Clinical characteristics and treatment patterns with histrelin acetate subcutaneous implants vs. leuprolide injections in children with precocious puberty: a real-world study using a US claims database.

OBJECTIVES: Gonadotropin-releasing hormone analogs are the treatment of choice for central precocious puberty (CPP). This study characterizes patients treated with histrelin implant or leuprolide injection. METHODS: A US claims database was used to identify patients aged ≤20 years with ≥1 histrelin or leuprolide claim (index treatment) between April 2010 and November 2017 and continuous enrollment ≥3 months before and ≥12 months after the index treatment date. RESULTS: Overall, 4,217 patients (histrelin, n=1,001; leuprolide, n=3,216) were identified. The percentage of patients with CPP diagnosis was greater in the histrelin (96.5%) vs. leuprolide (68.8%; p<0.0001) cohort. In patients with CPP (histrelin, n=966; leuprolide, n=2,214), mean age at treatment initiation was similar for histrelin (9.0 ± 2.0 years) and leuprolide (9.1 ± 2.3 years), with >50% of patients aged 6-9 years. Mean treatment duration was significantly longer for histrelin (26.7 ± 14.8 months) vs. leuprolide (14.1 ± 12.1 months; p<0.0001), and was longer in younger patient groups. More patients switched from leuprolide to histrelin (12.3%) than vice versa (3.6%; p<0.0001). Median annual total treatment costs were slightly lower for the histrelin cohort ($23,071 [interquartile range, $16,833-$31,050]) than the leuprolide cohort ($27,021 [interquartile range, $18,314-$34,995]; p<0.0001). CONCLUSIONS: Patients with CPP treated with histrelin had a longer duration of treatment, lower rates of index treatment discontinuation, and lower annual treatment costs vs. those treated with leuprolide.

Treatment patterns, health resource utilization and costs among central precocious puberty patients treated with leuprolide or histrelin: an examination of the commercial and Medicaid populations.

Aims: To compare treatment duration, healthcare resource utilization (HRU), and direct healthcare costs between patients with central precocious puberty (CPP) treated with leuprolide or histrelin, and between patients with Medicaid or commercial insurance. This information is important as it affects treatment choice and outcomes.Materials and methods: This retrospective cohort study identified commercial and Medicaid-insured CPP patients ≤12-years-old who were diagnosed between 1 January 2010 and 30 September 2014 and had ≥1 prescription for leuprolide or histrelin (first prescription = index date). Treatment patterns were measured for the duration of available data; whereas, all-cause and disease-monitoring HRU and all-cause costs were compared between treatment groups for the year following treatment initiation. Multivariable analysis was used to adjust healthcare costs for differences in baseline patient characteristics.Results: A total of 1,177 commercially-insured (907 leuprolide and 270 histrelin) and 658 Medicaid-insured (613 leuprolide and 45 histrelin) patients were identified. Mean age at treatment initiation ranged from 7.5-8.5-years-old, 11.1-20.5% of patients were male, and the mean treatment duration was over one year. Commercially-insured patients treated with histrelin used more services in general than those treated with leuprolide but had fewer office visits. Healthcare service utilization was similar between Medicaid-insured treatment groups. In both payer populations, costs were similar.Limitations: The number of Medicaid-insured patients who received a histrelin implant was low, and this may make the findings more sensitive to influence by outliers.Conclusions: Mean overall healthcare costs were similar between CPP patients treated with leuprolide and those treated with histrelin. Medicaid patients generally received less testing and were less likely to receive specialist care. Patients treated with histrelin had fewer office visits but also had a shorter overall treatment.

Effects of leuprorelin for the treatment of recurrent gynecological cancer by assessment including self-administered quality-of-life questionnaire.

