Mg Of Leuprolide Acetate Research Articles

Abstract OT3-04-01: A Phase 3 study evaluating ovarian suppression following three-month leuprolide acetate in combination with endocrine therapy in premenopausal subjects with HR+, HER2-negative breast cancer (OVELIA)

Abstract Background: In US clinical practice, GnRH agonists are widely used to suppress ovarian function in pre/perimenopausal patients with breast cancer that is moderate-to high-risk for recurrence. Despite extensive use of leuprolide acetate (LA) for ovarian suppression, regulatory approval for this indication has not been established in the US. Additionally, existing three month formulations may not reliably provide ovarian suppression, as demonstrated by escapes in estradiol (E2). An extended-release LA product with a 3-month dosing period specifically developed for ovarian suppression in patients with breast cancer could fill this unmet need. TOL2506 is a 3-month, extended-release formulation of 30 mg of LA. This combination of active drug and in situ polymeric extended release technology is expected to deliver higher exposure to drug than the currently available 3-month (22.5 mg) formulations of LA marketed for advanced prostate cancer and potentially reduce escapes in E2 over the dosing period. Methods: TOL2506A (OVELIA) is a phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 to suppress ovarian function in premenopausal women with HR+, HER2-negative breast cancer. Approximately 250 subjects will be enrolled targeting 220 evaluable subjects, with 30% aged 40 years or younger. Subjects must be premenopausal women, age 18-49 (inclusive), with a diagnosis of Stage I, II, or III HR+, HER2-negative breast cancer (ER>1% and/or, PR>1%, HER2-negative per ASCO CAP guidelines), who are candidates for ovarian suppression with endocrine therapy. For subjects receiving chemotherapy, premenopausal status will be determined prior to initiating chemotherapy. Male subjects with HR+, HER2-negative breast cancer may also be eligible, but will be evaluated for safety analyses only. Eligible subjects will enter the 48 week Treatment Period in 2 groups: those receiving tamoxifen concurrently with TOL2506 or those who initiate therapy with an aromatase inhibitor (AI; letrozole, anastrozole, or exemestane) beginning 6 weeks after the first administration of TOL2506, if E2 < 20 pg/mL has been achieved. After Week 12, subjects will be allowed to switch from receiving an AI to receiving tamoxifen or from tamoxifen to AI at the Investigator’s discretion. Subjects will receive 4 doses of TOL2506 every 12 weeks over the 48 week study duration. The primary endpoint to be evaluated is ovarian suppression, defined as ≥ 90% of subjects with LH levels < 4 IU/L at Week 6. Secondary endpoints include suppression of LH, E2 (< 20 pg/mL for tamoxifen cohort and < 2.72 pg/mL for AI cohort) and absence of menses at weeks 6, 12, 24, 36, and 48. NCT04906395 Citation Format: Ryan Turncliff, Erika Hamilton, Kerlin Lynch, Stuart N. Atkinson. A Phase 3 study evaluating ovarian suppression following three-month leuprolide acetate in combination with endocrine therapy in premenopausal subjects with HR+, HER2-negative breast cancer (OVELIA) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-04-01.

