Disease relevance of Dimetriose

• Endometrial patterns during therapy with danazol or gestrinone for endometriosis: structural and ultrastructural study [1].
• Long-term treatment of leiomyomas with gestrinone [2].
• 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 [3].
• In the present study, we demonstrated a reduction in the volume of uterine myomas and in the uterine artery blood perfusion over a 6-month period of gestrinone administration in premenopausal women [4].
• Gestrinone in the treatment of menorrhagia [5].

Psychiatry related information on Dimetriose

• Both dyspareunia and chronic pain were significantly reduced by the gestrinone treatment [6].
• RESULT(S): Side effects were infrequent in both groups, though the patients' personal satisfaction was in favor of gestrinone [7].

High impact information on Dimetriose

• Discovery, biosynthesis, and structure elucidation of metabolites of a doping agent and a direct analogue, tetrahydrogestrinone and gestrinone, using human hepatocytes [8].
• Due to high structure similarity, both THG and gestrinone had an analogous in vitro metabolic pathway leading to successive addition of a hydroxyl and a beta-glucuronic acid at C-18 [8].
• At 3 months of treatment, the endometria of the danazol-treated patients were more atrophic than those of the women who received gestrinone [1].
• 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 [1].
• THG was synthesized by hydrogenation of gestrinone and characterized by mass spectrometry and NMR spectroscopy [9].

Chemical compound and disease context of Dimetriose

• 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 [10].
• 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 [11].
• OBJECTIVES: To determine effectiveness of a) ovulation suppression with danazol, medroxy progesterone acetate, gestrinone, combined oral contraceptive pills and GnRH analogues versus placebo or no treatment and b) any of the above agents versus danazol, for the treatment of endometriosis explained infertility in terms of clinical pregnancy rate [12].

Biological context of Dimetriose

• 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 [13].
• The common OR for pregnancy after ovulation suppression (MPA, gestrinone, or GnRH agonist) versus danazol was also nonsignificant: 1.07 [14].
• 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 [15].
• It is hypothesized that incomplete endometrial involution could be due to differences in gestrinone pharmacokinetics in individual patients, in the quality and/or quantity of endometrial cytosolic receptors for sex steroids, or in endocrine compensation to administration of the drug [16].
• The histology and ultrastructure of small endometriotic lesions were studied in 19 patients before and after hormonal therapy with the anti-progesterone steroid R 2323 (Gestrinone) [17].

Anatomical context of Dimetriose

• The effect of a synthetic progestogen, ethylnorgestrienone, on hypothalamic-pituitary-ovarian function, cervical mucus, vaginal cytology, and endometrial morphology [18].
• 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 [19].
• Gestrinone inhibits macrophage function and mitogen-stimulated lymphocyte proliferation in vitro [15].
• The morphologic data demonstrate that the cellular involutionary response to the antiprogesterone drug Gestrinone involves an activation of the lysosomal system, an abortive apocrine secretion of cell remnants and finally, in some implants, an extrusion of individual epithelial cells [17].
• ANIMAL: 8 dogs (1 of which was treated with gestrinone) and 5 cats with intracranial meningiomas and 2 dogs with spinal cord meningiomas; tissue samples were also obtained from 1 clinically normal dog and 1 clinically normal cat [20].

Associations of Dimetriose with other chemical compounds

• The effects of gestrinone on the endometrium, a decrease in estrogen and progestin receptors, and induction of 17 beta-HSD are characteristic progestin actions [10].
• A comparison of the effects of danazol and gestrinone on testosterone binding to sex hormone binding globulin in vitro and in vivo [21].
• 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 [10].
• Mitotic index was similar in the group of untreated women (n = 32) and in the three groups of women treated either with lynestrenol (Organon, Oss, The Netherlands), gestrinone (Roussel UCLAF, Paris, France), or buserelin (Hoechst, Frankfurt, West Germany) [22].
• Comparative clinical trial of the progestins R-2323 and levonorgestrel administered by subdermal implants [23].

Gene context of Dimetriose

• The mean SHBG binding capacity in patients treated with danazol (400 mg/d, n = 7) and gestrinone (5 mg/week, n = 7) fell from 66.9 and 56.4 nmol/l to 36.1 and 28.1 nmol/l, after 1 week's treatment and to 11.1 and 7.1 nmol/l after 4 weeks respectively [21].
• Gestrinone's more avid affinity for estrogen receptor may be the reason for the ability to use a lower clinical dose of gestrinone [11].
• 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 [24].

Analytical, diagnostic and therapeutic context of Dimetriose

• Multicentre study of gestrinone in cyclical breast pain [25].
• 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) [3].
• Gestrinone was studied by HPLC for screening and by GC/MS for confirmation [26].
• Regression of uterine leiomyomas after treatment with gestrinone, an antiestrogen, antiprogesterone [6].
• Determination and excretion study of gestrinone in human urine by high performance liquid chromatography and gas chromatography/mass spectrometry [26].

References