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At least 19 recordsLinked to original sources
PubMed1996

Gestrinone versus a gonadotropin-releasing hormone agonist for the treatment of pelvic pain associated with endometriosis: a multicenter, randomized, double-blind study. Gestrinone Italian Study Group.

OBJECTIVES: To evaluate the efficacy of gestrinone versus leuprolide acetate (LA) in improving pelvic pain in women with endometriosis and to compare their effects on bone mineral density and serum lipid profile. DESIGN: Multicenter, double-blind, double-dummy, randomized clinical trial. SETTING: Six academic departments specialized in the study of endometriosis. PATIENT(S): Fifty-five women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis. INTERVENTION(S): Six-month treatment with oral gestrinone (n = 27) or IM depot LA (n = 28) followed by 6-month follow-up. MAIN OUTCOME MEASURE(S): Variations in severity of dysmenorrhea, deep dyspareunia, and nonmenstrual pain as shown by a visual analog scale and a verbal rating scale, modifications in bone mineral content as shown by dual-roentgenogram absorptiometry, and variations in serum cholesterol subfractions and lipoprotein(a) concentrations. RESULT(S): Significant improvements were observed in all three symptoms considered in both treatment arms. Moderate or severe pain symptoms recurrence on both pain scales was observed in 2 of 17 (11.8%) patients given gestrinone compared with 9 of 17 (52.9%) of those given LA (odds ratio, 0.12; 95% confidence interval, 0.02 to 0.69). Lumbar bone mineral density increased slightly in the gestrinone group but decreased by 3% in the LA one. High-density-lipoprotein cholesterol fell by 25% and lipoprotein(a) decreased by approximately 40% in the gestrinone-treated women but did not vary in those receiving LA. CONCLUSION(S): Oral gestrinone is at least as effective as depot LA for pain relief in women with symptomatic endometriosis. A tendency to prolonged pain reduction was observed after gestrinone compared with LA treatment. Gestrinone does not negatively affect bone density but variations in serum lipids need further evaluation.

Absorptiometry, Photon↗
PubMed1991

Rationale for frequency and dose of administration in gestrinone therapy for pelvic endometriosis in the experimental model of rabbit uterus.

1. Gestrinone has been used for treatment of pelvic endometriosis, in doses of 2.5 mg twice a week. This study is designed to clarify it from the dynamics of sex steroid receptors in rabbit uterus. 2. Four different regimens were scheduled, namely daily 1 microgram estradiol-17 beta (E2, consistent with endogenous level of women) for 3 days, and together with either 30, 60 (consistent with 2.5 microgram of clinical dose) or 120 microgram(s) gestrinone, in single dose or with 20 microgram(s) gestrinone daily (divided dose in single 60 microgram(s) gestrinone administration) for 3 days. Receptors for estrogen (ER, type I and II) or progestin (PR) were determined by charcoal adsorption in cytosol and KCl extract, or sedimentation in non-KCl extractable fraction, using [3H]E2 or [3H]promegestone respectively. 3. Gestrinone decreased total ER (type I and II) levels, dose-dependently, except the case of 20 micrograms gestrinone daily in ER type II. Total ER type I level did not return to the pre-level until 3 days only after 120 microgram(s) gestrinone administration. Total ER type II level was decreasing in 3 days after 30, 60 or 120 micrograms gestrinone therapy. Total PR level was decreased in the order of strength: 120 micrograms gestrinone greater than 60 micrograms gestrinone greater than 30 microgram gestrinone greater than 20 micrograms gestrinone in group, and the recovery was not obtained until 72 hr only after 120 micrograms gestrinone therapy. The uterine weight was decreasing with the same strength in 3 days of the therapy independently upon the regimen. 4. In conclusion, gestrinone dose of 60 micrograms (2.5 mg of clinical dose) every 3 days is considered to be effective for anti-steroid action in sex steroid receptor dynamics in the rabbit uterus, contributing to the rationale for gestrinone treatment of pelvic endometriosis.