AIM: To investigate the effects of leuprorelin using a self-administered quality-of-life (QOL) questionnaire in patients with recurrent gynecological cancer. METHODS: Records of patients who received 3.75 mg leuprorelin every 4 weeks for the treatment of recurrent gynecological cancer were retrospectively reviewed. The physical domain of the QOL questionnaire, Care Notebook, was used to assess physical symptoms. Symptom deterioration was defined as a ≥10-point increase in baseline score; otherwise, symptoms were defined as controlled. Radiological and serological responses were evaluated according to the 2011 Gynecological Cancer Intergroup criteria. RESULTS: From 2007 to 2015, 25 patients were administered leuprorelin for the treatment of epithelial ovarian cancer, granulosa cell tumor, endometrial cancer, endometrial stromal sarcoma and clear cell cervical cancer (in 13, 3, 6, 2 and 1 patients, respectively). Twenty patients had received a median of three lines (range 1-12 lines) of chemotherapy. Ten patients had progressive disease during their previous round of chemotherapy. Twenty patients completed the questionnaire every 4 weeks. Following leuprorelin treatment for 8 weeks, the symptom and disease control rates were 65% (13/20) and 44% (11/25), respectively. Two patients, one each with granulosa cell tumor and endometrial cancer, had stable disease at 6 months. Among the 20 patients who completed the QOL questionnaire, symptom control and disease control at 8 weeks showed a significant correlation (P = 0.016). CONCLUSION: Leuprorelin had minimal anticancer activity. The physical domain of the QOL questionnaire could be used to assess effects of hormonal treatment.

Neonate female to male ratio after assisted reproduction following antagonist and agonist protocols.

We retrospectively compared neonatal sex after antagonist- versus long-stimulation protocols followed by fresh in vitro fertilization (IVF) or fresh intracytoplasmic sperm injection (ICSI) with either protocol. We reviewed data for 762 IVF/ICSI cycles in 2015, including 23 IVF procedures. We summarized sex outcomes in the entire cohort, and for the additional subgroups: embryo transfer day and number of embryos transferred, and number of oocytes recovered and maternal age. Among 169 live births for all protocols combined, 50.9% of babies were male, and we saw no difference between the antagonist versus long-stimulation groups (52.3% vs 48.3% male babies, respectively; P = .740). Our results also showed no significant difference in sex proportion when comparing IVF versus ICSI, although a higher proportion of babies were male with the antagonist-ICSI protocol. Differences between the additional subgroups were also neither clinically nor statistically significant.

Artificial Cycle with or without a Depot Gonadotropin-releasing Hormone Agonist for Frozen-thawed Embryo Transfer: An Assessment of Infertility Type that Is Most Suitable.

The clinical outcomes of five groups of infertility patients receiving frozen-thawed, cleavage-stage embryo transfers with exogenous hormone protocols with or without a depot gonadotropin-releasing hormone (GnRH) agonist were assessed. A retrospective cohort analysis was performed on 1003 cycles undergoing frozen-thawed, cleavage-stage embryo transfers from January 1, 2012 to June 31, 2015 in the Reproductive Medicine Center of Wuhan General Hospital of Guangzhou Military Region. Based on the infertility etiologies of the patients, the 1003 cycles were divided into five groups: tubal infertility, polycystic ovary syndrome (PCOS), endometriosis, male infertility, and unexplained infertility. The main outcome was the live birth rate. Two groups were set up based on the intervention: group A was given a GnRH agonist with exogenous estrogen and progesterone, and group B (control group) was given exogenous estrogen and progesterone only. The results showed that the baseline serum hormone levels and basic characteristics of the patients were not significantly different between groups A and B. The live birth rates in groups A and B were 41.67% and 29.29%, respectively (P<0.05). The live birth rates in patients with PCOS in groups A and B were 56.25% and 30.61%,respectively (P<0.05). The clinical pregnancy, implantation and on-going pregnancy rates showed the same trends as the live birth rates between groups A and B. The ectopic pregnancy rate was significantly lower in group A than in group B. We concluded that the live birth rate was higher and other clinical outcomes were more satisfactory with GnRH agonist cotreatment than without GnRH agonist co-treatment for frozen-thawed embryo transfer. The GnRH agonist combined with exogenous estrogen and progesterone worked for all types of infertility tested, especially for women with PCOS.

