Decapeptyl Depot Research Articles

An 8-Year-Old Girl with Drug Hypersensitivity to First Triptorelin Acetate Administration

Triptorelin is a synthetic gonadotropin-releasing hormone agonist for the treatment of precocious puberty in children. Among the triptorelin side effects, drug hypersensitivity reactions, including anaphylaxis, can rarely occur, mostly after repeated exposure to the drug. We present a first case of an 8-year-old girl with central precocious puberty who developed anaphylaxis to the first injection of decapeptyl depot, which contains triptorelin acetate (D,L lactide coglycolide), dextran 70, and polysorbate 80. She showed 2 positive reactions in an intradermal test to decapeptyl depot, suggesting that it is an IgE-mediated reaction to one of its components. Considering this was the first exposure to triptorelin, it might be a reaction to polysorbate. As there are many therapeutic products containing polysorbate which can cross-react with polyethylene glycols, physicians should pay attention to immediate reactions to drugs containing polysorbate.

The Influence of GnRH Analog Therapy on Growth in Central Precocious Puberty.

Children with central precocious puberty (CPP) present various somatic and psychological abnormalities. The aim of the study was to evaluate growth changes in girls with central precocious puberty treated with GnRH analog therapy and to analyze the factors affecting the auxological response to this treatment. The study group consisted of 40 girls with puberty onset aged 6.0 ± 1.9 years (mean, ± SD), treated with 3.75 mg decapeptyl depot intramuscularly every 28 days. The treatment was initiated at the age of 7.5 ± 2.2 years and continued for 3.3 ± 2.3 years, until the age of 11.4 ± 0.9 years. Height (Ht), height standard deviation score (HtSDS), statural age, bone age and Ht prediction. During the treatment a decline in HtSDS from 2.0 ± 1.36 to 1.24 ± 1.0 was observed (p = 0.0002); and a deceleration in the maturation of bones of 1.0 ± 0.29 year in the first year and 0.66 ± 0.33 year in the following years (p = 0.0008). The HtSDS at the end of the treatment was significantly higher than was predicted in pretreatment (1.33 ± 1.04 vs. 0.07 ± 1.39, p = 0.0005). Ht and HtSDS after treatment were positively correlated with the predicted Ht (PAH) before treatment and negatively correlated with the bone age/statural age ratio before treatment (p < 0.05). The PAH before and after treatment correlated inversely with the bone age/statural age ratio (p < 0.05). Two subgroups were analyzed according to the patients' age when therapy was introduced: group 1 included girls who were under the age of 7 when therapy was introduced, and group 2 included girls aged 7 or older. There was a statistically significant difference in the PAH SDS before treatment between these two subgroups: Group I (-) 1.3 ± 1.8 vs. Group II (-) 0.14 ± 1.2 and there was no difference in the PAH SDS after treatment: Group I (-) 0.7 ± 1.1 vs. Group II 0.31 ± 1.2. The child's age at the beginning of GnRHa therapy was an important predictor of height prognosis; the therapy introduced under the age of 7 improves the PAH during treatment. Height prediction during the entire treatment period is worse in children with more advanced bone age for their statural age at the onset of treatment.

Menstrual cycle pattern during the first gynaecological years in girls with precocious puberty following gonadotropin-releasing hormone analogue treatment

Keywords Menarchetiming.Menstrualcycle.Centralprecociouspuberty.GnRHaOur aim was to longitudinally investigate menarche timingand menstrual cycle (MC) pattern during the first fivegynaecological years in 101 girls with idiopathic centralprecocious puberty (CPP) who had been treated withgonadotropin-releasing hormone agonists (GnRHa) for atleast two years. Our girls received Decapeptyl Depot(60

Effects of a preovulatory administered depot gonadotrophin-releasing hormone agonist on reproductive hormone levels and pregnancy outcome in gilts