Animals↗
PubMed1988

[Laparoscopic diagnosis and evaluation of danazol or gestrinone therapy for endometriosis in sterility].

In forty-six sterile women, endometriosis externa was diagnosed and classified laparoscopically. 21 patients were treated with Gestrinone 5mg-10mg/week and 25 patients were treated with Danazol 300mg-400mg/day for 6 months. The effects of these hormonal treatments were evaluated by second-look laparoscopy according to adhesion severity, number of blueberry spots and chocolate cyst size, as well as dysmenorrhea and other complaints. The results were as follows; 1) Dysmenorrhea was relieved in 60.0% of the Gestrinone-treated group and 45.5% of the Danazol group. 2) Adhesion was weakened or partially separated spontaneously in 66.7% of the Gestrinone group and 63.6% of the Danazol group. 3) Blueberry spots decreased in number or paled in 61.9% of the Gestrinone group and 75.0% of the Danazol group. 4) Chocolate cyst size became smaller in 60.0% of the Gestrinone group and 77.8% of the Danazol group. 5) Peritoneal fluid volume was not decreased after the hormonal treatments but the prostaglandin E2 concentration in peritoneal fluid was decreased (p less than 0.05) after Gestrinone therapy. 6) The patients complained of some side effects, liver function especially was disturbed in 48.0% of the Danazol group and 9.5% of the Gestrinone group. Hoarseness was complained of in 33.3% of the Gestrinone group and 12.0% of the Danazol group. 7) Finally, 23.8% of the Gestrinone group and 28.0% of the Danazol group conceived after the hormonal treatments.

Adult↗
PubMed1992

Multicentre study of gestrinone in cyclical breast pain.

Although the aetiology of cyclical mastalgia is poorly understood, the consistent finding of an increased prolactin stimulation response probably due to oestrogen dominance has led to the use of treatment with prolactin-lowering drugs and antioestrogens. The efficacy and safety in cyclical mastalgia of gestrinone, which has androgenic, anti-oestrogenic, and antiprogestagenic properties, were investigated in a multicentre study. In a double-blind randomisation procedure, 72 patients were allocated placebo and 73 treatment with gestrinone (2.5 mg twice a week) for 3 months. The patients recorded the severity of breast pain on a visual analogue scale before and during treatment and scored other breast symptoms as not present (0), mild (1), moderate (2), or severe (3). The gestrinone group had significantly greater reductions than the placebo group in breast pain score at months 1, 2, and 3 of treatment (mean reduction 59.5 [SD 22.6] to 11.7 [17.0] vs 58.2 [17.6] to 36.7 [23.0] at month 3; p less than 0.0001). All six breast symptoms had lower scores in the gestrinone than in the placebo group by the end of treatment. In a subset of 30 participants (15 from each group), serum concentrations of oestradiol, progesterone, and tri-iodothyronine were significantly lower than baseline after 3 months of gestrinone, but concentrations of luteinising hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone, and thyroxine did not change. 41% of gestrinone-treated and 14% of placebo-treated patients reported at least one side-effect; most of these were androgen-mediated. 11 placebo-treated patients and 4 on gestrinone discontinued treatment. Thus, gestrinone was very effective in the treatment of cyclical mastalgia and was well tolerated.

Adolescent↗
PubMed1991

Antiestrogenic effect of gestrinone as an inhibitor of [3H]-estradiol binding to nuclear type II sites.

