Disease relevance of Leuprorelin

• RESULTS: The 10 women with premenstrual syndrome who were given leuprolide had a significant decrease in symptoms as compared with base-line values and with values for the 10 women who were given placebo [1].
• METHODS: In a 48-week, open-label study, we randomly assigned 47 men with advanced or recurrent prostate cancer and no bone metastases to receive either leuprolide alone or leuprolide and pamidronate (60 mg intravenously every 12 weeks) [2].
• Leuprolide acetate therapy in luteinizing hormone--dependent Cushing's syndrome [3].
• In a group of 25 premenopausal patients with progressive advanced breast cancer, daily sc administration of 1-10 mg Leuprolide [D-Leu6-Pro9GnRH ethylamide (NEt)] induced objective tumor regression in 44% with a median duration of 9 months [4].
• The patient's nausea, vomiting, abdominal pain, and early satiety resolved after a short course of treatment with leuprolide acetate but returned after medication was discontinued [5].

Psychiatry related information on Leuprorelin

• In response to treatment with leuprolide acetate, the threshold measured in wakefulness decreased during carbon dioxide rebreathing in the presence of low (41.05 +/- 0.77 versus 39.40 +/- 0.83 Torr; P = 0.01) and high (46.32 +/- 0.56 versus 44.78 +/- 0.83 Torr; P = 0.01) oxygen levels [6].
• No published studies have examined women with major depression to determine whether leuprolide will exacerbate or improve depressive symptoms [7].
• The newly developed leuprorelin acetate 3M depot, as a refinement of the established 1M depot, offers an opportunity to improve patient compliance and provides individualized and optimized, patient-orientated treatment by reducing the number of injections to four per year [8].
• Leuprolide acetate for exhibitionism in Huntington's disease [9].
• OBJECTIVE: To propose a protocol for minimizing medical complications associated with the use of cyproterone, medroxyprogesterone, and depot leuprolide to treat paraphilia [10].

High impact information on Leuprorelin

• The contraceptive group received the following: 7.5 mg leuprolide acetate depot by intramuscular injection every 28 days; 0.625 mg conjugated estrogen by mouth for 6 days out of 7 every week; and 10 mg medroxyprogesterone acetate orally for 13 days every fourth 28-day cycle [11].
• Oocytes were donated by fertile women (28.1 [2.7] years) who provided gametes after pituitary downregulation with leuprolide acetate and routine ovarian hyperstimulation by human menopausal gonadotropin [12].
• Pseudotumor cerebri associated with leuprorelin acetate [13].
• INTERVENTIONS: Men received depot leuprolide acetate (Lupron, 7.5 mg intramuscularly) every 4 weeks for 3 months [14].
• There are notable examples, such as the lipophilic leutinizing hormone releasing hormone (LHRH) analogs, Nafarelin and Leuprolide, that exhibit down-regulation of their own transport across the skin under the influence of an iontophoretic current [15].

Chemical compound and disease context of Leuprorelin

• The 10 women with premenstrual syndrome who were given leuprolide plus estradiol or progesterone had a significant recurrence of symptoms, but no changes in mood occurred in 15 normal women who received the same regimen or in 5 women with premenstrual syndrome who were given placebo hormone during continued leuprolide administration [1].
• MATERIALS AND METHODS: Between 1989 and 1995, 213 patients with localized prostate cancer were treated with a 3-month course of NAAD that consisted of leuprolide acetate and flutamide before 3D-CRT [16].
• PATIENTS AND METHODS: In a 12-month, open-label study, we randomly assigned 52 men with prostate cancer and no bone metastases to receive either leuprolide or bicalutamide (150 mg by mouth daily) [17].
• PURPOSE: To assess the efficacy and toxicity of suramin, hydrocortisone, leuprolide, and flutamide in previously untreated metastatic prostate cancer [18].
• Twenty-four (39%) had characteristic polycystic ovaries on ultrasound, an exaggerated response of 17-hydroxyprogesterone to leuprolide, or both, suggesting ovarian hyperandrogenism and the diagnosis of mild polycystic ovary syndrome [19].

