Medical Treatment Of Endometriosis Research Articles

Endometriosis: aetiology, pathogenesis and treatment.

Endometriosis, which may be defined as the presence and proliferation of endometrial tissue outside the uterine cavity, causes pain and infertility for millions of women worldwide. Studies suggest a prevalence of 0.5 to 5% in fertile and 25 to 40% in infertile women. The most widely accepted aetiological theory is that retrograde flow of menstrual fluid through the Fallopian tubes deposits viable endometrial tissue, which implants on the peritoneal surface. Increasingly, the aetiology of endometriosis is being studied at the immunological and genetic levels. The aim of treatment of endometriosis is to remove or diminish disease deposits. This may be attempted through medical or surgical means. It has long been recognised that endometriotic glands are hormonally sensitive. Medical therapies work by inducing a hypoestrogenic, anovulatory state to induce atrophy within the glandular tissue. Conception is generally not possible during medical therapy and has not been demonstrated to increase afterwards. Medical treatment of endometriosis should be discouraged when infertility is the primary problem. In this situation surgery or an assisted reproduction treatment such as in vitro fertilisation may be more appropriate. Medical treatment of pain caused by endometriosis is generally effective. There is little difference in efficacy between the different medications but their adverse effect profiles differ greatly. It appears that gonadotropin-releasing hormone agonists, particularly when used with add-back estrogen, may be more acceptable to women than other treatments. Laparoscopic surgical treatment of minimal and mild endometriosis has been demonstrated to increase fecundity. Surgical treatment has also been shown to decrease pain scores compared with expectant management. Ongoing and future research examining the aetiology of endometriosis at the immunological and genetic levels should usher in new treatments directed at the actual cause of the disease. More randomised trials examining the role of surgery, and comparing surgical and medical treatments, are also required and are necessary if we are to continue in our attempts to adopt an evidence-based approach to treatment.

An Evidence-Based Medicine Approach to the Treatment of Endometriosis-Associated Chronic Pelvic Pain: Placebo-Controlled Studies

Objective Use an evidence-based medicine (EBM) approach to evaluate the evidence regarding efficacy of treatment of endometriosis-associated chronic pelvic pain (CPP) in placebo-controlled randomized clinical trials (RCT) Design Review of six randomized, controlled trials (Canadian Task Force classification I). Setting University of Rochester School of Medicine and Dentistry. Patients Three hundred eighty-one women with endometriosis enrolled in placebo-controlled randomized clinical trials. Intervention A MEDLINE search of published medical articles from January 1976, to January 1998. Measurements and Main Results Six placebo-controlled randomized clinical trials were found that addressed the treatment of pelvic pain associated with endometriosis and met validity criteria; one was a study of surgical treatment, two of medical therapies, and three of combined surgical and medical treatments. They clearly show that laparoscopic surgery and medical treatment with medroxyprogesterone acetate, danazol, or nafarelin are more effective than placebo. Evidence for efficacy of leuprolide acetate is weaker. At 6 months, absolute decreases in pain scores are quite similar with surgical or medical treatment. Medical therapy after surgical treatment significantly reduced pain, but six months after it was stopped there was no difference between women treated and not treated postoperatively. Conclusions Although either surgical or medical treatment of endometriosis in women with CPP is clearly indicated, pain relief of 6 or more months' duration can be expected in only 40 to 70% of women with endometriosis-associated CPP.

Effect of hormonal agents on monocyte chemotactic protein-1 expression by endometrial epithelial cells of women with endometriosis

Objective: To assess whether hormonal agents used in the medical treatment of endometriosis, such as danazol and GnRH agonist, exert direct regulatory action on monocyte chemotactic protein-1 (MCP-1) expression by endometrial epithelial cells. Design: Primary cultures of epithelial cells isolated from human endometrium were exposed to different concentrations of cytokines and steroid hormone analogs. Expression of MCP-1 was analyzed at the levels of protein and messenger RNA. Setting: Gynecology clinic and laboratory of endocrinology of reproduction. Patient(s): Women presenting for infertility or pelvic pain in whom endometriosis was diagnosed by using laparoscopy. Intervention(s): Endometrial tissue biopsy performed at laparoscopy. Main Outcome Measure(s): Secretion of MCP-1 protein was measured by using enzyme-linked immunosorbent assay, and mRNA steady-state levels were measured by performing Northern blot analysis. Result(s): Buserelin acetate, a GnRH agonist (0.1–10 ng/mL), had no significant effect on MCP-1 expression, whereas danazol (10 −7–10 −5 M), a testosterone analog, and dexamethasone, an anti-inflammatory glucocorticoid hormone (10 −12–10 −6M), showed a direct and a dose-dependent inhibitory effect on MCP-1 expression. This effect occurred at the level of protein and mRNA. Conclusion(s): The findings of the study may affect understanding of the mechanisms by which hormonal treatments act on endometriosis and influence its clinical manifestations.

