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PubMed1993

Therapeutic effects of danazol on endometrial cells may be activated by the presence of extracellular matrix.

OBJECTIVE: To demonstrate the direct effect of danazol on the endometrium in the presence of various types of extracellular matrix. STUDY DESIGN: Human endometrial cells (epithelial and stromal cells) were cultured over various extracellular matrix in the absence or presence of danazol. The effects of danazol on the growth of endometrial cells and the specific glandular structure were studied. RESULTS: Danazol (10(-7) mol/L) inhibited endometrial cell growth, and in the presence of Matrigel, the same danazol concentration demonstrated a stronger inhibitory effect on epithelial cell growth. Danazol inhibited the formation of the specific glandular structure. Its effect depended on the culture substrates used and was reversible. Danazol did not inhibit growth of cells cultured over type V collagen substrate, whereas growth of those grown over type IV collagen was greatly inhibited. CONCLUSION: The results indicate that a distinctive extracellular matrix around ectopic endometriotic tissue modulates cell growth and differentiation. Endometrium associated with a normal extracellular matrix is apparently protected from therapeutic drugs, whereas endometriotic tissue growing over a deranged extracellular matrix would be sensitive to therapeutic drugs, such as danazol.

Cell Differentiation↗
PubMed1991

Thermoregulatory and endocrine effects of a low dose of danazol in postmenopausal women: interaction with the effect of naloxone.

Before and on the 30th day of danazol administration (200 mg/day), in six postmenopausal women the activity of endogenous opioid peptides has been indirectly evaluated by the effect on LH secretion and body temperature (measured as rectal temperature) exerted by the infusion of the opioid antagonist naloxone (1.6 mg/h x 4 h preceded by 1.6 mg iv bolus). Before and during danazol administration a GnRH test (100 mcg iv bolus) was also performed to evaluate possible variations in pituitary responsiveness to GnRH. Danazol significantly reduced mean plasma levels of LH and FSH (p less than 0.01), and their response to GnRH stimulus (p less than 0.05). Either before or during danazol administration mean plasma LH and FSH levels did not vary during the infusion of naloxone, while body temperature significantly decreased (p less than 0.01). The decrease in body temperature was significantly greater (p less than 0.05) during danazol than before treatment. The present data suggest that in postmenopausal women a low dose of danazol exerts an antigonadotropic effect mainly reducing the pituitary responsiveness to GnRH. The enhanced hypothermic response to naloxone observed during danazol administration also seems to suggest that in postmenopausal women a low dose of danazol enhances the thermoregulatory role of endogenous opioid peptides.

Body Temperature Regulation↗
PubMed1996

Depot goserelin and danazol pre-treatment before rollerball endometrial ablation for menorrhagia.

OBJECTIVE: To compare the safety and efficacy of a GnRH agonist, depot goserelin, and danazol as preoperative treatments before rollerball endometrial ablation. METHODS: We performed an open, randomized study of women with clinically convincing histories of menorrhagia. Two treatment groups of equal size (goserelin acetate, 3.6 mg subcutaneous implant given monthly, n = 30; and danazol, 200 mg two times per day, n = 30) were treated for 2 months before undergoing endometrial ablation, which entailed using the rollerball with 80-100 watts of coagulating current. RESULTS: Measured menstrual blood loss decreased dramatically after ablation, with 74% of goserelin users and 62% of danazol users achieving complete amenorrhea by the end of the 6-month follow-up period. Among women who did not achieve complete amenorrhea, those in the danazol group were more likely to experience occasional episodes of moderate or heavy bleeding. Mean measured blood loss decreased from 94.8 to 1.1 mL at 3 months and 1.0 mL at 6 months after goserelin, and 97.9 to 15.0 mL and 7.4 mL after danazol. Menstrual pain also improved markedly. The median duration of surgery was 20 minutes (range 5-55) in both groups, median irrigation fluid deficit was 100 mL (range 0-800), and median operative blood loss was 20 mL (range 1-50). Endometrium was less than 2 mm thick in all goserelin and most danazol users. Side effects of goserelin and danazol therapy were all within the expected pattern for these drugs. CONCLUSION: Depot goserelin and danazol both provide adequate endometrial preparation before rollerball endometrial ablation for treatment of menorrhagia due to ovulatory dysfunctional uterine bleeding.