PMON70 Systemic Delivery of Leuprolide via Oral Administration

Abstract We have developed a technology platform employing enteric coating and permeation enhancement to enable systemic delivery of peptides via the oral route. To determine whether this platform can deliver therapeutic doses of the GnRH agonist leuprolide, we conducted a randomized, four-period, four-treatment, crossover pharmacokinetic and food effect study in 14 healthy female volunteers, which compared PK profiles following single administrations of 1 and 4 mg of leuprolide --- the latter under both fasting and fed conditions --- to that of a single subcutaneous injection of 1 mg of leuprolide acetate. Study objectives were to assess the relative bioavailability, dose proportionality, safety and tolerability of orally administered leuprolide, as well as the effect of food on drug absorption. Frequent blood sampling for 24 hours followed each dose, and each treatment was separated by 7 days. Of the 14 subjects enrolled and dosed, 12 completed the study. Mean Tmax occurred at 2.24 ±0.38, 2.77 ±0.46, and 3.49 ±0.23 hrs, for 1 mg po, 4 mg po (fasting), and 1 mg sc leuprolide, respectively. Mean Cmax was 1.9 ±1.3, 10.2 ±9.6, and 59.4 ±9.1 ng/mL, for the aforementioned treatments. Mean AUC0-24h was 3.5 ±2.1, 19.3 ±16.8, and 163.0 ±18.8 ng*h/mL, respectively. Relative to 1 mg sc leuprolide, oral doses of 1 mg and 4 mg (fasted) achieved 2.2 ±1.3% and 3.0 ±2.5% bioavailability. While differences in the dose-normalized parameters were not statistically significant, formal criterion of dose-proportionality (i.e. 90% CI within 80-125%) was not met. 'Fasting' conditions included an overnight (10-hr) fast prior to dosing, and no food consumption for 4 hours following dosing. The 'fed' condition involved consumption of a high-fat, high-calorie meal 30 minutes prior to drug administration. Significant negative impact of food on both rapidity and extent of drug absorption was observed in nearly all subjects, with measurable leuprolide levels sufficiently sparse as to prevent robust PK assessments in this group. The subject incidence of treatment-emergent adverse events (TEAEs) was comparable across all four treatment groups, including sc leuprolide, and was not dose-dependent. The most commonly observed TEAEs across all treatment groups combined were nausea (43%), headache (43%), and increased libido (21%). All other TEAEs were reported by only one or two subjects. The study drugs were well tolerated; most AEs were mild in severity (none were severe or serious), and 30 of 53 (57%) deemed unrelated to study drug. No notable changes were observed in laboratory values or vital signs. This study thus confirmed the successful oral delivery of leuprolide, a 1209-dalton nonapeptide, via the oral route. Investigations now in progress are assessing the feasibility of delivering substantially greater amounts of the drug orally, in order to provide an alternative to parenteral administration of this widely used therapeutic. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

A phase 3, single arm, open-label study evaluating ovarian suppression following 3-month leuprolide acetate for injectable suspension in combination with endocrine therapy in premenopausal subjects with HR+, HER2-negative breast cancer (OVELIA).

TPS608 Background: In US clinical practice, GnRH agonists are widely used to suppress ovarian function in pre/perimenopausal patients with breast cancer that is moderate-to high-risk for recurrence. Despite extensive use of leuprolide acetate (LA) for ovarian suppression, regulatory approval for this indication has not been established in the US. Additionally, existing three month formulations may not reliably provide ovarian suppression, as demonstrated by escapes in estradiol (E2). An extended-release LA product with a 3-month dosing period specifically developed for ovarian suppression in patients with breast cancer could fill this unmet need. TOL2506 is a 3-month, extended-release formulation of 30 mg of LA. This combination of active drug and in situ polymeric extended release technology is expected to deliver higher exposure to drug than the currently available 3-month (22.5 mg) formulations of LA marketed for advanced prostate cancer and potentially reduce escapes in E2 over the dosing period. Methods: TOL2506A (OVELIA) is a phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 to suppress ovarian function in premenopausal women with HR+, HER2-negative breast cancer. Approximately 250 subjects will be enrolled, with 30% aged 40 years or younger. Subjects must be premenopausal women, age 18-49, with a diagnosis of Stage I, II, or III HR+, HER2-negative breast cancer (ER > 1% and/or, PR > 1%, HER2-negative per ASCO CAP guidelines), who are candidates for ovarian suppression with endocrine therapy. For subjects receiving chemotherapy, premenopausal status will be determined, and confirmed by central lab hormone testing, prior to initiating chemotherapy. Male subjects with HR+, HER2-negative breast cancer may also be eligible, but will be evaluated for safety analyses only. Eligible subjects will enter the 48 week treatment period in 2 groups: those receiving tamoxifen concurrently with TOL2506 or those who initiate therapy with an aromatase inhibitor (AI; letrozole, anastrozole, or exemestane) beginning 6 weeks after the first administration of TOL2506, if E2 < 20 pg/mL has been achieved. After Week 12, subjects will be allowed to switch from receiving an AI to receiving tamoxifen or from tamoxifen to AI at the Investigator’s discretion. Subjects will receive 4 doses of TOL2506 every 12 weeks over the 48 week study duration. Achievement of ovarian suppression will be defined as ≥ 90% of subjects with luteinizing hormone (LH) levels < 4 IU/L at Week 6. Secondary endpoints include suppression of LH, E2 (< 20 pg/mL for tamoxifen cohort and < 2.72 pg/mL for AI cohort) and absence of menses at weeks 6, 12, 24, 36, and 48. Clinical trial information: NCT04906395.

