BACKGROUND: Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH. METHODS: Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0-3 months) and a follow-up phase (3-12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance). RESULTS: Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ± 2.3 mL and 4.1 ± 1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ± 1.8 cm and 5.1 ± 1.6 cm (P < 0.05, t = 3.083), the PD reached 2.4 ± 0.5 cm and 2.0 ± 0.6 cm (P < 0.05, t = 2.224), respectively, in the two groups. At the end of 6 months of treatment, biomarkers were in normal range in the two groups. Compared with the GnRH group, the testosterone (T) level and growth of PL and PD were significantly greater in the hCG/hMG group (all P < 0.05). While the TV of both groups increased, the difference was not statistically significant (P > 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference. CONCLUSIONS: The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research. TRIAL REGISTRATION ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.
Adolescent ; Adult ; Child ; Chorionic Gonadotropin/therapeutic use* ; Gonadotropin-Releasing Hormone ; Humans ; Hypogonadism/drug therapy* ; Male ; Menotropins/therapeutic use* ; Spermatogenesis ; Testosterone

To evaluate the efficacy and safety of aromatase inhibitor letrozole in treatment of male adolescents with idiopathic short stature (ISS). Seventy five boys with height less than 2 standard deviation (SD) below the mean who had entered puberty were enrolled in our study from 2004 to 2017, in the Pediatric Department of the First Affiliated Hospital, Sun Yat-Sen University. Among 75 patients, 28 in letrozole group received letrozole and spironolactone, 30 in gonadotrophin releasing hormone analogue (GnRHa) group received GnRHa injection and 17 had no intervention. Height velocity (HV), increment of bone age/chronological age (ΔBA/ΔCA), the final adult height (FAH) were compared among groups and the safety of letrozole treatment was evaluated. HV maintained faster during letrozole treatment when compared with other groups. HV during GnRHa treatment showed slightly decline in the first 6 months, but decreased remarkably after 6 months, and was significantly lower than that in letrozole group ( < 0.05). The maturation of BA slowed down in both letrozole and GnRHa groups. But the ΔBA/ΔCA in letrozole group during the first and the second year of treatment were significantly higher (0.67±0.09, 0.50±0.15, respectively) when compared with GnRHa group (0.59±0.16, 0.44±0.13, respectively) ( =2.78 and 2.20, all < 0.05). FAH in letrozole group and GnRHa group were (170±4) cm and (170±6)cm, there was no significant differences between the two groups ( >0.05), and both were higher than that in no intervention group (162±4 cm, < 0.01). After 6 months of letrozole treatment, testicular volumes and serum testerone levels increased; 39.2% (11/28) boys had clinical manifestations of hyperandrogenemia, and 82.1% (23/28) boys had decreased serum high-density lipoprotein (HDL) levels. Serum levels of HDL and testerone returned normal and the hyperandrogenemia disappeared after the cessation of letrozole treatment. No significant changes in serum triglyceride, serum low-density lipoprotein (LDL), fating serum levels of insulin and glucose, HOMA-IR were observed. No abnormal liver function, myalgia, scoliosis or aggravations of scoliosis was found. Long term letrozole therapy during puberty in boys with ISS can delay bone maturation without significant decrease of linear growth, and thus can improve the final adult height. No severe adverse reactions were found.
Adolescent ; Body Height ; Bone Development ; Child ; Gonadotropin-Releasing Hormone ; Growth Disorders ; Humans ; Letrozole ; therapeutic use ; Male

OBJECTIVETo observe the therapeutic efficacy and safety of gonadotropin-releasing hormone agonist (GnRHa) combined Wenshen Xiaozheng Decoction (WXD) in auxiliary treating endometriosis after laparoscopy.

METHODSOne hundred and thirty-four endometriosis patients with confirmative pathological diagnosis were assigned to three groups depending on whether they would receive adjuvant therapy or Chinese medicine treatment, i.e., the control group, the observation 1 group, and the observation 2 group. The 22 patients in the control group received no adjuvant therapy after laparoscopy. The 42 patients in the observation 1 group were treated with GnRHa 3.6 mg by subcutaneous injection starting from the 1st day to the 5th day of menstruation, once per 28 days. The 70 patients in the observation 2 group were treated with GnRHa 3.6 mg by subcutaneous injection in combination with WXD starting from the 1st day to the 5th day of menstruation, once per 28 days. They also took WXD for 7 doses, one cycle per every 28 days. The treatment lasted for three to six months. Serum levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and cancer antigen 125 (CA125), as well as clinical efficacy, and adverse drug reactions were observed before and after treatment.