Combined Modality Therapy↗
PubMed1978

A radioimmunoassay for danazol (17alpha-pregna-2,4-dien-20-yno[2,3-d]isoxazol-17-ol).

A method is described for the radioimmunoassay of circulating levels of the pituitary inhibiting agent, danazol. An antigen for danazol was prepared by reacting a 17-carboxy-methyloxime derivative of danazol with bovine serum albumin. By immunizing rabbits with this antigen, antiserum was generated which shows excellent specificity for danazol relative to its known metabolites as well as to many natural steroids. A radioimmunoassay was developed, without using separation or extraction techniques, involving competition for the antiserum between danazol in plasma and 14C-danazol. This assay has been successfully used to measure danazol in a series of normal human subjects receiving the drug at either 100 or 200 mg b.i.d. for 2 weeks. A significant relationship was seen between dosage of danazol and plasma concentrations.

Animals↗
PubMed2005

Adverse effects of danazol prophylaxis on the lipid profiles of patients with hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is a rare disorder caused by the deficiency of the C1-inhibitor gene (C1INH) . Patients experience recurrent bouts of edema, which can occur in almost any region of the body. As regards the treatment of the disease, danazol (an attenuated androgen) is used, among other agents, for long-term prophylaxis. OBJECTIVE: The aim of this study was to investigate the possible adverse effects of danazol on serum lipid profile, as well as to ascertain whether danazol treatment is associated with an increased risk of atherosclerosis. METHODS: Serum concentrations of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, apolipoprotein A-I, apolipoprotein B-100, and lipoprotein(a) were compared between danazol-treated patients with HAE and 2 control groups (ie, patients who did not receive long-term danazol prophylaxis and untreated healthy subjects). RESULTS: Serum concentrations of HDL ( P = .0002 and P < .0001) and apolipoprotein A-I ( P = .0015 and P < .0001) were significantly lower, whereas LDL ( P = .0129 and P = .0127) and apolipoprotein B-100 ( P = .0456 and P = .0013) were higher in the danazol-treated patients compared with the 2 control groups, respectively. No significant difference was found in total cholesterol, triglyceride, or lipoprotein(a) levels. Patients who received danazol had an 11.6 (95% CI, 2.7-49.7) times higher risk for abnormally low HDL levels and a 4.4 (95% CI, 1.2-16.0) times lower risk for high LDL concentrations. CONCLUSIONS: Our findings indicate that the long-term use of danazol is associated with an increased risk for early atherosclerosis in patients with HAE. Consequently, monitoring of HDL and LDL levels at regular intervals is recommended during follow-up.

Adult↗
PubMed2000

Effect of particle size on the prolonged action of subcutaneous danazol in male and female rats.

OBJECTIVE: To investigate the effects of two different particle sizes of danazol in male and female rats. DESIGN: Prospective, vehicle-controlled study. SETTING: Undergraduate college research facility and medical research laboratory. ANIMALS: 18 castrated male rats and 18 cycling female rats. INTERVENTION(S): Preparations of danazol with particle sizes of 2.05 microm or 5.2 microm were administered as a single subcutaneous injection of 400 mg/kg to castrated male rats or estrus-cycling females. MAIN OUTCOME MEASURE(S): Serum LH level in males and estrous cycle length in females. RESULT(S): In males, both preparations significantly (P<. 001) suppressed serum LH by day 5 of treatment. Gonadotropin levels remained low throughout the 35-day study in rats that received the larger-particle danazol, whereas LH levels began to increase after 25 days in rats that received smaller-particle danazol. In females, the normal 4- to 5-day estrous cycle interval was prolonged to 38.7 days (P<.001) in those that received the larger-particle danazol and 25.5 days in those that received the smaller-particle danazol. CONCLUSION(S): The results demonstrate the prolonged effectiveness of a single subcutaneous dose of danazol and indicate that one might be able to predict the effective duration of activity by changing the particle size of the danazol administered.

Administration, Cutaneous↗
PubMed1982

Danazol and gestagen displacement of testosterone and influence on sex-hormone-binding globulin capacity.