A new injectable liquid crystal system for one month delivery of leuprolide

An injectable liquid crystal-forming system (LCFS) was prepared by using sorbitan monooleate (SMO) as a new liquid crystal-forming material for injections, and its potential use of clinically available sustained-release formulation was evaluated. LCFS was prepared using SMO mixed with phosphatidyl choline and tocopherol acetate, and contained 3.75mg of leuprolide acetate as a monthly dose in 90μl in liquid form. The semi-solid mesophase was formed from the liquid LCFS when it contacted water. The mesophase showed typical characteristics of the liquid crystalline phase, which was classified as the hexagonal phase. The safety of the LCFS was studied by an in vitro extraction colony assay and by examining the injection site in rats and white rabbits after an autopsy. Both in vitro release test and in vivo pharmacokinetic and pharmacodynamic studies showed a sustained release of leuprolide. When compared with a commercial depot formulation of leuprolide, the LCFS showed a similar AUClast value and significantly reduced initial burst with sufficient suppression of testosterone after subcutaneous injections in rats and dogs. The LCFS can serve as a new type of sustained-release injection formulation for its safety, ease of preparation, and sustained release properties.

Secondary chemoprevention of localized prostate cancer by short-term androgen deprivation to select indolent tumors suitable for active surveillance: a prospective pilot phase II study

To investigate the impact of 3-month androgen deprivation therapy (st-ADT) a secondary chemoprevention of indolent-localized prostate cancer (PCa). A prospective phase II study enrolled men over 4 years with low-risk PCa and the following characteristics: PSA < 10 ng/mL, Gleason score of 6 (3 + 3) or less, three positive cores or less, and tumor stage T2a or less. Patients received a single sub-cutaneous injection of 22.5 mg of leuprolide acetate with Atrigel 3-month depot associated with a daily oral intake of bicalutamide 50 mg/day during 15 days around the injection. Follow-up included PSA and bioavailable testosterone blood tests every 3 months and yearly surveillance biopsies. Primary end point was the presence of PCa on biopsy at last follow-up. Secondary end points were detailed pathological features and adverse events. Overall, 98 men were included and 45 of them (45.9 %) had a negative biopsy after a median follow-up of 13 months [11-19.5]. Of the 53 patients with positive biopsy, 17 had pathologic progression because of upgraded Gleason score (11 patients), four or more positive cores (three patients) or both (three patients). The only significant predictive factor biopsy outcome was the number of positive cores at diagnosis. Secondary chemoprevention by st-ADT for localized PCa could be useful to pinpoint indolent tumors suitable for AS. Indeed, after st-ADT nearly one patient out of two had negative biopsies and 17 % had pathological progression. This is an innovative option to consider as an alternative to current AS protocols contingent upon confirmation in subsequent studies.

Sterile abscess formation in response to two separate branded long-acting gonadotropin-releasing hormone agonists

Background: Long-acting forms of gonadotropin-releasing hormone (GnRH) receptor agonists are commonly used for the treatment of central precocious puberty (CPP). Sterile abscess formation has been reported as a complication of leuprolide acetate, but not histrelin acetate. Objective: The aim of this study was to report an adverse drug reaction in a child with sterile abscess formation following treatment with 2 different branded long-acting forms of GnRH agonists. Case summary: An otherwise healthy 8-year-old white female (weight, 40.7 kg; height, 140.1 cm) with documented CPP and no known drug allergies developed a sterile abscess at the site of the monthly intramuscular injection of 15 mg of leuprolide acetate. Because of this site reaction, a 50-mg histrelin acetate insert was placed in the patient's left arm. A similar reaction occurred 2 weeks after insert placement on 2 separate occasions in different arms. At the time of the removal of the second insert, Gram stain and swab culture of the purulent wound discharge were negative. The child was subsequently treated with intranasal nafarelin (800 ug twice daily) and tolerated it well. The Naranjo Adverse Drug Reaction Causality Score was 10 (definite, ≥9). Conclusion: This report describes a case of sterile abscess formation definitely associated with 2 different forms of long-acting GnRH agonist treatment in a child.

