leuprolide and Uterine-Diseases

To assess the recurrence rate of endometrioma after laparoscopic cystectomy plus hormonal suppression treatment or plus dietary therapy compared to post-operative placebo.. A randomized comparative trial was conducted on 259 consecutive women who underwent laparoscopic unilateral/bilateral cystectomy for endometrioma. Seven days after surgery, the patients were randomly allocated on the basis of a computer-generated randomization sequence, to one of four post-operative management arms as follows: placebo (n=65) or gonadotrophin-releasing hormone analogue (tryptorelin or leuprorelin, 3.75 mg every 28 days) (n=65) or continuous low-dose monophasic oral contraceptives (ethynilestradiol, 0.03 mg plus gestoden, 0.75 mg) (n=64) or dietary therapy (vitamins, minerals salts, lactic ferments, fish oil) (n=65) for 6 months. At 18 months' follow-up after surgery, all patients were monitored with a clinical gynecologic examination, and a transvaginal ultrasonography for possible evidence of endometrioma recurrence.. At 18 months' transvaginal ultrasonographic follow-up after surgery, no significant recurrence rate of endometrioma was detected in women who received a postoperative course of hormonal suppression treatment or dietary therapy when compared with placebo (placebo vs. GnRH-a P=0.316, placebo vs. estroprogestin P=0.803, placebo vs. dietary therapy P=0.544). Second-look laparoscopy was performed on a clinical basis and confirmed the ultrasonographic suspicion of recurrence of endometrioma in all cases: 10 (16.6%) in the post-operative placebo group vs. 6 (10.3%) in the post-operative GnRH-a group vs. 9 (15.0%) in the post-operative continuous estroprogestin group vs. 11 (17.8%) in the post-operative dietary therapy group. Of 36 patients with recurrent ovarian endometriosis, 8 had recurrence on the treated ovary, 20 on the contralateral ovary that appeared to be normal at the time of the first-line surgery, and 8 on both the treated and untreated ovaries. Endometrioma recurrences were associated with moderate-to-severe painful symptoms in 14/36 patients (38.8%), while the remaining 22 (61.1%) patients were asymptomatic.. A 6-month course of hormonal suppression treatment or dietary therapy after laparoscopic cystectomy had no significant effect on the recurrence rate of ovarian endometriosis when compared with surgery plus placebo. So, treatment of endometrioma can be carried out exclusively by laparoscopic cystectomy without post-operative therapy, if a complete excision of ovarian endometriosis has been assured.

Topics: Adult; Combined Modality Therapy; Contraceptives, Oral, Combined; Diet Therapy; Dietary Supplements; Endometriosis; Endometrium; Ethinyl Estradiol; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Gynecologic Surgical Procedures; Humans; Laparoscopy; Leuprolide; Minerals; Norpregnenes; Secondary Prevention; Treatment Outcome; Ultrasonography; Uterine Diseases; Vitamins

We compared the effects of levonorgestrel-releasing intrauterine devices (LNG-IUD) and a gonadotropin-releasing hormone agonist (GnRHa) on uterine volume, uterine arteries pulsatility index (PI) and endometrial thickness before and after six months of endometriosis treatment. Sixty women aged 18-40 y were allocated randomly to one of two groups: LNG-IUDs were inserted in 30 women, and GnRHa monthly injections were performed on the other 30. All 60 women were submitted to transvaginal 2-D ultrasound scans on the day that the treatment started and then six months later. Measurements of uterine arteries PI, uterine volume and endometrial thickness were performed at both evaluations. The use of LNG-IUDs significantly decreased endometrial thickness (pre = 6.08 +/- 3.00 mm, post = 2.7 +/- 0.98 mm; mean +/- SD), as did the use of GnRHa (pre = 6.96 +/- 3.82 mm, post = 3.23 +/- 2.32 mm). The uterine volume decreased in the GnRHa group (pre = 86.67 +/- 28.38 cm(3), post = 55.27 +/- 25.52 cm(3)), but not in the LNG-IUD group (pre = 75.77 +/- 20.88 cm(3), post = 75.97 +/- 26.62 cm(3)). Uterine arteries PI increased for both groups; however, the increase was higher in the GnRHa group (0.99 +/- 0.84 vs. 0.38 +/- 0.84, p = 0.007; PI increase in GnRHa and in LNG-IUD groups, respectively). In conclusion, levonorgestrel released directly onto the endometrium by the LNG-IUD induced smaller uterine changes than did the hypoestrogenism induced by GnRHa. Nevertheless, both promoted similar effects on endometrial thickness.

