leuprolide and Atrophy

Thirty-four premenopausal women were randomized to receive 3.75 mg of leuprorelin acetate depot or placebo for 8 weeks before hysterectomy. Postoperatively, the myometrium was examined by two independent pathologists and the pathologic features were graded. Computer analysis was used to assess myometrial cellularity and arterial wall structure (on hematoxylin and eosin-stained sections) and vascularity (on sections immunostained for Factor VIII-related antigen). The cellularity of the gonadotrophin-releasing hormone agonist-treated myometrium was higher than the controls with less stromal edema. Focal myometrial hyalinization was present in a minority of cases, all in the gonadotrophin-releasing hormone agonist-treated cases. The arteries in the gonadotrophin-releasing hormone agonist-treated uteri underwent atrophy of the tunica media and had significantly more perivascular fibrosis. The number of vessels per 100 myocytes also was decreased. Hypoestrinism secondary to leuprorelin treatment leads to myocyte atrophy, decreased stromal edema, atrophy of the arcuate arteries, and decreased myometrial vascularity.

Topics: Arteries; Atrophy; Delayed-Action Preparations; Double-Blind Method; Edema; Estradiol; Female; Fibrosis; Humans; Leuprolide; Menopause; Models, Biological; Myometrium; Placebos; Stromal Cells

Organisms are constantly in a balance meaning that while new cells are produced, some of the older ones die which takes place in 2 ways: necrosis or apoptosis. Apoptosis is the programmed cellular death triggered by intrinsic or extrinsic stimuli. In this study we have evaluated the apoptosis of prostate tissue generated by surgical or medical orchiectomy.. In this experimental study, we used 36 adult male rats that were evaluated in 3 groups. The first group (Group 1) consisted of 12 rats that had bilateral orchiectomy; the second group (Group 2) included 12 rats that were given leuprolide acetate and the third group (Group 3) consisted of 12 control rats. Immunohistochemical staining of the prostate of all rats was performed and the presence of glandular atrophy and apoptosis were evaluated in the three groups. The statistical differences between the two groups were evaluated by the Fisher exact test.. Glandular atrophy was not determined in any rat of the control group, and the apoptotic staining was in the normal limits in all the control rats. In Leuprolide group, glandular atrophy was mild in 7 cases, and moderate in 3 rats. In 2 rats of the Leuprolide group, atrophy was not demonstrated. In surgical orchiectomy group, glandular atrophy was present in all cases. Atrophy was observed as cystic atrophy. Statistical analysis with the Fisher exact test revealed that glandular atrophy was statistically significantly more common in surgical orchiectomy group compared with Leuprolide group (p = 0,012).. If the aim of treatment in androgen dependent prostatic adenocarcinoma or benign prostate hypertrophy is the construction of a robust apoptosis, bilateral orchiectomy generates a more powerful apoptosis compared with Leuprolide.

Topics: Animals; Antineoplastic Agents, Hormonal; Apoptosis; Atrophy; Disease Models, Animal; Leuprolide; Male; Orchiectomy; Prostate; Rats; Reproducibility of Results

Lipopolysaccharide (LPS) causes acute thymic atrophy, a phenomenon that has been linked to immune dysfunction and poor survival during sepsis. The systemic response to LPS involves a rise in glucocorticoids and proinflammatory cytokines which contribute greatly to thymic involution and apoptosis. Gonadotropin-releasing hormone (GnRH) analog exerts thymopoietic regulatory effects and possesses immunostimulant properties. We determined whether leuprolide, a GnRH analog can be useful in LPS induced thymic involution and apoptosis. Mice injected with 100 μg of LPS intraperitoneally led to involution of thymus, to decrease of CD4(+)8(+) thymocyte subset, and to fragmentation of thymic DNA. Leuprolide (100 μg/mouse, s.c.) pretreatment significantly attenuated LPS induced thymic atrophy, and also reduced LPS induced systemic rise in corticosterone levels. The observed effect of leuprolide remained unaffected in castrated and ovariectomized mice. Collectively, leuprolide has protective action independent of gonadal steroids, which was mediated by blunting of the systemic corticosteroid response in LPS induced thymic atrophy model.