Use of F 18-fluoro-D-glucose–positron emission tomography–computed tomography to localize a hilar cell tumor of the ovary

To describe provocative testing and alternative imaging strategies used to localize an androgen-producing tumor in a 58-year-old woman with severe hirsutism. Case report. Clinical Research Center. A 58-year-old woman who was seen for evaluation of severe hirsutism. Serum androgen levels were measured at baseline, 4 hours after administration of 2000 IU of hCG, and 11 days after administration of 3.75 mg of leuprolide acetate (LA). Magnetic resonance imaging and F 18-fluoro-D-glucose-positron emission tomography-computed tomography (FDG-PET/CT) were performed. Description of preoperative provocative testing and imaging. In response to hCG, T rose from 243 to 288 ng/dL then decreased to 233 ng/dL after LA administration. The FDG-PET/CT scan demonstrated focal hypermetabolism in the right pelvis, corresponding to a soft-tissue density on the noncontrast CT scan. Magnetic resonance images were correlated with the PET/CT, and the right ovary was identified. Right salpingo-oophorectomy was performed, and final pathologic examination revealed a hilar cell tumor with ovarian cortical hyperplasia. This case demonstrates the utility of provocative testing in the evaluation of a patient with severe hirsutism and illustrates the value of FDG-PET/CT when traditional imaging is nondiagnostic.

Gonadotropin-releasing hormone (GnRH)-agonist versus GnRH-antagonist in ovarian stimulation for assisted reproductive techniques: Results of a prospective randomized trial

Gonadotropin-releasing hormone (GnRH)-agonist versus GnRH-antagonist in ovarian stimulation for assisted reproductive techniques: Results of a prospective randomized trial

Prolonged use of gonadotropin-releasing hormone agonist and tibolone as add-back therapy for the treatment of endometrial hyperplasia

Objectives: To investigate the response of the various hyperplastic disorders of the endometrium to a prolonged treatment with leuprolide acetate, a gonadotropin-releasing hormone agonist (GnRH-a), plus tibolone, as add-back therapy, and further to study if the tibolone addition reduces the hypoestrogenic actions of the GnRH-analogue. Methods: We treated 26 women with histologically confirmed simple ( n=9), complex ( n=15) or atypical ( n=2) endometrial hyperplasia (EH) for 12 months with monthly injections of 1Ampulle/3.75 mg of leuprolide acetate, followed by tibolone, 2.5 mg per day per os. Every woman unterwent a hysteroscopic evaluation and biopsy of the endometrium after 3 (in cases with atypical EH), 6 and 12 months of treatment, as well as after 12 and 24 months of follow-up. The clinical, paraclinical and laboratory course of the disease was followed-up by using of a climacteric scoring system and by testing of various parameters. Results: The histopathologic evaluation of the endometria revealed regression of EH in all women after 12 months of treatment, however, during the first 2 years of follow-up EH reappeared in four women (4/21, 19%). Bone mineral density and serum parameters did not show significant changes during treatment, whereas only a mild suffering from hypoestrogenic side-effects was noted. Conclusions: It seems that the combined GnRH-a/tibolone treatment in women with EH is a potent alternative, so far as the endometrial status and the clinical course of the disease are concerned, whereas tibolone appears to act sufficiently as add-back therapy to prolonged GnRH-a treatment. The probability of relapse of the disease during the follow-up period makes the close monitoring of the endometrium after cessation of the treatment absolutely necessary.

Comparison of FSH flare in poor responders undergoing in vitro fertilization (IVF) with and without prior oral contraceptive suppression

Objective: Early follicular phase leuprolide acetate (LA) has been used in poor responders to achieve a “flare” in the endogenous FSH prior to injectable gonadotropins. While studies have demonstrated this flare following natural cycles, none have documented the rise of FSH to LA following one-month administration of oral contraceptives (OCPs). OCPs are frequently used prior to IVF cycles, including LA flare protocols, to synchronize follicular development. However the duration of hypothalamic pituitary suppression following OCPs is unknown. This study aims to compare the endogenous gonadotropin (FSH, LH) and steroid (estrogen, progesterone) flare responses observed after administration of 1mg of LA subcutaneously in poor responders, with or without prior hypothalamic pituitary suppression with OCPs.