RESULTSThere was statistical difference in serum levels of E2, FSH, or LH between the control group and the observation 1 and 2 groups (P < 0.05). There was no statistical difference in serum levels of E2, FSH, or LH between the observation 1 group and the observation 2 group (P > 0.05). There was statistical difference in the clinical efficiency among the 3 groups (P < 0.05). There was statistical difference in the pre-post difference of CA125 levels among the three groups (P < 0.01). Compared with the control group, there was no statistical difference in the pre-post difference of CA125 levels between the observation 1 group and the observation 2 group (P > 0.05). No obvious adverse reaction occurred during the treatment.

CONCLUSIONSGnRHa combined WXD showed confirmative clinical efficacy in treating endometriosis after laparoscopy. It also could lower serum levels of E2, FSH, and LH levels. So it was an ideal solution for treatment of endometriosis.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Endometriosis ; drug therapy ; surgery ; Female ; Gonadotropin-Releasing Hormone ; therapeutic use ; Humans ; Laparoscopy ; Treatment Outcome

OBJECTIVETo evaluate the impact of the concentration of circulating luteinizing hormone (LH) in the late-follicle phase on the outcome of in vitro fertilization for normogonadotrophic women.

METHODSIntracytoplasmic sperm injection treatment was conducted in 432 consecutive cycles of normogonadotrophic women. A stimulation protocol with mid-luteal gonadotropin-releasing hormone (GnRH) agonist down-regulation and ovarian stimulation with follicle stimulating hormone (FSH) was used in all cycles. hMG was added when a follicle of > or = 14 mm was present (FSH + hMG group), not in the control group (FSH-alone). LH and oestradiol concentration in the serum on hCG day were detected. Based on LH levels, patients in the FSH + hMG group were again divided into four subgroups: LH < or = 1, 1 < LH < or = 2, 2 < LH < or = 3, and 3 < LH < or = 10 IU/L.

RESULTSOestradiol concentration on the day of hCG injection in the FSH + hMG group was higher than that in the FSH-alone group [(3435.51 +/- 2029.01) pg/ml vs (2620.62 +/- 1604.80) pg/ml, P < 0.05]. More embryos were transferred in the FSH-alone group than in the FSH + hMG group [(2.77 +/- 0.45) vs (2.22 +/- 0.46), P <0.001]. Fertilization rate, implantation rate, and clinical pregnancy rate were similar between the FSH-alone group and the FSH + hMG group (77.52% vs 78.31%, 41.42% vs 41.68%, 64.56% vs 62.64%, P > 0.05), as well as among the four subgroups of the FSH + hMG group (P > 0.05).

CONCLUSIONThe adding of suitable amount of hMG and physiologically limited LH concentration in the late-follicle phase have no negative effect on the outcome of in vitro fertilization/intracytoplasmic sperm injection for normogonadotrophic women.

Adult ; Down-Regulation ; Estradiol ; blood ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone ; therapeutic use ; Follicular Phase ; Gonadotropin-Releasing Hormone ; agonists ; Humans ; Luteinizing Hormone ; blood ; Ovulation Induction ; Treatment Outcome

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

BACKGROUNDRecently, conservative surgery is acceptable in young patients with borderline ovarian tumor and ovarian cancer. The preservation of these patients' future fertility has been the focus of recent interest. This study aimed to observe the effect of gonadotropin-releasing hormone agonists (GnRHa) cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients.

METHODSSixteen patients who were treated with fertility preservation surgery for borderline ovarian tumor and ovarian cancer and then administered GnRHa during chemotherapy in Peking University People's Hospital from January 2006 to July 2010 were retrospectively analyzed. This group was compared with a control group of 16 women who were treated concurrently with similar chemotherapy (n = 5) without GnRHa or were historical controls (n = 11). The disease recurrence, the menstruation status and reproductive outcome were followed up and compared between the two groups.