Formulation of 99mTechnetium-labeled leuprolide loaded liposomes and its biodistribution study in New Zealand white female rabbits for assessment of its uterine targeting efficiency.

Leuprolide acetate (LPA), a GnRH analogue, is drug of choice for treatment of uterine fibroids and endometriosis. The current marketed formulations of LPA show severe systemic side effects. This project aims to formulate LPA loaded liposomes to be administered by vaginal route for uterine targeting. Liposomes were prepared by thin film hydration method using 1:1 M ratio of DSPC: Cholesterol and characterized for vesicle size, zeta potential, entrapment efficiency, and loading. Radiolabeling of LPA was performed by direct labeling with reduced technetium-99m. Binding affinity of 99mTc-labeled complexes was assessed by diethylenetriaminepentaacetic acid (DTPA) challenge test. Biodistribution study was done in New Zealand white female rabbits by administering the formulation via vaginal route. Spherical and discrete vesicles of size 189 nm were seen in TEM results with entrapment efficiency and loading of 74.36% and 9.29%w/w, respectively. Liposomes were able to sustain the drug release for 5 days. 99mTc-labeled complexes showed high labeling efficiency and stability both in saline and serum. DTPA challenge test confirmed low transchelation of 99mTc-labeled complexes. Biodistribution study by gamma scintigraphy revealed the preferential uptake of the formulation by uterus when administered vaginally. Compared to plain drug, liposomes concentrated and were retained within the uterus for a longer period of time. Uterine targeting of liposomal LPA indicates its potential to overcome the limitations of presently available formulations. Hence, this seems to be a promising approach for targeting the drugs, whose site of action is uterus.

Cost analysis of leuprorelin acetate in Japanese pre-menopausal breast-cancer patients: comparison between 6-month and 3-month depot formulations.

AIMS: The aim in this study is to evaluate economic value for leuprorelin acetate 6-month depot compared with leuprorelin acetate 3-month depot in Japanese pre-menopausal breast cancer patients from a societal perspective. METHODS: The cost analysis was conducted by estimating direct and indirect cost, and intangible costs associated with one 6-month injection compared with two 3-month injections. Claims data were used for the analyses of direct and indirect cost and Medical Fee Schedule Table for direct cost. Discrete choice experiments were conducted by web-based survey to determine the intangible costs. Another web-based survey was also conducted on premenopausal breast cancer patients with injections of leuprorelin acetate, to calibrate the results of discrete choice experiments. RESULTS: The medical costs saved for having one less injection in pre-menopausal breast cancer patients with leuprorelin acetate injection were JPY 6,183. The productivity loss saving was JPY 1,419. An estimation of intangible costs saved for having one less injection of leuprorelin acetate was JPY 58,430, which included the disbenefit due to pain (JPY 8,535), injection site reactions (JPY 44,051), waiting time (JPY 9,595), and subtracting value in medical consultation (JPY 3,751). The total cost saved for having one less injection was JPY 66,032. LIMITATIONS: The respondents from the internet panel provided by a survey company do not necessarily reflect a population of Japanese society. CONCLUSIONS: Leuprorelin acetate 6-month depot demonstrates a higher value than leuprorelin acetate 3-month depot through saving medical costs and loss of productivity, as well as intangible costs saved for having one less injection when treating pre-menopausal breast cancer patients. In the costs for treating with leuprorelin acetate, the percentage of intangible costs might not be negligible. The intangible costs will probably be actively evaluated to proceed to patient-centered healthcare in society.

Cost analysis of leuprorelin acetate in Japanese prostate cancer patients: comparison between 6-month and 3-month depot formulations.