A six-month, open-label study assessing a new formulation of leuprolide 7.5 mg for suppression of testosterone in patients with prostate cancer

Objective: The safety, efficacy, and pharmacokinetics of monthly subcutaneous injections of a new leuprolide acetate (LA) depot formulation were investigated in patients with advanced prostate cancer. Methods: The 2-part, 6-month (168-day), open-label, multicenter study enrolled male patients diagnosed with adenocarcinoma of the prostate (Jewett stage C or D). LA-2500 7.5-mg (a new subcutaneous depot formulation containing 7.5 mg of LA) injections were administered at monthly (28-day) intervals. The primary efficacy parameter was total serum testosterone level. A breakthrough response was defined as a single testosterone measurement >50 ng/dL after achieving castration testosterone levels. Testosterone was isolated from sera by alumina column chromatography and measured by radioimmunoassay (RIA). LA was purified by solid-phase extraction and high-performance liquid chromatography and was then quantitated by RIA. Results: One hundred seventeen of the 120 enrolled patients completed the 6-month study. Three patients withdrew for reasons not related to treatment. LA had a mean (SD) maximal concentration of 26.3 (12.6) ng/mL at 4.66 (1.44) hours and was detected for a mean of 37 days (range, 28–49 days). By day 28, 94.1% (112/119) of the patients achieved medical castration (serum testosterone ≤50 ng/dL). By day 42, 100.0% (118/118) of the patients remaining in the study had serum testosterone levels ≤50 ng/dL and 97.5% (115/118) had levels ≤20 ng/dL. At study completion, the mean (SD) serum testosterone level was 6.12 (4.3) ng/dL (range, 3.0–27.0 ng/dL). No breakthrough or acute-on-chronic responses were reported throughout the study. From baseline to month 6, mean (SD) luteinizing hormone level decreased from 8.0 (7.3) mIU/mL to 0.09(0.1) mIU/mL, and mean (SD) prostate-specific antigen level decreased from 32.9 (86.3) ng/mL to 3.2 (12.0) ng/mL. Treatment-related adverse events were reported by 74.2% (89/120) of patients, the most common being hot flashes (56.7%). Conclusion: This 6-month, open-label, noncontrolled study showed LA-2500 7.5-mg depot was well tolerated and maintained testosterone suppression ( ≤50 ng/dL) in the patients completing the study without any testosterone breakthrough responses.

The Effect of Repeated Controlled Ovarian Stimulation in Donors

At the authors' institution, most oocyte donors are healthy young women who agree to an anonymous and no-charge donation and who undergo controlled ovarian stimulation (COS) with fertility drugs with the goal of promotingmultiple follicle development. Some donors undergo consecutive COS cycles with differing intervals between stimulations. This retrospective study examined the effects of multiple COS on oocyte retrieval rates and oocyte quality (as reflected by the recipient's outcome). In a 6-year period, 284 donors had at least two cycles of COS. Their mean age was approximately 25 years. Nearly half the women were nulliparous. Donors were 18 to 35 years of age and had no personal or family history of congenital malformation or hereditary disease. The pituitary was desensitized by daily subcutaneous injections of 1 mg of leuprolide acetate, starting in the luteal phase. After menses the dose was halved until chorionic gonadotropin treatment, begun on day 3 after menses. Human menopausal gonadotropin and purified FSH were given if ultrasonography showed no follicle activity. The gonadotropin dosage was tailored to each patient's follicular response as assessed by ultrasonography and serum estradiol estimates. After two or more follicles reached 21 mm in maximum diameter, human chorionic gonadotropin was administered, and oocyte retrieval was scheduled 36 hours later. A total of 1684 oocyte donation cycles was completed in 1017 recipients. Embryo transfer was achieved in 87% of cases. Similar oocyte retrieval rates were maintained through consecutive cycles up to nine consecutive COS cycles in the same donor (Fig. 1). Among 43 donors with five stimulations, there were no differences in fertilization, implantation, or pregnancy rates according to the origin of the oocyte cycle (Fig. 2). Semen characteristics were equally distributed. No differences were found in oocytes retrieved or fertilization, implantation, or pregnancy rates according to the interval between consecutive COS cycles. Similar numbers of oocytes may be retrieved from healthy young volunteer donors during repeated cycles of COS. Oocyte quality is maintained through at least five repeated cycles. The interval between cycles does not affect the outcome of COS.

"Co-Flare" stimulation in the poor responder patient: predictive value of the flare response.