RESULTSThere were no significant differences between both groups regarding age, body weight, height, marriage status, classification of the tumors, stage of the disease, as were the cumulative doses of each chemotherapeutic agent. One (1/16) patient in the study group while 2 (2/16) patients in the control group relapsed 2 years after conclusion of the primary treatment (P > 0.05). All of the 16 women in the study group compared with 11 of the 16 patients in the control group resumed normal menses 6 months after the termination of the treatment (P < 0.05). There were 4 spontaneous pregnancies in the study group while 2 in the control group, all of the neonates were healthy.

CONCLUSIONSGnRHa administration before and during chemotherapy in borderline ovarian tumor and ovarian cancer patients who had undergone fertility preservation operation may bring up higher rates of spontaneous resumption of menses and a better pregnancy rate. Long-term follow up and large scale clinical studies are required.

Adult ; Antineoplastic Agents ; therapeutic use ; Female ; Gonadotropin-Releasing Hormone ; agonists ; therapeutic use ; Humans ; Infertility, Female ; Ovarian Neoplasms ; drug therapy ; Pregnancy ; Pregnancy Rate ; Young Adult

OBJECTIVETo investigate the apoptosis-related mechanisms of levenorgestrel-releasing intrauterine system (LNG-IUS), oral medroxyprogesterone (MPA), and injective gonadotrophic hormone releasing hormone agonist (GnRHa) on eutopic endometrium of patients with endometriosis. Methods We collected the samples of endometrium from patients with endometriosis before operation and after insertion of LNG-IUS, administration of oral MPA, or injection of GnRHa. The ultrastructure of endometria was observed and compared by electron microscopy. Apoptotic cells were assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick-end labeling (TUNEL) assay, and the expressions of Bax, Fas, and Fas-L mRNA were determined by semi-quantitative reverse transcription-polymerase chain raction. Results After have been exposured to LNG-IUS, the apoptotic rate of endometrial epithelial cells and stromal cells increased from (24. 4 +/- 35.0)% to (51.0 +/- 37.8)% (P = 0.027) and (35.3 +/- 30.2)% to (76.4 +/- 11.2)% (P = 0.008), respectively. The degree of apoptosis under transmission electron microscopy was in an order of GnRHa > LNG-IUS > MPA. The expression of Fas-L mRNA in eutopic endometrium of patients with endometriosis was significantly higher than that of the normal control (P < 0.05). The expressions of three apoptosis-related proteins had no significant difference.

CONCLUSIONMedical treatments can increase the apoptosis of eutopic endometrial cells, and such effect was strongest in GnRHa and relatively weaker in LNG-IUS and MPA.

Apoptosis ; Endometriosis ; drug therapy ; pathology ; Endometrium ; drug effects ; pathology ; ultrastructure ; Female ; Gonadotropin-Releasing Hormone ; agonists ; Humans ; Intrauterine Devices, Medicated ; Levonorgestrel ; therapeutic use ; Medroxyprogesterone ; therapeutic use

OBJECTIVETo observe the effect of Kuntai Capsule (KC), a Chinese patent medicine, in add-back therapy for gonadotropin-releasing hormone agonist (GnRH-a) treatment for moderate-severe endometriosis (EM).

METHODSTotally 100 patients suffering from stage III/IV EM, who were confirmed by laparoscopic surgery were randomly assigned to the GnRH-a group (A) and the KC combined GnRH-a group (B), 50 in each group. Patients in Group A were hypodermically injected with goserelin (3.6 mg), once per 4 weeks. Those in Group B additionally took KC, 4 pills each time, three times per day. The therapeutic course for all was 12 weeks. Serum levels of estradiol (E2), follicle stimulating hormone (FSH), bone gamma-carboxyglutamic-acid-containing proteins (BGP) were measured respectively. Kupperman Menopausal Index (KMI) and bone mineral density (BMD) of the lumbar vertebra were also compared between the two groups.