Gestrinone has a biophysical antiestrogenic effect. But the mechanism of its antiestrogenic effect is not clear. Gestrinone blocked the increase of estrogen binding of nuclear type II sites and uterine weight in the estrogen-treated immature rabbit. Competitive assays indicated that gestrinone, at low concentrations (0.4 approximately 4 nM), inhibited [3H]-estradiol binding to nuclear type II sites. This inhibitory effect was the same as the addition of 20 microM diethyl-stilbestrol. This inhibition with gestrinone on [3H]-estradiol binding to nuclear type II sites appeared only when used at concentrations less than an equivalent molar of [3H]-estradiol. Time course analysis of the gestrinone binding inhibition showed that within the first 6 min gestrinone did not inhibit specific [3H]-estradiol binding to nuclear type II sites. This gestrinone-mediated inhibition was not observed in soluble fractions such as the cytosolic and KCl-extracted nuclear binding sites. These results suggest that gestrinone acts primarily on the nuclear fraction and then it operates the inhibitory mechanism on estradiol binding to nuclear type II sites.

Animals↗
PubMed1989

Gestrinone versus danazol in the treatment of endometriosis.

Thirty-nine infertile patients with laparoscopic diagnosis of endometriosis were allocated randomly to treatment with gestrinone 2.5 mg twice weekly (20 patients) or danazol 600 mg/day (19 patients) for 6 months. If amenorrhea was not obtained after 1 month of treatment, the gestrinone dose was increased to 2.5 mg three times a week (7 patients) and the danazol dose to 800 mg/day (2 patients). One month after the end of the treatment, a repeat laparoscopy was performed only in the women who agreed (7 of the gestrinone treated group, 9 of the danazol group). All of the patients were followed for at least 12 months after the end of the treatment, during which time they attempted to conceive. There was a marked improvement of pain symptoms during the treatment in the patients of both groups. The repeat laparoscopy did not reveal significant differences between the two groups in the reduction of the disease extent. Eighteen months after treatment suspension, the cumulative pregnancy rate was 33% in the patients treated with gestrinone and 40% in those treated with danazol. Pain symptoms recurred during the follow-up in 57% of the gestrinone and 53% of the danazol group. The side effects were more frequent and severe with the danazol treatment, whereas those caused by gestrinone were mostly weight gain and acne. The results of this study suggest that gestrinone is as effective as danazol in the treatment of infertility associated with endometriosis and is better tolerated.

Adult↗
PubMed1992

No inhibitory effects of gestrinone and medroxyprogesterone acetate on the estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins.

The in vivo effects of gestrinone (R2323) and medroxyprogesterone acetate (MPA) on the estrogen production by rat ovaries were investigated. Hypophysectomized immature female rats treated with 2.5 or 5 IU of pregnant mare serum gonadotropin (PMS) were daily given vehicle only, gestrinone (0.5 mg/kg body weight) or MPA (10 mg/kg body weight), and the activities of 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, 17, 20-lyase, 17 beta-hydroxysteroid dehydrogenase and aromatase in ovaries of these rats were measured. Gestrinone suppressed the 3 beta-hydroxysteroid dehydrogenase activity and increased activities of 17 alpha-hydroxylase, 17, 20-lyase and aromatase in ovaries stimulated by 5 IU of PMS, while MPA suppressed activities of 17 alpha-hydroxylase and aromatase in these ovaries. On the other hand, the aromatase activity in ovaries stimulated by 2.5 IU of PMS was suppressed by gestrinone and increased by MPA, and neither gestrinone nor MPA affected the production of aromatizable androgens from progesterone by these ovaries. Thus, gestrinone and MPA administrated in vivo showed divergent influences on steroidogenic enzyme activities in ovaries, but they did not affect the serum concentration of estradiol-17 beta. The present results suggest that neither gestrinone nor MPA reduced estrogen production by the rat ovary under the gonadotropin stimulation although they influenced some process of its steroidogenesis.

17-Hydroxysteroid Dehydrogenases↗
PubMed1986

Gestrinone (R2323) binding to steroid receptors in human uterine endometrial cytosol.