AIMS: This study aimed to evaluate the economic value for leuprorelin acetate 6-month depot compared with leuprorelin acetate 3-month depot from a societal perspective in Japanese prostate cancer patients. METHODS: The cost analysis estimated the reduction in direct and indirect costs as well as intangible costs saved by having one less injection. Claims data were used for the analyses of direct and indirect costs reduction. A discrete choice experiment based on a web-based survey estimated the monetary value of the intangible costs for one injection. Another web-based survey of prostate cancer patients, who had received treatment with leuprorelin acetate injections, was carried out to calibrate the results of the discrete choice experiment. RESULTS: Reductions in medical costs and loss of productivity for having one less injection in prostate cancer patients receiving leuprorelin acetate were JPY 5,670 and JPY 1,723, respectively. Intangible costs saved by using a 6-month depot formulation instead of a 3-month depot formulation for the injection of leuprorelin acetate were estimated to be JPY 19,872, including the values for a reduction in pain (JPY 3,131), injection site reactions (JPY 11,545), waiting time (JPY 9,479), and subtracting the value of medical consultation (JPY 4,283). The total cost reduction for having one less injection was JPY 27,265. LIMITATIONS: The respondents from the internet panel provided by a survey company are not necessarily a representative population of Japanese society. CONCLUSIONS: Leuprorelin acetate 6-month depot has an advantage in monetary value in the reduction in medical costs, loss of productivity, and intangible costs for having one less injection in prostate cancer patients compared with leuprorelin acetate 3-month depot. In the costs for treating with leuprorelin acetate, the percentage of intangible costs might not be negligible. The intangible costs will probably be actively evaluated to proceed to patient-centered healthcare in society.

Radical prostatectomy versus high-dose irradiation in localized/locally advanced prostate cancer: A Swedish multicenter randomized trial with patient-reported outcomes.

BACKGROUND: Treatment of localized prostate cancer (PC) is controversial. This is the first randomized study comparing an open surgery procedure (radical prostatectomy) with a combination of high-dose rate brachytherapy (2×10 Gy) and external beam radiotherapy (25×2 Gy) in PC patients in Sweden 1996-2001. The two randomization arms were compared regarding differences in patients-reported outcomes, such as complications and health-related quality of life (HRQoL). MATERIAL AND METHODS: The patients had localized/locally advanced PC, clinical category T1b-T3a, N0, M0 and PSA≤50 ng/ml. All underwent total androgen blockade (six months). Self-reported HRQoL and symptoms including urinary, bowel, and sexual side effects were investigated prospectively before randomization and 12 and 24 months after randomization. A total of 89 patients were randomized and completed the EORTC QLQ C-33 and EORTC PR-25 questionnaires. RESULTS: Over the study period, there were no discernible differences in HRQoL, or complications between the two groups. Emotional functioning, however, improved statistically significantly over time, whereas Social functioning decreased, and financial difficulties increased. No statistically significant differences in group-by-time interactions were found. The survival rate was 76%. Only eight patients (9%) died of PC. CONCLUSION: Open radical prostatectomy and the combined high-dose rate brachytherapy with external beam radiation appeared to be comparable in the measured outcomes. It was not possible to draw any conclusion on the efficacy of the two treatments due to insufficient power of the study.

Assessment of gonadotrophin suppression in girls treated with GnRH analogue for central precocious puberty; validity of single luteinizing hormone measurement after leuprolide acetate injection.