The mechanism of action of danazol is poorly understood, but this testosterone (T) derivate is frequently used in the clinical treatment of endometriosis, and its tendency to androgenic/anabolic side effects is well known. The interaction of danazol with T binding to sex-hormone-binding globulin (SHBG) was studied with the use of an aqueous two-phase system with polyethylene glycol (PEG) and dextran for equilibrium partition. Competitive binding studies were also performed with norethisterone (NET), d-norgestrel (d-Ng), medroxyprogesterone acetate (MPA), and tamoxifen (TMX). Danazol, d-Ng, and NET were found to exert a marked T displacing activity, while MPA and TMX had no significant effect. The low values for SHBG binding capacity that were found during danazol therapy mainly reflect occupation of binding sites by danazol and to a lesser degree a real decrease in protein concentration. It was calculated that during treatment the total SHBG capacity in serum is approximately 20 times exceeded. Therapeutic danazol serum levels are 1000 times those of normal female total T levels; and since the affinity to SHBG for danazol was found to be 1/20 that to T one should conclude an almost total occupation of binding sites. The endocrine effects of danazol might be interpreted in terms of T displacement and as a consequence of increased levels of free T during therapy.

Binding, Competitive↗
PubMed1996

Correlation of fecundability and serum estradiol after danazol treatment in patients with advanced endometriosis.

OBJECTIVE: To examine the relationship between pregnancy incidence and the level of serum E2 during danazol therapy. DESIGN: Danazol was given by 200 mg four times daily for 3 months. Serum E2 level was checked after completing the therapy, but before stopping medication. Patients then were advised to conceive at the appropriate time over a 6-month period. SETTING: Reproductive and Endocrine Laboratory of the Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. PATIENTS: Infertile women with invasive endometriosis receiving conservative surgery and danazol treatment. INTERVENTIONS: Serum E2 is checked before medication and at the end of danazol therapy, but before stopping medication. MAIN OUTCOME MEASURES: Whether pregnancy is related to the change of serum E2 caused by danazol therapy. RESULTS: There were 24 pregnancies in 38 patients with invasive endometriosis after treatment. Pregnant patients had significantly lower serum E2 levels as compared with the nonpregnant patients. CONCLUSIONS: After conservative surgery for invasive endometriosis associated with infertility, the therapeutic period of danazol treatment could be shortened to 3 months. Because there is significant correlation of fecundability and serum E2 after danazol medication, serum E2 could be a guideline for predicting pregnancy or for prolonging or changing of treatment after danazol therapy.

Danazol↗
PubMed2005

A randomized, parallel, comparative study of the efficacy and safety of nafarelin versus danazol in the treatment of endometriosis in Taiwan.

BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of nafarelin, a gonadotropin-releasing hormone (GnRH) analogue, versus danazol in the treatment of women with endometriosis in Taiwan. METHODS: Fifty-nine women with laparoscopically and pathologically confirmed endometriosis were randomized to receive nafarelin or danazol for 180 days. Efficacy was assessed from mean changes in laparoscopy score (LS) and total symptom severity score (TSSS). Adverse events (AEs) and laboratory parameters, including hematology, hepatic function, blood pressure, and lipid levels, were monitored for safety evaluations. RESULTS: All demographic and baseline factors, except body weight, were comparable between the 2 treatment groups. Both nafarelin and danazol satisfactorily resolved pelvic tenderness, induration, pelvic pain, dysmenorrhea and dyspareunia. No significant differences were noted in efficacy endpoints between nafarelin and danazol regarding LS and TSSS at 90 and 180 days of treatment. No significant difference was observed between the 2 groups regarding the overall incidence of AEs, except for laboratory-related AEs. However, nafarelin tended to have less impact than danazol on aspartate transaminase and alanine transaminase, and nafarelin was better tolerated than danazol regarding changes in lipid profiles. Both treatments had little or no effect on hematologic parameters. CONCLUSION: Nafarelin and danazol demonstrated similar clinical efficacy, but nafarelin was associated with fewer laboratory changes and a stable lipid profile, relative to danazol. Moreover, intranasally administered nafarelin is noninvasive, and may be a more comfortable and safer alternative to slow-release injectable GnRH agonists. Based on this study, we suggest that nafarelin, like other GnRH analogues, may be a treatment of choice for Taiwanese women with endometriosis. However, direct comparative studies of nafarelin with slow-release injectable GnRH agonists are now required.

Adult↗
PubMed1991

Tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM): treatment with an anabolic steroid danazol.