Biological context of Leuprorelin

• RESULTS: Mean (+/- standard error) bone mineral density of the posterior-anterior lumbar spine decreased by 2.5% +/- 0.5% in the leuprolide group and increased by 2.5 +/- 0.5 in the bicalutamide group from baseline to 12 months (P <.001) [17].
• We conclude that leuprolide administered to women with PCO decreases gonadal steroid production and is capable of preventing premature luteinization during hMG induction of ovulation [20].
• Among post-menarcheal PP girls (n = 69), shorter CAG number (biallelic mean </=20) was associated with higher 17-hydroxy-progesterone levels post leuprolide (P = 0.009), indicative of ovarian hyperandrogenism, higher testosterone levels (P = 0.02), acne (P = 0.03) and hirsutism scores (P = 0.01), and more menstrual cycle irregularities (P = 0.04) [21].
• Specific growth factors or intrafollicular hormones may contribute to this leuprolide acetate-induced difference in cell cycle kinetics [22].
• The mean (+/-SD) numbers of oocytes retrieved were 9.8 +/- 5.4, 8.7 +/- 4.5, and 8.3 +/- 3.3; the percentages of metaphase II oocytes were 72%, 85%, and 86%; and fertilization rates were 61%, 62%, and 56% in the triptorelin, leuprorelin, and hCG group, respectively (P = NS for all three comparisons) [23].

Anatomical context of Leuprorelin

• Preoperative leuprorelin acetate therapy increased levels of Egr-1 mRNA in normal myometrium only [24].
• We have previously shown that the proliferative index (PI), as determined by flow cytometry of luteinized granulosa cells obtained at oocyte retrieval, is greater in ovulation induction regimens which include the GnRH analog (GnRH-a) leuprolide acetate than those using human menopausal gonadotropin (hMG) only [22].
• Inhibition of in situ expression of aromatase P450 in leiomyoma of the uterus by leuprorelin acetate [25].
• To this end, we implemented a novel clinical investigative paradigm consisting of preadministration of an LH-down-regulating dose (3.75 mg) of leuprolide acetate followed, 3-4 wk later, by controlled challenge of the testis, with pulsatile iv infusions of saline vs. recombinant human (rh) LH [26].
• Furthermore, in a dose-dependent manner, GnRH agonist (leuprolide acetate) inhibited, but GnRH antagonist [D-pGlu1,D-Phe2,D-Trp3.6] (GnRH-Ant1) stimulated, the rate of [3H]thymidine incorporation into myometrial smooth muscle cells (P < 0.05), whereas GnRH-Ant2 (Ac-D-P-Cl-Phe1.2,D-Trp3,D-Arg6,D-Ala10) had no effect [27].

Associations of Leuprorelin with other chemical compounds

• Recent evidence that it depresses testosterone synthesis in humans prompted us to investigate the effects in rats of its administration alone or in combination with the gonadotropin releasing hormone superagonist analogue leuprolide [28].
• Androgen deprivation with leuprorelin inhibits mutant AR accumulation, resulting in rescue of neuronal dysfunction in a mouse model of SBMA [29].
• This study was performed to evaluate the effectiveness of depot leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a), for protection against POF during CYC therapy [30].
• All patients underwent leuprolide acetate and ACTH testing, dexamethasone and ovarian suppression tests, and pelvic ultrasonography [31].
• Serum 1,25-dihydroxyvitamin D levels increased in response to PTH infusion before leuprolide therapy (P = 0.022), but there was no difference in the rate of increase before or after leuprolide therapy (P = 0.66) [32].

Gene context of Leuprorelin

• Standard reverse transcription-PCR revealed that the unaffected myometrium and leiomyomata from leuprolide-treated and untreated patients express TGF beta 1-3 and TGF beta type I-III receptor mRNA [33].
• The expression and cellular distribution of transforming growth factor-1 (TGF beta 1) through TGF beta 3 and TGF beta type I-III receptor messenger ribonucleic acid (mRNA) and protein were analyzed in leiomyomata from patients receiving GnRH agonist (GnRHa; leuprolide acetate) compared to those in untreated controls [33].
• Leuprorelin acetate affects ERK1/2 activity in prostate cancer cells [34].
• Expression of estrogen receptor alpha and beta mRNAs in prostate cancers treated with leuprorelin acetate [35].
• However, hTERT mRNA expression showed a decrease in the leuprolide-treated cells [36].

Analytical, diagnostic and therapeutic context of Leuprorelin

• Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer [37].
• Five other patients received subcutaneous injections of leuprorelin and underwent scrotal skin biopsy [29].
• Regression of 7,12-dimethylbenz(a)-anthracene-induced mammary tumors in Sprague-Dawley rats by consecutive daily vaginal administration of leuprolide was investigated [38].
• Ovarian suppression was carried out with leuprolide acetate (1 mg, sc) daily until the serum estradiol level was 30 pg/mL and was continued thereafter during ovarian stimulation with im human menopausal gonadotropin or FSH [39].
• Results of long-term follow-up after treatment of central precocious puberty with leuprorelin acetate: evaluation of effectiveness of treatment and recovery of gonadal function. The TAP-144-SR Japanese Study Group on Central Precocious Puberty [40].

References