-
Frontiers in Pediatrics 2022Gonadotropin-releasing hormone agonists (GnRHa's) are the standard treatment for children with central precocious puberty (CPP). We aim to present data on available... (Review)
Review
Gonadotropin-releasing hormone agonists (GnRHa's) are the standard treatment for children with central precocious puberty (CPP). We aim to present data on available GnRHa options with an easy-to-review table and discuss factors that influence treatment selection. Five GnRHa's are currently FDA-approved and prescribed in the US and published data suggest similar safety and efficacy profiles over the first year of treatment. One- and 3-month intramuscular (IM) leuprolide acetate (LA) have long-term safety and efficacy data and allow for flexible dosing. Six-month IM triptorelin pamoate offers a longer duration of treatment, but without long-term efficacy and outcome data. Six-month subcutaneous (SQ) LA combines a SQ route of injection and long duration of action but lacks long-term efficacy and outcome data. The 12-month SQ histrelin acetate implant avoids injections and offers the longest duration of action, but requires a minor surgical procedure with local or general anesthesia. Factors in treatment selection include route of administration, needle size, injection volume, duration of action, and cost. The current GnRHa landscape provides options with varying benefits and risks, allowing physicians and caregivers to select the most appropriate therapy based on the specific needs and concerns of the child and the caregiver. Agents have different advantages and disadvantages for use, with no one agent displaying superiority.
PubMed: 36268040
DOI: 10.3389/fped.2022.968485 -
The New England Journal of Medicine Jul 2014Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer.
METHODS
In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials.
RESULTS
After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women.
CONCLUSIONS
In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.).
Topics: Adult; Androstadienes; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Estradiol; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Mastectomy; Middle Aged; Osteoporosis; Premenopause; Quality of Life; Tamoxifen; Triptorelin Pamoate
PubMed: 24881463
DOI: 10.1056/NEJMoa1404037 -
Investigative and Clinical Urology Jul 2019To investigate the changes in testosterone levels and rates of chemical castration following androgen-deprivation therapy (ADT) with goserelin, triptorelin, and... (Comparative Study)
Comparative Study
Effectiveness of three different luteinizing hormone-releasing hormone agonists in the chemical castration of patients with prostate cancer: Goserelin versus triptorelin versus leuprolide.
PURPOSE
To investigate the changes in testosterone levels and rates of chemical castration following androgen-deprivation therapy (ADT) with goserelin, triptorelin, and leuprolide.
MATERIALS AND METHODS
We retrospectively reviewed the medical records of 125 patients with prostate cancer treated with luteinizing hormone-releasing hormone (LHRH) agonists between January 2009 and December 2015. Changes in testosterone concentration during 9 months of ADT with goserelin 11.34 mg, triptorelin 11.25 mg, and leuprolide 11.25 mg were analyzed using a mixed model. The number of patients with serum testosterone below castration levels defined as various values (<50 ng/dL, <20 ng/dL, or <10 ng/dL) at 3, 6, and 9 months were also evaluated.
RESULTS
Of the 125 patients, 59 received goserelin, 44 received triptorelin, and 22 received leuprolide, respectively. The lowest mean testosterone levels during 9 months of treatment were achieved in patients treated with triptorelin, followed by those treated with leuprolide, and then by those treated with goserelin (p=0.001). Significant differences in chemical castration levels were observed only at <10 ng/dL, with 54.2% of goserelin, 93.2% of triptorelin, and 86.4% of leuprolide treated patients (p<0.001).
CONCLUSIONS
Three LHRH agonists showed comparable efficacy for achieving castration when the castration threshold was 50 or 20 ng/dL. However, triptorelin was the most potent LHRH agonist, achieving the lowest mean testosterone levels and the highest rate of chemical castration at <10 ng/dL testosterone.
Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Retrospective Studies; Treatment Outcome; Triptorelin Pamoate
PubMed: 31294133
DOI: 10.4111/icu.2019.60.4.244 -
Journal of Clinical Oncology : Official... Apr 2020The Tamoxifen and Exemestane Trial (TEXT)/Suppression of Ovarian Function Trial (SOFT) showed superior outcomes for premenopausal women with hormone receptor...
PURPOSE
The Tamoxifen and Exemestane Trial (TEXT)/Suppression of Ovarian Function Trial (SOFT) showed superior outcomes for premenopausal women with hormone receptor (HR)-positive breast cancer treated with adjuvant exemestane plus ovarian function suppression (OFS) or tamoxifen plus OFS versus tamoxifen alone. We previously reported the magnitude of absolute improvements in freedom from any recurrence across a continuous, composite measure of recurrence risk to tailor decision making. With longer follow-up, we now focus on distant recurrence.
METHODS
The TEXT/SOFT HR-positive/human epidermal growth factor receptor 2 (HER2)-negative analysis population included 4,891 women stratified by predetermined chemotherapy use. Kaplan-Meier estimates of 8-year freedom from distant recurrence were analyzed using subpopulation treatment effect pattern plot (STEPP) methodology across subpopulations defined by the continuous composite measure of recurrence risk. For each patient, the composite risk value was obtained from a Cox model that incorporated age; nodal status; tumor size; grade; and estrogen receptor, progesterone receptor, and Ki-67 labeling index expression levels.
RESULTS
The overall rate of 8-year freedom from distant recurrence was 91.1% and ranged from approximately 100% to 63% across lowest to highest composite risks. TEXT patients who received chemotherapy had an average absolute improvement with exemestane plus OFS versus tamoxifen plus OFS of 5.1%, and STEPP analysis showed improvements from less than 1% to more than 15% from lowest to highest composite risks. SOFT patients who remained premenopausal after chemotherapy had an average 5.2% absolute improvement with exemestane plus OFS versus tamoxifen and reached 10% across composite risks; for tamoxifen plus OFS versus tamoxifen, the maximum improvement was approximately 3.5%. Women who did not receive chemotherapy had a more than 97% rate of 8-year freedom from distant recurrence, and improvements with exemestane plus OFS ranged from 1% to 4%.
CONCLUSION
Premenopausal women with HR-positive/HER2-negative breast cancer and high recurrence risk, as defined by clinicopathologic characteristics, may experience a 10% to 15% absolute improvement in 8-year freedom from distant recurrence with exemestane plus OFS versus tamoxifen plus OFS or tamoxifen alone. The potential benefit of escalating endocrine therapy versus tamoxifen alone is minimal for those at low recurrence risk.
Topics: Androstadienes; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Female; Humans; Neoplasm Recurrence, Local; Ovariectomy; Ovary; Premenopause; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Triptorelin Pamoate
PubMed: 31618131
DOI: 10.1200/JCO.18.01967 -
Aging Oct 2022As a widely applied traditional Chinese medicine (TCM), Jian-Pi-Yi-Shen (JPYS) decoction maybe applied in curing premature ovarian failure (POF) besides chronic kidney...
As a widely applied traditional Chinese medicine (TCM), Jian-Pi-Yi-Shen (JPYS) decoction maybe applied in curing premature ovarian failure (POF) besides chronic kidney disease (CKD). experiments, 40 female SD (8-week-old) rats were randomized into four groups, namely, control group (negative control), POF model group, JPYS treatment group, and triptorelin treatment group (positive control). JPYS group was treated with JPYS decoction (oral, 11 g/kg) for 60 days, and the triptorelin group was treated with triptorelin (injection, 1.5 mg/kg) for 10 days before the administration of cyclophosphamide (CTX) (50 mg/kg body weight) to establish POF model. We examined apoptosis, mitochondrial function, and target gene (ASK1/JNK pathway and mitochondrial fusion/fission) expression. experiments, the KGN human granulosa cell line was used. Cells were pretreated with CTX (20, 40, and 60 μg/mL) for 24 h, followed by JPYS-containing serum (2, 4, and 8 %) for 24 h. Thereafter, these cells were employed to assess apoptosis, mitochondrial function, and target gene levels of protein and mRNA. , JPYS alleviated injury and suppressed apoptosis in POF rats. In addition, JPYS improved ovarian function. JPYS inhibit apoptosis of granulosa cells through improving mitochondrial function by activating ASK1/JNK pathway. , JPYS inhibited KGN cell apoptosis through inhibited ASK1/JNK pathway and improved mitochondrial function. The effects of GS-49977 were similar to those of JPYS. During POF, mitochondrial dysfunction occurs in the ovary and leads to granulosa cell apoptosis. JPYS decoction improves mitochondrial function and alleviates apoptosis through ASK1/JNK pathway.