OBJECTIVE: Intravenous GnRH stimulation test has often been used as gold standard test for the evaluation of hypothalamic-pituitary-gonadal axis in the diagnosis of central precocious puberty (CPP) and in the assessment of pubertal suppression. However, this test is time-consuming, costly and uncomfortable for the patients. We aimed to analyse the validity of single LH sample 90 min after GnRH analogue (GnRHa) administration in the evaluation of gonadotrophin suppression during CPP therapy and to determine a cut-off level for LH indicating adequate suppression. DESIGN: Prospective study. PATIENTS AND METHODS: One hundred and forty-two patients with CPP were included in this study. Peak LH level during iv GnRH stimulation test after the third dose of GnRHa was compared with LH level 90 min after injection of the 3rd dose of GnRHa. RESULTS: There was a positive correlation between LH level following a GnRHa injection and peak LH during standard iv GnRH stimulation test (r = 0·83; P < 0·0001). A LH value of 2·5 mIU/ml or less 90 min after GnRHa injection was considered to be the cut-off for the determination of pubertal suppression (sensitivity and specificity was 100% and 88%, respectively). In 117 patients, gonadotrophin suppression was existed according to both GnRHa and iv GnRH tests. In 25 patients, gonadotrophin suppression was not found in the GnRHa test. However, 16 of them were suppressed according to the iv GnRH test. CONCLUSION: Single LH determination 90 min after GnRHa administration using a cut-off level of 2·5 mIU/ml reflects pubertal suppression with a high sensitivity and specificity. However, this test may fail to show pubertal suppression in some cases. Those patients who appear to be inadequately suppressed should be reassessed using standard iv GnRH stimulation test for optimal dose adjustment.

Cost-effectiveness analysis of LHRH agonists in the treatment of metastatic prostate cancer in Italy.

OBJECTIVES: Luteinizing hormone-releasing hormone (LHRH) agonists represent one of the main cost factors in the management of patients with metastatic prostate cancer. We compared the cost-effectiveness of the five different 3-month formulations of LHRH agonists currently available for advanced prostate cancer in Italy, because these differ both in their capacity to suppress testosterone and in their acquisition costs. METHODS: A probabilistic, patient-level simulation model was developed to compare the cost-effectiveness, from the perspective of the Italian National Health Service (INHS), of leuprorelin 11.25 mg and 22.5 mg, triptorelin 11.25 mg, buserelin 9.9 mg, and goserelin 10.8 mg. The model incorporated testosterone-dependent progression-free and cancer-specific survival functions, LHRH agonist effectiveness data, and national costs and tariffs. Cox's proportional hazard models were used to compute total and progression-free survival functions based on clinical data from 129 patients with metastatic prostate cancer treated in an Italian center. Bayesian random effects models were employed to summarize evidence from published literature on testosterone suppression obtained with the available LHRH agonists. RESULTS: Estimated total survival was ≈5 years, with a maximum difference between treatment options of ≈2 months. There was a mean difference of almost €2,500 in lifetime total costs between the least costly option (leuprorelin 22.5 mg) and the most expensive (goserelin). In the incremental cost-effectiveness analysis, leuprorelin 22.5 mg dominated all alternatives except buserelin, which had an incremental cost-effectiveness ratio versus leuprorelin 22.5 mg of ≈€12,000 per life-month gained. CONCLUSIONS: Based on modelling with meta-analysis of comparative survival data, leuprorelin 22.5 mg was the most cost-effective treatment of the available depot formulation LHRH agonists.

Semiquantitative assessment of MR imaging in prediction of efficacy of gonadotropin-releasing hormone agonist for volume reduction of uterine leiomyoma: initial experience.

PURPOSE: To prospectively determine if semiquantitative assessment of R2* images and T1-weighted magnetic resonance (MR) images of leiomyomas correlates with the efficacy of gonadotropin-releasing hormone (GnRH) agonist treatment for volume reduction. MATERIALS AND METHODS: Internal review board approval and informed consent were obtained for this study. Twenty women (mean age, 36.3 years) with intramyometrial leiomyomas were enrolled in this study. Single-section double-echo dynamic MR imaging was performed before GnRH agonist administration. T2-weighted images were obtained before and after two or three GnRH agonist injections (1.88 mg leuprorelin acetate). The steepest signal intensity (SI) upslope on T1-weighted images and the area under the curve (AUC) on R2* images were determined by using a 16 x 16-voxel matrix that was placed in the center of a leiomyoma. Pearson correlation analysis was performed to compare the percentage of volume reduction with SI upslope and AUC. Unpaired t test was performed to evaluate the difference between leiomyomas with AUC and SI upslope values that were less than or greater than the mean. RESULTS: Percentage of volume reduction ranged from 6.2% to 51.1%. The mean AUC and mean SI upslope were 39.2 and 9.83% per second, respectively. There was a significant correlation between the AUC and the percentage of volume reduction (r = 0.81, P < .001), although no significant correlation was observed between the SI upslope and the percentage of volume reduction. A significant difference in percentage of volume reduction was observed in leiomyomas by using mean AUC as a cutoff value (P = .003). CONCLUSION: AUC on R2* images correlates with the efficacy of GnRH agonist before initiation of treatment for volume reduction of leiomyoma.