Topics: Adolescent; Adult; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Intrauterine Devices, Medicated; Leuprolide; Levonorgestrel; Pulsatile Flow; Ultrasonography; Uterine Diseases; Uterus; Young Adult

It is generally assumed that delayed endometrial development observed in luteal phase deficiency (LPD) is the result of abnormally low progesterone (P) levels. This hypothesis has never been tested by direct experiment.. Our objective was to evaluate the effects of P concentrations on human endometrium.. A randomized trial was conducted at an academic medical center.. Twenty-nine healthy, ovulatory 18- to 35-yr-old women participated.. Endometrial samples were obtained from women in natural cycles and two groups of experimentally modeled cycles. Women undergoing modeled cycles were treated with GnRH agonist and a fixed physiological dose of transdermal estradiol, followed by randomization to 10 or 40 mg daily im P administration to achieve either normal circulating luteal P or 4-fold lower P concentrations, the latter representing an experimental model of LPD.. Tissue specimens, obtained after 10 days of P exposure, were analyzed by histological dating, immunohistochemistry, immunoblot, and real-time quantitative RT-PCR (qRT-PCR).. Histological dating of endometrium, immunohistochemistry for endometrial integrins, and qRT-PCR analysis for nine putative functional markers showed no differences between the three groups. Preliminary data from Western analysis suggest that some proteins may be affected by low serum P concentrations.. Histological endometrial dating does not reflect circulating P concentrations and cannot serve as a reliable bioassay of the quality of luteal function. Assessment of selected functional markers by either immunohistochemistry or qRT-PCR is similarly insensitive to decreased circulating P. Preliminary evidence suggests that abnormally low luteal phase serum P concentrations may have important functional consequences not otherwise detected.

Topics: Administration, Cutaneous; Adolescent; Adult; Dose-Response Relationship, Drug; Endometrium; Estradiol; Female; Fertility Agents, Female; Humans; Leuprolide; Luteal Phase; Organ Size; Progesterone; Uterine Diseases

A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain.. This multicentre, 18 month, evaluator-blinded, comparator-controlled trial randomized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA (DMPA-SC 104) every 3 months or leuprolide (3.75 mg monthly or 11.25 mg every 3 months), with 12 months post-treatment follow-up. Endpoints included patient response to treatment in five signs/symptoms (dysmenorrhoea, dyspareunia, pelvic pain, pelvic tenderness, induration) and changes in bone mineral density (BMD) and productivity at 6 and 18 months.. DMPA-SC 104 and leuprolide produced equivalent (P < 0.02) reductions in at least four pain categories and significant (P < 0.001) improvements in composite score at months 6 and 18. At month 6, reductions in total hip and lumbar spine BMD were significantly less (P < 0.001) with DMPA-SC 104 versus leuprolide. BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group. Total productivity also significantly (P < or = 0.05) improved in both groups at 6 and 18 months.. DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline.