Tropical spastic paraparesis or HTLV-I-associated myelopathy is a progressive spastic disorder associated with the human T-lymphotropic virus type I. Some cases have responded to prednisone. Danazol is an attenuated androgen with minimal virilizing effects. It is used in the treatment of endometriosis and various autoimmune hematologic diseases shown to be responsive to prednisone. Because danazol is anabolic, useful in prednisone-responsive diseases, and less toxic than prednisone, we gave danazol to 6 patients with TSP and 1 with HIV, HTLV-I-associated myelopathy. Five patients had a favorable response. Two became ambulatory after having been confined to a wheelchair. Three were able to ambulate greater distances (in walkers) than prior to danazol. Three had noticeable decreases in spasticity. Urinary incontinence resolved in two. Physical therapy was variably employed in all except one patient. Two patients who had not responded to physical therapy responded to physical therapy and danazol. One patient did not tolerate danazol and one patient did not improve. Toxicities noted were mild elevations in liver enzymes in 4 patients; these responded to a decrease in dose of danazol; amenorrhea in one and mild fluid retention in one. We conclude that danazol is a useful agent in the management of TSP.

Adult↗
PubMed1989

Danazol therapy renders red cells resistant to osmotic lysis.

Danazol, an attenuated androgen, is useful in endometriosis, idiopathic thrombocytopenic purpura (ITP), and autoimmune hemolytic anemia (AIHA). However, its mechanism of action is unknown. We investigated the possibility that danazol affects cell membranes directly. Red cell osmotic fragility was studied in patients receiving danazol. A significant decrease in osmotic fragility was observed. Accompanying the change, peripheral blood smears showed many target cells and electron microscopy revealed extra folds in erythrocyte membranes. Twenty-two patients were studied prospectively before and after danazol. Osmotic fragility decreased significantly (P less than 0.001) in 1 month of therapy and progressed with further treatment. A rebound increase (P less than 0.01) was observed in 1 month after discontinuation of danazol among 16 patients. Incubation experiments showed that danazol-induced changes are not reversed with normal sera. Patient sera did not induce the changes in normal red cells. Danazol in vitro protected red cells from osmotic lysis at low concentrations but enhanced lysis at high concentrations. We suggest that danazol alters red cell membranes directly to increase their surface area, inducing target cell formation and increasing their resistance to osmotic lysis.

Danazol↗
PubMed1991

Danazol treatment of myelodysplastic syndromes.

Peripheral cytopenias are common in patients with myelodysplastic syndromes. We previously successfully treated three such patients with improvement of some cytopenias with the impeded androgen danazol. To confirm this finding and elucidate the mechanism of response, we treated an additional 22 patients with myelodysplasia with oral danazol (600-800 mg daily) for 3-12 months. Eleven of 22 evaluable patients taking danazol met our criteria for improvement of peripheral counts, mainly thrombocytopenia. Chromosome analysis, marrow culture studies and serial bone marrow biopsies revealed no alteration of the abnormal clone or normal haematopoiesis in patients on danazol therapy. This suggested that improvement in blood counts was not related to modulation of ineffective haematopoiesis. Investigation of the thrombocytopenia in these patients revealed that most patients presented with markedly elevated platelet associated IgG (PAIgG), elevated plasma platelet-bindable IgG (PBIgG), and an elevated number of monocyte Fc gamma receptors. Treatment with danazol was associated with a decline in monocyte Fc gamma receptor number without significantly altering the elevated PAIgG or PBIgG levels. These results are similar to our observations in patients treated with danazol for chronic idiopathic thrombocytopenia purpura (ITP). Our data suggest that a component of the thrombocytopenia occurring in patients with myelodysplasia may be due to enhanced peripheral blood cell destruction by abnormal macrophages. Danazol may modulate cytopenia by decreasing the number of monocyte Fc gamma receptors. Danazol treatment was associated with minimal toxicity, but clinically meaningful responses were rare.

Adult↗
PubMed1983

The interaction of human endometrial and myometrial steroid receptors with danazol.