Injection systems for two luteinising hormone-releasing hormone agonists: a comparative assessment of administration times and nurses' perceptions.

The aim of this study was to compare the speed of administration (preparation and delivery) and nurses' perceived ease of use and relative safety of two injection systems used to administer luteinising hormone-releasing hormone agonists: a depot system used to administer goserelin acetate ('Zoladex', AstraZeneca) and a vial system used to administer leuprorelin acetate ('Prostap', Wyeth). This was a randomised, crossover study with 82 volunteer nurses (50 pre-registration and 32 post-registration). All nurses were timed in the administration of both systems and all were required to assess the two systems by completing a questionnaire. Results indicate that both pre- and post-registration nurses administered the depot system in less time than the vial system. Overall mean times for administration of the depot system and the vial system were 1.70 and 3.34min, respectively. In questionnaire responses, significantly more nurses thought that the depot system had 'good safety precautions' compared with the vial system (85% versus 40%; P<0.001) and significantly more nurses also expressed a preference for the depot system (58% versus 42%; P=0.036). In conclusion, this study demonstrates that nurses prefer the one-step depot system used to administer goserelin acetate over the vial system used to administer leuprorelin acetate.

Antral follicle assessment after down-regulation may be a useful tool for predicting pregnancy loss in in vitro fertilization pregnancies.

Women with diminished ovarian reserve (OR) have a high rate of pregnancy loss. The relationship between hormonal OR tests and pregnancy loss has been studied previously, but, to our knowledge, that between the antral follicle count (AFC) and pregnancy loss has not. Therefore, we aimed to determine whether OR tests, including the AFC, can predict pregnancy loss in women achieving pregnancy by means of in vitro fertilization (IVF), and also to compare their predictive value. All women underwent a fresh cycle of intracytoplasmic sperm injection with a long protocol with mid-luteal start of the gonadotropin-releasing hormone analog, and antral follicles were counted on cycle day 3 following down-regulation. Pregnancy losses up to 12 gestational weeks (n=28) were compared with apparently healthy deliveries (n=34) in this retrospective analysis. Receiver operating characteristic analysis of consecutive pregnancies (n=71) was performed to analyze the optimum cut-off value for the significantly different OR tests. Women with a pregnancy loss had a lower AFC than those with healthy deliveries. Age and hormonal OR tests were comparable between groups. The optimum cut-off value for the AFC to predict pregnancy loss was 7.5. AFC may be a useful tool for predicting pregnancy loss in IVF pregnancies.

Coping and health-related quality of life in men with prostate cancer randomly assigned to hormonal medication or close monitoring.

Prostatic carcinoma and its treatment have been associated with adverse effects on health-related quality of life (HRQoL). Individual differences in appraisal and coping have been suggested to mediate these HRQoL outcomes. A randomized trial of 65 men with non-localized prostate cancer compared several treatments and tested associations between appraisal, coping, and HRQoL. These patients, and 16 community volunteers matched for age and general health, undertook psychosocial assessments before treatment and after 6 months of treatment. Compared with baseline assessments, men on hormonal treatments reported impaired sexual function. Groups did not differ on emotional distress, existential satisfaction, subjective cognitive function, physical symptoms, or social and role functioning. For individuals, hormonal treatments were more frequently associated with decreased sexual, social and role functioning, but were also associated with improved physical symptoms. In hierarchical regression analysis, HRQoL was lower for men who had more comorbid illnesses, a history of neurological dysfunction, higher threat appraisals, or higher use of coping strategies at baseline. These results showed that pharmacological hormonal ablation for prostate cancer can improve or decrease HRQoL in different domains. HRQoL in men with prostate cancer was associated more strongly with appraisal and coping than with medical variables.