Topics: Administration, Cutaneous; Adult; Antineoplastic Agents, Hormonal; Bone Density; Contraceptive Agents, Female; Endometriosis; Female; Fertility Agents, Female; Hip; Humans; Leuprolide; Lumbar Vertebrae; Medroxyprogesterone Acetate; Pelvic Pain; Quality of Life; Radiography; Treatment Outcome; Uterine Diseases

In order to assess the endocrinological changes associated with 2 types of low-dose GnRH agonists depot as well as their clinical efficacy, we performed a randomized prospective comparison study of patients having uterine leiomyomas or endometriosis.. A prospective randomized study involving 67 patients with uterine leiomyomas or endometriosis was carried out. These patients were randomly administered either buserelin MP 1.8 mg (Group B, n = 34) or leuprolide 1.88 mg (Group L, n = 33). In each group we evaluated the symptoms of genital bleeding and hot flashes during GnRHa treatment, as well as the levels of serum LH, FSH, and estradiol 8 weeks after the start of treatment. In addition, the endometrial thickness was measured by transvaginal ultrasonography, and changes in the volume of the uterine leiomyoma or endometrial cyst at the end of treatment. The GnRHa depot was administered from 3 to 8 times, 28 days apart, in both groups.. The incidence of menstruation-like genital bleeding 8 weeks after treatment was significantly (p < 0.01) higher in Group B. However this difference disappeared by 12 weeks after treatment. The climacteric symptom of hot flashes was found to be significantly (p < 0.01) more severe in Group L, and this tendency continued until 20 weeks after treatment. The 2 groups did not differ significantly with regard to the levels of the serum LH, FSH, and estradiol at 8 weeks after treatment or in the endometrial thickness at the end of the GnRHa treatment. In both groups, the volumes of the uterine leiomyomas were significantly (p < 0.01) lower after the treatment. In contrast, the volumes of the endometrial cysts did not decrease after administration of GnRHa in both groups.. Leuprolide 1.88 induced pituitary down regulation more rapidly than buserelin MP. However the hypoestrogenic symptoms such as hot flashes were more severe in cases treated with leuprolide 1.88 than in those treated with buserelin MP. Our data confirm that the therapeutic efficacy of buserelin MP and leuprolide 1.88 are similar, with both being sufficient to treat uterine leiomyomas and endometriosis.

Topics: Adult; Antineoplastic Agents, Hormonal; Buserelin; Endometriosis; Endometrium; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hot Flashes; Humans; Leiomyoma; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Ovarian Diseases; Prospective Studies; Treatment Outcome; Ultrasonography; Uterine Diseases; Uterine Hemorrhage

To investigate the effects of GnRH antagonist (GnRH-ant) and agonist (GnRH-a) in the prevention of postoperative pelvic adhesions by a visual scoring system and immunohistochemical methods in a rat uterine horn model.. Controlled experimental animal study.. Animal laboratory at an academic research environment.. Twenty-one Wistar albino rats.. Rats were randomized into three groups. One week before the operation the rats received either GnRH-ant or GnRH-a or saline solution; they then underwent surgical laparotomy, and both uterine horns were traumatized by a scalpel. Three weeks later, all rats were sacrificed and extension and severity of the adhesions in each group were scored by a visual scoring system. Adhesion tissues were evaluated immunohistochemically for vitronectin and u-PAR.. Scores of extend and severity of adhesions and staining of vitronectin and u-PAR.. The extent of adhesion scores were 1.85 ± 0.86, 0.78 ± 1.05, and 0.42 ± 0.64, and the severity of adhesion scores were 1.71 ± 0.91, 0.57 ± 0.85, 0.50 ± 0.75 for control, GnRH-ant, and GnRH-a groups, respectively. The extent and severity of adhesions were significantly lower in both GnRH-ant and GnRH-a groups when compared with the control group. Adhesion extent scores in the GnRH-a group were lower than in the GnRH-ant group, but this difference was not significant. vitronectin and u-PAR staining were significantly greater in both the GnRH-ant and GnRH-a groups than in the control group.. GnRH-ant as well as GnRH-a reduced postoperative adhesion formation in a rat model. This finding was supported immunohistochemically by vitronectin and u-PAR staining.

