinone two times per week for 6 months., Main Outcome Measure: Laparoscopy was performed before treatment, and clinical responses were determined by second laparoscopy after 6 months. Plasma lipid and bone density measurements during and after therapy were compared with baseline., Result: Median total endometriosis scores decreased from 7.5 to 1.0 in the 1.25-mg group and from 7.0 to 0 in the 2.5-mg group. There were no significant between-group differences in endometriosis scores. At both doses, bone density in the spine and the proximal femur was conserved, but plasma concentrations of low-density lipoproteins rose by 13% and those of high-density lipoproteins fell by 40%., Conclusions: Reducing the dose of gestrinone to 1.25 mg appeared to maintain the therapeutic effectiveness of this treatment but was still associated with potentially unfavorable effects on lipids and lipoproteins.

Objective: To determine the long-term recurrence rate of endometriosis after treatment with gonadotropin-releasing hormone analogues (GnRH-a)., Design: A historical prospective study., Setting: Royal Free Hospital, London, a tertiary referral center for the treatment of endometriosis., Patients: One hundred thirty patients with endometriosis had treatment with GnRH-a buserelin acetate, goserelin, and nafarelin acetate between the years 1985 and 1987. Patients no longer being followed in the gynecology clinic were sent a questionnaire to determine their state of health. Information was also requested from the patient's general practitioner., Main Outcome Measures: The cumulative recurrence rate for the fifth year after treatment ended was 53.4%., Results: Patients with a higher disease stage at the outset were more likely to experience recurrence and experience it earlier than patients with minimal disease. Fifth-year recurrence rates were 36.9% for minimal disease and 74.4% for severe disease. The change in endometriosis stage classification scores at second-look laparoscopy for those patients whose disease recurred after treatment was not significantly different from those whose disease did not recur during the study period., Conclusions: Patients with endometriosis treated with GnRH-a are highly likely to suffer a recurrence of their disease, particularly if their disease is severe at the outset.

Objective: To test the effect of peritoneal fluid from infertile women with minimal or mild endometriosis on sperm movement characteristics in comparison with fertile and infertile women with no endometriosis., Design: A prospective observer-blind trial., Setting: Academic infertility department., Subjects: 57 women undergoing diagnostic laparoscopy or laparoscopic sterilisation., Main Outcome Measures: Changes in sperm movement characteristics in semen samples provided during routine infertility investigation or from sperm donors. Computer assisted semen analysis (CASA) performed using a Celltrack-S system., Results: Significant reductions in linearity (P < 0.05), amplitude of lateral head displacement (P < 0.01), straight line velocity (P < 0.01), and curvilinear velocity (P < 0.01) (but not percentage motility) were observed., Conclusions: Peritoneal fluid from women with minimal or mild endometriosis adversely effects sperm movement characteristics in comparison to fertile women.

Laparoscopy was performed on a consecutive series of 174 women complaining of infertility. Forty of these women were the partners of oligospermic or azoospermic men. There was no difference in the prevalence of endometriosis between those women whose partners were fertile and those whose partners were infertile. Women with azoospermic partners had a prevalence of endometriosis of 20.7%, and this is likely to reflect the true prevalence of endometriosis in a group of randomly selected normal women.

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.

Several modalities can be employed in managing the patient with endometriosis, but the ultimate selection is determined by evaluating a number of criteria including age, extent of disease, severity of symptoms and pain. Scoring systems used in many clinical trials are based on the Revised American Fertility Society system but have their limitations. There is a possibility of using such innovations as receptor studies to individualize therapies in the future. Future research must also include dose-response studies, not only for the new GnRH agonists but also for danazol. These are essential to investigate efficacy. It may be that the different subtypes of endometriosis require quite dissimilar approaches to achieve the therapeutic goal. Despite advances in therapy for endometriosis, the disease remains largely a mystery in terms of its aetiology and pathogenesis, but we are drawing closer to refining our diagnostic and scoring techniques and individualizing our approach to therapy.