Serum luteinizing hormone rises within minutes after depot leuprolide injection: implications for monitoring therapy.

OBJECTIVE: To find the time of the serum gonadotropin peak after depot leuprolide injection in children and to show that depot leuprolide therapy can be monitored by measuring serum luteinizing hormone (LH) immediately after injections. STUDY DESIGN: We measured concentrations of leuprolide, LH, and follicle-stimulating hormone (FSH) at multiple time points before and after the first dose of depot leuprolide in 14 pubertal children beginning therapy. Gonadotropins and sex steroids were measured again after the fourth dose. RESULTS: Serum leuprolide, LH, and FSH levels rose rapidly after initial injection, reaching sustained elevations at 30 to 120 minutes. The median LH level increased from 2.1 mIU/mL at baseline to a peak of 27.5 mIU/mL at 45 minutes, and FSH increased from 5.2 to 16.5 mIU/mL. After 3 months on therapy, median serum LH after depot leuprolide injection was only 0.83 mIU/mL, similar to levels observed after intravenous or subcutaneous gonadotropin-releasing hormone stimulation in comparable subjects on depot leuprolide. CONCLUSION: Our pharmacokinetic data demonstrate that free leuprolide present in a depot leuprolide injection is equivalent to gonadotropin-releasing hormone in stimulating a rapid rise in serum gonadotropin concentrations. We propose that a single serum sample for LH obtained 30 to 60 minutes after depot leuprolide injection in children provides a convenient and accurate assessment of treatment efficacy.

Presence of LH in gonadotropins associated with higher IVF pregnancy rates when basal serum LH is increased.

PURPOSE: To determine if pregnancy rates following in vitro fertilization-embryo transfer (IVF-ET) correlate with the presence or not of luteinizing hormone (LH) in the gonadotropins used for stimulation. Furthermore to see if the early follicular phase serum LH level affects pregnancy outcome according to the type of gonadotropins used. METHODS: The type of gonadotropins were prescribed randomly according to finances and convenience. Serum LH was obtained on day 2 or 3 of the menstrual cycle. RESULTS: When LH was > the median, significantly higher pregnancy rates were obtained in those treated with the follicle stimulating hormone (FSH)/human menopausal gonadotropin combination. When LH was < or = the median, significantly more oocytes were retrieved with FSH exclusively. No confounding variables were found to explain the data. CONCLUSIONS: Considering concerns of published studies that LH may have a toxic effect on pregnancy outcome, and if LH is suppressed too low, gonadotropins with exclusive FSH may not stimulate sufficient oocytes, the results were opposite to expectations.

Serum testosterone-based luteinizing hormone-releasing hormone agonist redosing schedule for chronic androgen ablation: a phase I assessment.