Topics: Animals; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Immunohistochemistry; Leuprolide; Postoperative Complications; Rats; Rats, Wistar; Receptors, Urokinase Plasminogen Activator; Severity of Illness Index; Time Factors; Tissue Adhesions; Uterine Diseases; Uterus; Vitronectin

Uterocutaneous fistula is a rare complication of uterine surgery. All published cases have been surgically treated with hysterectomy and excision of the fistulous tract. We report a case of uterocutaneous fistula that was successfully treated with gonadotropin-releasing hormone agonist administration.. A 25-year-old woman reported bloody discharge during her periods from a previous Pfannenstiel incision. A fistulous tract leading from the incision scar to the uterus was diagnosed. Leuprolide acetate depot was administered twice subcutaneously at a dose of 11.25 mg. The fistulous tract closed spontaneously, and the patient was symptom free thereafter.. Medical treatment with gonadotropin-releasing hormone agonists should be considered before resorting to surgery for treatment of uterocutaneous fistulae.

Topics: Adult; Antineoplastic Agents, Hormonal; Cesarean Section; Cutaneous Fistula; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Uterine Diseases

Vesicouterine fistula is a rare complication of cesarean section. Although surgical repair was mandatory for the management of the fistula previously, a recent review showed high efficacy of hormonal manipulation by the induction of amenorrhea. Herein, we report a new case of vesicouterine fistula secondary to cesarean section successfully treated by luteinizing hormone-releasing hormone analog for 6 months. Conservative hormonal treatment for vesicouterine fistula caused by cesarean section should be considered before surgical repair.

Topics: Adult; Cystoscopy; Female; Fertility Agents, Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leuprolide; Magnetic Resonance Imaging; Urinary Bladder Fistula; Uterine Diseases

To investigate whether GnRH agonists or danazol therapy normalizes estrogen metabolism in the eutopic endometrium of women with endometriosis, adenomyosis, or leiomyomas.. Prospective clinical study.. University hospital.. Fifty-three women with endometriosis, adenomyosis, or leiomyomas.. Patients received GnRH agonist or danazol. Biopsy samples of the endometrium were obtained before and after endocrine therapy. Nontreated endometrial explants were cultured in the presence of either drug.. Reverse transcription polymerase chain reaction-Southern blot and immunohistochemical analyses of the endometrial expression of aromatase cytochrome P450, estrogen receptor, progesterone receptor, and Ki-67. Nontreated endometrial explants were cultured in the presence of either drug.. Messenger RNA and protein of aromatase cytochrome P450 were greatly reduced in the eutopic endometrium of patients treated with GnRH agonist for 2 months or more or with danazol for 1 month or more. Culture of endometrial explants with GnRH agonist (10(-9)-10(-7) M) did not change the amount of aromatase cytochrome P450, whereas danazol (10(-7)-10(-6) M) efficiently reduced aromatase cytochrome P450 expression.. Therapy with GnRH agonist or danazol decreases expression of aromatase cytochrome P450 in diseased eutopic endometrium. Endocrine therapy normalized in part the impaired hormonal expression of the eutopic endometrium. GnRH agonist reduced aromatase cytochrome P450 expression mainly by promoting a hypoestrogenic state, whereas danazol reduced aromatase cytochrome P450 in part by direct action on the eutopic endometrium.

Topics: Adult; Antineoplastic Agents, Hormonal; Aromatase; Buserelin; Danazol; Endometriosis; Estrogen Antagonists; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; In Vitro Techniques; Ki-67 Antigen; Leiomyoma; Leuprolide; Middle Aged; Prospective Studies; Receptors, Estrogen; Receptors, Progesterone; RNA, Neoplasm; Uterine Diseases; Uterine Neoplasms