Topics: Animals; Apoptosis; Atrophy; Castration; Corticosterone; Disease Models, Animal; DNA Fragmentation; Female; Gonadal Hormones; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Lipopolysaccharides; Lymphopoiesis; Male; Mice; Ovariectomy; T-Lymphocytes; Thymus Gland

To investigate the effects of cyclooxygenase-2 (COX-2) inhibitor rofecoxib on endometrial explants and on peritoneal vascular endothelial growth factor (VEGF) levels in the rat endometriosis model.. Prospective, placebo-controlled study.. Laboratory at Dokuz Eylül University.. Twenty-six rats with experimentally induced endometriosis.. Rats were treated for 3 weeks with oral rofecoxib (3 mg/kg per day; n = 9); single subcutaneous injection of depot leuprolide acetate (1 mg/kg; n = 9); or vehicle (control; n = 8).. Change in explant area and histologic examination by semiquantitative analysis of endometriotic explants and measurement of peritoneal VEGF levels.. Three weeks of treatment with rofecoxib statistically significantly decreased the implant size (62.4%) compared with control (16.6%), and this effect was comparable with the decrease in leuprolide (64.3%). Histologic examination of the explants indicated mostly atrophy and regression in treatment groups, and semiquantitative analysis showed statistically significantly lower scores in rats treated with rofecoxib and leuprolide compared with controls. Both rofecoxib and leuprolide statistically significantly decreased VEGF levels compared with controls.. Rofecoxib causes regression and atrophy of the endometriotic lesions and is as effective as a GnRH agonist with an accompanying decrease in the VEGF levels.

Topics: Administration, Oral; Animals; Ascitic Fluid; Atrophy; Cyclooxygenase Inhibitors; Endometriosis; Female; Gonadotropin-Releasing Hormone; Injections, Subcutaneous; Lactones; Leuprolide; Rats; Rats, Wistar; Sulfones; Vascular Endothelial Growth Factor A

Aging in the male human is accompanied by testicular atrophy, although relatively little is known about the mechanisms underlying germ cell loss. Testicular atrophy in the aged Brown Norway rat, an animal model for studies of aging in the human, has been attributed to a loss of spermatogonial stem cells. However, examination of testicular cross-sections from 27-mo-old Brown Norway rats indicated that approximately 14% of type A spermatogonia were stem cells. Furthermore, using bromodeoxyuridine labeling, we found that approximately 47% of these stem cells were actively dividing, with a cell cycle time of approximately 12.6 days. Both serum and testicular interstitial fluid testosterone levels were depressed in the aged rat. Therapy with the GnRH agonist, leuprolide, which has been empirically shown to reverse testicular atrophy in other models of germ cell loss, also partially restored spermatogenesis in the aged Brown Norway rat. The extent of testicular atrophy varied considerably, not only within the control and leuprolide-treatment groups but also between the left and right testes of the same animals. No significant difference was found between the mean percentage of populated tubules in 31-mo-old control animals (16.2 +/- 28%, mean +/- SD) and 31-mo-old leuprolide-treated animals (20.9 +/- 19.8%), but categorical comparisons showed that significantly fewer leuprolide-treated animals and testes contained < or = 1% populated tubules, indicating that GnRH agonist therapy stimulates differentiation of type A spermatogonia. An increase in the ratio of soluble to membrane stem cell factor mRNA levels was present in aged rats and partially reversed following leuprolide therapy.

Topics: Aging; Animals; Atrophy; Cell Division; Extracellular Space; Gene Expression; Leuprolide; Male; Rats; Rats, Inbred BN; RNA, Messenger; Sertoli Cells; Spermatogenesis; Spermatogonia; Stem Cell Factor; Stem Cells; Testis; Testosterone

Future fertility is a major concern for cancer patients who undergo intensive chemotherapy. There has been controversy about whether hormonal treatments may have protective effects against the severe spermatogenic damage caused by chemotherapy or irradiation. Recently, it has been proposed that gonadotrophin-releasing hormone (GnRH) analogs administered after testicular damage stimulate the recovery of spermatogenesis. In this study, we have investigated the effects of GnRH agonist, leuprorelin, on the damage to spermatogenesis induced by busulfan.. Fisher rats were treated with busulfan, 25 mg/kg, intraperitoneally. The effects of subcutaneous injections of leuprorelin before or after treatment were evaluated histologically 18 weeks later.. The percentage of 'recovered' seminiferous tubules was 27.7 +/- 12.6% in control rats without leuprorelin and 26.9 +/- 10.2% in rats with leuprorelin injected 4 weeks before busulfan. Rats in both groups showed poor recovery of spermatogenesis with an increase of intratesticular fluid. However, rats treated with leuprorelin three times (4 weeks apart) after busulfan showed an improvement of up to 56.5 +/- 12.0% (P < 0.05). A focal but massive necrotic lesion in the testis was observed only in this group of rats.. The results demonstrated that leuprorelin administered after chemical testicular damage enhanced the recovery of spermatogenesis. At the same time, a possible significant side-effect of leuprorelin was noted.