OBJECTIVES: To assess the potential for using the serum testosterone level as the guide for redosing depot luteinizing hormone-releasing hormone (LHRH) agonist and to characterize the duration of castrate level testosterone after the last 22.5-mg leuprolide injection repeatedly administered for the control of prostate cancer. METHODS: Informed consent was obtained from 32 men with prostate cancer (Stage T3N+/- M+/- or greater) treated with 3-month (22.5-mg) leuprolide acetate injection. Serum testosterone and prostate-specific antigen levels were obtained every 28 days beginning on the 90th day after the last 22.5-mg leuprolide injection. The duration of action was the calculated interval, in months, between the last injection and the first noncastrate serum testosterone (greater than 0.2 ng/mL) value. RESULTS: The median duration of castrate level testosterone was 6.0 months (SE +/- 0.15; upper and lower quartile 5.3 and 7.0, respectively). Prostate cancer biochemical (prostate-specific antigen) activity at enrollment and when the castrate testosterone threshold of 0.2 ng/mL was exceeded remained stable, with no significant change observed during this interval (P = 0.52). A significant association was observed between an increasing duration of castration after LHRH agonist injection and advancing patient age (P = 0.03) and increasing duration of hormonal therapy (P = 0.05). CONCLUSIONS: These results suggest that using the serum testosterone level to guide in redosing of long-acting LHRH agonist may provide a novel, effective, and economical method to administer hormonal ablative therapy in patients with prostate cancer. These observations have important implications for product dosing and the design and interpretation of neoadjuvant and intermittent androgen ablative trials.

Depot leuprolide acetate versus danazol in the treatment of women with symptomatic endometriosis: a multicenter, double-blind randomized clinical trial. II. Assessment of safety. The Lupron Endometriosis Study Group.

OBJECTIVES: This is the first multicenter, double-blind randomized clinical trial that compares a depot gonadotropin-releasing hormone agonist with danazol in the treatment of endometriosis. Efficacy results have been previously reported; this report focuses on safety data. STUDY DESIGN: A total of 270 patients from 22 centers were randomly selected to receive either leuprolide acetate depot (3.75 mg injected monthly) or danazol (800 mg administered orally daily). Safety outcomes included adverse effects, clinical laboratory changes, and bone mineral density changes. RESULTS: Most patients receiving either drug reported side effects, most of which were related to the hypoestrogenism of leuprolide (e.g., vasodilatation) and relative hyperandrogenism of danazol (e.g., weight gain). Similarly small numbers of patients dropped out of the two treatment groups because of the side effects encountered. Leuprolide depot caused a greater decrease in bone density; preliminary data suggest a return to baseline on cessation of the drug. Danazol was associated with alteration of serum lipids, specifically a significant decrease in high-density lipoprotein. CONCLUSIONS: Although side effects were commonly reported in both groups, the drugs were similarly safe in terms of the absence of serious complications and the results of cessation of therapy. Side effects were largely reversible on discontinuation of medication. More longitudinal data are necessary before the possibility of long-term risks can be excluded, especially as they pertain to bone mineral density and lipids.

Risk of repeated spontaneous luteinizing hormone surges in ovarian stimulation for in vitro fertilization.

Although spontaneous luteinizing hormone (LH) surges are preventable with gonadotropin releasing hormone agonist (GnRH-a) inclusion in ovarian stimulation protocols, GnRH-a-containing protocols are more expensive and associated with an increased risk of ovarian hyper-stimulation syndrome. The present study assessed whether spontaneous LH surges occur in predictable patterns, allowing GnRH-a to be utilized selectively. We assessed 1,103 patients receiving clomiphene citrate/human menopausal gonadotropin (CC/hMG) without GnRH-a for their first in vitro fertilization (IVF) cycle and observed spontaneous LH surges in 30.4%. When patients who demonstrated a spontaneous LH surge received a second CC/hMG stimulation protocol, 45.9% surged again. Of those patients who did not demonstrate a spontaneous LH surge in their initial CC/hMG cycle, only 23.0%, significantly less (P < .001), surged in their second cycle. Of those patients who did not surge in their first two cycles, only 15.7% had an LH surge in their third cycle (P < .001). Thus, if all patients received CC/hMG without GnRH-a as their first IVF stimulation protocol, GnRH-a could be reserved for patients who have demonstrated a spontaneous LH surge. By tailoring the treatment plan, the pregnancy rate would be optimized while decreasing cycle cancellations due to spontaneous LH surges in those patients susceptible to LH surges and limiting costs and inconvenience for patients unlikely to surge spontaneously.