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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.
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PMID:LHRH analogues in the treatment of endometriosis--comparative results with other treatments. 306 68

A 20-year-old woman presented with a 3-year history of intermittent focal headaches and a generalized seizure. Computerized tomography demonstrated a hypodense ring-enhancing cystic right parietal lobe lesion. At operation, a chocolate-colored cyst was excised which on histological examination proved to be endometriosis.
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PMID:Cerebral endometriosis. Case report. 355 27

21 women with endometriosis were treated with Danazol, a derivative of 17-alpha-aethinyltestosteron in an open study over a period of 6 months. 20 women had previously undergone an operation because of the spread of endometriosis and its symptoms, in no case was it possible to remove the source of the endometriosis entirely. Histological confirmation of the endometriosis was ensured in each case. The initial dose was 600 mg Danazol daily. In 17 cases the dose was reduced in the course of 6 months and in 5 cases treatment had to be stopped between the 4th and 6th month. An improvement of the symptoms arising occurred under this treatment. Side-effects, observed during the treatment with Danazol, such as acne vulgaris, seborrhoea, flushes and headaches occurred in 6 respectively 5 cases (28,6 respectively 23,8%). Very occasionally pain in the joints was reported. Almost all women put on weight. The effect of this treatment on fat- and glycometabolism, on liver- and kidney function, on blood-coagulation as well as bloodpressure was examined, no divergence from the norm was observed.
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PMID:[Treatment of endometriosis, Clinical trial with danazol]. 645 71

A review of the composition, usage, and side effects of hormonal contraceptives is presented. The estrogens ethinyl estradiol, mestranol, ethinyl estradiol sulfonate, and quinestrol, as well as the gestagens chlormadinon acetate, norethindrone acetate, and d-norgestrel, are used in combination, sequential, and depot preparations, mini-pills, and morning-after pills. The failure rate of combination preparations is 1/100 women-years and of sequential preparations is 1-5/100 woman-years. Gestagen-intensive preparations can be used for women showing symptoms of gestagen deficiency (e.g. hypermenorrhea, endometriosis), while estrogen-intensive preparations are indicated for women with e.g. hypomenorrhea, acne, or hirsuitism. Preparations containing chlormadinon acetate are indicated for women with signs of androgen imbalance or for women who sing or use their voices professionally. Control check-ups of patients using hormonal contraceptives should occur every 6 months. Women who still want to bear children should discontinue hormonal contraceptive use for a certain period every 2 years. Hormonal contraceptives can be prescribed to adolescents 2 years after menarche and after one year of regular menstruation. The side effects of hormonal contraceptive use are listed. Subjective side effects such as nausea and headaches are frequently reported. Hormonal contraceptives can cause menstrual irregularities; spottings or break-through bleedings during hormonal contraceptive use indicate a reduced contraceptive effectiveness. Hormonal contraceptive use causes increases in laboratory values, e.g. SGOT, SGPT; lipid metabolism and carbohydrate metabolism are also affected by hormonal contraceptives. Hormonal contraceptives have been shown to cause an increase in blood pressure and affect the circulatory system, liver and gall bladder function, and blood coagulation. Neoplasms may be affected positively or negatively by hormonal contraceptive use. Relative and absolute contraindications for hormonal contraceptive use as well as indications for discontinuing hormonal contraceptive use are listed.
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PMID:[Hormonal contraception--side effects and surgical aspects (author's transl)]. 701 44