Topics: Animals; Antineoplastic Agents, Alkylating; Atrophy; Busulfan; Gonadotropin-Releasing Hormone; Leuprolide; Male; Necrosis; Rats; Rats, Inbred F344; Regeneration; Seminiferous Tubules; Spermatogenesis; Testis

To study the pathological changes of the effect of combined endocrine therapy on normal prostate, benign prostatic hyperplasia, prostatic adenocarcinoma and testis.. 11 radical prostatectomy specimens, 3 core-needle biopsies of prostate and 3 testes obtained after at least 3 months of enatone-flutamide inhibition therapy were studied. Step-section was performed on radical specimens and average 16 sections per case were reviewed. PSA, PSAP and AE1/AE3 were immunostained on 14 cases of prostate cancer and a comparative study pre- and post-treatment was made.. No residual tumor was recognized in 2 cases. Such characteristic changes were found in 9 cases as prominent acinar atrophy, decreased ratio of acini to stroma, stromal fibrosis, squamous metaplasia of carcinoma, cytoplasmic vaculation, nuclear shrinkage, and nucleolar shrinkage. No apparent change was discovered in 3 cases. Secretory epithelial atrophy and basal cell hyperplasia were the popular change in BPH and normal prostate. The expressions of both PSA and PSAP were markedly reduced in prostate carcinoma and nonneoplastic glands. Pathological downstaging of the tumor was not found statistically. Epithelial atrophy also existed in seminal vesicles and Leydig cells of the testes after hormone therapy.. Combined endocrine therapy results in histologically distinctive changes that can be found in both nonneoplastic and neoplastic prostate tissue. However, the drugs can not eradicate prostate cancer completely. Testis atrophy is the direct action of the therapy.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Atrophy; Drug Therapy, Combination; Flutamide; Humans; Leuprolide; Male; Middle Aged; Prostate; Prostatic Neoplasms; Testis

2,5-Hexanedione (2,5-HD) exposure in the rat produces irreversible testicular atrophy, a model of human male infertility that can be used for mechanistic and therapeutic studies. Following testicular injury by 2,5-HD, stem cell factor (SCF), a Sertoli cell-derived growth factor that binds the c-kit receptor on spermatogonia, is altered in its expression, changing from predominantly membrane SCF to predominantly soluble SCF. The goals of this study were 2-fold: first, evaluate leuprolide, a GnRH agonist, as a therapy for 2,5-HD-induced testicular atrophy, and second, examine changes in SCF expression during testicular injury and following recovery from injury. Rats exposed to 2,5-HD showed a nearly complete testicular atrophy that could be reversed by leuprolide therapy. Using RT-PCR, preferential expression of membrane SCF was associated with spermatogenesis, whereas soluble SCF expression was associated with atrophy. In conclusion, 2,5-HD exposure altered the form of SCF expressed and disrupted spermatogenesis; leuprolide therapy allowed recovery of spermatogenesis, which correlated with a normalization in growth factor expression in an otherwise irreversibly atrophic testis.

Topics: Animals; Atrophy; Hexanones; Leuprolide; Male; Rats; Rats, Inbred F344; Spermatogenesis; Stem Cell Factor; Testis

To study a standardized technique for endometrial rollerball ablation and various methods of preoperative preparation.. All patients had refractory symptomatic menorrhagia and previously failed conservative surgery and other forms of medical therapy, such as progestogens. Patients received a preoperative regimen of either leuprolide acetate, danazol, Nolvadex or Depo-Provera. They then underwent hysteroscopically controlled rollerball ablation at 80-100 W with 1.5% glycine as the distending medium. The endometrium was evaluated hysteroscopically and considered to be completely atrophic, intermediate or no response.. Refractory symptomatic menorrhagia was treated successfully in 38 of 40 patients. Nineteen reported amenorrhea; the other 21 reported subjective and objective improvement of bleeding. Three patients, despite improvements in flow, were unhappy with the overall result. Two did not wish repeat ablation and subsequently underwent vaginal hysterectomy. The third underwent repeat ablation and became amenorrheic. The ability to achieve complete endometrial atrophy prior to ablation was improved with leuprolide acetate (19/24) and danazol (5/6) when compared to tamoxifen (0/4) and Depo-Provera (0/6). Attainment of amenorrhea after ablation was significantly improved when complete atrophy (19/24) was achieved prior to ablation as compared to the ability to achieve amenorrhea when no endometrial response was achieved (0/7). The only significant complication was one uterine perforation in a patient undergoing repeat ablation.. Endometrial rollerball ablation is a safe, effective means of controlling refractory menorrhagia. Amenorrhea is best attained when complete preoperative atrophy is achieved. Leuprolide and danazol were superior to tamoxifen and Depo-Provera.

Topics: Antineoplastic Agents; Atrophy; Danazol; Dilatation and Curettage; Electrocoagulation; Endometrium; Estrogen Antagonists; Female; Humans; Hysteroscopy; Leuprolide; Medroxyprogesterone Acetate; Menorrhagia; Preoperative Care; Retrospective Studies; Tamoxifen; Treatment Outcome