The present study aimed to explore the influence of a preovulatory administered depot gonadotrophin-releasing hormone (GnRH) agonist (GnRHa; Decapeptyl Depot) on the endocrine parameters and pregnancy outcome of gilts (n = 6). A GnRHa-supported preovulatory luteinising hormone (LH) surge was detected in all treated gilts. LH pulses were abolished completely by depot GnRHa on Day 7 and partly on Day 21 of pregnancy. In this treatment group (n = 6) four gilts were pregnant at slaughter on Day 28. In the control group receiving Gonavet, a non-formulated GnRHa (n = 6), all pigs showed LH pulses and were pregnant at slaughter on Day 28 of gestation. Mean progesterone concentrations were elevated in controls during the early luteal phase and were similar for both groups during the implantation period. Mean concentration of unoccupied progesterone receptor was significantly higher in uterine myometrium than in endometrium, but without treatment effects. Peripheral estrone sulfate concentrations showed a similar increase in all pregnant gilts on Days 17 and 18, and remained elevated. In summary, treatment with a depot GnRHa for synchronisation of ovulation alters pulsatile LH secretion during early pregnancy in pigs. In general, this alteration seems not to exert an injurious influence on luteal function and, therefore, on embryo and early fetal development.

Management and outcome of central precocious puberty

Management and outcome of central precocious puberty

When to stop GnRH analog therapy: the experience of the Italian Study Group for Physiopathology of Puberty.

Data reported in this study have been recently published elsewhere. The authors retrospectively analyzed the auxological response to GnRH agonist treatment and the final height (FH) outcome in 71 girls with idiopathic and truly precocious (onset before 8 years) central puberty (CTPP), who had been treated with the same therapy protocol (Decapeptyl Depot at the dose of 60 microg/kg i.m. every 28 days) for at least 2 years (since 7.0 +/- 1.3 yr) and followed until puberty was completed and FH was reached. During the entire treatment period we observed: A) a decrease of height standard deviation scores (SDS) (from 1.5+/-1.7 to 0.9+/-1.3 SDS, p<0.01); B) a striking deceleration of BA, revealed by the subnormal deltaBA:deltaCA ratio (0.2 +/- 0.1); C) an increase of predicted adult height (from 155.6+/-7.0 to 160.7+/-6.7 cm, p<0.0005). Treatment interruption was followed by notable catchdown growth, with FH (158.4 +/- 5.8 cm) lower (p < 0.025) with respect to that predicted at the end of therapy. However FH fell within the population norm and the target range in 87.3% and 90% of patients, respectively. The tallest FH was recorded in the patients who discontinued treatment at a BA of 12.0-12.5 years. We conclude that: 1) Most girls with idiopathic CTPP treated by GnRH agonists may achieve an adult height within the population norm and/or their target range; 2) The height gain from therapy onset until FH attainment, however, is generally rather limited (on average 2.9 cm) and only few patients are able to reach their target percentile; 3) The most favorable height prognosis with respect to target height (TH) is generally observed in the patients with the tallest H2 and the lowest BA2:CA2 ratio, due to the notable deterioration of height prognosis which frequently follows therapy interruption; 4) In order to strengthen the weak therapeutic effect of GnRH agonists in CTPP, this treatment should be discontinued at a BA of 12-12.5 years.

Analysis of the factors affecting auxological response to GnRH agonist treatment and final height outcome in girls with idiopathic central precocious puberty.