Aetiology and medical treatment of endometriosis

Aetiology and medical treatment of endometriosis

Medical treatment of endometriosis.

Medical treatment of endometriosis.

Gonadotrophin-releasing hormone analogues for pain associated with endometriosis.

Endometriosis is a common gynaecological condition that frequently presents with the symptom of pain. The precise pathogenesis (mode of development) of endometriosis is unclear but it is evident that endometriosis arises by the dissemination of endometrium to ectopic sites and the subsequent establishment of deposits of ectopic endometrium. The observation that endometriosis is rarely seen in the hypo-oestrogenic (low levels of oestrogen) post-menopausal woman led to the concept of medical treatment by induction of a pseudo-menopause using Gonadotrophin Releasing Hormone Analogues (GnRHas). When administered in a non-pulsatile manner (the pituitary is normally stimulated by pulses of natural GnRH and all analogues act on the pituitary at a constant level) their use results in down regulation (switching off) of the pituitary and a hypogonadotrophic hypogonadal state (low levels of female hormones due to non stimulation of the ovary). To determine the effectiveness of Gonadotrophin Releasing Hormone analogues (GnRHas) in the treatment of the painful symptoms of endometriosis by comparing them with no treatment, placebo, other recognised medical treatments, and surgical interventions. The search strategy of the Menstrual Disorders and Subfertility review group (please see Review Group details) was used to identify all randomised trials of the use of GnRHas for the treatment of the painful symptoms of endometriosis. Trials were included if they were randomised, and considered the effectiveness of GnRHas in the treatment of the painful symptoms of endometriosis. Twenty-six studies had data appropriate for inclusion in the review. The largest group (15 studies) compared GnRHas with danazol. There are 5 studies comparing GnRHas with GnRHas plus add-back therapy, 3 comparing GnRHa with GnRHa in a different form or dose, one compares them with gestrinone, one with the combined oral contraceptive pill, and one with placebo. Data was extracted independently by two reviewers. The authors of 11 studies have been contacted to clarify missing or unclear data. Only 4 have replied to date. Data on relief of pain, change in revised American Fertility Society (rAFS) scores, and side effects was collected. No difference was found between GnRHas and any of the other active comparators with respect to pain relief or reduction in endometriotic deposits. The side effect profiles of the different treatments were different, with danazol and gestrinone having more androgenic side effects, while GnRHas tend to produce more hypo-oestrogenic symptoms. There is little or no difference in the effectiveness of GnRHas in comparison with other medical treatments for endometriosis. GnRHas do appear to be an effective treatment. Differences that do exist relate to side effect profiles. Side effects of GnRHas can be ameliorated by the addition of addback therapy.

WITHDRAWN: Gonadotrophin-releasing hormone analogues for pain associated with endometriosis.

Endometriosis is a common gynaecological condition that frequently presents with the symptom of pain. The precise pathogenesis (mode of development) of endometriosis is unclear but it is evident that endometriosis arises by the dissemination of endometrium to ectopic sites and the subsequent establishment of deposits of ectopic endometrium. The observation that endometriosis is rarely seen in the hypo-oestrogenic (low levels of oestrogen) post-menopausal woman led to the concept of medical treatment by induction of a pseudo-menopause using Gonadotrophin Releasing Hormone Analogues (GnRHas). When administered in a non-pulsatile manner (the pituitary is normally stimulated by pulses of natural GnRH and all analogues act on the pituitary at a constant level) their use results in down regulation (switching off) of the pituitary and a hypogonadotrophic hypogonadal state (low levels of female hormones due to non stimulation of the ovary). To determine the effectiveness of Gonadotrophin Releasing Hormone analogues (GnRHas) in the treatment of the painful symptoms of endometriosis by comparing them with no treatment, placebo, other recognised medical treatments, and surgical interventions. The search strategy of the Menstrual Disorders and Subfertility review group (please see Review Group details) was used to identify all randomised trials of the use of GnRHas for the treatment of the painful symptoms of endometriosis. Trials were included if they were randomised, and considered the effectiveness of GnRHas in the treatment of the painful symptoms of endometriosis. Twenty-six studies had data appropriate for inclusion in the review. The largest group (15 studies) compared GnRHas with danazol. There are five studies comparing GnRHas with GnRHas plus add-back therapy, three comparing GnRHa with GnRHa in a different form or dose, one compares them with gestrinone, one with the combined oral contraceptive pill, and one with placebo. Data was extracted independently by two reviewers. The authors of eleven studies have been contacted to clarify missing or unclear data. Only four have replied to date. Data on relief of pain, change in revised American Fertility Society (rAFS) scores, and side effects was collected. No difference was found between GnRHas and any of the other active comparators with respect to pain relief or reduction in endometriotic deposits. The side effect profiles of the different treatments were different, with danazol and gestrinone having more androgenic side effects, while GnRHas tend to produce more hypo-oestrogenic symptoms. There is little or no difference in the effectiveness of GnRHas in comparison with other medical treatments for endometriosis. GnRHas do appear to be an effective treatment. Differences that do exist relate to side effect profiles. Side effects of GnRHas can be ameliorated by the addition of addback therapy.