The affinity of danazol for oestrogen, androgen and progesterone receptors in human endometrium and myometrium was determined, to study the mechanism of action of this drug in the treatment of endometriosis. The ability of danazol to combine with each of the three types of receptor was similar in both endometrium and myometrium. The capacity of danazol to compete with oestradiol-17 beta for the oestrogen receptor was very low (1.72 +/- 0.48 X 10(-3%) cross reaction, mean +/- SEM) and danazol, at the maximum concentration used, was unable to saturate the receptor; but danazol's ability to compete with progesterone for its receptor was considerably higher (8.41 +/- 1.65% using progesterone, 1.95 +/- 0.41% using R5020) and was saturable. Danazol was also able to displace dihydrotestosterone from the cytosol androgen receptor (6.29 +/- 1.82% cross reaction). The association constant of oestradiol for the endometrial and myometrial oestrogen receptors was 2.19 X 10(9)M-1 and 7.45 X 10(9)M-1 respectively, while that of progesterone and dihydrotestosterone for their receptors was similar in endometrium and myometrium (mean 0.25 +/- 0.06 X 10(9) M-1 and 3.62 +/- 1.67 X 10(9) M-1 respectively). Using R5020, the association constant for the myometrial progesterone receptor was 2.50 +/- 0.73 X 10(9) M-1. We conclude that, in view of the high circulating levels of danazol present in patients being treated for endometriosis, it is possible that danazol may bind to, and partly saturate, endometrial and myometrial oestrogen, progesterone and androgen receptors during treatment. An explanation may thus be provided for some of the diverse actions of this drug.

Binding, Competitive↗
PubMed1991

Cholesterol fractions and apolipoproteins during endometriosis treatment by a gonadotrophin releasing hormone (GnRH) agonist implant or by danazol.

OBJECTIVE: The evaluation of cholesterol fractions and apoproteins during ovarian suppression by a GnRH agonist implant vs danazol in the treatment of endometriosis. DESIGN: A randomized study in 33 patients comparing goserelin (3.6 mg/4 weeks s.c., n = 20) with danazol (2 x 400 mg/day p.o., n = 13) in patients with a laparoscopic diagnosis of endometriosis and treated for 6 months. MEASUREMENTS: Triglycerides, cholesterol (C), LDL-C, HDL-C subfractions and apoproteins A-1 and B were measured at admission, at months 2, 4 and 6 of treatment and at month 2 post-treatment. RESULTS: After 1 month of therapy, serum oestradiol levels were maintained in the menopausal range with goserelin and in the early follicular phase range with danazol. Goserelin induced a significant elevation in HDL-C (by 31.4%), in HDL2-C (24.6%) and in HDL3-C (45.7%) but no significant change in LDL-C or in ApoA-1 and ApoB. By contrast, danazol caused significant diminutions in HDL-C (23.9%), HDL2-C (56.6%) and ApoA-1 (35.6%). Moreover, danazol increased LDL-C (10.5%) and ApoB (29.0%, P less than 0.05). The lipoprotein changes during goserelin had a favourable effect on the atherogenic index (cholesterol/HDL-C) and ApoA-1/ApoB ratio whereas those of danazol had opposite effects. These changes reverted 2 months after danazol while HDL was still elevated after goserelin. CONCLUSIONS: In relation to cholesterol, goserelin is a safe medication. The significance of temporary adverse changes in cholesterol fractions due to danazol is still unknown.

Adult↗
PubMed1981

In vitro effect of danazol on luteinizing hormone-releasing hormone-stimulated luteinizing hormone release in rat anterior pituitary cell cultures in vitro.

Monolayer cultures of anterior pituitary glands from female rats were exposed to 5 X 10(-6) M danazol for 0, 4, 24, 48, and 72 h in Dulbecco's Modified Eagle's Medium supplemented with 10% horse serum and 2.5% fetal calf serum. After this treatment, the cell cultures were rinsed and challenged with 10(-8) M LHRH for 6 h. The media were collected and assayed for LH by a hormone-specific RIA using the double antibody precipitation technique. A control incubation was carried out by exposing cell cultures for the same length of time in the absence of danazol but in the presence of 0.5% ethanol in which danazol was dissolved, then challenging the culture with 10(-8) M LHRH, as was done in the experimental group, and assaying the LH released in the medium. The results showed that exposure of cell cultures to danazol caused a significant decrease in LH release in response to LHRH from 13,800 +/- 500 to 3,500 +/- 200 ng/ml. The inhibition of LH release was dependent on both the duration of danazol exposure and its concentration. Danazol exposure had, however, little effect on basal LH secretion by the pituitaries, which remained at about 600 ng/ml at all time points examined. Under the experimental conditions, danazol exerted no effect on the incorporation of amino acid into protein in the cell culture. These results suggest that one of the mechanisms of the antigonadotropic effect of danazol is inhibition of the responsiveness of the pituitary to LHRH-induced LH release.