To assess whether the adhesion-preventing effect of gonadotropin-releasing hormone agonist (GnRHa) is through hypoestrogenism.. Four groups of previously ovariectomized rats received various combinations of depot leuprolide acetate injection (3.75 mg/kg/mo) subcutaneously, conjugated equine estrogens (50 micrograms/kg/d) orally and phosphate-buffered saline injection subcutaneously, yielding group 1, saline only; group 2, saline and conjugated equine estrogens; group 3, depot leuprolide acetate only; and group 4, depot leuprolide acetate and conjugated equine estrogens. Surgical adhesions were induced by monopolar cautery on the right uterine horn through laparotomy and were then scored on day 21 after surgery.. Adhesion scores for rats that received conjugated equine estrogens and saline were significantly higher than scores of those given conjugated equine estrogens and depot leuprolide acetate, depot leuprolide acetate only and saline only (P = .019, .026 and .027, respectively). However, there was no significant difference in the adhesion scores for these three groups.. Hypoestrogenism results in the development of fewer peritoneal adhesions postoperatively. Our findings also indicated that other mechanisms, in addition to those inducing hypoestrogenism, are at work in the adhesion-preventing effects of GnRHa therapy.

Topics: Animals; Delayed-Action Preparations; Estrogens, Conjugated (USP); Female; Horses; Leuprolide; Ovariectomy; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions; Uterine Diseases

This randomized blind study evaluated the effect of pantothenic acid on postoperative adhesion formation in euestrogenic and hypoestrogenic environment. We used the rat uterine horn model in a university-based laboratory setting. Thirty-six Sprague-Dawley rats were randomized into two estrogenic environments: euestrogenic and hypoestrogenic. The hypoestrogenic condition was achieved in 21 rats by either the administration of gonadotropin releasing hormone agonist or ovariectomy. The remaining 15 rats were untreated and remained in the regular estrogenic state. The left uterine horn was subjected to a lesion by serosal denudation at laparotomy. Following the uterine horn surgery, the rats within each environment were randomized into three treatment groups: saline (control), intraperitoneal pantothenic acid and intramuscular pantothenic acid. The degree of adhesions ten days following surgery was scored by an evaluated blinded to the rat's estrogenic condition and treatment. In the hypoestrogenic environment, there were no differences in the mean adhesions scores by treatment. In euestrogenic rats, the intraperitoneal pantothenic acid group had a higher mean adhesion score than intramuscular pantothenic acid, but neither treatment mean differed from that of the saline group. There was no difference in the mean adhesion scores of the saline groups by estrogenic environment. We concluded that pantothenic acid was not found to decrease adhesions formation when administered intraperitoneally or intramuscularly at these dosages. Contrary to previous reports, the hypoestrogenic condition alone was not found to be associated with decreased adhesion formation in our study.

Topics: Animals; Disease Models, Animal; Estradiol; Female; Injections, Intramuscular; Injections, Intraperitoneal; Leuprolide; Pantothenic Acid; Random Allocation; Rats; Rats, Sprague-Dawley; Single-Blind Method; Tissue Adhesions; Uterine Diseases; Uterus

Fifty adult female rats were randomly divided into five groups. Before the standard surgical procedure which consisted of creating a lesion with electrocautery over the uterus, leuprolide acetate (LA) together with its diluent, the diluent alone and medroxyprogesterone acetate (MPA) were injected to the third, fourth, and fifth groups, respectively. Ringer's lactate (RL) solution was applied intraperitoneally to the second group at the end of the surgery. Group I received no medication. Relaparotomy was performed 3 weeks later to evaluate the adhesions. The mean adhesion scores were (mean +/- SD) 2.6 +/- 0.7, 1.4 +/- 0.8, 0.9 +/- 0.6, 2.3 +/- 0.8, and 0.8 +/- 0.6 in groups I, II, III, IV, and V, respectively. The postsurgical adhesions were significantly less in the groups treated with RL, LA, and MPA.

Topics: Animals; Female; Isotonic Solutions; Leuprolide; Medroxyprogesterone Acetate; Postoperative Complications; Rats; Ringer's Lactate; Tissue Adhesions; Uterine Diseases; Uterus

The Arias-Stella reaction (ASR) is a common and universally recognized feature of gestational endometrium. That identical cytologic changes may, on occasion, occur outside the endometrium or in nonpregnant women is not as well documented. This report describes the clinical and pathologic findings in nine nonpregnant women whose endometria demonstrated ASR. The defining characteristics of ASR, associated pathologic changes, and differential diagnosis are discussed. All of these women were peri- or postmenopausal, and eight of nine had received exogenous hormones, most (n = 7), progestational agents. ASR did not persist in the four patients who underwent subsequent endometrial examination. None of these patients developed adenocarcinoma, although follow-up was short. ASR is an unusual response to hormonal therapy in nonpregnant patients. It is important to recognize the phenomenon in this setting and not overinterpret the characteristic cytologic atypia as adenocarcinoma.