To understand the mechanism of biological action of gestrinone (R2323), which has a therapeutic effect against endometriosis, the binding of gestrinone to numerous classes of intracellular steroid binding proteins was studied in the human uterine endometrium. Gestrinone bound to endometrial receptors for estrogen, progesterone and androgen, but seemed not to bind to endometrial intracellular corticosteroid-binding globulin and sex hormone-binding globulin. Gestrinone occupies all specific binding sites of steroids in the steroid target cells despite the presence of endogenous steroids. It is speculated that the binding behavior of gestrinone may be related to its therapeutic effect on endometriosis. Gestrinone's more avid affinity for estrogen receptor may be the reason for the ability to use a lower clinical dose of gestrinone.

Cytosol↗
PubMed2000

Determination and excretion study of gestrinone in human urine by high performance liquid chromatography and gas chromatography/mass spectrometry.

Gestrinone was studied by HPLC for screening and by GC/MS for confirmation. Three unknown peaks were found by HPLC which are probably the metabolites of gestrinone, and conjugated gestrinone in dosed human urine. The metabolites and gestrinone were excreted as the conjugated forms. The total amounts of metabolite 1 and conjugated gestrinone, recovered after 48 h, were 0.20 and 0.32 mg, respectively. When metabolite 1 was tested by LC/MS and LC/MS/MS, the parent ion was m/z 327, [MH](+), and fragment ions were seen at m/z 309 [MH - H(2)O](+), 291 [MH - 2H(2)O](+), 283, 263 and 239. The TMS-enol-TMS ether derivative of gestrinone has three peaks in the GC/MS chromatogram formed by tautomerism. The reproducibility of the derivatization method was stable and recoveries were over 87% when spiked into blank urine.

Chromatography, Liquid↗
PubMed1994

Gestrinone inhibits macrophage function and mitogen-stimulated lymphocyte proliferation in vitro.

Clinical and experimental evidence supports the hypothesis that some steroidal drugs with androgenic effects might influence the immune system. The present study investigated whether gestrinone is able to affect macrophage and lymphocyte activity in vitro. Macrophage function was determined by phagocytosis of fluorescent microspheres, whilst lymphocyte proliferation was assessed by cell counting. Macrophage phagocytosis was evaluated after an overnight incubation in the presence or absence of gestrinone at serial dilutions; lymphocyte proliferation was detected in basal conditions and after stimulation with Concanavalin A (Con A) in the presence or absence of gestrinone. The results of this study showed that gestrinone significantly inhibited macrophage phagocytosis at the concentrations of 10(-8), 3 x 10(-8) and 10(-7) M. Furthermore, a significant suppression of lymphocyte blastogenesis was observed when lymphocytes were incubated with gestrinone at the concentration of 10(-7) M for 6 days. The biological significance of gestrinone as an inhibitor of immune functions under experimentally defined conditions is discussed in relation to its potential mechanism for fertility enhancement.

Adult↗
PubMed1996

Individual and combined effects of triptoreline and gestrinone on experimental endometriosis in rats.

OBJECTIVES: To evaluate the effects of triptoreline, gestrinone, and both, on experimental endometriosis in rats. STUDY DESIGN: Experimental endometriosis was surgically induced in 225 Wistar rats. Of these, 202 rats showed at least one grown implant, 22 of which composed the control group, while 180 were treated with triptoreline, gestrinone, or both, for 28 days. The implants were evaluated again after 25 days. RESULTS: There were no changes in size in the control group. About 73% of the implants treated with triptoreline showed a high reduction (> 50%), vs. 51% with gestrinone (P < 0.0005) and 65% with both (P < 0.005). Triptoreline caused macroscopic resolution in 40% of the implants vs. 31% for gestrinone (not significant) and 26% for both substances (P < 0.05). In the triptoreline group, the mean size of the implants decreased by 65% between the 25th and 28th days, 58% between the 29th and the 35th, and 39% after the 36th day. This reduction was 51%, 36%, and 33%, respectively, in gestrinone group. CONCLUSIONS: Triptoreline was more effective than gestrinone, but perhaps not in the long run. Their association did not improve the results.

Animals↗
PubMed1997

Clinical, endocrine, and metabolic effects of two doses of gestrinone in treatment of pelvic endometriosis.