In a large, double-blind, multicentre study, 269 patients with confirmed endometriosis were randomly allocated to receive either danazol (200 mg twice daily; n = 137) or gestrinone (2.5 mg twice weekly; n = 132) for 6 months. The two groups were comparable in terms of the staging of endometriosis by the American Fertility Society (1979) score. After the sixth month of treatment, repeat laparoscopy was performed. Clinical assessment, haematological and biochemical investigations were carried out during the 6 months of treatment and for a further 12 months' follow-up and are compared between the two groups. A total of 15 patients from the gestrinone group, including four patients with hirsutism, and 17 patients from the danazol group, including six patients with headache, withdrew because of adverse symptoms. An additional 22 patients, including 10 from the gestrinone group and 12 from the danazol group withdrew because of lack of efficacy, pregnancy, elevated hepatic function tests or for reasons unrelated to the trial. Total American Fertility Society scoring showed an improvement of 73.3% in 101 patients receiving gestrinone and 72.7% in 99 patients receiving danazol. The results showed a significant reduction in the severity of dysmenorrhoea by the third month in the danazol group and at 6 months in both groups. There was a significant (P < 0.001) increase in weight observed in both groups during treatment. Overall, the tolerability of danazol and gestrinone was good; however, significantly more patients with gestrinone complained of hirsutism while significantly more with danazol complained of leg cramps. During the 12 months of follow-up, mild, moderate or severe degrees of lower abdominal pain, dysmenorrhoea and deep dyspareunia all fluctuated, with no statistically significant increase in frequency in either group.
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PMID:Updating the clinical experience in endometriosis--the European perspective. 757 49

In an open, non-randomized prospective phase-III-study the clinical and endocrine efficacy as well as the safety of leuprorelin acetate depot (Enantone-Gyn Monats-Depot) were investigated. The therapeutic results of 198 patients, gathered from 5 university institutions and two city hospitals, are reported. Endometriosis was classified by the revised American Fertility Society score (r-AFS) before and at the end of treatment. Serum levels of LH, FSH, prolactin, estradiol, progesterone, androstenedione, testosterone and leuprorelin acetate were determined by radioimmunoassay. The mean total r-AFS score changed as follows: before surgical intervention during first-look laparoscopy 21 +/- 24 at the end of first-look laparoscopy 15 +/- 19 at the end of the GnRH-treatment 8 +/- 14 During leuprorelin acetate treatment the r-AFS stages changed as follows: [table; see text] Using the scoring system 85.2% of the patients improved. Relief of dysmenorrhoea could be achieved in 95.4%, relief of dyspareunia in 64% and of pelvic pain in 69.4% of patients. Baseline hormone levels dropped sharply during treatment. [table; see text] Androstenedione, testosterone, blood pressure, body weight, haematological parameters, liver enzymes, creatinine, electrolytes and HDL-/LDL-cholesterin remained more or less unchanged. Side effects being hot flushes, sweating, sleeplessness, headache, nausea, depression and vaginal dryness were due to estradiol deprivation. In 135 patients resumption of menstruation occurred in 95.6% within the first three months post-treatment. 23 patients of whom 21 were judged as infertile, became pregnant immediately after treatment was finished. The study results confirm the efficacy of leuprorelin acetate depot in the treatment of even advanced stages of endometriosis.
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PMID:[Treatment of endometriosis with the GnRH agonist leuprorelin acetate depot (Enatone-Gyn monthly depot): a multicenter study]. 784 80

Gonadotropin-releasing hormone (GnRH) agonists are synthetic derivatives of the native decapeptide produced by the hypothalamus. These agents cause a reversible suppression of the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the anterior pituitary gland. With GnRH agonist therapy, there is a resulting loss of endogenous ovarian gonadotropin stimulation and a severe hypo-estrogen state consistent with castrate levels of estrogen. Recently, GnRH agonists such as leuprolide and goserelin have been noted to be effective in treating mild to severe endometriosis. Side effects of these agents are consistent with the physiological effects of ovarian suppression, such as vasomotor instability, vaginal dryness, and headaches. However, despite some reports of emotional lability as an adverse effect of GnRH agonists, it appears that the occasional, rather severe psychiatric consequences of these agents are underappreciated. In this article, we present the case reports of 4 women of reproductive age with no prior psychiatric history who were treated with a GnRH agonist for endometriosis. These women developed symptoms consistent with various psychiatric disorders, including panic disorder and major depression with and without psychotic features. Three of these patients were given sertraline while on GnRH agonist therapy, which improved their mood and anxiety symptoms. Women undergoing GnRH agonist therapy may provide a model with which to investigate mood disorders during the perimenopausal stage of life.
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PMID:Anxiety and mood disorders associated with gonadotropin-releasing hormone agonist therapy. 923 Jun 49