Topics: Adult; Aged; Aged, 80 and over; Endometrium; Estrogens, Conjugated (USP); Female; Follow-Up Studies; Hormones; Humans; Leuprolide; Middle Aged; Postmenopause; Progesterone Congeners; Uterine Diseases

A patient with a 10-year history of secondary infertility underwent GnRH-a therapy with LA for 5 months to control symptoms of severe adenomyosis and to avoid an unwanted hysterectomy. Shortly after cessation of treatment, the patient conceived. A healthy male was delivered at term by cesarean section, which makes this the first report of a live birth after treatment of severe adenomyosis with a GnRH-a.

Topics: Adult; Endometriosis; Female; Humans; Infertility, Female; Injections, Intramuscular; Leuprolide; Pregnancy; Pregnancy Outcome; Treatment Outcome; Ultrasonography; Uterine Diseases; Uterus

Attempts at inhibiting the thickness and vascularity of the endometrium in preparation for endometrial ablation by using different types of hormones have been reported. To evaluate the effects of two different progestins, danazol, and leuprolide acetate on the endometrium, compared with the features of early proliferative endometrium, histologic studies were done for at least five patients treated with each hormone who then underwent resectoscopic endometrial ablation for treatment of abnormal uterine bleeding. Significant and at times dramatic differences among the treatment groups were found, with progestin-prepared endometrium being the least successful and leuprolide-prepared endometrium the most successful. In addition, the prolonged suppression provided for a period of time after the procedure by depot leuprolide is likely to help inhibit endometrial regeneration and provide even better long-term success of the procedure.. Four hormonal treatments to inhibit endometrial development were compared, medroxyprogesterone acetate, norethindrone, danazol and leuprolide, before resectoscopic ablation of the endometrium in 25 women with hypermenstruation. The patients all had excessive and or prolonged heavy menstrual flow not helped by curettage or combined estrogen-progestins. They ranged in age from 37-48, and none were menopausal. The pretreatments were Depo-Provera 200 mg im for 6-9 weeks, norethindrone acetate (Norlutate, Parke Davis) 5 mg daily for 6 weeks, 600 or 800 mg danazol (Danocrine, Winthrop) daily orally for 6 weeks, or leuprolide acetate (Depot Lupron, TAP Pharmaceuticals) on Day 20-24 of the cycle 4-5 weeks before ablation. The resectoscopic ablation consisted of shaving the endometrium from the cornual areas and fundal surface to the internal os to a depth of 3-4 mm with a Storz gynecologic resectoscope, size 24 Fr., with a 90 degree angle wire loop electrode, at 110 W. Histologic sections showed a fluffy decidual response to progestins such that blunt dissection or suction curettage was needed to the ablation. Danazol produced inconsistent responses from atrophy to thick deciduoid, but all had a relatively thick endometrium. Leuprolide produced a consistently thin, but not atrophic endometrium, with spindle-like fibroblast-type stromal cells, and few glands. Untreated women in early proliferative phase, Days 4-8, had atypical, thin, hypovascular endometria, with dysynchronous mild hyperplasia of some glands and stroma in some cases. Ablation was easy in untreated women. The thickness of thermally damaged tissues was 217 mm in progestin-treated women, 175 mm in danazol-treated and 141 in leuprolide-treated women. Leuprolide produced the most dependable suppression of the endometrium of the 4 drug treatments.

Topics: Adult; Danazol; Electrosurgery; Endometrium; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Middle Aged; Postoperative Complications; Postoperative Period; Premedication; Progestins; Uterine Diseases