OBJECTIVE: Our purpose was to determine and compare the efficacy and hormonal and metabolic effects of 1.25 mg with 2.5 mg of gestrinone given twice a week in the treatment of mild and moderate pelvic endometriosis. STUDY DESIGN: A phase II, prospective, randomized, double-blind study involving 11 patients given gestrinone 1.25 mg (five patients) or 2.5 mg (six patients) orally twice a week for 24 weeks was performed. Revised American Fertility Society scores were determined by laparoscopy before and at the end of treatment. Serum hormone (free thyroxine, free testosterone, estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone), sex hormone binding globulin, and lipid concentrations were measured before, throughout, and for 6 months after treatment. Quantitated computerized tomography of thoracic 12 through lumbar 4 vertebral bodies were determined before, at the end of, and 6 months after treatment. RESULTS: Gestrinone 2.5 mg significantly reduced the endometriosis implant score from 10.3 +/- 2.8 to 3.8 +/- 0.8 (p = 0.05). Both doses significantly reduced serum progesterone and sex hormone binding globulin levels. Estradiol, free testosterone, free thyroxine, follicle-stimulating hormone, and luteinizing hormone levels were not significantly affected. Spinal bone increased significantly by 7.1% with 2.5 mg but lost significantly by 7.1% with 1.25 mg gestrinone; these changes had not reversed completely 6 months after stopping treatment. CONCLUSIONS: In mild to moderate pelvic endometriosis 2.5 mg of gestrinone twice a week was more effective and had a more positive effect on bone mass than did 1.25 mg of gestrinone.

Adult↗
PubMed1995

[Effects of gestrinone on experimental endometriosis in rabbits].

OBJECTIVE: To study the therapeutic effects of gestrinone on experimental endometriosis in rabbits. METHODS: Mature female rabbits were laparotomized under sterile condition and three or four segments of endometrium (7 mm x 7 mm) were sutured to the mesentery of uterus. Seven weeks after operation these animals were divided into 5 groups: control; treated with danazol 20mg/kg; gestrinone 0.06, 0.12, 0.24 mg/kg for 4 weeks respectively. At the end treatment they were laparotomized again. The ectopic endometrial implants were weighted and their morphologic features were analysed quantitatively by semi-automatic image analysis system, meanwhile serum follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone (P) concentrations were determined by radioimmunoassay. RESULTS: Decreased weight and atrophy of ectopic endometrial implants were shown in all experimental groups, except for control and 0.06 mg/kg gestrinone treated-group. In 0.12, 0.24 mg/kg gestrinone treated-group, except for P serum FSH, LH and E2, concentrations decreased significantly. The degree of inhibition on ectopic lesions of 0.12 mg gestrinone group was similar to that of danazol group. CONCLUSIONS: Gestrinone inhibits the growth of ectopic endometrial implants in a dose-dependent manner and showed a significant therapeutic effects on experimental endometriosis in rabbits.

Animals↗
PubMed1985

Effect of gestrinone in endometriosis tissue and endometrium.

The effects of gestrinone (R 2323) on endometrial and endometriosis tissue concentrations of cytosol estrogen and progestin receptors and the activity of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) were investigated in 11 patients operated on because of suspected external endometriosis. Serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol (E2), progesterone, testosterone (T), and sex-hormone-binding globulin (SHBG) were also investigated. After one control cycle, the patients received 2.5 mg of oral gestrinone twice weekly from the fifth day of the first treatment cycle until the eighth day of the second treatment cycle, the day of operation being day 10. Treatment with gestrinone decreased serum concentrations of T during the second treatment cycle and effected a major decrease in SHBG during both treatment cycles, resulting in highly increased free T and free E2 indices. The effects of gestrinone on the endometrium, a decrease in estrogen and progestin receptors, and induction of 17 beta-HSD are characteristic progestin actions. These parameters remained unchanged in endometriosis tissue. Our data indicate that gestrinone has effects that are typical of androgens and progestins in patients with endometriosis.