The aim of this retrospective study was to analyze the factors which affected the auxological response to GnRH agonist treatment and the final height (FH) outcome in 71 girls with idiopathic and truly precocious (onset before 8 years) central puberty (CTPP) who had been treated with the same therapy protocol (Decapeptyl Depot, 60 microg/kg i.m. every 28 days) for at least 2 years (since 7.0+/-1. 3 (S.D.) years of age) and followed until puberty was completed and FH was reached. During the entire treatment period we observed: (a) a decrease of height standard deviation scores (SDS) (from 1.5+/-1.7 to 0.9+/-1.3 SDS, P<0.01); (b) a striking deceleration of bone age (BA), revealed by the subnormal DeltaBA:Deltachronological age (CA) ratio (0.2+/-0.1); (c) an increase of predicted adult height (from 155.6+/-7.0 to 160.7+/-6.7 cm, P<0.0005). Treatment interruption was followed by an important catch-down growth, with an FH (158.4+/-5.8 cm) lower (P<0.025) than that predicted at the end of therapy. However, FH fell within the population norm and the target range in respectively 87.3 and 90% of the patients. The tallest FH was recorded in the patients who started therapy at less than 6 years of age and in those who discontinued treatment at a BA of 12.0--12.5 years. At stepwise regression analysis, FH in the whole study population was positively affected by the following independent factors: (a) height at the end of therapy (F=45.45, P<0.0001); (b) pretreatment height (F=13.91, P<0.0005); (c) treatment duration (F=8. 51, P<0.005); (d) target height (TH) (F=7.70, P<0.01). We conclude that: (i) most girls with idiopathic CTPP treated by GnRH agonists may achieve an adult height within the population norm and/or their target range; (ii) the height gain from therapy onset until FH attainment, however, is generally rather limited (on average 2.9 cm) and only few patients are able to reach their target percentile; (iii) the most favorable height prognosis with respect to TH is generally observed in the subjects with the tallest height at the end of treatment and the lowest BA2:CA2 ratio, due to the important deterioration of height prognosis which frequently follows therapy interruption; (iv) FH is also significantly conditioned by both TH and treatment duration; (v) in order to strengthen the weak therapeutic effect of GnRH agonists in CTPP this treatment should be started as early as possible and discontinued at a BA of 12.0--12.5 years.

Effectiveness and tolerance of 1 dosage forms (subcutaneous and intramuscular) of decapeptyl depot in patients with advanced prostate carcinoma

The intramuscular (i.m.) administration of Decapeptyl Depot has been approved in Germany for the treatment of advanced hormone dependent prostate cancer since July 1990. In this study a reformulated Decapeptyl Depot, administered as a first-line endocrine therapy, was injected intramuscularly (i.m.) or subcutaneously (s.c.) every 28 days for 6 months. At 12 different hospitals, 52 prostate cancer patients were treated, whereby 25 patients received a s.c. injection and 27 patients a i.m. injection. Testosterone was measured as the main parameter: after 28 days, both the s.c. and the i.m. application form of Decapeptyl Depot successfully reduced initial testosterone levels of at least 2.3 ng/ml to steady-state castration levels below 1.2 ng/ml, maintaining this complete suppression for the entire length of the trial (168 days). Decapeptyl Depot was well tolerated and very acceptable to the patients in both groups. Side effects were few and predictable, being largely associated with decreased testosterone concentrations. No cumulation in triptorelin serum levels was observed within the 6 months of treatment. Decapeptyl Depot, administered subcutaneously or intramuscularly was effective and safe in the treatment of patients with advanced prostate cancer.

Efficacy of the subcutaneous reformulated triptorelin depot in children with central precocious puberty.

The efficacy, safety and acceptance of newly formulated triptorelin s.c. (Decapeptyl Depot, DDsc) was compared to triptorelin i.m. (DDim) in seven children with central precocious puberty (CPP) in a prospective study. Both formulations were given for 6 months consecutively. During both treatment periods suppression of basal and gonadotropin-releasing hormone (GnRH)-stimulated levels of luteinizing hormone and follicle-stimulating hormone, suppression of sex steroids, arrest of the maturation of gonads and uterus, and slowing of bone maturation were achieved. The height standard deviation score for bone age increased significantly during DDsc treatment (-1.33+/-0.90 to 1.07+/-0.92, p < 0.05). The ratio bone age/chronological age decreased significantly during both treatment periods (1.25+/-0.24 to 1.20+/-0.23,p < 0.05, and 1.20+/-0.23 to 1.16+/-0.22, p < 0.05). With the injection of DDsc in the abdominal wall, a palpable, non-irritating resistance which gradually decreased in size occurred in one patient. With injection into the thigh no indurations were seen. No allergic reactions were encountered. Five of the patients considered DDsc therapy as more pleasant and described a definite decrease in fear of injections. All parents considered DDsc treatment as equal or better than DDim in respect to the suppression of their child' s puberty. It was concluded that DDsc is equipotent to DDim in the treatment of CPP. For the majority of patients DDsc was more acceptable than DDim. The thigh is recommended for the subcutaneous application of DD.