In this study we review our experience with a day 2 start, "Co-Flare" protocol analyzing the flare response as a predictor of outcome in patients with a history of a poor response. This study was conducted at a university based IVF Center. A total of 564 patient cycles over a 2.5-year time frame in patients that had either elevated FSH levels or a previous poor response to conventional leuprolide acetate down-regulated stimulation were retrospectively analyzed. These patients were treated with our co-flare protocol (1.0 mg of leuprolide acetate administered on day 2 and decreased on day 5 to 0.5 mg; gonadotropins initiated on day 3). We analyzed the initial flare response and the outcome for these patients. A total of 564 patients attempted to initiate an IVF cycle. The patients mean age was 39.4+/-3.7 years. Of the 450 cycles that started, the outcomes were as follows: 24% (108/450) cancellation, 20.4% (92/450) clinical pregnancy per initiated cycle, and a 14.0% delivery rate per initiated cycle. Patients with an estradiol flare that doubled were less likely to have cycles cancelled (13.6% vs. 35.6%, P < 0.01), but no differences were noted in pregnancy outcome if the cycle was not cancelled once the patient made it to retrieval. We have demonstrated an overall 14.0% delivery rate per initiated cycle in these "poor prognosis" patients. While the initial flare response (as indicated by a doubling of the estradiol by the second day of stimulation) was indicative of a better stimulation, no difference in pregnancy outcome was seen if the patient underwent retrieval.

The hemodynamic effect of GnRH agonist therapy on uterine leiomyoma vascularity: a prospective study using transvaginal color Doppler sonography.

The objective of this study was to correlate, during 12 weeks of therapy with gonadotropin releasing hormone agonist (GnRH-a), the chronological effect and the hemodynamic changes on the uterine artery and the leiomyometrial supplying vessels. Twenty-three premenopausal women with clinically diagnosed uterine leiomyomas received 3.75 mg of leuprolide acetate intramuscularly every 4 weeks for 12 weeks. Pretreatment values of serum estradiol, uterine and leiomyoma volumes and blood flow characteristics of the main uterine artery and leiomyoma supplying vessels-resistance index (RI), pulsatility index (PI) and peak-systolic velocity, obtained by transvaginal color Doppler sonography-were compared with treatment values at 4, 8 and 12 weeks of leuprolide acetate therapy. The first event in the chronological response to the GnRH-a therapy was a statistically significant increase in RI and PI values for major leiomyoma vessels, observed at the end of the 4th week (p < 0.05), which increased significantly after 8 and 12 weeks (p < 0.01 and p < 0.001, respectively). These findings were in direct correlation with a significant decrease of estradiol levels after 4, 8 and 12 weeks (p < 0.05, p < 0.001 and p < 0.001, respectively). The significant decrease of blood flow in the leiomyometrial vessels was followed by a significant decrease of the main uterine artery blood flow after 8 weeks and uterine and leiomyoma volumes by 42% and 55%, respectively, after 12 weeks of GnRH-a therapy. We concluded that a significant increase in leiomyometrial vessels RI and PI values, which was found 4 weeks after the first dose of GnRH-a, but without major leiomyoma volume decrease, emphasizes that the first significant effect of GnRH therapy in the process of uterine and leiomyoma volume shrinkage is the reduction of leiomyometrial rather than uterine blood flow. This effect is followed by a considerable reduction of uterine vascularity and a significant decrease of uterine and leiomyoma volumes. If a decrease of blood loss during myomectomy is the main aim of GnRH-a therapy, we believe that 8 weeks would be an appropriate therapy duration.

Effects of a long-acting gonadotrophin-releasing hormone agonist (Leuprolide) on ovarian follicular development in prepubertal heifer calves