Topics: Rats; Female; Humans; Animals; Primary Ovarian Insufficiency; Triptorelin Pamoate; Drugs, Chinese Herbal; Apoptosis; Granulosa Cells; Mitochondria
PubMed: 36309912
DOI: 10.18632/aging.204320 -
Frontiers in Pediatrics 2023Central precocious puberty (CPP) results from premature activation of hypothalamic-pituitary-gonadal axis, with the consequent increase of gonadotropin-releasing hormone...
INTRODUCTION
Central precocious puberty (CPP) results from premature activation of hypothalamic-pituitary-gonadal axis, with the consequent increase of gonadotropin-releasing hormone (GnRH); GnRH agonists (GnRHa) represent the gold-standard therapy in children with CPP although their use might be responsible for pituitary GnRH receptors down-regulation, that in turn suppresses luteinizing hormone (LH) and follicle stimulating hormone (FSH) and blocks of gonadal sex hormones release. The most prescribed GnRHa in the clinical practice are leuprolide and triptorelin, whose use is generally safe and well tolerated; however, mild menopausal-like side effects could appear. The aim of the present study was to investigate and compare the efficacy and tolerability profile of leuprolide and triptorelin in CPP patients.
METHODS
110 girls affected by CPP were enrolled in this retrospective study, carried out from 2018 to 2020. The enrolled patients received leuprolide ( = 48) or triptorelin ( = 62). Efficacy was investigated by the means of clinical parameters and radiological changes and side effects were also recorded to evaluate the possible relationship between the two GnRHa treatments and side effects appearance.
RESULTS
At baseline triptorelin patients had significantly higher LH and LH peak levels than leuprolide patients, whereas no significant difference in other patient characteristics was observed between the two groups. The leuprolide treatment lasted 971 days [790-1,171 days] while the duration of triptorelin administration was 792 days [760-1,003 days] ( < 0.001). Overall 46 (41.8%) of the studied patients reported mild menopausal-like symptoms: among these 27 were treated with triptorelin and 19 with leuprolide ( = 0.558). Patients treated with triptorelin, or leuprolide showed headache (27.4% vs. 16.7%), mood swings (12.9% vs. 16.7%), increased appetite (12.9% vs. 18.8%) and nausea (1.6% vs. 10.4%) respectively. Moreover, the onset of side effects appearance related to GnRHa therapy significantly reduces with the increase of the initial bone age ( = 0.038).
CONCLUSION
Leuprolide and triptorelin treatment appear to be effective and safe without significant difference between the two drugs in term of efficacy and tolerability, making both good options for treating CPP.
PubMed: 37266535
DOI: 10.3389/fped.2023.1170025 -
Translational Pediatrics Sep 2021This study aimed to explore the effects of triptorelin and leuprolide on serum hormone levels and the clinical efficacy of girls with idiopathic central precocious...
BACKGROUND
This study aimed to explore the effects of triptorelin and leuprolide on serum hormone levels and the clinical efficacy of girls with idiopathic central precocious puberty (ICPP).
METHODS
Retrospective analysis was performed on 128 girls with ICPP who were diagnosed and treated in our hospital from January 2017 to January 2020, including 71 girls in the leuprolide group and 57 girls in the triptorelin group. The differences of serum sex hormone level, ovarian volume, uterine volume, follicle diameter, bone age, growth rate (height change within half a year), maturity (bone age/living age), and other aspects between the two groups of girls were compared.