Central precocious puberty in girls: Internal genitalia before, during, and after treatment with long-acting gonadotropin-releasing hormone analogues

Pelvic ultrasonography was systematically performed on 33 girls with idiopathic central precocious puberty to investigate the impact of treatment with gonadotropin-releasing hormone analogues on female internal genitalia. All girls were treated with a long-acting gonadotropin-releasing hormone analogue (Decapeptyl Depot; Ferring Co., Copenhagen, Denmark) 75 μg/kg every 4 weeks. Before, during, and after treatment, pelvic ultrasonography was performed and ovarian and uterine volumes were calculated. The size of follicles > 5 mm were accurately measured. The results were related to a normative study of healthy Danish schoolgirls. Our data demonstrated that ovaries and uterus are enlarged in a significant number of girls (50%) with the diagnosis of central precocious puberty at the time of diagnosis. Median ovarian volume at time of diagnosis was 1.1 standard deviation scores (range –0.6 to 3.2 SD), median uterine volume was 1.8 standard deviation scores (range 0.0 to 3.5 SD). Within 3 months of treatment, both ovarian and uterine volumes decreased significantly ( p < 0.01) to normal values appropriate for age. Median ovarian volume after 3 months of treatment was 0.0 SD (range –2.4 to 1.5 SD); median uterine volume was 0.7 SD (range –0.6 to 4.1 SD). Ovarian and uterine volume remained within normal range (<2 standard deviation scores) after discontinuation of treatment. Follicles and macrocysts regressed during treatment. None of the girls' ovaries had a polycystic appearance during or after treatment with the gonadotropin-releasing hormone analogue. Our results confirmed pelvic ultrasonography as a reliable tool for investigation of internal genitalia in girls with precocious puberty and as a valid method for evaluation of the efficacy of treatment with gonadotropin-releasing hormone analogues. We suggest that repeated investigations be performed when evaluating treatment because the morphologic changes, including follicular maturation or regression, reflect ovarian stimulation or suppression. We found no evidence that girls with precocious puberty treated with long-acting gonadotropin-releasing hormone analogues have enlarged polycystic ovaries develop. (J Pediatr 1998;132:105-8)

OGO 6105 Ultrasound evaluation of uterine myomas in women treated with Decapeptyl depot

OGO 6105 Ultrasound evaluation of uterine myomas in women treated with Decapeptyl depot

Diagnosis and treatment of uterine septum

We assessed the efficacy of different methods of diagnosing and correcting uterine septa in 80 women. Hysterosalpingography revealed a uterine malformation, but failed to specify its character, and ultrasound scan was performed to screen the malformations. In 74 women hysteroscopy combined with laparoscopy was performed to define the malformation, and estimate the volume of uterine cavity and extent of septum. Preoperatively the patients received danazol or decapeptyl depot; a few cases were performed in the early follicular phase. Forty-six uterine septa were managed by laparoscopic-controlled resectoscopy. The distending medium was polyglukin or 2.7% sorbitol and 0.54% mannitol. Operating time ranged from 10 to 60 minutes (average 30 min). There was no significant blood loss. Postoperative hospital stay was 1 to 3 days. Twenty-five patients underwent hysteroscopy with curettage 2 to 4 months later, and filmy synechiae were found in four (16%). Histology and electron microscopic examination of endometrial tissue revealed its complete restoration. Of 29 women followed for 3 to 17 months, 12 (41.4%) conceived and 9 had a full-term infant. In this series, resectoscopy was atraumatic, operating time was short, blood loss was insignificant, and hospital stay was brief.

Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty: effects of two different treatment regimens with gonadotropin-releasing hormone agonists, without or in combination with an antiandrogen (cyproterone acetate).

Central precocious puberty (CPP) is characterized by early activation of the pituitary-gonadal axis, which leads to increased growth velocity and development of secondary sexual characteristics. It is generally believed that gonadal sex steroids stimulate pulsatile GH secretion, which, in turn, stimulates insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) production. However, little is known about GH, IGF-I, and IGFBP-3 serum levels in children with precocious puberty. Treatment of CPP by GnRH agonists has become the treatment of choice. However, the effect of long term treatment with GnRH in combination with an antiandrogen (cyproterone acetate) to block the possible effect of adrenal androgens has not previously been evaluated. We, therefore, studied 40 patients with idiopathic CPP that were treated for 24 months with either GnRH analog (Buserelin) in combination with cyproterone acetate (Androcur; n = 23) or with long acting GnRH analog (Decapeptyl Depot; n = 17). We found that serum IGF-I levels were increased before treatment in both groups (mean +/- SE, 446 +/- 35 and 391 +/- 35 micrograms/L; P < 0.0001, respectively) compared to those in normal age-matched prepubertal children. Similarly, IGFBP-3 levels were significantly elevated (4675 +/- 209 and 4305 +/- 162 micrograms/L, respectively; P < 0.0001) in the two groups. Treatment with GnRH analog in combination with cyproterone acetate significantly decreased height velocity and serum IGF-I and IGFBP-3 levels to normal levels after 2 yr of treatment (P < 0.0001). Serum IGF-I levels remained unchanged during monthly im treatment with long acting GnRH analog, whereas IGFBP-3 levels significantly increased during the first year of this treatment despite unmeasurable estradiol levels. Thus, in both groups, the molar ratio between IGF-I and IGFBP-3 (i.e. free biologically active IGF-I) declined concomitantly with a decrease in growth velocity. Serum levels of IGF-I and IGFBP-3 (expressed as the SD score for bone age), but not those of estradiol, correlated with height velocity before and during treatment (r = 0.34; P < 0.0001 and r = 0.24; P = 0.003, respectively). Six of the patients with a subnormal GH response to clonidine had similar IGF-I and IGFBP-3 serum levels and growth velocity compared to the other 34 girls with CPP and a normal GH response.(ABSTRACT TRUNCATED AT 400 WORDS)

The use of long-acting gonadotropin-releasing hormone agonist (GnRH-a; decapeptyl) and gonadotropins versus short-acting GnRH-a (Buserelin) and gonadotropins before and during ovarian stimulation for in vitro fertilization (IVF)

The efficiency of two ovarian stimulation protocols using different gonadotropin-releasing hormone agonists (GnRH-a) for in vitro fertilization (IVF) was examined and compared with human menopausal gonadotropin (hMG)-only stimulation. Fifty-four patients who had 57 aspiration cycles were treated with protocol 1, which consisted of long-acting GnRH-a D-Trp6 (Decapeptyl Depot) and hMG. Protocol 2 entailed intranasal administration of short-acting GnRH-a (Buserelin) and human menopausal gonadotropin (hMG) in 66 women who underwent 70 aspiration cycles. Fifty-five patients who had 59 ovum pickups (OPU) treated with hMG only served as a control. No differences were observed in cycle parameters and hormonal concentrations among the three groups. The total clinical pregnancy rates per OPU for patients receiving protocols 1 and 2 were 12.3 and 27.1%, respectively (P less than 0.05). The pregnancy loss was significantly lower in protocol 2 than in protocol 1 (26.3 versus 71.4%; P less than 0.05). Our data show superiority of short-acting GnRH-a over the long-acting agents in achievement of pregnancy and its outcome, though neither was significantly different from the hMG-only protocol.