A 43-year-old woman was suffered from an increasing headache with nausea and vomiting for nine days. She had received danazol 400 mg daily for endometriosis last two months. CT scan and neurological examinations revealed no evidence of abnormality. MRI showed isosignal intensity on T1-weighted images and high signal intensity on T2-weighted images in the superior sagittal, right transverse, sigmoid and straight sinuses suggesting thrombosis. With angiography, we confirmed extensive dural sinus thrombosis in the superior sagittal, straight, right transverse and sigmoid sinuses. She, then, developed progressing neurological deterioration with dysarthria and drowsy. Microcatheter was placed directly into the thrombus at dural sinus via transfemoral route. Thrombolytic therapy with urokinase was performed in right transverse, confluens sinuum, superior sagittal and straight sinuses. Successful recanalization with remarkable improvement of symptoms was achieved except right transverse sinus. We believe danazol played a role in the occurrence of dural sinus thrombosis. MRI and MRV were noninvasive and useful for diagnosis and follow-up of dural sinus thrombosis. Direct thrombolysis should be considered for dural sinus thrombosis, especially when clinical symptoms are rapidly deterioration with conventional anticoagulant therapy.
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PMID:[Successful direct thrombolysis in a patient with extensive dural sinus thrombosis induced by danazol]. 924 40

A correct classification of female pelvic pain originating from gynaecological disorders is essential if the most appropriate therapy is to be chosen. Certain types of non-steroidal anti-inflammatory drugs and oral contraceptives reduce the production of prostaglandins, which are responsible in large part for primary dysmenorrhoea. Oestroprogestin formulations become the drugs of choice if the patient also requests contraception. Secondary dysmenorrhoea and chronic pelvic pain may require combined medical and surgical treatment. Oral contraceptives can also be used as post-treatment agents in endometriosis, one of the most common causes of pelvic pain, whereas more specific compounds (GnRH-analogues and Danazol) are used to produce anatomical regression of endometriosis.
Cephalalgia 1997 Dec
PMID:Chronic pelvic pain: oral contraceptives and non-steroidal anti-inflammatory compounds. 949 75

GnRH analogues (GnRH-a) are well established in the treatment of endometriosis. However, due to hypooestrogenic effects, treatment is limited to 6 months. The aim of this randomized, double-blind, comparative study was to evaluate whether symptoms and signs of hypooestrogenism, e.g. hot flushes, sweating and sleeplessness, could be avoided by a steroidal add-back regimen, while the beneficial effect of a GnRH-a on endometriosis could be maintained. In group A, 14 patients were treated with 3.75 mg leuprorelin acetate depot per month i.m. in combination with 20 mg ethinyloestradiol plus 0.15 mg desogestrel orally for 3 weeks. In group P, 13 patients received leuprorelin acetate, following the same schedule as in group A, and placebo. Treatment duration was 6 months. At first-look laparoscopy (postoperatively) group A had an r-AFS score of 23.57 and group P of 24.23. After 6 months of treatment with leuprorelin acetate depot r-AFS scores had dropped to 16.14 in group A and to 6.25 in group P at second-look laparoscopy, achieving statistical significance in both groups (p < 0.001). Hypooestrogenic adverse drug reactions (e.g. hot flushes, sweating and sleeplessness) were more frequently reported in group P, whereas the occurrence of headache was comparable in both groups. Dysmenorrhoea was significantly reduced in both groups, whereas dyspareunia was only decreased in group P. Variations in laboratory values were within normal ranges and did not give any concern about drug safety. Loss of bone mineral density caused by the GnRH-a was reduced by the combined oestrogen/progestin add-back therapy. In conclusion, this therapy can lead to a reduction in hypooestrogenic adverse drug reactions and mostly preserves agonist efficacy with the chance of treatment prolongation.
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PMID:Steroidal 'add-back' therapy in patients treated with GnRH agonists. 962 21


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