17-Hydroxysteroid Dehydrogenases↗
PubMed1987

Impact of gestrinone on the course of asymptomatic endometriosis.

A new drug, gestrinone, was subjected to the first double blind, randomised placebo controlled trial of any treatment of endometriosis. The disease deteriorated in eight (47%) of the 17 patients prescribed placebo (95% confidence limits 23% and 71%) compared with none of the 18 patients prescribed gestrinone (p = 0.002). There was a difference in elimination of the endometriosis in the gestrinone group compared with placebo but this was not statistically significant (p = 0.057). There was a significant difference in improvement of the disease in the gestrinone group compared with placebo (p = 0.004), confirming that gestrinone is an effective treatment of endometriosis. Endometriosis deteriorates in at least 23% of patients; as it is impossible to predict in whom this will happen, treatment appears to be warranted in all cases.

Adult↗
PubMed1992

Endometrial patterns during therapy with danazol or gestrinone for endometriosis: structural and ultrastructural study.

We treated 36 women with laparoscopically proven endometriosis with danazol 600 mg/d (n = 17) or gestrinone 5.0 mg/wk (n = 19) for 6 months. Endometrial samples were obtained before and at 3 and 6 months of treatment and were studied by light, scanning, and transmission electron microscopy. At 3 months of treatment, the endometria of the danazol-treated patients were more atrophic than those of the women who received gestrinone. Some cell organelle involution was evident in patients of both treatment groups. After 6 months of treatment, marked endometrial atrophy was observed in all the patients, including those in whom spotting had occurred. The ultrastructural investigation demonstrated complete involution of the cytoplasmic organelles with cytoplasmic collapse in glandular cells of patients treated with danazol, whereas in the gestrinone group degeneration phenomena were observed in both nucleus and cytoplasm. Irregular secretory transformation was seen in the endometria of patients in both groups. Long-term treatment with danazol caused endometrial atrophy similar to that induced by gestrinone, but it appeared earlier; thus, the former drug seems preferable in short-term treatment.

Adult↗
PubMed1990

A randomized double-blind prospective trial of two doses of gestrinone in the treatment of endometriosis.

The purpose of this randomized double blind prospective trial was to study the efficacy and safety of two doses of oral gestrinone in the treatment of endometriosis. Six patients received gestrinone 1.25 mg twice weekly (group I) and six patients received gestrinone 2.5 mg twice weekly (group II). Patients underwent pretreatment and post-treatment laparoscopies and their endometriosis scores were recorded. The mean total endometriosis scores declined significantly from 20.0 +/- 5.2 (mean +/- standard error of the mean) pretreatment to 9.5 +/- 3.9 post-treatment in group I and from 19.1 +/- 4.8 pretreatment to 7.1 +/- 2.1 post-treatment in group II. A total of 67% of patients reported side effects. This study suggests that oral gestrinone 1.25 mg or 2.5 mg twice weekly is efficacious and safe in the treatment of endometriosis.

Adult↗
PubMed1988

The inhibitory effects of danazol, danazol metabolites, gestrinone, and testosterone on the growth of human endometrial cells in vitro.

Danazol and gestrinone are effective drugs in the treatment of endometriosis. Their mechanism of action remains uncertain, but may be related to their androgenic activity. The authors examined the effect of danazol on human endometrial cells cultured in vitro, its two major metabolites, ethisterone and 2 hydroxymethyl ethisterone, gestrinone, and testosterone (T) at 1X and 10X expected plasma concentrations. Danazol and T suppressed growth by 20.8 and 25.0% (P less than 0.01), respectively, at the lower dose, and by 26.9 and 35.5% (P less than 0.01), respectively, at the 10-fold higher dose. No significant suppression of growth occurred with gestrinone, ethisterone, or 2 hydroxymethyl ethisterone. The results provide further evidence that danazol and T (but not gestrinone) may act by a direct effect on endometrial tissue.

Cell Division↗