Influence of luteinizing hormone-releasing hormone agonists on human mammary carcinoma cell lines and their xenografts

The specific binding of luteinizing hormone-releasing hormone (LH-RH) agonist in estradiol-dependent MCF-7 and estradiol-independent MDA-MB-231 human breast cancer cells has been studied using [ 3H]Ovurelin [ d- 3H-Phe 6),des-Gly 10-LH-RH-ethylamide]. The results of Scatchard analyses suggest the presence of a single class of receptor sites, both in cell suspensions and membrane fractions. Evaluation of these peptide receptors appears to reflect additional characteristics of biological behaviour of these human breast cancer cells. The synthetic LH-RH agonist Ovurelin [( d-Phe 6),des-Gly 10-LH-RH-ethylamide] can directly interfere (25–30%) with the proliferation of MDA-MB-231 human breast cancer cells in culture. The inhibitory effect of Ovurelin in vitro was negligible in the MCF-7 cell line. In the in vivo experiments the treated immunosuppressed mice bearing either MCF-7 or MDA-MB-231 xenografts responded to the high-dose LH-RH analogue Zoladex depot and Decapeptyl depot therapy. Since the MDA-MB-231 tumour was found to be ER-negative it seems possible that the regression of this xenograft results from the direct antitumour action of the LH-RH agonist.

Treatment of children with central precocious puberty by a slow-release gonadotropin-releasing hormone agonist

A total of 82 patients (74 girls, 8 boys) are presently participating in an international multicentre trial for treatment of central precocious puberty (CPP) with a slow release gonadotropin-releasing hormone (GnRH) agonist depot preparation: Decapeptyl-Depot (DD). Of these patients, 53 (3 boys) were previously untreated (group 1) and 29 (5 boys) have been treated before with either a short-acting GnRH analogue or cyproterone acetate (group 2). Fifty-one patients (44 girls, 7 boys) were treated with DD for 12 months or more. Basal plasma luteinizing hormone (LH) levels decreased in both groups after 1 year of therapy. The LH response to intravenous GnRH was reduced in both groups. Basal plasma follicle stimulating hormone (FSH) levels decreased in both groups. Stimulated FSH levels were reduced in both groups after 1 year of DD treatment. Plasma oestradiol levels in the girls decreased to prepubertal levels in both groups. In all patients the clinical signs of precocious gonadarche such as breast development and menstruations (girls) and an increased testis volume (boys), did not further progress and sometimes regressed in several patients. Growth velocity decreased in the girls of group 1 from 9.0 +/- 0.72 cm/year (mean +/- SEM) in the last half-year before treatment to 6.3 +/- 0.50 in the first half-year of treatment (P less than 0.01) and to 4.5 +/- 0.23 cm/year in the second half-year (P less than 0.01). After 12 months a stabilization of growth velocity was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression with Gonadotropin-Releasing Hormone Analogues Prior to Stimulation with Gonadotropins: Comparison of Three Protocols

This study compared three groups of patients treated with three different protocols of suppression of the pituitary-ovarian axis prior to and during gonadotropin stimulation for in vitro fertilization with a nonsuppressed control group. Patients treated with daily injections of DTRp6 (Decapeptyl 0.5 mg) or with a single injection of Decapeptyl depot (3.2 mg CR) had a longer folicular phase than patients treated with Buserelin (1.2-1.5 mg daily) and the patients in the control group. The number of human menopausal gonadotropin ampules required to reach adequate stimulation was also significantly higher in the former two groups of patients. The number of oocytes recovered (6-7 per patient), fertilized (45-58%) and cleaved (92-100%) did not differ among the groups. Peak estradiol levels and the pregnancy rate were highest in the group treated with Buserelin. The overall picture would indicate that suppression with Buserelin was the least profound.