We studied the effects of reducing gonadotrophin secretion on ovarian follicular development in young prepubertal heifer calves. Calves received a GnRH agonist (n = 5, 15 mg of Leuprolide acetate, i.m.) or carrier (n = 5) at 8 and 12 w of age. Starting at 8 and 34 w of age, ovarian follicles were monitored daily for 17 d, and at 10, 15, 25 and 35 w of age, blood samples were collected every 15 min for 12 h for measurement of serum concentration of LH and FSH. GnRH agonist treatment did not affect the age and body weight at puberty (P &gt; 0.05). Agonist treatment suppressed follicle numbers and in two heifers follicle emergence (growth above 4–5 mm) was blocked immediately. In three agonist-treated heifers, follicle emergence was blocked after one extended wave of follicular growth. At 34 w of age the pattern of ovarian follicular growth did not differ between groups but oestradiol secretion was lower in agonist-treated heifers. During agonist treatment basal and mean concentrations of FSH, and LH and FSH pulse amplitude were decreased but basal LH concentrations increased (P &lt; 0.05). At 25 and 35 w of age some rebound in gonadotrophin secretion was seen.We concluded that disrupting gonadotrophin secretion in young prepubertal heifer calves by GnRH agonist treatment, suppressed ovarian follicular growth but that a rebound in gonadotrophin secretion prevented long term-effects on sexual development. Key words: Follicle stimulating hormone, gonadotrophin-releasing hormone, heifer calves, luteinising hormone ovarian follicles

The effects of RU 486 and leuprolide acetate on uterine artery blood flow in the fibroid uterus: A prospective, randomized study

OBJECTIVE: Our purpose was to examine the effects of RU 486 and leuprolide acetate on uterine artery blood flow and uterine volume. STUDY DESIGN: Patients were randomly assigned to group A (eight patients) receiving 25 mg of RU 486 daily for 3 months or group B (six patients) receiving 3.75 mg of leuprolide acetate monthly for 3 months. Uterine artery blood flow change was determined by resistive index by means of vaginal color Doppler ultrasonography. Uterine volume was measured before and during the study with abdominal ultrasonography. RESULTS: Both groups showed an increase in resistive index. Patients receiving RU 486 had uterine artery blood flow decreased by 40%, and those receiving leuprolide acetate had a 21% decrease. We noted a sigificant decrease in uterine volume compared with pretreatment in both groups at 3 months. There was no significant decrease between groups. CONCLUSION: Both RU 486 (25 mg daily) and leuprolide acetate (3.75 mg monthly) are effective in decreasing blood flow to the uterus (increasing resistive index) and decreasing uterine volume at 3 months. A significant decrease in uterine artery blood flow may provide a mechanism for the decrease in uterine size and the decrease in uterine blood loss at the time of surgery. (AM J Obstet Gynecol 1994;170:1623-8.)

The effects of RU 486 and leuprolide acetate on uterine artery blood flow in the fibroid uterus: A prospective, randomized study

Our purpose was to examine the effects of RU 486 and leuprolide acetate on uterine artery blood flow and uterine volume. Patients were randomly assigned to group A (eight patients) receiving 25 mg of RU 486 daily for 3 months or group B (six patients) receiving 3.75 mg of leuprolide acetate monthly for 3 months. Uterine artery blood flow change was determined by resistive index by means of vaginal color Doppler ultrasonography. Uterine volume was measured before and during the study with abdominal ultrasonography. Both groups showed an increase in resistive index. Patients receiving RU 486 had uterine artery blood flow decreased by 40%, and those receiving leuprolide acetate had a 21% decrease. We noted a significant decrease in uterine volume compared with pretreatment in both groups at 3 months. There was no significant decrease between groups. Both RU 486 (25 mg daily) and leuprolide acetate (3.75 mg monthly) are effective in decreasing blood flow to the uterus (increasing resistive index) and decreasing uterine volume at 3 months. A significant decrease in uterine artery blood flow may provide a mechanism for the decrease in uterine size and the decrease in uterine blood loss at the time of surgery.

Management of urinary retention due to benign prostatic hyperplasia using luteinizing hormone-releasing hormone agonist

A common affliction of older men is bladder outlet obstruction secondary to benign prostatic hyperplasia for which the standard treatment is surgical prostatectomy. We report on six men with urinary retention from benign prostatic hyperplasia who were not medically able to undergo surgical prostatectomy but were successfully treated with the luteinizing hormone-releasing hormone (LH-RH) agonist, leuprolide acetate. This therapy is exemplified by the case of a sixtysix-year-old man with hemophilia B and urinary retention. The patient was treated with daily subcutaneous injections of I mg of leuprolide acetate, and prostatic size decreased from 132 g to 42 g, with initiation of spontaneous micturition while on treatment. For patients with symptomatic benign prostatic hyperplasia who are not candidates for surgery, treatment with an LH-RH agonist, such as leuprolide acetate, should be considered as a possible alternative.