Animals↗
PubMed1979

A comparison of plasma protein changes induced by danazol, pregnancy, and estrogens.

Analysis of 25 plasma proteins was performed on blood drawn from 7 females before and during treatment with danazol. This steroid was found to induce a pattern of plasma protein changes similar to but not identical with that of other 17 alpha-alkylated anabolic steroids. For comparison, the same 25 plasma proteins were analyzed in blood from pregnant women in their third trimester, when the estrogen influence on plasma protein synthesis is most pronounced. Five major types of response were found. 1) Albumin and orosomucoid were not influenced by danazol or, after correction for volume expansion, by pregnancy. 2) Prealbumin, C1-esterase inhibitor, and haptoglobins increased substantially during danazol treatment but were not significantly influenced by pregnancy. 3) Transferrin, antithrombin III, prothrombin, and plasminogen showed marked increases after administration of danazol and during pregnancy. 4) Transcortin, ceruloplasmin, and alpha 1-antitrypsin doubled in pregnancy but were not influenced by danazol. 5) The concentrations of T4-binding globulin, pregnancy zone protein, and sex hormone-binding globulin more than doubled in pregnancy, and all three decreased to one third or less on administration of danazol. The plasma estradiol content fell correspondingly. The different types of plasma protein response found in these two groups of patients fit the hypothesis that hepatocytes contain steroid receptors capable of reacting with estrogens and/or other steroids such as danazol and, thus, influence the biosynthetic rate of many but not all plasma proteins according to a specific pattern. The synthesis of some of the estrogen-sensitive proteins is depressed after intake of danazol, which suggests that there is a competition for the receptors in the hepatocytes as there is for other estrogen target tissues.

Adult↗
PubMed1990

[Inhibition of cytochrome P-450-dependent monoxygenase activities by a synthetic androgen danazol in mouse hepatic microsomes].

The inhibitory effect of danazol, a synthetic androgen, on the hydroxylations of testosterone as a model for endogenous steroids and the dealkylations of aminopyrine and 7-ethoxycoumarin as models for xenobiotics in mouse hepatic microsomes in vitro was studied. Danazol inhibited these enzyme activities in a dose-dependent fashion. The inhibition constants (Ki) of danazol for these enzyme activities were 1-4 orders of magnitude lower than those of cimetidine, while there was a great difference among the inhibitory potencies of danazol for each enzyme activity. Addition of danazol to microsomal preparation resulted in a reverse type I difference spectrum and the spectrophotometric analysis revealed that danazol had a high affinity for cytochrome P-450 with dissociation constants (Ks) of 0.9 and 4.2 microM, which were 2 orders of magnitude lower than those of cimetidine. On the other hand, danazol did not significantly affect reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase activity and levels of cytochrome P-450 in the microsomes. These results suggest that danazol is a highly potent inhibitor for several cytochrome P-450-mediated metabolisms of testosterone and xenobiotics in mouse hepatic microsomes.

Animals↗
PubMed1990

Danazol. A synthetic steroid with diverse biologic effects.

Danocrine (danazol) is a synthetic steroid with multiple and diverse biologic effects. It exerts these effects by binding to steroid transport proteins in the circulation and to specific receptors in target tissues. Centrally, danazol inhibits gonadotropins, suppressing gametogenesis and steroidogenesis. Gonadal and adrenal steroidogenesis are suppressed further through danazol's direct effect on specific enzyme systems. Danazol also displays immunoregulatory effects both in vivo and in vitro. In endometriosis, danazol induces amenorrhea and a hypoestrogenic state, resulting in endometrial atrophy. The drug's direct binding to androgen and progesterone receptors in endometriotic tissue may contribute further to the suppression of endometriosis. In women with endometriosis who produce autoantibodies against endometrial cells and endometrial cell-derived phospholipids, histones and nucleotides, danazol may improve reproductive performance through the suppression of abnormal autoantibody levels. In several other autoimmune and genetic disorders danazol brings about a clinical improvement by lowering abnormal autoantibody production or by increasing the concentration of genetically deficient protein. In order to explore the full clinical potential of the drug and to better understand danazol's mechanism of action and especially its immunoregulatory effects in autoimmune diseases and endometriosis, further investigation is necessary.

Animals↗