Individualized therapy of sterility caused by endometriosis

In the case of infertility the macroscopically and/or histologically confirmed diagnosis of endometriosis alone is not an indication for surgical or medical treatment of endometriosis. Treatment is necessary only when additional clinical symptoms of pain caused by the disease, active proliferative implants, severe mechanical disturbances of Fallopian tubes and ovaries, or deep infiltration endometriosis is judged as a relevant cause of sterility. The presence of implants alone – especially in mild or minimal stages – is probably an accidental finding with no correlation to the infertility problems. The therapeutic options are surgical – mainly endoscopic surgery – medical or a combination of both. Regression of the implants and shrinkage of the cysts can be achieved with medically induced ovarian suppression. Clinical trials have demonstrated that high doses of progestins, Danazol and GnRH agonists are effective. Because low differentiated types of endometriosis and deep infiltration nodules can only be influenced with permanent estrogen deprivation, an endoscopic surgical procedure– resection, coagulation or vaporisation of endometriotic tissue, plus resection of adhesions and fibrosis – is the main therapeutic principle. Because microscopic implants and deep infiltration foci surrounded by fibrosis can not be treated sufficiently with endoscopic surgery alone, an individual therapeutic strategy must be adopted in each case of endometriosis and infertility. Taking in account the age of the patient, the duration of infertility, and other factors we have to consider medical and/or surgical treatment of endometriosis.

Alternative Medical Treatment for Endometriosis

Although a limited number of drugs make up the mainstay of treatment of endometriosis, many alternative medications have been used in an attempt to improve efficacy. Some have been rigorously evaluated and are of proven benefit, while others show promise in preliminary trials or in animal models. Proper methods of evaluating medical therapy and outcomes are essential. This chapter provides a review of new medical therapies for the treatment of endometriosis and their evaluation.

Evaluation of gestrinone after surgery in treatment of endometriosis.

The clinical and histological efficacy of gestrinone in the treatment of endometriosis was evaluated. A prospective study was performed with longitudinal follow-up of 4 years duration (minimum) for each patient. Twenty-five cases of endometriosis were treated with gestrinone (as a drug of choice or associated with other local surgical treatment) during 6 months. The total or partial response to pain was induced with treatment in 19 of the 20 cases (95%), and posttreatment pregnancies were induced in 3 of the 9 cases of infertility (33.3%). The global clinical efficacy was as follows: none (n = 5, 20%), poor (n = 2, 8%), moderate (n = 2, 8%), good (n = 3, 12%) and excellent (n = 13, 52%). The pretreatment American Fertility Society score was 23.1 +/- 3.8 points (2-58) and that after treatment (re-examination) 7.8 +/- 3.7 points (0-52), p < 0.01. Global histological efficacy (n = 17) results were as follows: none (23.6%), poor (0%), moderate (5.8%), good (35.3%) and excellent (35.3%). Gestrinone is presented as a drug with an efficacy comparable to other pharmacological agents currently available in the medical treatment of endometriosis. Adequate posology and acceptable effectiveness were also observed.

The expression of human chorionic gonadotropin/human luteinizing hormone receptors in ectopic human endometrial implants.