Whole body lean and fat mass measurements by dual energy x-ray absorptiometry were performed in 14 premenopausal women undergoing danazol treatment for endometriosis. After 6 months, there was a significant increase in lean tissue mass. Body fat decreased but this was significantly less in the android (upper body segment) region than in the gynoid (lower body segment) region. Danazol thus has both anabolic and androgenic effects on body composition. Dual energy x-ray absorptiometry provides a new, noninvasive, and rapid means of studying body composition.

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.

As part of a large, multicenter trial, 82 patients with endometriosis were randomized to 6 months of treatment with either nafarelin or danazol. Among 73 patients who had subjective symptoms (dysmenorrhea, dyspareunia, or pelvic pain) at baseline, 94% of patients treated with nafarelin and 91% of those treated with danazol had improvement. Resolution of physical findings also was observed in similar percentages of patients in each treatment group. Long-term studies are needed to determine whether these two agents are associated with different cure rates or times to recurrence of disease.

In summary then, Zoladex depot (Goserelin 3.6 mg) administered monthly for a period of six months proved highly efficacious in achieving endocrine parameters of pituitary desensitization and hypo-oestrogenism. Initial studies treating symptomatic patients with endometriosis shows satisfactory relief of symptoms and significant impact on the disease process as shown by resolution or reduction in number and size of disease deposits. The depot can be given as a subcutaneous injection without the need of local anaesthesia and its duration of action is 28 days. Zoladex depot should offer a suitable, acceptable form of treatment for patients with endometriosis.

Thirteen premenopausal women who each received 400 micrograms three times daily of intranasal buserelin for 6 months as treatment for endometriosis participated in this study. Cortical bone mineral content (BMC) in the mid-shaft of the right femur measured by dual photon densitometry, and trabecular bone density (TBD) in the lumbar vertebrae (L2-4) measured by quantitative computed tomography, were evaluated prior to, at the end of 6 months' buserelin treatment and after 6 months off treatment. Significant hypo-oestrogenism (P less than 0.001) was sustained during the period on treatment. The significant reduction in the mean lumbar vertebral TBD of 5.9% (P less than 0.02) observed at the end of treatment with buserelin was regained within 6 months following resumption of ovarian activity. There was a marginally significant (P = 0.07) reduction of only 0.9% in the mean femoral cortical BMC at the end of treatment. Six months after the end of treatment cortical BMC values were not significantly different from the pretreatment values. There was no significant correlation between the degree of hypo-oestrogenism and the corresponding change in vertebral TBD, (r = 0.20; P less than 0.10).

In addition to surgery, several hormonal treatments are available for endometriosis. Although efficacious, drug treatment is limited by side effects. Recent work with LHRH analogues as a potential treatment for endometriosis has shown promising results.

The induction of a state of hypo-oestrogenism has been found to be effective in the treatment of endometriosis. Continued administration of agonistic analogues of luteinizing hormone-releasing hormone (LHRH) results in the normal menstruating female developing normogonadotrophic-amenorrhoea with reduced circulating levels of oestradiol-17B, often within the menopausal range. Uncontrolled studies reported the efficacy of LHRH analogues in patients with mild, moderate and even severe endometriosis (American Fertility Society classification) following 6 months therapy. A number of large multi-centre randomized open or double blind trials comparing various LHRH analogues against danazol are currently underway. Published results available to date indicate that LHRH analogues and danazol are equally effective at reducing the symptoms of endometriosis and inducing complete or partial resolution of endometriotic deposits. Side-effects are, however, more severe with danazol therapy. The side-effects experienced with LHRH analogues are those expected from an induced state of hypo-oestrogenism--hot flushes, dry vagina, headaches, superficial dyspareunia--but are well tolerated by patients. The alterations observed in bone and calcium metabolism are comparable to those in the menopause--increased Ca++ loss and reversible loss of trabecular bone density have been reported. These effects may limit the duration and/or frequency of LHRH analogue treatment regimens. The valuable role of LHRH analogues in the treatment of endometriosis has been established and, as newer formulations become available, they are likely to play an increasingly important part in patient management.