RESULTS
Before treatment, there was no significant difference in the baseline levels of sex hormones [estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH)] between the triptorelin group and the leuprorelin group (P>0.05). After 1 year of treatment, serum levels of E2 and FSH in the triptorelin group were lower than those in the leuprolide group (P<0.05). There was no significant difference in LH levels between the two groups after 1 year of treatment (P>0.05). At baseline, there was no significant difference in the ovarian volume, follicle diameter, and uterine volume between the triptorelin group and the leuprolide group (P>0.05). After 1 year of treatment, the ovarian volume, follicle diameter, and uterine volume of the girls in the triptorelin group were all lower than those in the leuprolide group (P<0.05). Before treatment, there was no statistical difference in bone age, growth rate, and maturity between the triptorelin group and the leuprolide group (P>0.05). After 1 year of treatment, the growth rate and maturity of participants in the triptorelin group were lower than those in the leuprolide group (P<0.05). There was no significant difference in bone age between the two groups after 1 year of treatment (P>0.05).
CONCLUSIONS
For girls with ICPP, triptorelin is superior to leuprolide in reducing sex hormone level, reducing uterine volume, follicle diameter, ovarian volume, slowing down the growth rate, and decreasing maturity. Triptorelin should be selected as a priority for the treatment of girls with ICPP.
PubMed: 34733671
DOI: 10.21037/tp-21-352 -
The Journal of Clinical Endocrinology... Jun 2023Limited data exist regarding whether the endocrine response to the gonadotropin-releasing hormone receptor agonist (GnRHa) triptorelin differs in women with polycystic... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Limited data exist regarding whether the endocrine response to the gonadotropin-releasing hormone receptor agonist (GnRHa) triptorelin differs in women with polycystic ovary syndrome (PCOS) compared with healthy women or those with hypothalamic amenorrhea (HA).
OBJECTIVE
We compared the gonadotropin response to triptorelin in healthy women, women with PCOS, or those with HA without ovarian stimulation, and in women with or without polycystic ovaries undergoing oocyte donation cycles after ovarian stimulation.
METHODS
The change in serum gonadotropin levels was determined in (1) a prospective single-blinded placebo-controlled study to determine the endocrine profile of triptorelin (0.2 mg) or saline-placebo in healthy women, women with PCOS, and those with HA, without ovarian stimulation; and (2) a retrospective analysis from a dose-finding randomized controlled trial of triptorelin (0.2-0.4 mg) in oocyte donation cycles after ovarian stimulation.
RESULTS
In Study 1, triptorelin induced an increase in serum luteinizing hormone (LH) of similar amplitude in all women (mean peak LH: healthy, 52.3; PCOS, 46.2; HA, 41.3 IU/L). The AUC of change in serum follicle-stimulating hormone (FSH) was attenuated in women with PCOS compared with healthy women and women with HA (median AUC of change in serum FSH: PCOS, 127.2; healthy, 253.8; HA, 326.7 IU.h/L; P = 0.0005). In Study 2, FSH levels 4 hours after triptorelin were reduced in women with at least one polycystic morphology ovary (n = 60) vs normal morphology ovaries (n = 91) (34.0 vs 42.3 IU/L; P = 0.0003). Serum anti-Müllerian hormone (AMH) was negatively associated with the increase in FSH after triptorelin, both with and without ovarian stimulation.
CONCLUSION
FSH response to triptorelin was attenuated in women with polycystic ovaries, both with and without ovarian stimulation, and was negatively related to AMH levels.
Topics: Female; Humans; Polycystic Ovary Syndrome; Triptorelin Pamoate; Amenorrhea; Retrospective Studies; Prospective Studies; Luteinizing Hormone; Follicle Stimulating Hormone; Anti-Mullerian Hormone
PubMed: 36653328
DOI: 10.1210/clinem/dgad026