RESULTSSerum levels of E2 and FSH both significantly decreased in the two groups at week 12 of the treatment (P < 0.05), when compared with pre-treatment. Compared with before treatment in the same group, KMI increased in the two groups (P < 0.05). Compared with before treatment in the same group, BMI decreased in the two groups with no statistical difference (P > 0.05). Serum BGP increased after 12-week treatment (P < 0.05). Compared with Group A after treatment, serum levels of E2 and FSH both significantly increased in Group B (P < 0.05). There was no statistical difference in KMI between the two groups (P > 0.05). As for the incidence of menopausal symptoms, better effects in improving symptoms such as hot flashes, sleep disorders, and vaginal dryness were obtained in Group B than in Group A (P < 0.05). There was no significant difference in the post-pre-treatment difference of BMI between the two groups, but with statistical post-pre-treatment difference in the BGP level (P < 0.05).

CONCLUSIONSHKC combined GnRH-a could effectively reduce GnRH-a treatment induced partial low estrogen symptoms, improve increased serum BGP levels after GnRH-a therapy.

Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Endometriosis ; drug therapy ; Estradiol ; blood ; Female ; Follicle Stimulating Hormone ; blood ; Gonadotropin-Releasing Hormone ; agonists ; Humans

OBJECTIVETo evaluate the application of gonadotrophin-releasing hormone antagonist (GnRH-ant) in patients with risk of poor response to controlled ovarian stimulation in IVF-ET.

METHODSClinical data of 48 patients undergoing IVF with or without ICSI were retrospectively analyzed. Among them 24 patients were allocated to the GnRH-ant protocol and 24 to the long gonadotrophin-releasing hormone agonist (GnRH-a) protocol. The duration of down-regulation, duration of stimulation, amps of gonadotropin estradiol level on hCG day, number of oocytes retrieved, fertilization rate, total embryos obtained, high quality embryo obtained, embryos transferred, embryos frozen, implantation rate per transfer, clinical pregnancy rate per transfer, embryo survival rate, clinical pregnancy rate per frozen embryos transfer and per cycle were compared between two groups.

RESULTThe duration of down-regulation, duration of stimulation, the amps of gonadotropin were significantly lower in the antagonist group than those in agonist group (P <0.001, <0.05, <0.05), the estradiol level on hCG day, the number of oocytes retrieved were significantly lower in the antagonist group than those in the agonist group (P<0.05, <0.05). No significant differences were noted in fertilization rate, total embryos obtained, high quality embryo obtained, embryos transferred, embryos frozen, implantation rate per transfer, clinical pregnancy rate per transfer, embryo survival rate, clinical pregnancy rate per frozen embryos transfer and per cycle.

CONCLUSIONCompared with long GnRH-a protocol, the GnRH-ant protocol in patients with risk of poor response can reduce the dosage of gonadotropin and shorten the duration of stimulation, although the estradiol level on hCG day and the number of oocytes retrieved are lower, which does not affect the implantation rate and clinical pregnancy rate.

Adult ; Embryo Transfer ; Female ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone ; agonists ; antagonists & inhibitors ; Hormone Antagonists ; pharmacology ; therapeutic use ; Humans ; Infertility, Female ; therapy ; Ovulation Induction ; methods ; Retrospective Studies

This study was performed to analyze retrospectively outcomes of stimulated in vitro fertilization (IVF) cycles where the gonadotropin-releasing hormone (GnRH) antagonist was omitted on ovulation triggering day. A total of 92 consecutive IVF cycles were included in 65 women who are undergoing ovarian stimulation with recombinant FSH. A GnRH antagonist, cetrorelix 0.25 mg/day, was started when leading follicle reached 14 mm in diameter until the day of hCG administration (Group A, 66 cycles) or until the day before hCG administration (Group B, 26 cycles). The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and the number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in Group B compared to Group A (2.7+/-0.8 vs. 3.2+/-0.9 ampoules). There was no premature luteinization in the subjects. The proportion of mature oocytes (71.4% vs. 61.7%) and fertilization rate of mature (86.3+/-19.7% vs. 71.8+/-31.7%) was significantly higher in Group B. There were no significant differences in embryo quality and clinical pregnancy rates. Our results suggest that cessation of the GnRH antagonist on the day of hCG administration during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising IVF results.
Adult ; Chorionic Gonadotropin/administration & dosage ; Drug Administration Schedule ; Estradiol/blood ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone/administration & dosage/blood ; Gonadotropin-Releasing Hormone/*antagonists & inhibitors ; Hormone Antagonists/*administration & dosage ; Humans ; Ovulation Induction/*methods ; Recombinant Proteins/therapeutic use ; Retrospective Studies