Our laboratory previously demonstrated that normal human endometrium contains hCG/human LH receptors. Since ectopic endometrial implants in endometriosis arise directly at least in part from uterine endometrium, we investigated whether the implants continue the expression of these receptors. The presence of hCG/LH receptor mRNA and/or immunoreactive receptor protein in ectopic endometrial implants on pelvic peritoneum, uterine endometrium, and unaffected or normal peritoneum from patients with (n = 12) and without (n = 14) clinically apparent endometriosis was examined by in situ hybridization and immunocytochemistry analyses. The results showed that the peritoneal biopsies with visible or microscopic endometrial implants contain receptor mRNA and receptor protein. The glands contain more receptor mRNA and receptor protein than stromal cells in implants similar to uterine endometrium from patients with or without endometriosis. However, there is no consistent difference in the expression of receptors in implants compared to uterine endometria from patients with or without endometriosis. Contrary to ectopic endometrial implants, unaffected or normal peritoneum contain neither receptor mRNA nor receptor protein. In summary, we conclude that ectopic endometrial implants contain hCG/LH receptor mRNA and receptor protein, which suggests new possibilities in the medical treatment of endometriosis.

Goserelin (Zoladex ) depot in the treatment of endometriosis

To evaluate the safety and efficacy of Goserelin (Zoladex depot; ICI Pharmaceuticals, Macclesfield, Cheshire, United Kingdom) in the treatment of endometriosis. Open study. Eleven centers in Germany and 1 center in Austria. One hundred forty-six patients with pelvic endometriosis. Goserelin (Zoladex depot) therapy, one depot (3.6 mg) subcutaneously every 4 weeks for 6 months. Total subjective score and total pelvic symptom score showed a reduction by 86% and 93%, respectively, at the end of the treatment and did not exceed one fifth of the pretreatment value throughout the follow-up period of 48 weeks. One hundred seven women underwent a second laparoscopy at the end of the therapy for determination of objective efficacy: 54% of the patients showed a reduction of implants and adhesions by at least 50% or more, and 31.5% had a complete resolution of visible deposits. The mean reduction of implants and adhesions was 50%, and the mean reduction of implants 72%. Twenty of 64 (31.3%) previously infertile patients successfully conceived within 12 months after discontinuation of the therapy. Goserelin led to a down regulation of the pituitary ovarian axis and as a pharmacological effect of this hypoestrogenism most patients had hot flushes and vaginal dryness. Zoladex depot therapy proved to be safe and effective in the medical treatment of endometriosis.

Medical treatment of endometriosis: a comparison of the suppressive effects of danazol and nafarelin on reproductive hormones

Patients with endometriosis were studied to investigate hormonal suppression by the gonadotropin-releasing hormone against nafarelin acetate compared with danazol. We hypothesized that the pattern, time course, and degree of gonadotropin and ovarian suppression would be different. The study included 16 patients who were randomized into one of three 6-month treatment protocols. Patients were recruited from a university hospital setting. Eligible candidates were 18 to 45 years of age, with regular menses and documented pelvic endometriosis. Six-month treatment protocols included nafarelin 800 or 400 micrograms/d, or danazol 800 mg/d. Serum estradiol (E2), progesterone (P), luteinizing hormone (LH), and follicle-stimulating hormone were determined before treatment and then monthly. Thirteen patients consented to a 12-hour hospital admission during the 5th and 6th month of treatment to determine LH pulse frequency and amplitude. Estradiol and P were suppressed in all groups, but E2 significantly more by nafarelin than danazol (P less than or equal to 0.01). Nafarelin, 800 micrograms, significantly depressed LH pulse amplitude compared with danazol (P less than or equal to 0.05). Two patients in the nafarelin group had the administration of their medication observed, and both demonstrated single, high-amplitude pulses immediately after administration. Nafarelin is a more potent LH and E2 suppressor than danazol, and the agonist effect of nafarelin may continue to provoke transient gonadotropin responses despite long-term therapeutic suppression.

Medical treatment of endometriosis in infertile patients.

MEDICAL treatment of endometriosis is suitable as primary therapy in young patients with minimal disease confirmed by laparoscopy. Medical treatment consists of simple analgesia, treatment with combined oestrogen/progestogen preparations, or progestogen therapy alone. Danazol therapy is now widely used in a dose of about 400 mgs daily for a minimum of six months.

463 Medical treatment of endometriosis: Double blind randomized study of a progestin (gestrinone) versus danazol

463 Medical treatment of endometriosis: Double blind randomized study of a progestin (gestrinone) versus danazol

Medical treatment of endometriosis

Medical treatment of endometriosis