We know that there is a wide range of clinical applications for GnRH analogues in the field of benign gynaecological disorders. As we understand more of the physiology and mechanism of these GnRH agonists, and there appear more varied and perhaps efficient delivery systems, and antagonists become available, it may be possible to develop a graded approach in suppression of the hypothalamic pituitary axis. The true potential of these agents is then yet to be fully realized. There can be no doubt they are going to influence practice dramatically over the next decade. The potency of these agents, perhaps specifically their effects of oestrogen deficiency and calcium bone metabolism, suggests that limitation of duration of use and timing of recurrent administration to individuals is likely to be necessary.

The levels of CA 125 in the serum of 54 patients with endometriosis were measured before, during and after treatment with Danazol or LHRH analogues. Patients with minimal and mild endometriosis had mean pre-treatment values significantly higher than control subjects in the luteal phase of the cycle or postmenopausal women (p less than 0.05), but levels were within the overall control range. In contrast, 78.6% of patients with moderate or severe endometriosis had levels in excess of 30 mu/ml and the mean values for these groups were significantly elevated (p less than 0.005). Levels of CA 125 fell, to those found in normal controls, during treatment, but rose again following cessation of treatment. Six of 12 subjects whose follow-up values of CA 125 exceeded 30 U/ml had a proven recurrence of endometriosis, whilst only 2 of 31 patients with values less than 30 U/ml had laparoscopically proven recurrence.

Plasma lipid risk markers for coronary heart disease (CHD) are influenced by sex steroid concentrations. Therapies that alter sex hormone levels have the potential to affect CHD risk. Zoladex had no effect on plasma lipids, but increased high density lipoprotein (HDL) subfraction 3, a lipoprotein of uncertain clinical significance. Danazol increased low density lipoprotein and decreased HDL concentrations to give a lipid profile associated with increased risk of CHD.

Buserelin [D-Ser(TBU)6-des Gly NH2(10) LHRH ethylamide], an LHRH agonist, was administered intranasally at two dose levels, 200 micrograms t.d.s or 300 micrograms t.d.s., to 20 women with proven endometriosis, many with recurrent disease. Both dose schedules achieved significant suppression of circulating 17 beta-oestradiol levels often to within the postmenopausal range, the larger dose inducing significantly greater suppression (P less than 0.05). Serum FSH values were suppressed below baseline but serum LH remained at pretreatment levels or above, whilst on treatment. Complete resolution of endometriotic deposits was achieved in 68% of cases following 6 months treatment with dramatic and long-standing relief of symptoms with no apparent dose difference. In all other subjects there was significant reduction in the extent of endometriotic deposits and improvement in American Fertility Society classification of disease stage. The most commonly occurring side effect was hot flushes; their intensity and frequency related to the degree of suppression of serum oestradiol and the dose of Buserelin administered.

The skeletal effects of two therapies for endometriosis that produce hypo-oestrogenism in 23 premenopausal women have been studied. Eleven women received goserelin 3.6 mg monthly by subcutaneous implant and 12 women received danazol 600 mg daily, orally, both for 6 months. Goserelin causes a small decline in spinal bone density, but a greater loss of density in the proximal femur. Preliminary results show no evidence that bone loss is reversible after stopping therapy. Danazol treatment is not associated with loss of bone. Prolonged or repeated courses of treatment with goserelin alone could lead to a clinically significant adverse effect on the skeleton.

An agonist analogue of luteinising hormone releasing hormone (buserelin) was successfully used to treat women with endometriosis. A dose of 200 micrograms administered intranasally thrice daily was found to be effective in five patients, in whom the endometriotic lesions resolved after six months' treatment. Failure occurred in a sixth patient, who received only 400 micrograms once daily. Anovulation was induced in all subjects together with suppression of menstruation after the first month of treatment. Symptoms of abdominal pain, dysmenorrhoea, and dyspareunia were relieved during treatment, and one previously infertile patient conceived within two months of stopping treatment. No side effects were reported with this dosage, and the results suggest a new form of treatment for patients with endometriosis.